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Qi Xun Lim, Stavros Vellisaris, Christina Garnavou‐Xirou, Caroline Cobb
Published: 3 January 2022
Acta Ophthalmologica, Volume 100; https://doi.org/10.1111/j.1755-3768.2022.073

Abstract:
Purpose Trabeculectomy is the gold standard surgical option in managing glaucoma when intraocular pressure (IOP) is uncontrolled with topical anti-hypertensive. Bleb failure is not uncommon in trabeculectomy. Bleb needling is a relatively straightforward procedure that can be conducted to re-establish flow from the trabeculectomy.1,2 We aim to investigate treatment outcomes of MMC augmented needling of failing trabeculectomy blebs in NHS Tayside. Methods Retrospective cohort study was performed by reviewing clinical notes of all MMC-augmented bleb needling procedure after trabeculectomy performed in NHS Tayside from May 2012 to June 2016, patients were identified from surgical records. Data were analysed using IBM® SPSS software and R software (R Foundation for Statistical Computing, Vienna, Austria). Results 111 patients were identified, 34 excluded as they were lost to follo- ups or did not have clinical notes.86 eyes (77 patients) were included in this study. Median number of months between index filtration surgery and the first needling was 23 months. Mean IOP was reduced by 32.6% by the end of Year 1 (23.94 vs 16.14) and 40.4% by the end of Year 3 (23.94 vs 14.28).This was statistically significant at the 0.05 level.28 eyes (32.6%) required further surgical procedures to control IOP (repeat trabeculectomy, glaucoma drainage device, cyclodiode). 9 eyes (10.5%) had complications related to needling with 3 hyphema, 2 post-operative needling spike,and 1 each had bleb leak, aqueous misdirection, choroidal effusion and hypotony respectively. Conclusions Bleb needling is a safe procedure that can be carried out re-establish flow in failing trabeculectomy to achieve satisfactory control. Bibliography 1. Lin S, Byles D, Smith M. Long-term outcome of mitomycin C-augmented needle revision of trabeculectomy blebs for late trabeculectomy failure. Eye. 2018;32(12):1893-1899. 2. Panarelli J, Vinod K, Huang G, Sidoti P. Transconjunctival Revision With Mitomycin-C Following Failed Trabeculectomy. Journal of Glaucoma. 2016;25(7):618-622.
Julia Duwe
Published: 1 January 2022
The publisher has not yet granted permission to display this abstract.
Harry J. Levinson
Journal of Micro/Nanopatterning, Materials, and Metrology, Volume 21; https://doi.org/10.1117/1.jmm.21.1.010101

Abstract:
Editor-in-Chief Harry Levinson looks back on 2021. At the beginning of 2021, a plan that had long been in the making was executed, and SPIE’s Journal of Micro/Nanolithography, MEMS, and MOEMS was split into two parts. One piece became the Journal of Optical Microsystems, focused on the science and engineering of integrated photonic and optical systems, while the other became the current JM3, the Journal of Micro/Nanopatterning, Materials, and Metrology – this journal. Much of the work to make JM3 a high-quality journal is done by our senior and associate editors. Since most of the people serving on the JM3 editorial board in 2021 had been supporting our journal previously, their continuing contributions ensured a smooth transition at the beginning of last year. During 2021, a few new associate editors were added to the editorial board in order to bring expertise in subjects that are newly relevant to patterning technology or that have increased in significance in recent years. Our current editorial board is listed in Table 1. Table 1 Senior Editors Martin Burkhardt (IBM Corp., USA) Moshe Preil (Carl Zeiss. Inc., USA) Steven Hansen (ASML, USA) Martha Sanchez (LytEn. Inc., USA) Associate Editors Vivek Bakshi (EUV Litho Inc., USA) Catherine Labelle (Intel, USA) Xuemei Chen (KLA, USA) Lars Liebmann (Intel, USA) Chris Clifford (Siemens, USA) Qinghuang Lin (Lam Research, USA) Ralph Dammel (EMD Performance Materials, USA) Uzodinma Okoroanyanwu (University of Massachusetts, Amherst, USA) Danilo De Simone (imec, Belgium) Leo Pang (D2S, USA) Yasin Ekinci (Paul Scherrer Institute, Switzerland) Danping Peng (TSMC, USA) Hiroshi Fukuda (Hitachi High Technologies, Corp., Japan) Douglas J. Resnick (Canon Nanotechnologies, Inc., USA) Emily Gallagher (imec, Belgium) Kurt Ronse (imec, Belgium) Greg Gallatin (ASML, USA) Daniel G. Smith (Nikon Research, Corp., USA) Roel Gronheid (KLA, Belgium) Alexander Starikov (I&I Consulting, USA) Erik R. Hosler (PsiQuantum, LLC, USA) Bo Su (D2S, USA) Ryoung-han Kim (imec, Belgium) Yayi Wei (Chinese Academy of Sciences, China) Seong Sue Kim (Yonsei University, Republic of Korea) Notably during 2021 there were two special sections and one special series, compared to none during the prior year, as shown in Table 2. Nearly half of the papers published in JM3 in 2021 were in special sections. Creating a special section requires more work on the part of the editors than normal submissions, because a call for papers needs to be generated and contributions solicited. It should be noted that three of the guest editors are also on the editorial board, so they were doing double duty to serve the patterning community. Table 2 Special Section or Series Title Guest Editors EUV Masks Martin Burkhardt and Vicky Philipsen Masks and Lithography in the Era of Multi-beam Mask Writers Alan Brodie and Martha Sanchez Deep Learning for Lithography and Photomask Applications Leo Pang For a peer-reviewed journal such as JM3, it is expected that a significant amount of information be included by authors in their papers. However, JM3 serves engineers and scientists in industry, and the need for companies and many research institutes to protect certain information is recognized. Accordingly, a set of guidelines was generated in 2021 to provide guidance to authors, editors, and reviewers for balancing between disclosure typical for a peer-reviewed journal and the needs of people in industry. These were published in a series of editorials in JM3 during the past year, and they are included in the overall guidelines for authors. Our technical community is fortunate to have a committed staff at SPIE for assistance and support. All that was accomplished in 2021 resulted from the efforts of SPIE staff, who continued to provide excellent support to editors, authors, and reviewers. With a good start in 2021, it is hoped that the Journal of Micro/Nanopatterning, Materials, and Metrology will continue the tradition of quality established by prior journals that went by the acronym JM3, and that this journal will remain a valuable resource for the community of engineers and scientists in the semiconductor industry who are involved with patterning technology.
Revista Rosa dos Ventos - Turismo e Hospitalidade, Volume 13, pp 1-26; https://doi.org/10.18226/21789061.v13i4p26

Abstract:
The purpose of this study is to reveal the effect of Covid-19 fear on travel intention and to test the mediating effect of reliance on vaccine in the relationship between fear of Covid-19 and travel intention. In this context, a structural model was created to examine these three variables: the relationship among fear of Covid-19, travel intention and trust in the vaccine. The quantitative study was carried out through a structural model in order to verify the behavior of the three variables together using Ibm Amos 24 package. A case study based on data collected from 467 public employees across Turkey supported empirically the study. At the end of the analysis, it was found that the fear of Covid-19 significantly and negatively affected the travel intention, while the fear of covid-19 significantly and negatively affected the trust in the vaccine, and no significant relationship was found between the trust in the vaccine and the travel intention. In the model in which the mediation effect was tested, it was found that trust in vaccine did not have a mediating effect on the relationship between fear of Covid-19 and travel intention. Considering these results, suggestions were made for the decision makers of travel, tourism and hospitality industry to be able to recover after the pandemic to create plan for policy and strategies. KEYWORDS Tourism; Covid-19; Fear; Vaccine; Intention to Travel; Turkey.  RESUMO O objetivo deste estudo é o de revelar o efeito do medo da Covid-19 na intenção de viajar, e testar o efeito mediador da confiança na vacina na relação entre este medo e a intenção de viajar. Neste contexto, foi criado um modelo estrutural para examinar a relação entre essas três variáveis: medo da Covid-19, intenção de viajar e confiança na vacina. Um estudo de caso quantitativo empírico, a partir de dados coletados junto a 467 funcionários públicos da Turquia, foi conduzido utilizando um modelo estrutural para testar o comportamento das três variáveis juntas, utilizando o pacote Ibm Amos 24. No final da análise, verificou-se que o medo da Covid-19 afetou significativa e negativamente a intenção de viajar, enquanto o medo da Covid-19, a confiança na vacina, e não foi encontrada nenhuma relação significativa entre a confiança na vacina e a intenção de viagem. No modelo em que o efeito de mediação foi testado, descobriu-se que a confiança na vacina não teve um efeito mediador na relação entre o medo da Covid-19 e a intenção de viagem. Considerando estes resultados, foram feitas sugestões para que os tomadores de decisão no segmento de viagens, turismo e hospitalidade, pudessem se recuperar após a pandemia para criar um plano de políticas e estratégias. PALAVRAS-CHAVE Turismo; Covid-19; Medo; Vacina; Intenção de Viajar, Turquia.  AUTORIAGökhan Onat: Master. PhD candidate in the Department of Gastronomy and Culinary Arts at Nevşehir Hacı Bektaş Veli University. He is a research assistant at Recep Tayyip Erdogan University, Rize, Turkey. Orcid: https://orcid.org/0000-0001-5072-948X Email: [email protected] Yusuf Karakuş: Doctor. Professors in the Ardeşen Vocational School, Department of Tourism and Travel Services at Recep Tayyip Erdoğan University in Turkey, Rize, Turkey. He is also associate editor of Journal of Multidisciplinary Academic Tourism. Orcid: https://orcid.org/0000-0002-4878-3134 Email: [email protected] , Thiago Duarte Pimentel: Doctor. PhD of Social Sciences/UFJF (2012). Professor and full time researcher at Universidade Federal de Juiz de Fora, Juiz de For a, MG, Brasil. Curriculum: http://lattes.cnpq.br/9841188234449467 E-mail: [email protected] Yunus Doğan: Master. PhD candidate in the Department of Tourism Management, Nevşehir Hacı Bektaş Veli University. He works as a full-time employee at the Social Security Institution of Turkey, Rize, Turkey. Orcid: https://orcid.org/0000-0003-3145-8404 Email: [email protected]  REFERENCES Ahorsu, D. K., Lin, C. Y., Imani, V., Saffari, M., Griffiths, M. D., & Pakpour, A. H. (2020). The fear of Covid-19 scale: development and initial validation. International Journal of Mental Health and Addiction, 1-9. Link Aljazeera. (2020, 03 junho). Coronavirus: travel restrictions, border shutdowns by country | coronavirus pandemic news. Al Jazeera. Link Atay, L. (2020). KOVID-19 Salgını ve Turizme Etkileri. Seyahat ve Otel İşletmeciliği Dergisi, 17(1), 168–172. Link Ayittey, F. K., Ayittey, M. K., Chiwero, N. B., Kamasah, J. S., & Dzuvor, C. (2020). Economic impacts of Wuhan 2019‐nCoV on China and the world. Journal of Medical Virology, 92(5), 473–475. Link Bentler, P. M. (1992). On the fit of models to covariances and methodology to the Bulletin. Psychological Bulletin, 112(3), 400-404. Link Boğan, E., & Dedeoğlu, B. B. (2019). The influence of corporate social responsibility in hospitality establishments on students’ level of commitment and intention to recommend. Journal of Hospitality, Leisure, Sport and Tourism Education, 25, 100205. Link Büyüköztürk, Ş., Çakmak, E. K., Akgün, Ö. E., Karadeniz, Ş., & Demirel, F. (2009). Bilimsel Araştırma Yöntemleri. Ankara: Pegem Akademi Yayıncılık. Byrne, B. M....
O. S. Slavityak, N. V. Kovaleva, A. Yu. Bychkov, M. G. Semerzhyan, O. V. Voichun
Ukraïnsʹkij žurnal medicini, bìologìï ta sportu, Volume 6, pp 326-330; https://doi.org/10.26693/jmbs06.06.326

Abstract:
The purpose of the study was a comparative analysis of training programs in bodybuilding and an assessment of their influence on the frequency of traumatization of the musculoskeletal system of athletes. Materials and methods. Theoretical analysis of scientific and methodological literature was conducted. For a practical assessment of the primary data on the types of injuries, a survey of medical staff was conducted. We analyzed 54 journals with records of athletes' appeals to medical personnel. Mathematical processing of research results was carried out using the software packages IBM SPSS Statistics 2.0. The study, which was conducted during 4 months – from March to the end of June 2021, involved 60 bodybuilders aged 18-19 years old. Three research groups of 20 athletes each were formed. They were divided according to age, qualifications and anthropometric characteristics. The created groups did not have significant differences in these characteristics; the intergroup difference applied only to the proposed training programs. Results and discussion. In the course of the study, it was found that among the athletes of the control group who used the generally accepted program of training sessions with a certain sequence of using exercises of a basic and formative nature, the number of calls with certain pain sensations during four mesocycles of training decreased by 30.7% (p <0.05) compared to a similar period before the start of the study. At the same time, the results obtained show that among the athletes of the first main group, who used the combined program of training sessions in bodybuilding during the study, the controlled indicator of the number of calls decreased significantly – by 33.4% (p <0.05). Conclusion. In the process of studying the peculiarities of the influence of various programs of training sessions on the dynamics of morpho-functional indicators of the athletes’ organisms during four mesocycles of training sessions, a certain regularity was established regarding the ratio of the manifestations of types of injuries when performing strength exercises, depending on the sequence of their use. In the process of applying the methodical procedure "premature fatigue" on the dynamics of morphometric indicators of body weight of athletes it is shown that it is the third version of the program that contributes to a significant decrease in the number of calls (by 75%, p <0.05), compared with the results obtained over the period of the previous four mesocycles of intensive bodybuilding at the stage of specialized basic training of athletes
Alexandra Briasouli, Daniela Minkovska, Lyudmila Stoyanova
Technology transfer: fundamental principles and innovative technical solutions pp 13-16; https://doi.org/10.21303/2585-6847.2021.002228

Abstract:
Big Data has been created from virtually everything around us at all times. Every digital media interaction generates data, from computer browsing and online retail to iTunes shopping and Facebook likes. This data is captured from multiple sources, with terrifying speed, volume and variety. But in order to extract substantial value from them, one must possess the optimal processing power, the appropriate analysis tools and, of course, the corresponding skills. The range of data collected by businesses today is almost unreal. According to IBM, more than 2.5 times four million data bytes generated per year, while the amount of data generated increases at such an astonishing rate that 90 % of it has been generated in just the last two years. Big Data have recently attracted substantial interest from both academics and practitioners. Big Data Analytics (BDA) is increasingly becoming a trending practice that many organizations are adopting with the purpose of constructing valuable information from BD. The analytics process, including the deployment and use of BDA tools, is seen by organizations as a tool to improve operational efficiency though it has strategic potential, drive new revenue streams and gain competitive advantages over business rivals. However, there are different types of analytic applications to consider. This paper presents a view of the BD challenges and methods to help to understand the significance of using the Big Data Technologies. This article based on a bibliographic review, on texts published in scientific journals, on relevant research dealing with the big data that have exploded in recent years, as they are increasingly linked to technology
Oryza L Sari, Bobby Zafnat Fanneah Elwore, Basyaruddin Basyaruddin
Published: 20 December 2021
UKaRsT, Volume 5, pp 188-203; https://doi.org/10.30737/ukarst.v5i2.1615

Abstract:
In building construction, the implementation of maintenance activities plays an important role in the quality of the building. By carrying out these activities regularly, it’s hoped to minimize and prevent damage to buildings and make users feel comfortable. Kalimantan Institute of Technology must have comfortable study spaces. This study aims to determine the effect of the class maintenance factor on the user's comfort level. The analysis brought by determining what factors are influencing, these factors influence, and the most dominant factors affecting the most. Primary data was obtained by distributing questionnaires to respondents, secondary data inactive students, and lecturers at the Kalimantan Institute of Technology, and supporting research data in ministerial regulations, books, research journals, and others. The data analysis process uses IBM SPSS as an auxiliary program with multiple linear regression analysis methods. Based on the research and data processing conducted, it’s concluded that 8 factors influence the maintenance, namely the maintenance of user comfort by 80.8% and the variable maintenance of the room walls. The room wall maintenance variable is the most dominant factor influencing the comfort of classroom users. Knowing these factors can implement optimal implementation to support the comfort of class users at the Kalimantan Institute of Technologists.
, Evandro Aparecido de Oliveira Callegaro, Armando Sérgio De Aguiar Filho,
International Journal of Knowledge Engineering and Management, Volume 9, pp 144-164; https://doi.org/10.47916/ijkem-vol9n25-2020-82351

Abstract:
Objetivo: A Educação Corporativa é uma temática regida pelo intento das empresas de preencher uma lacuna deixada pelo Estado na educação tradicional. Contudo, trata-se de uma temática recente, tanto nos Estados Unidos, lócus de sua gênese, quanto no Brasil. Neste sentido, esta pesquisa tem por objetivo analisar quais as referências seminais e os autores mais prolíficos em Educação Corporativa, bem como estabelecer uma relação de quais referencias embasam as publicações dos autores que mais publicam nesse campo científico. Design/Metodologia/Abordagem: Trata-se de um estudo exploratório-descritivo de cunho bibliográfico, que emprega a abordagem quantitativa bibliométrica para analisar os resultados de buscas realizadas nas bases SCOPUS, SPELL e Scielo. Resultados: Por resultado, têm-se uma lista de 15 autores mais prolíficos, dos quais alguns também são os mais citados por outros pesquisadores Limitações da pesquisa: O diminuto número de pesquisa encontradas nas bases científicas restringe a amostragem desta pesquisa. Originalidade/valor: Acredita-se que esta pesquisa tende a contribuir para a academia por revelar bibliografias a serem consideradas por entrantes nessa temática. A busca por estabelecer os contornos temáticos que dialogam com a Educação Corporativa é uma sugestão de pesquisa futura. Referências ALBERTIN, A. L.; BRAUER, M. Resistência à educação a distância na educação corporativa Fonte: Revista de Administração Pública, v. 46, n. 5, p. 1367-1389, 2012. ALMEIDA, M. I. R.; TEIXEIRA, M. L. M.; MARTINELLI, D. P. Por que administrar estrategicamente recursos humanos? Revista de Administração de Empresas, v. 33, n. 2, p. 12-24, 1993. ALPERSTEDT, C. Universidades corporativas: discussão e proposta de uma definição. Revista de Administração Contemporânea, Curitiba, v. 5, n. 3, p. 149 165, set./dez. 2001. ANDRADE, R. J. F.; RODRIGUES, M. V. R. Educação corporativa: prática de treinamento na sociedade do conhecimento. In: CONGRESSO NACIONAL DE EXCELÊNCIA EM GESTÃO, 4., 2008, Niterói. Anais ... Niterói, RJ, 2008. BALM, G. J. Continuing Engineering Education at IBM. International Journal of Continuing Engineering Education and Life-Long Learning, v.1, n.1, p. 98-103, 1990. BIANCHI, E. M. P. G. Didática e educação corporativa: o desafio empresarial da educação continuada. Revista Ibero-Americana de Estratégia, v. 7, n. 1, p. 73-82, Janeiro-Junho, 2008. DRESCH, A.; LACERDA, D. P.; JÚNIOR, J. A. V. A. Design science research: método de pesquisa para avanço da ciência e tecnologia. Bookman Editora, 2015. EBOLI M. P.; MANCINI, S. Corporate education for sustainability. International Journal of Environment and Sustainable Development, v.11, n.4, p.339-354, 2012. EBOLI, M. P. (coord.). Coletânea Universidades Corporativas - Educação para as empresas do século XXI. São Paulo: Schmukler Editores, 1999. EBOLI, M. P. Educação Corporativa e desenvolvimento de competências. In: DUTRA J. S.; FLEURY, M. T. L.; RUAS, R. L. Competências: conceitos, métodos e experiências. São Paulo: Atlas, 2008. EBOLI, M. P. Educação corporativa no Brasil: mitos e verdades. 4. ed. São Paulo: Ed. Gente, 2004. EBOLI, M. P. Gestão do Conhecimento como Vantagem Competitiva: o surgimento das Universidades Corporativas. In: EBOLI, M. P. (coord.). Coletânea Universidades Corporativas - Educação para as empresas do século XXI. São Paulo: Schmukler Editores, 1999b. EBOLI, M. P. Universidade corporativa: ameaça ou oportunidade para as escolas tradicionais de Administração? RAUSP Management Journal, v. 34, n. 4, p. 56-64, 1999a. ESTEVES, L. P.; MEIRIÑO, M. J. A educação corporativa e a gestão do conhecimento. Anais... XI Congresso Nacional de Excelência em Gestão. 2015. FERNANDES, H. S.; PULZI, JR, S. A.; COSTA, FILHO, R. Qualidade em terapia intensiva. Revista da Sociedade Brasileira de Clínica Médica, v. 8, 2010, p. 37-45. HOURNEAUX JR, F.; EBOLI, M. P., MARTINS, E. C. Educação corporativa e o papel do Chief Learning Officer Fonte: Revista Brasileira de Gestão de Negócios, v. 10, n. 27, p. 105-117, Abril-Junho, 2008. MEISTER, J. C. Educação corporativa. São Paulo: Pearson, 1999. NONAKA, I.; TAKEUCHI, H. Criação de Conhecimento na Empresa: como as empresas japonesas geram a dinâmica da inovação. 19. ed. Rio de Janeiro: Elsevier, 1997. REIS, G. G., SILVA, L. M. T., EBOLI, M. P. A prática reflexiva e suas contribuições para a educação corporativa Fonte: Revista de Gestão, v. 17, n. 4, p. 403-419, Outubro-Dezembro, 2010. TACHIZAWA, T. FERREIRA, V. C. P.; FORTUNA, A. A. M. Gestão com pessoas: uma abordagem aplicada às estratégias de negócios. 5. ed. Editora FGV, Rio de Janeiro, 2006. TARAPANOFF, K. Aprendizado organizacional: panorama da educação corporativa no contexto internacional. In: TARAPANOFF, K. (org.). Inteligência, informação e conhecimento em corporações. Brasília: IBICT, UNESCO, 2006. p. 12-84. TRONDSEN E.; VICKERY, K. Learning on Demand. Journal of Knowledge Management, v.1, n.3, p.169-180, 1997.
Corrigendum
, Emilia Dimitrova, , Maya Stoimenova-Popova, Petranka Chumpalova, Ivanka Veleva, Eleonora Mineva-Dimitrova, Dancho Dekov
Published: 6 December 2021
Frontiers in Psychiatry, Volume 12; https://doi.org/10.3389/fpsyt.2021.812498

Abstract:
A Corrigendum onSocio-Demographic and Clinical Characteristics of Psychiatric Patients Who Have Committed Suicide: Analysis of Bulgarian Regional Suicidal Registry for 10 Yearsby Stoychev, K., Dimitrova, E., Nakov, V., Stoimenova-Popova, M., Chumpalova, P., Veleva, I., Mineva-Dimitrova, E., and Dekov, D. (2021). Front. Psychiatry 12:665154. doi: 10.3389/fpsyt.2021.665154 An author name was incorrectly spelled as Kalyan Stoychev. The correct spelling is Kaloyan Stoychev. In the original article, there was an error. “Pearson correlation coefficient” was incorrectly written as “Person correlation coefficient.” A correction has been made to Materials and Methods, Statistical Analysis, paragraph 1: “Study results, i.e., demographic, clinical, and suicide methods characteristics, were described as prevalence rates, means, and correlation coefficients. Categorical variables were presented as numbers and percentages, while continuous variables (when normally distributed) were expressed as means ± standard deviations (SDs). Comparisons between continuous variables for each pair of groups were performed by the Student's t-test (for normally distributed variables) and the Mann-Whitney U test (for variables with skewed distribution). Comparisons among continuous variables in three or more groups were performed by means of one-way ANOVA (for normally distributed variables) and the Kruskal-Wallis H test (for variables with skewed distribution). The magnitude of the relationship between continuous variables was measured by the Pearson correlation coefficient for linear relationships. Analysis was performed using IBM SPSS v. 25.0 software running on top of Windows 10 operating system equipped with Microsoft 2016 office pack. Statistical significance was set at p ≤ 0.05, i.e., a 95% confidence level was established.” The authors apologize for these errors and state that this does not change the scientific conclusions of the article in any way. The original article has been updated. All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. Keywords: suicide, risk factors, study, Bulgaria, mental disorders Citation: Stoychev K, Dimitrova E, Nakov V, Stoimenova-Popova M, Chumpalova P, Veleva I, Mineva-Dimitrova E and Dekov D (2021) Corrigendum: Socio-Demographic and Clinical Characteristics of Psychiatric Patients Who Have Committed Suicide: Analysis of Bulgarian Regional Suicidal Registry for 10 Years. Front. Psychiatry 12:812498. doi: 10.3389/fpsyt.2021.812498 Received: 10 November 2021; Accepted: 19 November 2021; Published: 06 December 2021. Approved by: Copyright © 2021 Stoychev, Dimitrova, Nakov, Stoimenova-Popova, Chumpalova, Veleva, Mineva-Dimitrova and Dekov. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. *Correspondence: Kaloyan Stoychev, [email protected]; Emilia Dimitrova, [email protected]; Vladimir Nakov, [email protected]
, Sidra Aamer, Fizza Sahar Anwar, Farah Farhan, Mehreen Wajahat,
European Journal of General Dentistry; https://doi.org/10.1055/s-0041-1739510

Abstract:
Objectives The aim of this study was to survey the educational experiences, knowledge, and attitude of dentists in Pakistan about the professional use of silver diamine fluoride (SDF). This study also aimed to determine if SDF educational experience at the undergraduate level can result in a more positive attitude and increased clinical usage of SDF. Materials and Methods This was a cross-sectional survey, conducted at multiple dental institutes across Pakistan using a pre-validated questionnaire to assess the knowledge, experience, and professional expertise of dentists regarding the use of SDF. The data were entered and analyzed using the SPSS (version 23.0) data management software by IBM. Results The results of this study were deemed significant in terms of achievement of the study aims. The majority of the responders, 178 (79.8%), reported online resources to be the main source of information about SDF treatment, whereas 103 (46.1%) responders gained information from a dental journal. A higher number of consultants were reported to be well educated regarding SDF treatment during their residency training as compared with demonstrators, house officers, and postgraduate trainees (p < 0.001). About 64 (28.7%) responders agreed that SDF is a better alternative treatment for children with behavioral issues, 74 (33.2%) agreed that it is a better treatment option for medically fragile patients, and 79 (35.4%) agreed that it can be used as an alternative for patients with dental anxiety. It was agreed by 82 (36.8%) responders that SDF is a good treatment option for patients who recently have received chemotherapy radiation therapy. Conclusion It is the need of time to put all educational efforts together to enhance knowledge regarding the use, advantages, and potential problems of SDF.
Baiyan Liu, Bing Yan, Hailin Jiang, Xuewei Zhao, Luyao Wang, Tie Li, Fuchun Wang
Published: 24 November 2021
Abstract:
Background: Functional diarrhea (FDr), one of the most common functional gastrointestinal diseases, is a kind of functional bowel disease characterized by repeated paste feces or watery feces. However, no relevant systematic review or meta-analysis has been designed to evaluate the effects of herbal acupoint application (HAA) on FDr. There is also a lack of systematic evaluation and analysis of acupoints and herbs. Methods: We will search the following 8 databases from their inception to October 15, 2021, without language restrictions: the Cochrane Central Register of Controlled Trials, PubMed, Embase, the Web of Science, the Chinese Biomedical Literature Database, the Chinese Scientific Journal Database, the Wan-Fang Database, and the China National Knowledge Infrastructure. The primary outcome measures will be clinical effective rate, functional outcomes, and quality of life. Data that meets the inclusion criteria will be extracted and analyzed using RevMan V.5.3 software (Available at: https://community.cochrane.org/help/tools-and-software/revman-5 ). Two reviewers will evaluate the studies using the Cochrane Collaboration risk of bias tool. We will use the Grading of Recommendations Assessment, Development and Evaluation approach to assess the overall quality of evidence supporting the primary outcomes. We will also use SPASS software (Version 19.0 (Available at: https://www.ibm.com/analytics/spss-statistics-software )) for complex network analysis to explore the potential core prescription of acupoint herbal patching for FDr. Results: This study will analyze the clinical effective rate, bristol stool scale, number of daily bowel movements, clinical symptom scale of diarrhea, and effective prescriptions of HAA for patients with FDr. Conclusion: The conclusion of our findings will provide evidence for the effectiveness and potential treatment prescriptions of HAA for patients with FDr.
Paola Ghanem, Joseph Murray, Melinda Hsu, David Ettinger, Josephine Feliciano, Patrick Forde, Christine Hann, Vincent Lam, Benjamin Levy, Julie Brahmer, et al.
Published: 10 November 2021
by BMJ
Journal for ImmunoTherapy of Cancer, Volume 9; https://doi.org/10.1136/jitc-2021-sitc2021.296

Abstract:
Background: Five-year survival analyses of patients receiving immune checkpoint inhibitors (ICIs) for metastatic non-small cell lung cancer (NSCLC) have demonstrated continued clinical benefit compared to chemotherapy.1 2 Our study aims at understanding and defining the unique clinical and genomic underpinnings of a durable response to ICI in advanced NSCLC.Methods: We conducted a retrospective case-control study using information abstracted from a Johns Hopkins IRB-approved database of NSCLC patients treated with an ICI-containing regimen. We defined long-term responders (LR) as patients who have achieved an overall survival (OS) of at least 3 years. We identified a comparison arm (C) of patients whose OS was less than a year. Univariate and multivariate analyses of the clinical and molecular characteristics were conducted between the LR and C groups using IBM Statistical Package for Social Sciences version 25.Results: A cohort of 89 patients were included; 41 patients as LR and 48 as C. Mean duration of ICI was 21.6 months and 3.5 months for LR and C, respectively. On univariate analysis, there was no statistically significant difference in age, sex, race, histology or treatment characteristics between arms. However, ECOG performance status (PS) of 2 (p=0.011) and evidence of liver metastases were independently associated with a shorter response to ICI (p=0.012). Increased PD-L1 expression was significantly associated with likelihood of LR status (OR= 1.018, p=0.027). 65.9% (n=27) of LR patients developed an immune-related adverse event (irAE), of which 20 patients required discontinuation of therapy. In the C arm, 16.7% (n=8) of patients developed an irAE of which 4 patients required discontinuation. On multivariate analysis, including age, sex, race, ethnicity, smoking status, BMI, PS, liver and brain metastases as well as the presence of common oncogenic molecular alterations, PS of < 2 was statistically significantly associated with an OS ≥3 years (OR=16.7, p= 0.017). Molecular profiling was completed in 53 patients (LR=29, C=24). Common molecular alterations were identified in 28 out of 53 patients (LR=16, C=12). KRAS mutation was assessed in 34 patients (LR=16, C=18) and was associated with LR status versus C (Fisher’s exact test value p=0.0386).Conclusions: Our retrospective study assessing multiple clinical and molecular determinants of patients with long-term response to immune checkpoint blockade, identified PS at diagnosis and KRAS mutation status to be associated with long-term response. Current efforts are ongoing to interrogate more deeply molecular features of LR, as well as their relationship to clinical aspects of a sustained benefit from ICI in NSCLC.References: Borghaei H, et al. Five-year outcomes from the randomized, phase III trials checkMate 017 and 057: nivolumab versus docetaxel in previously treated non–small-cell lung cancer. Journal of Clinical Oncology 0, JCO.20.01605, doi:10.1200/jco.20.01605 (2021) Reck M, et al. Five-year outcomes with pembrolizumab versus chemotherapy for metastatic non-small-cell lung cancer with PD-L1 tumor proportion score ≥ 50. J Clin Oncol 39:2339–2349, doi:10.1200/jco.21.00174 (2021) Ethics Approval: The retrospective case-control study has obtained ethics approval from the Institutional Review Board at the Johns Hopkins School of Medicine.
Megan B Sears-Smith, Lillian Charboneau, Renju Raj, R. Eric Heidel
Published: 5 November 2021
Blood, Volume 138, pp 4085-4085; https://doi.org/10.1182/blood-2021-147895

Abstract:
Introduction: Autologous stem cell transplant (ASCT) is considered standard of care in young and fit patients with newly diagnosed multiple myeloma. ASCT has shown to improve depth of response, progression free survival and overall survival compared to systemic therapy alone in myeloma patients (Harousseau et al. New England Journal of Medicine). Proximity to a stem cell transplant center may influence the utilization of this therapeutic option in transplant eligible multiple myeloma patients. Our cancer center did not have a stem cell transplant program in the 100-mile driving radius. The goal of this study was to assess the referral patterns and utilization of ASCT in newly diagnosed, young (age <65 years) multiple myeloma patients in a setting where patients are lacking proximity to a transplant center. Methods: The study was an IRB-approved retrospective cohort study. Patients between 18 and 65 years of age at the time of diagnosis who were diagnosed with multiple myeloma between January 1, 2014, and December 31, 2020, were included. Data including age at diagnosis, sex, race, zip code, treatment regimen, clinical data-including referral to a transplant center, stem cell collection and transplant-were collected and analyzed. Staging was calculated using lab values at the time of diagnosis or within 2 weeks of starting treatment. Date of diagnosis was defined as the date of bone marrow biopsy confirming systemic disease. All frequency and descriptive analyses were performed using SPSS Version 26 (Armonk, NY: IBM Corp.) Results: There were n = 62 patients that met the study inclusion criteria. Patients were mainly white (86%) and male (58%) with an average age at diagnosis of 55.9 (SD = 6.83) years. All patients (n = 62, 100%) lived at zip codes that were more than 100 miles from the closest transplant center. ISS staging showed 37% (n = 23, 95% CI 25% - 50%), 29% (n = 18, 95% CI 18% - 42%), and 18% (n = 11, 95% CI 9% - 30%) to have stage I, II, and III disease respectively. Twelve patients (n = 12, 19.4%, 95% CI 10.4% - 31.4%) had insufficient data for staging. The most common first line regimens were bortezomib, lenalidomide, and dexamethasone (n = 39, 62.9%, 95% CI 49.7% - 74.8%) and bortezomib, cyclophosphamide, and dexamethasone (n = 13, 21%, 95% CI 11.7% - 33.2%). Most patients (n = 48, 77.4%, 95% CI 65% - 87.1%) achieved a very good partial response or better. Eight (n = 8, 13%, 95% CI 5.7% - 23.9%) patients had refractory disease to first line therapy. Forty-six (n = 46, 74%, 95% CI 62% - 85%) patients were referred for HSCT evaluation, n = 16 (26%, 95% CI 15.5% - 38.5%) patients were not. Of the forty-six (n = 46) patients that were referred, n = 44 (96%, 95% CI 85% - 99.5%) patients had a clinical consultation with the transplant team. Of the entire cohort, n = 36 (58%, 95% CI 44.9% - 70.5%) patients underwent stem cell collection and n = 34 (55%, 95% CI 42% - 68%) patients underwent an ASCT after induction therapy. Conclusions: Our study found that more than one third of young patients with newly diagnosed multiple myeloma did not undergo stem cell collection or stem cell transplant. Lack of geographic access to a transplant center may be a contributing factor to the under utilization of this highly effective therapeutic strategy. Further investigation into interventions to improve ASCT referral and completion rates is imperative for improving outcomes for patients in such geographic locations. Disclosures: Raj: Amgen: Membership on an entity's Board of Directors or advisory committees; Jazz pharmaceuticals: Speakers Bureau; Glaxo-Smith Kline: Speakers Bureau.
, Layla Fatima, Abdul Moiz Ahmed, , , , , Sana Gul, , Farheen Malik, et al.
Published: 28 October 2021
by Cureus
Abstract:
Vaccine hesitancy has been a huge challenge in controlling preventable diseases. With the emergence of coronavirus disease 2019 (COVID-19) vaccines, it is vital to know their acceptance rates among the masses. No comparative data is available on the current subject from Pakistan yet. Therefore, this study aimed to evaluate the acceptance of a potential COVID-19 vaccine among the general population and healthcare workers (HCWs) of Pakistan, along with their perceptions and barriers to acceptance. An online cross-sectional study was carried out in Pakistan from December 19, 2020, to January 10, 2021, using convenience sampling. A self-administered questionnaire consisting of 31 items was distributed after informed consent. Inclusion criteria consisted of HCWs and non-HCWs (general population) aged 18 years and above, residing in Pakistan. All analyses were done using Statistical Package for Social Sciences (SPSS) version 23.0 (IBM Corp., Armonk, NY, USA). Chi-square and T-test were used and a p-value of less than 0.05 was considered significant for all cases. Of the 404 respondents (n=196 general population and n=208 HCWs), 73.5% were willing to get a proven, safe, and effective COVID-19 vaccine if it was free of cost. This was reduced to only 64.3% if the vaccine was not free and had to be paid for. A total of 168 (41.6%) participants agreed to get vaccinated immediately, while 149 (36.9%) participants concurred to get it on a delayed basis. Eighty-seven (21.5%) participants refused to receive the COVID-19 vaccine, amongst which a significant majority (p<0.001) of the participants were from the general population. Doctors or scientists/scholarly journals were found to be the most trusted source of information (67.6%; n=273), while fear of unknown side effects (45.5%; n=184) was found to be the most common barrier towards COVID-19 vaccination. More than half (53.5%) participants believed that the vaccine is safe, effective, and has minimal side effects, amongst which a significantly large fraction (p<0.001) belonged to the HCWs. The acceptance rate of a safe, effective, proven, and free COVID-19 vaccine was 73.5%. The fear of unknown side effects was the most common barrier to COVID-19 vaccine uptake. The general population demonstrated less knowledge, more false perceptions, and barriers to COVID-19 vaccine. Adequate measures should be taken to educate the masses about the COVID-19 vaccine, and its safety, and further studies are required.
Farzaneh Tofighi Zavareh, Yasser Bagheri, Abbas Ali Keshtkar
Published: 13 October 2021
Immunology and Genetics Journal; https://doi.org/10.18502/igj.v3i4.7464

Abstract:
Background: Common variable immunodeficiency (CVID) is the most frequent symptomatic primary immunodeficiency, which manifests a wide range of clinical phenotypes from recurrent infections of the respiratory system to autoimmunity, enteropathy and lymphoproliferative disorders. Some abnormalities in T and B lymphocyte subpopulations may associate with the development of such clinical complications. Aim of study: The main objective of this case-control study is to investigate the frequency and absolute count of different lymphocyte subsets in CVID patients as well as the cellular proliferation response. Correlation between lymphocyte abnormalities and different clinical phenotypes of the disease such as infection only (IO), autoimmunity (AI), chronic enteropathy (CE) and lymphoproliferative disorders (LP) are determined. We also aim to evaluate the prognosis of CVID for each clinical manifestation based on lymphocyte phenotype. Methods: A population of genetically unsolved CVID patients after whole exome sequencing (WES) will be subdivided into 4 clinical phenotypes i.e. IO, AI, CE and LP and an equal number of age and sex-matched healthy controls (HC) will be examined for the frequency of distinct subgroups of CD19+ B cells, CD4+ T cells and CD8+ T cells by flow cytometry. The proliferation response of their CD4+ T cells is then evaluated by Carboxyfluorescein succinimidyl ester (CFSE) test, using stimulation of isolated peripheral blood mononuclear cells with anti-CD3 and anti-CD28 antibodies. Data analysis will be assessed by parametric or nonparametric tests based on normality of data distribution using IBM SPSS Statistics, V.24 and Stata software V.14. Ethics and dissemination: Ethical approval of this study is received from the Ethics Committee of Tehran University of Medical Sciences (ID number: IR.TUMS.VCR.REC.1396.3380) and all participants will be asked to sign the informed consent statement. Due to the wide range of variables, objectives and questions, the findings of this study are intended to release as multiple publications in peer-reviewed journals and presented at national and international conferences.
Shaarna Shanmugavadivel, Danilo Buonsenso, Jo-Fen Liu, Tessa Davis, Damian Roland
Published: 30 September 2021
by BMJ
Abstract:
Background There is increasing recognition of the lack of diversity representation in all areas of medicine, in particular within medical education. Studies assessing diversity of skin tone image representation among textbooks and major scientific journals showed that the majority of images reported are in children with light skin tones. However, the impact of the lack of diversity of skin tone representation in medical resources on the ability of healthcare workers to recognise childhood skin conditions has not been explored. Objectives To assess diversity in medical training resources and its impact on self-confidence in diagnosing skin conditions on different skin tones of healthcare workers across the globe. Methods Participants were asked to log in to the online platform (www.dftbskindeep.com) and self-declare the following information: continent of practice, ethnicity, profession, specialty, years of experience, majority Training Resources (white skin, a mix of skin tones, darker skin tones only), and confidence in diagnosing skin conditions. Data analyses were performed using IBM SPSS 26.0 for Windows (IBM Corp, Armonk, NY USA). Categorical variables were presented as proportions, and Chi-squared or Fisher’s exact tests were used to compare the distribution between groups as appropriate. A p-value of <0.05 was deemed statistically significant in all analyses. Results 600 eligible participants were included in the analysis. Demographics Participants responded from all continents, although Europe (56%) and Oceania (23%) were the most represented. The majority of participants were white/Caucasian (69%). 439 (73%) were clinicians, mostly paediatricians (37%), emergency doctors (22%) paediatric emergency doctors (12%) and a minority were dermatologists (3%). Just over half of participants (56%) reported at least six years of practice since graduation. Training resources Participants were asked to report the majority of training resources used during their training. 441 (74%) reported that only white skin was usually represented, while resources including a mix of skin tones (24%) or other skin tones (3%) were rarely used. Self-confidence When diagnosing skin conditions in darker skin tones, participants reported that they are ‘generally uncertain if correct’ in 43% cases, ‘sometimes uncertain but clinically safe’ (43%), and ‘confident across a range of skin tones’ in a minority of cases (5%). Self-confidence levels were associated with geographical location (higher in Africa (4/14, 29%) and Latin America (1/9, 11%), (P < 0.001); diversity of training resources used (higher with a mix of skin tones (15/144, 10%) or darker skin tones only (3/15, 20%) (< 0.001); with longer working experience (6 to 10 (9/188, 5%) or >10 years of practice (18/159, 11%) (P < 0.001) and with specialty (higher in dermatologists (9/17, 53%, P < 0.001). Self-confidence was very low among paediatricians, emergency medicine and paediatric emergency medicine specialists (0.05). Conclusions Our study provides further support of the lack of diversity in training resources used by healthcare professionals on a global scale. Moreover, our findings provide preliminary evidence that this lack of diversity affects self-confidence in diagnosing skin conditions on a variety of skin tones.
Suripto Suripto, Dedy Suhendra, Sukiman Sukiman
Jurnal Pengabdian Magister Pendidikan IPA, Volume 4; https://doi.org/10.29303/jpmpi.v4i4.1031

Abstract:
The implementation of science and technology for community (IbM) farmer groups who are facing the problem of the cabbage caterpillar population explosion was carried out in Sembalun Lawang Village, East Lombok Regency. The IbM activity was designed based on the agreement between the IbM team and the Village Head of Sembalun Lawang together with the Sangka Bira Farmers Group and the Sebun Kedit Farmers Group in Sembalun Lawang Village. IbM activities are carried out with the stages of socialization, practice, and tutorials with various media used including blackboards, LCDs, manuals (leflet), seeds, saplings, specimens, and leaf dry powder of jayanti plants (S. sesban). Partners also provide media for this IbM activity, which includes cabbage plantations and water facilities. The results achieved at this stage are that farmers in Sembalun Lawang Village recognize jayanti plants as a source of natural insecticides, are skilled at drying leaves properly and making leaf solutions from Jayanti plants and trying to apply them as natural insecticides to control cabbage caterpillars on cabbage plants. The results of trials by farmers showed that direct administration of 50 ppm Jayanti leaf solution could kill 52 to 56% of cabbage caterpillars on cabbage plants. If the Jayanti leaf solution was stored for the previous 24 hours, then 50 ppm of the solution could only kill 15 to 16% of cabbage caterpillars. After participating in this IbM activity, the farmers were also able to identify the type of parasitoid insect, Diadegma semiclausum, which can control the cabbage caterpillar population. The outputs of this IbM activity include 1) Farmer's Guide Book (leflet) Making and Application of Insecticides from Jayanti Plants for Integrated Control of Cabbage Caterpillars, 2) IbM results publication at national seminars (poster presenter certificate), and 3) Publication of IbM results in national scientific journal (submitted). The next stage to be carried out is to monitor and continue the mentoring (tutorial) by the team to IbM participants in the implementation of Jayanti plant cultivation and the manufacture and use of Jayanti insecticide in controlling cabbage caterpillars on cabbage plantations in Sembalun Lawang Village, East Lombok Regency.The implementation of science and technology for community (IbM) farmer groups who are facing the problem of the cabbage caterpillar population explosion was carried out in Sembalun Lawang Village, East Lombok Regency. The IbM activity was designed based on the agreement between the IbM team and the Village Head of Sembalun Lawang together with the Sangka Bira Farmers Group and the Sebun Kedit Farmers Group in Sembalun Lawang Village. IbM activities are carried out with the stages of socialization, practice, and tutorials with various media used including blackboards, LCDs, manuals (leflet), seeds, saplings, specimens, and leaf dry powder of jayanti plants (S. sesban). Partners also provide media for this IbM activity, which includes cabbage plantations and water facilities. The results achieved at this stage are that farmers in Sembalun Lawang Village recognize jayanti plants as a source of natural insecticides, are skilled at drying leaves properly and making leaf solutions from Jayanti plants and trying to apply them as natural insecticides to control cabbage caterpillars on cabbage plants. The results of trials by farmers showed that direct administration of 50 ppm Jayanti leaf solution could kill 52 to 56% of cabbage caterpillars on cabbage plants. If the Jayanti leaf solution was stored for the previous 24 hours, then 50 ppm of the solution could only kill 15 to 16% of cabbage caterpillars. After participating in this IbM activity, the farmers were also able to identify the type of parasitoid insect, Diadegma semiclausum, which can control the cabbage caterpillar population. The outputs of this IbM activity include 1) Farmer's Guide Book (leflet) Making and Application of Insecticides from Jayanti Plants for Integrated Control of Cabbage Caterpillars, 2) IbM results publication at national seminars (poster presenter certificate), and 3) Publication of IbM results in national scientific journal (submitted). The next stage to be carried out is to monitor and continue the mentoring (tutorial) by the team to IbM participants in the implementation of Jayanti plant cultivation and the manufacture and use of Jayanti insecticide in controlling cabbage caterpillars on cabbage plantations in Sembalun Lawang Village, East Lombok Regency.
Jasper Debrabander,
Published: 15 September 2021
by BMJ
Abstract:
Many ethical concerns have been voiced about Clinical Decision Support Systems (CDSSs). Special attention has been paid to the effect of CDSSs on autonomy, responsibility, fairness and transparency. This journal has featured a discussion between Rosalind McDougall and Ezio Di Nucci that focused on the impact of IBM’s Watson for Oncology (Watson) on autonomy. The present article elaborates on this discussion in three ways. First, using Jonathan Pugh’s account of rational autonomy we show that how Watson presents its results might impact decisional autonomy, while how Watson produces knowledge might affect practical autonomy. Second, by drawing an analogy with patient decision aids we identify an empirical way of estimating Watson’s impact on autonomy (ie, value-congruence). Lastly, McDougall introduced the notion of value-flexible design as a way to account for the diverging preferences patients hold. We will clarify its relation with the established domain of value-sensitive design. In terms of the tripartite methodology of value-sensitive design, we offer a conceptual clarification using Pugh’s account of rational autonomy, an empirical tool to evaluate Watson’s impact on autonomy and situate a group of technical options to incorporate autonomy in Watson’s design.
Eda Tülek, Filiz Yarici, Dudu Özkum Yavuz, Mustapha Bulama Modu, Filiz Meriçli
Journal of Pharmaceutical Research International pp 487-504; https://doi.org/10.9734/jpri/2021/v33i43a32515

Abstract:
Objective: To identify the herbal medicinal products used in pregnancy in community pharmacies, the approach of pharmacists in Northern Cyprus and to compare the availability of the most commonly mentioned medicinal plants in accessible databases, in Northern Cyprus. Design: Questionnaire was designed and administered to 263 community pharmacists in Northern Cyprus and gathered the data on herbal medicinal products they had and recommended to pregnant women. Databases such as ScienceDirect, PubMed, OpenAcces Journals were searched through the Near East University Grand Library’s Online Resources for keywords relating to the ‘herbal medicine’, ‘pregnancy’ ‘pregnant women’, ‘herbal products’. Descriptive statistics was used with IBM® Statistical product and service solutions software platform. Location/Setting: Northern Cyprus Outcome Measures: Herbal medicinal products used and recommended in pregnancy by community pharmacists in Northern Cyprus were identified. It has also been determined which of the most used plants in the world are grown in Northern Cyprus. Results: The most recommended herbal pharmaceutical forms were herbal lozenges (n = 76, 31%), then herbal form of teas (n = 60, 24%), herbal oils (n = 57, 23%), herbal capsules (n = 36, 14%), other pharmaceutical forms (n=20, 8%). Within the limitation of our literature search, totally 650 medicinal plants (single or formula) used in pregnancy were determined. Out of these 74 were mostly used worldwide, and it was discovered that 56 species out of these plants are grown or cultivated; 18 of the compiled species were imported species some of the genera have species growing naturally growing in Cyprus. Conclusion: Pregnant women in Cyprus also follow their counterparts in other countries in developing interest in herbal medicines. The number of herbal medicines in the pharmacies owned by Turkish Cypriots is small. Interestingly, the result of this study showed that the pharmacists that were mainly Turkish Cypriots were found not to be selling herbal medicinal products to pregnant women without doctor’s prescriptions. This study recommends that the herbal medicines use in pregnancy should be the ones that have undergone in-depth evidence-based scientific researches with clinically proven efficacy that are known not only to the healthcare professionals such as medical doctors, midwives but also the pharmacists and the general public.
2021 IEEE 14th International Conference on Cloud Computing (CLOUD); https://doi.org/10.1109/cloud53861.2021.00005

Abstract:
Welcome to the 2021 edition of The IEEE World Congress on Services (SERVICES). It has been a privilege to serve as the Chair of the Steering Committee since summer 2017. After having completed three rounds in 2018, 2019 and 2020, we continue to experiment with new ideas and have launched new initiatives in the 2021 edition. First, I am very pleased to announcee that SERVICES and IEEE Trans. on Services Computing (TSC) has signed a multiyear agreement to phase in the Journal-First-Conference-Second (J1C2) cooperation mode, the first of its kind in the Computer Society. We also launched the inaugural edtion of the IEEE International Conference in Digital Health (ICDH) to join the set of conferences already affiliated with SERVICES, namely CLOUD, ICWS, SCC, and SDMS. Due to logistics reason we decided to move 2021 IEEE EDGE to December, still considered as part of the 2021 Congress. Rapid advances of Digital Health (DH) technologies, in conjunction of the pervasive and revolutionary nature of entering an Internet of Things (IoT) era, made us believe that we ought to engage digital healthcare technologies as an integral part of SERVICES. We are fortunate to be able to recruit well known DH pioneers and seasoned researchers in this emerging domain, and have developed a highly robust program with the strong support from US National Science Foundation and National Institutes of Health, and private industry, including IBM. The Steering Committee has been keen in undertaking such an approach to always be on the outlook to timely plan for a new international forum as a new conference, a symposium or a workshop, should any emerging service-centric technologies emerge on the horizon outside our current technology coverage and offerings.
2021 IEEE International Conference on Digital Health (ICDH); https://doi.org/10.1109/icdh52753.2021.00005

Abstract:
Welcome to the 2021 edition of The IEEE World Congress on Services (SERVICES). It has been a privilege to serve as the Chair of the Steering Committee since summer 2017. After having completed three rounds in 2018, 2019 and 2020, we continue to experiment with new ideas and have launched new initiatives in the 2021 edition. First, I am very pleased to announcee that SERVICES and IEEE Trans. on Services Computing (TSC) has signed a multiyear agreement to phase in the Journal-First-Conference-Second (J1C2) cooperation mode, the first of its kind in the Computer Society. We also launched the inaugural edtion of the IEEE International Conference in Digital Health (ICDH) to join the set of conferences already affiliated with SERVICES, namely CLOUD, ICWS, SCC, and SDMS. Due to logistics reason we decided to move 2021 IEEE EDGE to December, still considered as part of the 2021 Congress. Rapid advances of Digital Health (DH) technologies, in conjunction of the pervasive and revolutionary nature of entering an Internet of Things (IoT) era, made us believe that we ought to engage digital healthcare technologies as an integral part of SERVICES. We are fortunate to be able to recruit well known DH pioneers and seasoned researchers in this emerging domain, and have developed a highly robust program with the strong support from US National Science Foundation and National Institutes of Health, and private industry, including IBM. The Steering Committee has been keen in undertaking such an approach to always be on the outlook to timely plan for a new international forum as a new conference, a symposium or a workshop, should any emerging service-centric technologies emerge on the horizon outside our current technology coverage and offerings.
Cristina A F Román, Sarah Pillemer
Archives of Clinical Neuropsychology, Volume 36, pp 1091-1091; https://doi.org/10.1093/arclin/acab062.68

Abstract:
Objective MS impacts individuals from diverse racial/ethnic groups, yet they are not always well represented in research. The objectives of the current study are to examine how often neuropsychologically-focused MS research (NFMSR) studies: (1) include diverse populations; (2) explicitly describe the race/ethnicity of their participants; and (3) discuss generalizability/cultural implications. Methods A sample of NFMSR studies (defined here as studies examining cognitive functioning, mood, neuroimaging, fatigue, and quality of life) published within major journals between 2017–2020 were identified. Articles focusing on clinically isolated syndrome or pediatric populations were excluded. Variables of interest included sample size, sex/gender, race/ethnicity, age, education, socioeconomic status (SES), generalizability/cultural limitations, discussion of racism/disparities, and recruitment procedures. Data were coded and analyzed in IBM’s Statistical Package for the Social Sciences (SPSS; version 27). Results Race/ethnicity was not often reported in NFMSR studies, and when described, the representation of diverse individuals with MS was low (i.e., samples were mostly Caucasian). In addition, specific information about recruitment methods and SES was lacking. Generalizability/cultural implications or disparities were not discussed in the majority of studies. Report of education was variable, while sex, age, disease course, and EDSS were more often reported. Conclusions To the authors’ knowledge, this is the first study to highlight the significant gaps in representation in NFMSR. These results have significant implications for how we should be using the current literature to characterize patients or guide treatments. In addition, the current study serves as a call to action for MS researchers to work toward more inclusive and generalizable studies.
Ali Ghorbi, Mohsen Fazeli-Varzaneh, Erfan Ghaderi-Azad, Marcel Ausloos, Marcin Kozak
Published: 29 August 2021
Abstract:
This study aims to analyze 343 retraction notices indexed in the Scopus database, published in 2001-2019, related to scientific articles (co-)written by at least one author affiliated with an Iranian institution. In order to determine reasons for retractions, we merged this database with the database from Retraction Watch. The data were analyzed using Excel 2016 and IBM-SPSS version 24.0, and visualized using VOSviewer software. Most of the retractions were due to fake peer review (95 retractions) and plagiarism (90). The average time between a publication and its retraction was 591 days. The maximum time-lag (about 3,000 days) occurred for papers retracted due to duplicate publications; the minimum time-lag (fewer than 100 days) was for papers retracted due to ''unspecified cause'' (most of these were conference papers). As many as 48 (14%) of the retracted papers were published in two medical journals: Tumor Biology (25 papers) and Diagnostic Pathology (23 papers). From the institutional point of view, Islamic Azad University was the inglorious leader, contributing to over one-half (53.1%) of retracted papers. Among the 343 retraction notices, 64 papers pertained to international collaborations with researchers from mainly Asian and European countries; Malaysia having the most retractions (22 papers). Since most retractions were due to fake peer review and plagiarism, the peer review system appears to be a weak point of the submission/publication process; if improved, the number of retractions would likely drop because of increased editorial control.
, Pin-Yu Chen, Xue Lin, Bo Li
Published: 6 August 2021
Frontiers in Big Data, Volume 4; https://doi.org/10.3389/fdata.2021.731605

Abstract:
Editorial on the Research Topic Safe and Trustworthy Machine Learning Machine learning (ML) provides incredible opportunities to answer some of the most important and difficult questions in a wide range of applications. However, ML systems often face a major challenge when applied in the real world: the conditions under which the system was deployed can differ from those under which it was developed. Recent examples have shown that ML methods are highly susceptible to minor changes in image orientation, minute amounts of adversarial corruptions, or bias in the data. Susceptibility of ML methods to test-time shift is a major hurdle in a universal acceptance of these solutions in several high-regret applications. To overcome this challenge, in this research topic “Safe and Trustworthy Machine Learning”, a wide range of solutions are contributed as potentially viable solutions to address trust, safety and security issues faced by ML methods. Song, et al., considered the problem of dataset shift detection for safety-critical graph applications. The authors proposed a practical two-sample test approach for shift detection in large-scale graph structured data. Anirudh, et al., considered the problem of post-hoc interpretability tasks, such as, prediction explanation, noisy label detection, adversarial example detection. The authors introduced MARGIN, a simple yet general approach, that exploits ideas rooted in graph signal analysis to determine the most influential nodes in a graph to solve the aforementioned tasks. Majumdar, et al., considered the problem of mitigation of bias arising due to unbalanced representation of sub-groups in the training data. The authors proposed a bias mitigation algorithm to generate Subgroup Invariant Perturbation (SIP) which when added the input dataset reduces the bias in model predictions. Huang, et al., showed that seq2seq models, successful in natural language correction, is also applicable in programming language correction. Their results show that seq2seq models can provide suggestions to potential errors and have a decent correct rate in code auto-correction task. Qayyum, et al., conducted a systematic evaluation of literature of cloud-hosted ML/DL models along both the important dimensions -- attacks and defenses -- related to their security. The authors identified the limitations and pitfalls of the analyzed papers and highlight open research issues that require further investigation. Berghoff, et al., presented a comprehensive list of threats and possible mitigations of IT security of connectionist artificial intelligence (AI) applications. AI-specific vulnerabilities such as adversarial attacks and poisoning attacks as well as their AI-specific root causes are discussed in detail. The article concluded that single protective measures are not sufficient but rather multiple measures on different levels must be combined to achieve a minimum level of IT security for AI applications. Kusters, et al., analyzed key challenges to interdisciplinary AI research, and deliver three broad conclusions: 1) future development of AI should not only impact other scientific domains but should also take inspiration and benefit from other fields of science, 2) AI research must be accompanied by decision explainability, dataset bias transparency as well as development of evaluation methodologies and creation of regulatory agencies to ensure responsibility, and 3) AI education should receive more attention, efforts and innovation from the educational and scientific communities. The papers included in this research topic “Safe and Trustworthy Machine Learning” discussed some promising solutions, highlighted open research issues, and offered visionary perspectives regarding trust, safety and security issues faced by machine learning. We hope that challenges and potential solutions presented here will help researchers better understand the current limitations of machine learning methods and motivate future work in the direction of developing trustworthy, safe, and robust machine learning methods, and their applications to high-regret application areas. All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication. Author P-YC was employed by the company IBM Research. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. Keywords: robust machine learning, safe machine learning, trust, deep neural network, adversarial example defense Citation: Kailkhura B, Chen P-Y, Lin X and Li B (2021) Editorial: Safe and Trustworthy Machine Learning. Front. Big Data 4:731605. doi: 10.3389/fdata.2021.731605 Received: 27 June 2021; Accepted: 27 July 2021;Published: 06 August 2021. Edited and Reviewed by: Copyright © 2021 Kailkhura, Chen, Lin and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. *Correspondence: Bhavya Kailkhura, [email protected]
Sisilia Alvionita, Eveline Gaby Sutanto, Natasha Dyah Ayuningtyas, Nyoman Krisna Wati, Made Handijaya Dewantara
Masyarakat Pariwisata : Journal of Community Services in Tourism, Volume 2, pp 35-58; https://doi.org/10.34013/mp.v2i1.372

Abstract:
This study aims to determine the differences in social electronic word-of-mouth and travel motivation for Generation Z who are living in the Jabodetabek area. This research was conducted because it had never been done by previous researchers. The data collection used is by using a survey through Google Forms and literature studies from various journals. This study uses a quantitative approach by analyzing data through the IBM SPSS system. The results showed that there was a positive and significant relationship that the efficacy of generation Z travel decisions in choosing tourist destinations in the Jabodetabek area was influenced by the existence of the social electronic word of mouth and travel motivation. However, the differences in social electronic word-of-mouth and travel motivation among Generation Z who live in the Jabodetabek area are not homogeneous. Therefore, the calculation of the efficacy of their travel decisions also cannot be equated. The goals and motivations for the journey of Generation Z who live in Jakarta are not necessarily the same as Generation Z who live in other regions.
A Ioannidis, A Pechlevanis, M Paraskelidou, A Fragkiskou
European Journal of Cardiovascular Nursing, Volume 20; https://doi.org/10.1093/eurjcn/zvab060.003

Abstract:
Funding Acknowledgements: Type of funding sources: None. Background: Clinical guidelines recommend taking into account the patient’s preference when deciding on the options of direct oral anticoagulation (DOAC) therapy. Therefore, education is a prerequisite for informed, involved patients and patient-centred care. Purpose: The aim of this study was to assess the patient’s awareness about the existence of the dabigatran specific reversal agent (Idarucizumab) and whether the patient was involved in the decision of the specific DOAC regimen. Methods: Non-valvular atrial fibrillation (AF) patients on DOAC who visited the outpatient clinics of a city hospital in northern Greece were invited to participate. This project was part of the validation study of the Greek version of the Jessa Atrial fibrillation Knowledge Questionnaire. Analyses were performed by IBM SPSS Statistics. Results: In total, there were 312 participants (168 females, 53.8%) with mean age: 64 ± 5.3 years old. The vast majority of patients (256, 82.1%) were not aware of the existence of any specific reversal agent regardless the socio-economic status (annual income, years of schooling) or the duration and type of AF. Patients that were switched from a vitamin-K antagonist (acenocoumarol) to a DOAC were more likely to be informed about specific reversal agents (31 out of 63 patients switched to DOAC, 49.2% vs. 10.0%, p < 0.05). Similarly, patients taking more than 5 pills per day were more likely to know about the reversal agent (41 of the 193 patients, 21.2% vs. 12.6%). Moreover, the majority of patients that reported any bleeding event that lead to seeking medical advice (minor or major bleeding) were informed about the specific reversal agent (35 out of 52 patients reporting bleeding event, 67.3% vs. 8.1%, p < 0.05). Inappropriately, only seven of the 38 patients (18.4%) that were also taking antiplatelet agents (mainly acetylsalicylic acid or clopidogrel) were aware of specific DOAC reversal agents. Patients with history of stoke or transient ischaemic attack were also better informed (38 out of 53 patients, 71.7% vs. 6.9%). Only about one of five patients on dabigatran (27 out of 129, 20.9%) knew about the dabigatran specific reversal agent, mainly from sources other than their doctor (e.g. journal in office waiting room). All patients agreed that they would prefer to have been informed about the current specific reversal agents when deciding on DOAC therapy. No data could be collected why patients who were informed about specific reversal agent were not prescribed dabigatran. Conclusions: The sample of Greek non-valvular AF patients showed a noticeably low awareness of the existence of the specific DOAC reversal agent. It seems that DOAC prescription was a rather limited shared decision. Further research is warranted to confirm the aforementioned results.
, Adrienne Alayli, Franziska Krebs, Laura Lorenz, Arim Shukri, Anne-Madeleine Bau, Stephanie Stock
Published: 1 July 2021
by BMJ
Abstract:
Introduction Pregnancy is a vulnerable period that affects long-term health of pregnant women and their unborn infants. Health literacy plays a crucial role in promoting healthy behaviour and thereby maintaining good health. This study explores the role of health literacy in the GeMuKi (acronym for ‘Gemeinsam Gesund: Vorsorge plus für Mutter und Kind’—Strengthening health promotion: enhanced check-up visits for mother and child) Project. It will assess the ability of the GeMuKi lifestyle intervention to positively affect health literacy levels through active participation in preventive counselling. The study also explores associations between health literacy, health outcomes, health service use and effectiveness of the intervention. Methods and analysis The GeMuKi trial has a hybrid effectiveness–implementation design and is carried out in routine prenatal health service settings in Germany. Women (n=1860) are recruited by their gynaecologist during routine check-up visits before 12 weeks of gestation. Trained healthcare providers carry out counselling using motivational interviewing techniques to positively affect health literacy and lifestyle-related risk factors. Healthcare providers (gynaecologists and midwives) and women jointly agree on Specific, Measurable, Achievable Reasonable, Time-Bound goals. Women will be invited to fill in questionnaires at two time points (at recruitment and 37th−40th week of gestation) using an app. Health literacy is measured using the German version of the Health Literacy Survey-16 and the Brief Health Literacy Screener. Lifestyle is measured with questions on physical activity, nutrition, alcohol and drug use. Health outcomes of both mother and child, including gestational weight gain (GWG) will be documented at each routine visit. Health service use will be assessed using social health insurance claims data. Data analyses will be conducted using IBM SPSS Statistics, version 26.0. These include descriptive statistics, tests and regression models. A mediation model will be conducted to answer the question whether health behaviour mediates the association between health literacy and GWG. Ethics and dissemination The study was approved by the University Hospital of Cologne Research Ethics Committee (ID: 18-163) and the State Chamber of Physicians in Baden-Wuerttemberg (ID: B-F-2018-100). Study results will be disseminated through (poster) presentations at conferences, publications in peer-reviewed journals and press releases. Trail registration German Clinical Trials Register (DRKS00013173). Registered pre-results, 3rd of January 2019, https://www.drks.de
Published: 21 June 2021
Nutrition & Dietetics, Volume 78, pp 333-342; https://doi.org/10.1111/1747-0080.12678

Abstract:
Aim Dietitians must be statistically literate to effectively interpret the scientific literature underpinning the discipline. Despite this, no study has been conducted that objectively identifies common statistical methods and packages specific to current nutrition and dietetics literature. This study aimed to identify statistical methods and software frequently used in nutrition and dietetics research. Methods A text mining approach using the bag-of-words method was applied to a random sample of articles obtained from all journals in the ‘Nutrition and Dietetics’ subject category within the SCImago Journal and Country Rank portal and published in 2018. A list of 229 statistical terms and 19 statistical software packages was developed to define the search terms to be mined. Statistical information from the methods section of included articles was extracted into Microsoft Excel (2016) for data cleaning. Statistical analyses were conducted in R (Version 3.6.0) and Microsoft Excel (2016). Results Seven hundred and fifty-seven journal articles were included. Numerical descriptive statistics were the most common statistical method group, appearing in 83.2% of articles (n = 630). This was followed by specific hypothesis tests (68.8%, n = 521), general hypothesis concepts (58.4%, n = 442), regression (44.4%, n = 336), and ANOVA (30.8%, n = 233). IBM SPSS statistics was the most common statistical software package, reported in 41.7% of included articles. Conclusion These findings provide useful information for educators to evaluate current statistics curricula and develop short courses for continuing education. They may also act as a starting point for dietitians to educate themselves on typical statistical methods they may encounter.
Corrigendum
, Geert E. Smid, Barbara Goodfellow, Rachel Wilson, Paul A. Boelen
Published: 10 June 2021
Frontiers in Psychiatry, Volume 12; https://doi.org/10.3389/fpsyt.2021.668178

Abstract:
A Corrigendum on The UK National Homicide Therapeutic Service: A Retrospective Naturalistic Study Among 929 Bereaved Individuals by Soydas, S., Smid, G. E., Goodfellow, B., Wilson, R., and Boelen, P. A. (2020). Front. Psychiatry 11:878. doi: 10.3389/fpsyt.2020.00878 1. In the original article “Djelantik AAAMJ, Smid GE, Kleber RJ, Boelen PA. Symptoms of prolonged grief, post-traumatic stress, and depression after loss in a Dutch community sample: a latent class analysis. Psychiatry Res. (2017) 247:276–281.” and “Lenferink LIM, van Denderen M, de Keijser J, Wessel I, Boelen PA. Prolonged grief and post-traumatic stress among relatives of missing persons and homicidally bereaved individuals: a comparative study. J Affect Disord. (2017) 209:1–2. doi: 10.1016/j.jad.2016.11.012” were not cited in the article. The citations have now been inserted in “Introduction,” “Paragraph 1” and should read: “In response to the death of a loved one, many people experience acute emotional distress and symptoms of mental health disorders, which generally decrease over time. However, for a significant minority, these symptoms may persist and develop into psychopathology, such as post-traumatic stress disorder (PTSD), major depressive disorder (MDD), anxiety disorders and prolonged grief disorder (PGD) [e.g., (1, 2)].” 2. In the original article “IBM Corp. IBM SPSS Statistics for Windows, Version 25.0. Armonk, NY: IBM Corp (2017).” was not cited in the article. The citation has now been inserted in “Method,” “Data analyses,” “Paragraph 1” and should read: “Descriptive analyses were performed and assumptions were checked using SPSS [version 25.0; (43)].” The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated. 1. Djelantik AAAMJ, Smid GE, Kleber RJ, Boelen PA. Symptoms of prolonged grief, post-traumatic stress, and depression after loss in a Dutch community sample: a latent class analysis. Psychiatry Res. (2017) 247:276–81. doi: 10.1016/j.psychres.2016.11.023 PubMed Abstract | CrossRef Full Text | Google Scholar 2. Lenferink LIM, van Denderen M, de Keijser J, Wessel I, Boelen PA. Prolonged grief and post-traumatic stress among relatives of missing persons and homicidally bereaved individuals: a comparative study. J Affect Disord. (2017) 209:1–2. doi: 10.1016/j.jad.2016.11.012 PubMed Abstract | CrossRef Full Text | Google Scholar 43. IBM Corp. IBM SPSS Statistics for Windows, Version 25.0. Armonk, NY: IBM Corp (2017). Keywords: homicide, bereavement, loss, grief, posttraumatic stress disorder, bereavement interventions, psychological interventions Citation: Soydas S, Smid GE, Goodfellow B, Wilson R and Boelen PA (2021) Corrigendum: The UK National Homicide Therapeutic Service: A Retrospective Naturalistic Study Among 929 Bereaved Individuals. Front. Psychiatry 12:668178. doi: 10.3389/fpsyt.2021.668178 Received: 15 February 2021; Accepted: 07 May 2021; Published: 10 June 2021. Edited and reviewed by: Andrea Fagiolini, University of Siena, Italy Copyright © 2021 Soydas, Smid, Goodfellow, Wilson and Boelen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. *Correspondence: Suzan Soydas, [email protected]
Corrigendum
Fan Yang, Junjie Kou, Zizhao Liu, Wei Li,
Frontiers in Cell and Developmental Biology, Volume 9; https://doi.org/10.3389/fcell.2021.705769

Abstract:
A Corrigendum on MYC Enhances Cholesterol Biosynthesis and Supports Cell Proliferation Through SQLE by Yang, F., Kou, J., Liu, Z., Li, W., and Du, W. (2021). Front. Cell Dev. Biol. 9:655889. doi: 10.3389/fcell.2021.655889 In the original article, there was a mistake in Figure 1I and Figure 1J as published. The statistical significance was calculated between the siCtrl and siMYC+cho group. However, the correct comparison is between siMYC and siMYC+cho group. The corrected Figure 1I and Figure 1J appear below. Figure 1. In the original article, there was a mistake in Figure 3E and Figure 3F as published. The statistical significance was calculated between the siCtrl+pRK5-V and siMYC+pRK5-SQLE group. However, the correct comparison is between siMYC+ pRK5-V and siMYC+pRK5-SQLE group. The corrected Figure 3E and Figure 3F appear below. The authors apologize for these errors and state that this does not change the scientific conclusions of the article in any way. The original article has been updated. Figure 3. Keywords: cholesterol synthesis, cell proliferation, cancer, SQLE, MYC Citation: Yang F, Kou J, Liu Z, Li W and Du W (2021) Corrigendum: MYC Enhances Cholesterol Biosynthesis and Supports Cell Proliferation Through SQLE. Front. Cell Dev. Biol. 9:705769. doi: 10.3389/fcell.2021.705769 Received: 06 May 2021; Accepted: 12 May 2021; Published: 09 June 2021. Edited and reviewed by: Binghui Li, Capital Medical University, China Copyright © 2021 Yang, Kou, Liu, Li and Du. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. *Correspondence: Wenjing Du, [email protected]; [email protected] †These authors have contributed equally to this work
Gideon Iheme, Chinwe Uzokwe, Happiness Ezenwa, Chinaza Nwamadi, Elizabeth Okonkwo
Current Developments in Nutrition, Volume 5, pp 875-875; https://doi.org/10.1093/cdn/nzab048_010

Abstract:
Objectives The study was designed to assess the application of WHO 2007 growth reference by local studies published from 2008 to 2020 in data generation of Nigerian adolescents’ anthropometric status. Methods Meta-analysis of literatures on anthropometric status of adolescents in Nigeria by articles published from 2009–2020 was conducted. A bibliographic survey was carried out in several databases –Google Scholar, PubMed and African Journal Online. Review of abstracts and full texts followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The methodology for anthropometric assessment of these eligible studies were compared to WHO 2007 growth reference. Data was analysed using IBM SPSS version 25. Results A total of 24 articles which captured 12,482 adolescents met the inclusion criteria. More than one fifth (20.8%) of the studies adopted the WHO 2007 growth references in their data generation. A weak positive correlation was observed between year of publication and application of WHO 2007 reference in data generation (r = .0.28; p = 0.04). Conclusions The low application of an age long guideline by local researchers is of concern. Hence, the need to ensure quick adoption of standard indicators/guidelines in local studies will not only promote the generation of pooled evidence to reveal cross-cutting gaps but also ensure that the public health situation is not under/over estimated. Funding Sources This research work received no funding.
Vaibhav Aggarwal
Turkish Journal of Surgery, Volume 37, pp 116-125; https://doi.org/10.47717/turkjsurg.2021.5106

Abstract:
Objective: The term ‘citation classics’ is used for highly cited papers in the scientific literature. It was aimed to understand the current landscape of academic surgery and the quality of the scientific contribution of authors belonging to Asia using citation classics. Material and Methods: We searched the WoS core collection database under the category ‘surgery’ to include the 50 most cited articles whose lead author was affiliated to an Asian country during the research period. We noted the following characteristics for each article: total citations, average cita- tions per year, year of publication, publishing journal, institution and country, journal quartile and impact factor, authorship, field of surgical research. Results were analyzed using IBM SPSS Statistics v26. Results: The number of citations ranged from 447 to 1170 (mean +/- SD is 616.9 +/- 150.16) and citations per year ranged from 10.04 to 98.17 (mean +/- SD is 30.87 +/- 17.27). Most productive decade was 1991-2000 (n= 19 articles). Majority of the articles were published in ‘Annals of Surgery’ (28%). Four authors contributed two or more articles as lead author with ‘Poon RTP’ taking the lead. Japan’s contribution was highest (60%) followed by China and its dependents’ (26%). University of Hong Kong was the leading institution (n= 7). Observational study was the most commonly used design (n= 24). Most papers belonged to gastrointestinal surgery (n= 28) and surgical oncology (n= 26). 66% articles originated from a single institution, 22% had inter-institutional collaboration and 12% had national collaboration from countries outside Asia. Conclusion: The study identified the most influential papers in surgery from Asia. This should provoke interest in academic surgery and research col- laboration with other nations in Asia and the rest of the world.
Adele Pacquette, Eugene J. O'Sullivan, Mahadevaiyer Krishnan
ECS Meeting Abstracts, pp 934-934; https://doi.org/10.1149/ma2021-0124934mtgabs

Abstract:
For technology nodes beyond 5 nm, copper metal may not be feasible as conductor material in Damascene interconnects.1 The bulk resistivity of copper increases exponentially and electromigration of copper is possible with the scaling down of the technology nodes. Metals such as inert platinum group metals have been proposed as alternative metal conductors for interconnects.2 Platinum group metals exhibit less electron scattering and lower electromigration in narrow line widths compared to copper; the electron scattering is proportional to the bulk resistivity. Thus, certain platinum group metals, e.g., ruthenium2, have been proposed as alternative conductors for interconnects.3 Ruthenium electrodeposition needs further development because of slow kinetics, resulting in poor control of morphology, and defects in the film due to hydrogen evolution at the high overpotential required to initiate ruthenium deposition.4 Another challenge is that ruthenium has multiple oxidation states, which may result in disproportionate reactions, and, thus, electrodeposition may not occur reproducibly.3This study investigates the electrodeposition of ruthenium from nitrosyl ruthenium complexes, and/or inorganic ruthenium compounds such as chlorides, sulfates or phosphates in acidic electrolytes. Figure 1 shows ruthenium electrodeposited on an ultrathin seed layer with high sheet resistance. Electrodeposition techniques such as chronoamperometry and chronopotentiometry are compared for the initiation of ruthenium nuclei on such highly-resistive (up to 400 Ω/sq) seed layers. In this study, a multi-step electrodeposition process was developed for the nucleation, then growth of a uniform, void-free ruthenium film. A constant voltage was applied for a short time (few seconds) to initiate plating by providing the overpotential necessary to form ruthenium nuclei. Next, a low current density was applied to grow the film to the desired thickness (50 – 100 nm). This method allows for minimal hydrogen evolution and prevents void formation since the high potential is applied for a short time compared to other typical pulse plating methods. The multi-step method is reproducible and results in uniform plating on 200 mm wafer scale by utilizing plating tool shields that can control center and edge plating rates. This talk describes the effect of electrolyte bath composition and plating parameters on the morphology, adhesion and uniformity of the electrodeposited ruthenium.Figure 1: Electrodeposited ruthenium on Si substrate with ultrathin seed layer.1) Chen, Q.; Lin, X.; Valvede, C.; Paneccasio, V.; Hurtubise, R.; Ye, P.; Kudrak, E.; Abys, J., Electroless copper deposition on ruthenium for damascene interconnects. ECS Transactions. 2007, 6 (8), 179-184.2) Mainka, G.; Beitel G.; Schnabel R.F.; Saenger, A.; Dehm, C., Chemical mechanical polishing of iridium and iridium oxide for damascene process. Journal of the Electrochemical Society. 2001, 148, G552-G558.3) Bernasconi, R.; Magagnin, L., Review—Ruthenium as diffusion barrier layer in electronic interconnects: Current literature with a focus on electrochemical deposition methods. Journal of the Electrochemical Society. 2019, 166 (1), D3219-D3225.4) Oppedisano, D.K.; Jones, L.A.; Junk, T.; Bhargava, S.K., Ruthenium electrodeposition from aqueous solution at high cathodic overpotential. Journal of the Electrochemical Society. 2014, 161 (10), D489-D494.AcknowledgementThe authors acknowledge the researchers of the Microelectronics Research Laboratory (MRL) at the IBM T. J. Watson Research Center, for the fabrication work.Figure 1
Isabel Shamsudeen, Mehr Jain, Jeffrey Ding, Faisal Khosa
Journal of the Endocrine Society, Volume 5; https://doi.org/10.1210/jendso/bvab048.888

Abstract:
Background: Subscription-based (SB) is the traditional publication model for peer-reviewed research; however, open-access (OA) models have been rising in popularity in recent years. Journals may be owned by commercial, professional society, university or government publishers. SCImago Journal Rank (SJR) indicator is a measure of the scientific influence of scholarly journals. Objectives: The purpose of this study is to assess the publication model, ownership and SJR indicator of the top Endocrinology journals. This will help inform researchers’ decisions when selecting a journal to submit their work to. Methods: The SCImagoJR website was used to obtain a database of active, peer-reviewed Endocrinology journals worldwide. Publishers were grouped by parent company and categorized as commercial, professional society, university or government. Journals were searched on the National Library of Medicine catalogue to determine whether they are indexed on MEDLINE. Data was analyzed using IBM Statistics version 25. Fischer’s exact test was performed to assess the distribution of publication model and indexing status. Kruskal-Wallis H test was used to assess the distribution of SJR. Results: 207 Endocrinology journals were included; 134 SB (64.73%) and 73 OA (35.27%). 122 journals are indexed in MEDLINE. The top three publishers of Endocrinology journals are Elsevier, Springer Nature and Wiley, all of which are commercial entities. They collectively own 91/207 (43.96%) Endocrinology journals and 70/122 (57.38%) MEDLINE-indexed journals. The top three publishers own more SB than OA journals, though this difference was not statistically significant (p = 0.080). There was no significant difference in the distribution of indexing status across the top three publishers (p = 0.250) and the four publisher types (p = 0.928). There were significantly more SB than OA journals indexed in MEDLINE (p<0.001). There was no significant difference in the distribution of SJR indicator across the top three publishers (p = 0.283) and publisher types (p = 0.873) (see Table 1). SB journals had significantly higher SJR indicators compared to OA journals (all journals, p = 0.002; indexed journals only, p = 0.013). CONCLUSIONS: Endocrinology journals are largely controlled by a few commercial entities and are primarily SB. Compared to OA, SB journals have significantly higher SJR indicators, meaning they are more influential. This is an important consideration for researchers when considering where to submit their work.
Hayden Robert Lewis
Published: 11 April 2021
Abstract:
This research analyzes coverage of major artificial intelligence events representing the thematic concept of "man versus machine." Rooted in grounded theory and rhetorical criticism, this research applies symbolic convergence theory and fantasy theme analysis to reporting from The New York Times, The Wall Street Journal and The Washington Post immediately surrounding three cultural and scientific milestones in the development of artificial intelligence technology: IBM Deep Blue's 1997 defeat of chess grandmaster Garry Kasparov; IBM Watson's 2011 defeat of Jeopardy! champions Ken Jennings and Brad Rutter; and Google DeepMind AlphaGo's 2016 defeat of Lee Sedol. This research analyzes how symbolic realities are dramatized in the context of these events such that the competitions themselves represent ideological battles between humanism or technological superiority. This research also demonstrates subtle variations in how fantasy themes and rhetorical visions manifest in coverage from each outlet, amounting to what is effectively a competition for shared consciousness between these two competing ideological constructs.
Oliver Y. Chén, Bryn Roberts
Frontiers in Digital Health, Volume 3; https://doi.org/10.3389/fdgth.2021.595704

Abstract:
Personalized health care and public health are essential to one's well-being and societal welfare. The former focuses on symptoms and disease progression at the individual level, whereas the latter looks at health issues at the population level (from a group of patients to everyone on the planet). Recent years have seen a digital revolution in personalized health care and public health (1–4). As such, the World Health Organization regards mobile health (mHealth) as a vital resource for health services delivery and public health (5) and urges its Member States to prioritize the development and use of digital technologies in health to promote Universal Health Coverage and advance the Sustainable Development Goals (6). Here, we discuss how digital health contributes to personalized health care and public health and how it may evolve. Specifically, we present its roles, challenges, and potential future. Traditional health assessments require in-clinic visits, with bio-signals measured by professionals using specialized devices. To practice these frequently in a broad population is, however, inconvenient and expensive. Digital devices are mobile (or wearable), with fast data transmission done wirelessly. This enables remote and non-invasive health assessments and encourages users to self-care for their health (Figure 1A) (7, 8). Frequent assessments facilitate early disease discovery and longitudinal monitoring (7). Self-monitoring benefits those whose diseases may progress between hospital visits; the relatively affordable price (compared to hospital costs) makes health service accessible to many without in-hospital accesses (9). Self-monitoring does not confront in-clinic assessments. The former is as-of-yet not as accurate or comprehensive, but it provides complementary services and is more ecological to capture fluctuating symptoms. Figure 1. Building a Digitalized Ecosystem. (A) Digitalization cycle—bridging digital health, data, and digitally enabled decision-making. From 1 to 2: Phenotypic information is recorded by, and made available on, digital devices. From 2 to 4 via 3: Advanced modeling and analyses are applied on digital data to guide health-care decisions by physicians, such as recommending potential treatments (see bottom of item 4) and suggesting conducting further diagnostic tests or analyses (from 4 to 1). (B) Semi-automated disease diagnosis and monitoring. Individual data are de-identified, encrypted, and transferred remotely via the cloud to secured data centers—where population-level disease analyses are performed. The individual data are then analyzed and compared with the population features to generate an automated preliminary diagnosis report. Should red flags be raised, the report is passed on to a medical professional. The medical professional looks at both the report and the individual-specific data to offer medical recommendations or to arrange for an on-site visit or remote consultation (e.g., telemedicine), depending on which further tests are anticipated. This process continues between an individual's periodic health checks to ensure earliest possible detection of symptoms and to compensate for long consultation intervals when regular assessment is too expensive or inconvenient. (C) Automated deep-geno/phenotyping. The digital health applications facilitate ensemble-learning, where multivariate genotypic and phenotypic (e.g., digital biomarker, imaging, and molecular diagnostics) data are combined to provide rich subject-specific and group-level information, which are used to position individuals within a relevant population or to predict outcomes for individuals, based on population norms. (D) The marriage between personalized health care and public health. There is a powerful interdependent and synergistic relationship between personalized health care and public health in the digital age. Top: When shared, personal digital health data bring rich heterogeneous information into the population data pool. In return, features identified in large-scale public health data will provide a reference for individuals, positioning them relative to comparable cohorts in the population, based on age, sex, ethnicity, etc. Bottom: Integrating individual and population data. Data collected longitudinally over months and years enable risk estimation and disease forecasts, such as estimating the likelihood of disease progression or quantifying response to different treatments. Semi-automated health service alleviates a shortage in medical data, personnel, and equipment in several ways. First, it automates large-scale data collection. Next, automated data de-identification, encryption, and transfer (10) allow comparing personal data with population counterparts (11). Third, automation supports early disease detection, intervention, and treatment (12–15). For example, algorithms generate alerts suggesting medical consultation or delivering reports, with consent, to clinicians to assign interventions (16, 17) (see Figure 1B and telemedicine below). Naturally, one would ask, will digitalization and automation of health service result in job losses, for example, rendering health-care personnel, nurses, and physicians redundant? Likely not. First, such posts are in shortage (18). Although much of monitoring and assessment can be done digitally, the majority of high-value medical interventions cannot be automated at present or in the near future. The expansion of overall coverage, therefore, results in an increasing need for service to deal with the tasks that cannot be automated. Second, digital transformation and revolution (see section Long-Term Outlooks) grow the labor market by creating new jobs, such as data labeling, medical testing and analysis, and remote medical service (e.g., telemedicine). It also creates and expands domain-specific positions, such as programming, posts requiring interdisciplinary knowledge, and educational jobs training the next-generation digital-health workforce (19). The diagnosis made by physicians are not always correct (20, 21). Automated health services also make mistakes. Some machine-based predictions, however, have begun to outperform specialists in mammographic screening (22), certain cancer diagnosis (4) [e.g., urothelial carcinoma (23)], and retinal analyses (24). They also contribute to predicting cardiovascular disease (17), Lyme disease (11), neurodegenerative diseases (15), and treatment response (25). Yet, algorithmic caution and human safeguard, such as introducing a two-layer (digital plus human) verification system, are high-priority (Figure 1B). Although one can fine-tune parameters to balance false positives and negatives, better methods and higher-quality and larger data aggregation are needed to improve model performance. Digital health connects and facilitates personalized health care and public health (Figure 1D). First, accumulating individual data expands the population data repertoire. The convenience of digital data collection enables the inclusion of representative samples with balanced group sizes. This is helpful for distinguishing diseases with subcategories. Suppose a dataset has dominating Type 1 diabetes patients. The extracted knowledge would reflect Type 1 diabetes-specific features and the Type 2 diabetes-specific features may be overlooked or treated as noise. Currently, the majority of phenotypic health data are generated in the clinic from patients with relatively advanced diseases, where symptoms are clearly present and diagnostic procedures are being or have been performed. There is a lack of comparable data at scale from the healthy population and those in the very early stages of disease development. With representative samples and balanced group sizes, digital data support building more robust predictive models. Second, information learned from population data improves personalized treatment. Digital devices are sensitive, objective, and collect data semi-continuously; they facilitate deep phenotyping (26, 27), finer disease categorization, and timely treatment (Figure 1C). If a patient displays features similar to those of a population, one can assign treatments shown safety and efficacy in the population. Comparing subject-specific treatment responses, side-effects, and symptoms with population counterparts, one can refine personalized treatments (28–30). Integrating population and individual data yields better longitudinal inference. The longitudinal analysis helps painting health trajectories and forecasting future events. Frequently comparing individual information with personal and population history helps making better inference (Figure 1D). The digital age is still at its dawn. Here, we first examine, exemplarily, digital health's short-term focus in managing pandemics. We then discuss the mid-term challenges, for which one can actively prepare and make constructive improvements. Finally, we speculate, in an informed way, its long-term perspectives. Testing is chief during pandemics. It identifies and isolates infected individuals (especially the asymptomatic ones), facilitates timely treatment, and provides governments with feedback on “social distancing” measures. Unfortunately, by January 2020, manufacturers could only produce 100,000 COVID-19 testing kits per day when three million were in quarantine around Wuhan (31). From February to April 2020, the United States performed about 4.5 million tests (32), compared to suggested daily tests of 5–20 million (33). Digital devices support testing, track-and-trace, and marking high-risk populations and areas (but see privacy concerns in section Mid-Term Challenges and Potential Solutions). Tencent and Alibaba provided users in China with a “health code”: one with a green, yellow, or red code, respectively, can travel, should stay home, or is a confirmed case and quarantined (34). Several European countries introduced smartphone apps to identify and inform individuals at risk (35). Real-time in-hospital monitoring enables staff to assist more people or focus on critical patients (36) (Figure 1C). Digital health enables frequent, remote, and semi-automated health services. Yet, it is not without challenges. Immediate concerns are data privacy (37) and quality (38). To secure data collection, transfer, storage, and analyses, we need improved government policies (39), company regulations (40), and computational and storage technology (1). To warrant the quality, we need quality controls, enhanced algorithms, and rigorous training and test. Most digital solutions are domain-specific: for each disease, a new model needs to be developed (2, 4, 11, 15, 17). Yet, for those wishing to detect disease early without knowing which disease(s) may develop, a battery of bio-signals needs to be analyzed on a single device (Figure 1C). The fragmentation of health care and a lack of global data standards, however, make combining datasets and algorithms difficult (29, 41–43). Beginnings, however, are made, for example, by introducing a digital ward (36), the findability, accessibility, interoperability, and reusability (FAIR) data principles, and ensemble learning (41), to provide transparent, reproducible, and reusable services (44) and to better connect devices, algorithms, and datasets. Although the elderly benefit from digital health (7, 45), they may not accept it (46, 47). It is partially because it is a recent concept, and partially because devices are difficult to use. Better introduction and developing easy-to-use devices may make digital health more accessible to them. Finally, the talent challenge—the rarity of professionals with interdisciplinary knowledge. At present, a doctor may need to consult with data scientists to interpret the output of automated algorithms. A deep-learning engineer may need domain experts to explain the clinical concepts and medical situation. Disciplinary experts together with multi-disciplinary teams are essential in research and development today and will continue to be an integral, indispensable part in the future. A new generation of professionals with interdisciplinary training in life science, medicine, public health, and the computational domains, however, will be in high demand in the coming years. Positioned at the nexus of disciplines, they will be the integrators in complex teams, bridging multiplex interactions, multi-domain operations, and disciplinary experts. Digital health will continue to support personalized health care and public health. Yet, it is difficult to fully predict its long-term outlooks. We can only speculate, in an informed way, through what we see today. We may see an expedited digital health revolution, thanks to the fourth industrial revolution (Industry 4.0) supported by 5G and the Internet of Things (48). Leveraging real-time analytics, machine learning, commodity sensors, and embedded systems (49), Industry 4.0 connects patients, machines, and medical personnel (50). Such connectivity allows multivariate big data collection from heterogeneous populations. The frequent, longitudinal analyses on big data improve patient identification, severity estimation, and progression monitoring (Figure 1C). Future may witness digital therapy. The augmented and virtual-reality exergaming, brain-machine interface (51) may treat substance-use disorder (52) and children with attention deficit hyperactivity disorder (53), among others (51, 54–57). For broad adoption and reimbursement, however, these interventions need to demonstrate safety and health-economic benefits (58). Eventually, digital health ecosystems and digital clouds may emerge (Figure 1B). With more data and improved algorithms, the ecosystems become ever-smarter (59) (Figure 1D). They automate labor-intensive tasks and reshape the roles humans play (e.g., humans will focus on developing and maintaining digital devices and systems or deploying interventions when results are modest and sensitive decisions are needed). Timing is important: the ecosystems are multi-dimensional (e.g., scientific, technical, social, political, and economic); a stagnation in one dimension may delay the whole. Equally important is making applications that are powerful and easy-to-use (“killer applications”). Unfortunately, timing and “killer applications” are oftentimes obvious retrospectively. New ideas and enthusiasm, despite failures, will bring us progressively closer to success. Central to digital health is ethics (60, 61). To ensure digital recommendations do not disadvantage particular groups, we need representative samples and reproducible models. Representative samples span characteristics (e.g., gender, ethnicity, age, and devices) of the target population. Reproducible models are generalizable to out-of-sample individuals (Figure 1C). Additional quality control can ascertain the quality and ethical standards of different artificial intelligence algorithms (62). Future devices need to demonstrate robust services in a live, potentially noisy environment (63, 64). They also need to incorporate user feedback, such as emotions and verbal inputs, to improve personalized medical judgements (65–70). Brain studies inspired early deep-learning models (71, 72). The layers in the convolutional neural networks in vision studies are reminiscent of the hierarchy in the visual cortex (73). Future may see more models resembling biological systems. Some may produce human-like characteristics. But we need to evaluate whether the similarities are generalizable to other models, higher functions, and organs, and to ensure the machine follows ethics and autonomy (74, 75). We have covered the responsibility and functionality aspects of the digital health above. Digital health ecosystems, however, need to also consider explainability and interpretability (76, 77). Many state-of-the-art (deep learning) models at present, however, are potentially explainable [one may not understand the model after it is fit but can use another model (or test) to make sense of it (76, 78)] but not interpretable [one cannot understand how the model produces outcomes causally (76)]. Additionally, between interpretability and performance, there is typically an inverse relationship (77). For security or privacy, companies or governments may even obfuscate models. Digital health benefits all of us, current or future patients desiring early diagnosis and timely treatment. But there are sizeable challenges we must overcome. Combining efforts from academia, industry, hospitals, non-profit, and government, we are hopeful to make digital health services effective and affordable. 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(2018) 51:93. doi: 10.1145/3236009 CrossRef Full Text Keywords: digital health, personalized healthcare, public health, AI in healthcare, digital biomarkers, FAIR data, telemedicine, mHealth Citation: Chén OY and Roberts B (2021) Personalized Health Care and Public Health in the Digital Age. Front. Digit. Health 3:595704. doi: 10.3389/fdgth.2021.595704 Received: 17 August 2020; Accepted: 17 February 2021; Published: 30 March 2021. Edited by: Reviewed by: Copyright © 2021 Chén and Roberts. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. *Correspondence: Oliver Y. Chén, [email protected] These authors have contributed equally to this work
Frontiers in Computer Science, Volume 3; https://doi.org/10.3389/fcomp.2021.628773

Abstract:
The use of brain–computer interfaces (BCIs) based on electroencephalography (EEG) in video games has been widely investigated. Research in adaptive training, single-trial classification (Congedo, 2013; Barachant and Congedo, 2014) and the creation of affordable EEG acquisition devices (Vos et al., 2014; Yohanandan et al., 2018) has paved the way for the development of a ubiquitous BCI technology. For example, Congedo (2013) developed “Brain Invaders,” a BCI game inspired by the famous vintage game Space Invaders (Taito, Tokyo, Japan) and based on the so-called visual P300—an electromagnetic potential produced by the brain about 300 ms after a visual stimulation. Brain Invaders uses an adaptive algorithm that allows the player to plug the material and play without the need for calibration (Barachant and Congedo, 2014), while still achieving a high accuracy rate (Barachant et al., 2012). The game also demonstrates a good understanding of game design by naturally incorporating visual stimulations in the virtual environment. In this respect, Kaplan et al. (2013), Cattan et al. (2018b), and Rashid et al. (2020) provided a set of guidelines to adapt game implementation for BCI games, such as the use of turn-based games with a slow gameplay. Although Brain Invaders use a research-grade amplifier, the feasibility of using a low-cost EEG acquisition system for BCI has been demonstrated by Vos et al. (2014) and Yohanandan et al. (2018). These affordable headsets are comparable with research-grade amplifiers. In addition, Lotte et al. (2008) and Debener et al. (2012) demonstrated promising results when BCIs were used out of the lab for BCIs based on visual stimulation and movement imagination. The feasibility of using BCIs outside the lab has also been demonstrated in different context and at events. For instance, in the BCI game developed by Mentalista (Paris, France) for the 2016 European Football Championship, two players were asked to score against each other by moving a ball toward the opposite player's cage by concentrating1. Although a positive step forwards, these achievements have led to the false opinion that BCIs are ready for entertainment – a belief that is supported by enthusiastic visions claiming, for example, that brains will be connected to the internet through USB2. This opinion is rather qualified in the scientific community, which reported that BCIs suffer from (1) a low transfer rate, (2) a lack of market-ready, affordable, and user-friendly research-grade EEG acquisition devices, and (3) a gap between the game design and graphics of video games available on the market vs. in laboratories. Priorities of these limitations for video game development are discussed in the literature (Nijholt et al., 2009; Ferreira et al., 2013; Marshall et al., 2013; van de Laar et al., 2013; Ahn et al., 2014; Cattan et al., 2018b; Kerous et al., 2018; Vasiljevic and Miranda, 2019; Pierce et al., 2020), and in general preponderance of quantitative over qualitative aspects is criticized (Nijholt et al., 2009; Vasiljevic and Miranda, 2019). This article supports the claim that BCIs are not ready for general public use, based on other aspects than performance. Limitations are further detailed in section Limitations of BCI Games of the present study, and the obstacles to public use are analyzed. The conclusion is presented in section Discussion and Conclusion. The transfer rate (in bits per second) is a computed measure for communication devices that reflects the speed and accuracy of a device. This measure is derived from information theory and was adapted for BCIs (Wolpaw and Wolpaw, 2012) to compare different implementations. Following the development of Riemannian Geometry during the last decade (e.g., Barachant et al., 2012), the transfer rate of BCIs has considerably increased to reach, for example in the case of a P300-based BCI, a 90% accuracy within a couple of seconds (Cattan et al., 2018b). For comparison, the Guinness World Records reports a record of stenotype writing of around 360 words per minutes with 97% accuracy3. In practice, this means that BCIs are unusable in traditional inputs, such as in keyboards or mice. Another concern is that the algorithm complexity [in terms of mathematics and set-up (e.g., Cattan et al., 2018a; Andreev et al., 2019)] behind BCIs might be an obstacle for game developers. This is true for VR games especially, as the VR market is mostly represented by small, independent companies with limited resources4,5. Until the early 2000s, research-grade amplifiers were medical and were made of expensive materials and could mostly only be afforded by institutions or consortia (e.g., g.USBAmp, g.tec, Schiedlberg, Austria). Emotiv (San Francisco, US) was among the first manufacturers to release a commercial EEG cap for individual customers in 2009. However, low-cost versions of the Emotiv headsets omit a proper electrode location for P300-based BCIs, while research-grade versions still practice dissuasive pricing. Similar concerns apply to most customer-grade EEGs (Ahn et al., 2014; Vasiljevic and Miranda, 2019). That is, cheap materials only include a few and unmovable channels which are inappropriate for BCI based on visual stimulation, whereas medical-grade EEG caps are expensive. In 2013, OpenBCI (New York, US) finished a successful fundraising campaign, with the aim of providing a high-quality EEG acquisition system for <1,000 euros. Nevertheless, concerns were raised about the usability of the technology, such as its association with unstable wireless communication, non-standardized sampling rate and use of gel electrodes (e.g., Chabance et al., 2019). Some researchers (e.g., Yohanandan et al., 2018) demonstrated that similar performance could be obtained with an in-house, and thus cheaper, EEG headset. A Huffington Post (New York, US) publication presented an EEG headset that was ergonomic (i.e., with dry electrodes and wireless) for <500 euros6,7. However, such headsets are not available for public use, in the sense that, even though some are open-source, developers cannot build them in practice. Another consideration is that any development is material-dependant, as all are based on different hardware, drivers and protocols (e.g., Ahn et al., 2014; Pierce et al., 2020). Despite the lack of standards, commercial brands such as Emotiv (San Francisco, the US) or NeuroSky (San Rose, the US) have developed plugins for game development. For instance, Rosca and Leba (2019) developed a pool game by integrating the Emotiv SDK with Unity 3D (San Francisco, the US), a notorious game engine. A review of existing BCI software can be found in Pierce et al. (2020). That said, the lack of middleware supported by a large and independent community creates maintenance and portability issues, as long as plugins are constructor-dependent or rely on the willingness of a research team. Graphics and game design are a key concern and expectation for games on the market, from AAA to indie games. This is why video game studios hire developers as well as graphic designers, art work designers, concept artists and game designers. However, graphics and game design have been underestimated in the development of BCI games in laboratories. For instance, the number of frames per second (FPS) is a major concern for stimulation-based BCI, as they require the exact onset of the stimulation with a precision of around ±2 ms (Andreev et al., 2016). Indeed, if the tagging of such stimulation on the ongoing EEG does not happen all the time in the same frame in which the stimulation is displayed, a jitter is observable, which varies as an inverse function of the frame rate. For example, an FPS of around 50 Hz will output a frame every 20 ms and generate a jitter of a similar amplitude in the worst cases. This is particularly true for VR games where low FPS can result in a higher jitter (Cattan et al., 2018a). However, to our knowledge, the impact of graphical quality in FPS resulting in jitters is poorly understood in the context of BCI entertainment. Ahn et al. (2014) conducted an opinion survey on the importance of BCI games elements. One aspect of this study was to outline the difference of perspective between developers and researcher communities regarding BCI development. For example, easiness of playing was one of the most important elements for 58% of the developers but only 19% of the researchers. However, the importance of graphics was minimized in the study when it should be a major concern for video games. In fact, the authors reported a developer opinion (later confirmed by the opinion survey for the two communities) that aesthetic is rather not considered as one of the most important factors for BCI games. However, we believe this only means that graphics are a basic requirement for video games. In Schell (2014), a pillar reference for game design, the author said about one of his work experiences in virtual reality: “We had to make things look beautiful. […]. We used high-end graphics hardware and rich textures and models […].” In general, laboratory BCI games demonstrate good design, being turn-based and having slow gameplay—in this aspect following the guidelines stated by the scientific community (e.g., Nijholt et al., 2009; Marshall et al., 2013). For example, Lotte et al. (2008) and Andreev et al. (2016) presented the BCI game Use the force!, which consisted of lifting up a vessel with motor imagery. Meanwhile, in the game Alphawow (van de Laar et al., 2013), the avatar's character changes its behavior according to the player's state of relaxation. These two games consider the low-transfer rate of the BCI by mapping it to a feature that is expected to fail from time to time (it can be agreed that using the mind to move objects is difficult to realize) and to not compete with traditional inputs (a keyboard cannot determine a person's relaxation state). Nevertheless, the use of BCI was restricted to a unique aspect of these games. On one hand, if this aspect is a side aspect (e.g., Alphawow), the use of BCI is not valuable because of its cost. On the other hand, if this aspect is the main aspect of the game, it means that the player's ability to finish the game depends on an unreliable input and thus leads to frustration. A subjective study on the use of BCI for gaming (Cattan et al., 2019) also reported a lack of feedback for error quantification from participants. This couples with the fact that around 20% of the users are not proficient using a typical BCI. In fact, BCI illiteracy is an issue which is also well-established in the existing literature (e.g., Nijholt et al., 2009; Allison and Neuper, 2010; Marshall et al., 2013; Vasiljevic and Miranda, 2019), although the idea that physiological traits are responsible for BCI illiteracy is controverted (Thompson, 2019; Riquelme-Ros et al., 2020). These limitations impact replay and the difficulty of games, as players who do not succeed in a BCI task will become stuck in the game without knowing how to improve. In fact, except for a proof of concept or a contest, such as the game created by Mentalista (Paris, France), these games are not suitable for public. This section discusses BCI limitations and explains why overcoming these limitations to develop a ubiquitous BCI game is challenging. These difficulties include a plateau in performance compared with mechanical inputs, technical and algorithmic complexity behind BCI, a lack of middleware for BCI development and an underestimation of graphics and design complexity compared with games in the market. Transfer rate is the most common limitation discussed in the literature. For example, Rashid et al. (2020) has argued that “most BCI games demonstrate very low accuracy and speed as compared to conventional interfaces, suggesting that there are issues that must be addressed to facilitate the acceptance of BCI games.” According to Cattan et al. (2018b) and Rashid et al. (2020), this is particularly true for games requiring movements, such as VR games, as muscular artifacts interfere with the detection of brain signals. In this regard, the complexity of signal detection and classification is, to our belief, a key obstacle to creating effective BCIs for use in games. From our perspective, recent developments in non-metric (e.g., Quemy, 2019) or quantum classification (Grant et al., 2018; Havenstein et al., 2019) might lead to significant improvements in BCI acceptance and performance. Indeed, non-metric classification reduces the need for data pre-processing and engineering, while quantum classification takes advantage of quantum physics to improve the speed and accuracy of classification. The emerging field of quantum machine learning has become increasingly mature thanks to the availability of open-source toolkits (e.g., Abraham et al., 2019) and cloud-based quantum machines (such as the IBM quantum experience by IBM, Armonk, US). Havenstein et al. (2019) showed the advantages of using a quantum vs. classical support vector machine for multi-class classification. Further interesting developments are expected in this field in the next decade. Nevertheless, in our opinion, the impact of a low-transfer rate on BCI games is overestimated. In practice, if BCIs are considered an interesting yet dispensable device for video games, this is mostly due to design issues because BCIs are either used as an ancillary feature of games (despite requiring expensive materials) or as a means of competing with traditional inputs (e.g., keyboards and mice) to achieve the same task faster and with less concentration. In other words, BCIs in games should be limited to a set of aspects that cannot be achieved by traditional inputs, but at the same time should create sufficient value to justify the cost and encumberment of the material. However, despite some of the positive features previously enumerated (e.g., the use of BCIs for naturally imprecise behavior), a complete game concept that can be sold for concrete video game entertainment is lacking. Further, design reflection for BCI games is still in its infancy and is close to the prototypal-use cases created in the early 2000s (e.g., Bayliss and Ballard, 2000). Similar concerns were broached in recent studies, such as Vasiljevic and Miranda (2019) which reported that only a few studies focused on qualitative aspects of the interaction with BCI games. In short, developers should above all be concerned with game design and game portability. In practice, BCI games cannot be downloaded and run independently of the EEG acquisition system, which is an impediment for both researchers and game developers. In this respect, the work achieved by platforms such as OpenVibe (Renard et al., 2010) or open-source initiatives that rely on a standard protocol, such as Lab Streaming Layer (Stenner et al., 2015), should be emphasized (see text footnote 7). Nevertheless, there is no support for developers (at any level, technologic, mathematical, usability) to integrate BCI in concrete game production. To our knowledge, practical obstacles such as compilation and integration of LSL DLL into game engines, along with the lack of command-line support or synchronization solutions between OpenVibe acquisition server and recreational applications, are rarely mentioned in the existing literature. The author confirms being the sole contributor of this work and has approved it for publication. GC was employed by the company IBM. 1. ^ https://mentalista.fr/foot 2. ^ https://www.thequint.com/explainers/what-is-neuralink-and-how-does-it-work-explained 3. ^ https://www.guinnessworldrecords.com/world-records/fastest-realtime-court-reporter-(stenotype-writing)/ 4. ^ https://www.vrfocus.com/2020/05/why-now-is-the-time-for-aaa-studios-to-consider-vr/ 5. ^ https://labusinessjournal.com/news/2015/jun/17/independent-virtual-reality-studios-benefit-early-/ 6. ^ https://www.youtube.com/watch?v=GgKEOlcX9R8 7. ^ http://alexandre.barachant.org/eeg.io/ Abraham, H., AduOffei Agarwal, R., Akhalwaya, I. 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Brain-Computer Interfaces: Principles and Practice. New York, NY: Oxford University Press. Google Scholar Yohanandan, S. A. C., Kiral-Kornek, I., Tang, J, Mshford, B. S., Asif, U., and Harrer, H. (2018). A robust low-cost EEG motor imagery-based brain-computer interface. Conf. Proc. Annu. Int. Conf. IEEE Eng. Med. Biol. Soc. 2018, 5089–5092. doi: 10.1109/EMBC.2018.8513429 PubMed Abstract | CrossRef Full Text | Google Scholar Keywords: brain–computer interfaces, games, virtual reality, electroencephalography, perspectives Citation: Cattan G (2021) The Use of Brain–Computer Interfaces in Games Is Not Ready for the General Public. Front. Comput. Sci. 3:628773. doi: 10.3389/fcomp.2021.628773 Received: 12 November 2020; Accepted: 02 March 2021; Published: 24 March 2021. Edited by: Reviewed by: Copyright © 2021 Cattan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. *Correspondence: Grégoire Cattan, [email protected]
International Journal of Surgery: Protocols, Volume 25, pp 123-128; https://doi.org/10.29337/ijsp.149

Abstract:
Barriers to care cause delays in seeking, reaching, and getting care. These delays affect low-and middle-income countries (LMICs), where 9 out of 10 LMIC inhabitants have no access to basic surgical care. Knowledge of healthcare utilization behavior within underserved communities is useful when developing and implementing health policies. Little is known about the neurosurgical health-seeking behavior of African adults. This study evaluates public awareness, knowledge of availability, and readiness for neurosurgical care services amongst African adults. The cross-sectional study will be run using a self-administered e-survey hosted on Google Forms (Google, CA, USA) disseminated from 10th May 2021 to 10th June 2021. The Questionnaire would be in two languages, English and French. The survey will contain closed-ended, open-ended, and Likert Scale questions. The structured questionnaire will have four sections with 42 questions; Sociodemographic characteristics, Definition of neurosurgery care, Knowledge of neurosurgical diseases, practice and availability, and Common beliefs about neurosurgical care. All consenting adult Africans will be eligible. A minimum sample size of 424 will be used. Data will be analyzed using SPSS version 26 (IBM, WA, USA). Odds ratios and their 95% confidence intervals, Chi-Square test, and ANOVA will be used to test for associations between independent and dependent variables. A P-value <0.05 will be considered statistically significant. Also, a multinomial regression model will be used. The study findings will be published in an academic peer-reviewed journal, and the abstract will be presented at an international conference. The burden of neurosurgical diseases is enormous in low- and middle-income countries, especially in Africa.Unfortunately, most neurosurgical needs in Africa are unmet because of delays in seeking, reaching, and getting care.Most efforts aimed at reducing barriers to care have focused on improving the neurosurgical workforce density and infrastructure. Little or no efforts have been directed towards understanding or reducing the barriers to seeking care.We aimed to understand public awareness, willingness to use, and knowledge of the availability of neurosurgical care in Africa.The study findings can inform effective strategies that promote the utilization of neurosurgical services and patient education in Africa.
Arnab Ghosh
Published: 8 March 2021
SAE Technical Paper Series; https://doi.org/10.4271/2021-28-0016

Abstract:
Andrew Grove (founder CEO Intel) defines strategic inflection points as what happens to a business when a major event alters its fundamentals. The Covid-19 pandemic is one such historic event that is changing fundamental business assumptions in the Oil industry. Companies with a hunter-gatherer mindset will ride this wave with the help of technologies that make their operations lean and efficient. Current developments in AI, specifically around Cognitive Sciences is one such area that will empower the early adopters to a many-fold improvement in engineering and research productivity. This paper explores 'how to augment the human intelligence with insights from engineering literature, leveraging Cognitive AI techniques?'. The key challenge of acquiring knowledge from engineering literature (patents, books, journals, articles, papers etc.) is the sheer volume at which it grows annually (100s of millions existing and new papers growing at 40% year-on-year as per IDC). 6 million+ patents are filed every year, of which a mere 20-40% are relevant to any technology domain. It is humanely impossible to scour, review and take the right decisions by reading them all. This paper describes key cognitive techniques like concept extraction, cause-effect formulation, sentiment analysis, document summarization, topic modeling, automatic metadata extraction etc., that conforms to the analytical methodology used by E&P researchers worldwide. Such techniques can also be applied to legacy internal data of energy companies, empowering digitalization and knowledge management initiatives. Cognitive techniques have been around for a while now (first generic patents from IBM in early 1990s) but have never been applied to the engineering world, until the 2010s when IHS Markit (under entity Invention Machine Corp.) patented and productized this as an engineering research, problem solving and innovation platform. This paper also explores the efficiency gains and values accrued by the researcher community, while using IHS Markit's Cognitive AI platform.
Marina Rankovic, Vladimir Jakovljevic, Jovana Bradic, Biljana Jakovljevic, Vladimir Zivkovic, Ivan Srejovic, Sergey Bolevich, Isidora Milosavljevic, , Marko Ravic, et al.
Published: 22 February 2021
Frontiers in Physiology, Volume 12; https://doi.org/10.3389/fphys.2021.534127

Abstract:
Cardiovascular disease (CVD), such as heart ischemic or coronary artery disease, continues to be one of the major causes of death worldwide. Risk factors that have been considered to contribute to CVD development involve genetic features in combination with age and factors such as dyslipidemia, atherosclerosis, and hypertension. Additionally, the severity of these diseases is strongly affected by excess caloric intake and a lack of physical activity in a patient's lifestyle (Feng et al., 2019). Exercise as a category of physical activity is frequently regarded as an effective treatment to improve cardiovascular function, and it is also hypothesized that exercise training may be cardioprotective against ischemia–reperfusion (I/R) injury (Ghahremani et al., 2018). Although numerous data support the fact that regular physical activity improves heart function (Green and Smith, 2018; Pinckard et al., 2019), the optimal duration, frequency, and intensity of exercise (Serrano-Ostáriz et al., 2011) as well as the exact mechanism of this training-induced beneficial effect remains a matter of debate. It is well-established that exercise training is beneficial not only for cardiovascular but also for non-cardiovascular systems such as endocrine, immune system, and osteomuscular apparatus. Moreover, physical exercise possesses the capability of enhancing the antioxidant defense system, thus decreasing the level of lipid peroxidation both in adults and in aged individuals (Meijers and de Boer, 2017; Bouzid et al., 2018; Simioni et al., 2018). High-volume endurance training (ET), characterized by repeated sessions of continuous moderate intensity exercise, usually involves walking or cycling for 30–60 min to reach 40–80% peak oxygen uptake (VO2max) (Fletcher et al., 2013). On the other hand, endurance training induces numerous physiological and biochemical adaptations that improve the oxidative capacity of skeletal muscles, modify the energy source used during effort episodes, and increase aerobic capacity (de Lade et al., 2018; Kelly et al., 2018). Furthermore, positive adaptations of this type of exercise on the cardiovascular system are also based on physiological remodeling with elevated O2 consumption and improvement of cardiac contractile function (Rivas-Estany et al., 2013). Nevertheless, ET offers not only protection against regional ischemia; it also prevents decreasing of heart oxygen consumption subsequently after ischemia/reperfusion (I/R) injury (Li et al., 2014). While this type of exercise offers significant training adaptations, it requires a large time commitment. Therefore, researchers have been encouraged to begin studying new approaches to exercise such as high-intensity interval training (HIIT) with possibly the same positive effects on the cardiovascular system as ET. HIIT refers to repeated sessions of brief intermittent high-intensity exercise, between 80 and 100% of peak heart rate, interspersed with recovery periods or light exercise (Costa et al., 2018). It is often performed with maximal effort or intensity (i.e., to achieve ≥90% VO2max) and proposed as an alternative regimen to traditional ET to improve cardiovascular health in individuals with CVD (Xie et al., 2017). During the past decades, great scientific attention has been focused on investigating the impact of HIIT due to its potential superior ability to improve cardiorespiratory fitness for a lesser weekly time commitment in comparison to ET. Literature data suggest that HIIT improves flow-mediated dilation in individuals with impaired vascular function related to obesity, hypertension, metabolic syndrome, type 2 diabetes, and coronary artery disease to a greater magnitude than ET (Costa et al., 2018; Hannan et al., 2018). Also, this type of training improves mitochondrial biogenesis, insulin sensitivity (Kessler et al., 2012) and glucose regulation (Gibala et al., 2012), HDL cholesterol, blood pressure (Kessler et al., 2012), and deep abdominal adiposity (Boutcher, 2011) more than ET, which is of great importance for patients with CVD. To have a more complete picture of the effects of HIIT in cardioprotection, we also created a pathological heart model. Animal studies have shown that physical exercise including both HIIT and ET confers cardioprotection against all levels of I/R-induced injury (Calvert, 2011; Frasier et al., 2011). Exercise-induced cardiovascular adaptations are considered to be intensity-dependent; however, there is still a knowledge gap regarding the exact and precise intensity of training leading to optimal cardiac effects, and the underlying mechanisms are still lacking. Taking into consideration that many people avoid regular exercise due to lack of time, the main question of our research was to investigate if high-intensity interval exercise could provide favorable effects on the cardiovascular system as well as usual moderate activity. Moreover, the purpose of this study was to reveal potential differences between two exercise regimens with emphasis on changes in redox status. The present study was carried out on 36 male Wistar albino rats (11 ± 1 week, bodyweight 180 ± 20 g). They were housed under controlled environmental conditions, at room temperature (22 ± 2°C) with an established photo-period of 12 h light/day in the Institute of Cardiovascular Physiology, Faculty of Medical Sciences, University of Kragujevac. For research purposes, all experimental animals were obtained from the Military Medical Academy, Belgrade, Serbia. The rats had free access to food and tap water—ad libitum. Animals in this study were healthy and had not been treated with any drugs or supplements. Rats were randomly divided into three groups (12 animals per group): a sedentary control group (CTRL), an endurance training group (ETr), and a high-intensity interval training group (HIITr). Animals from the second group received an endurance training treatment before in vitro ischemia/reperfusion injury on the Langendorff apparatus (ETr), and the animals from the third group received a high-intensity interval training treatment prior to in vitro ischemia/reperfusion injury on the Langendorff apparatus (HIITr). The experimental protocol was approved by the Faculty of Medical Sciences Ethics Committee for the welfare of experimental animals, University of Kragujevac, number 01-13340/1 and by the Ministry of Agriculture, Forestry and Water Management, Authority for Veterinary of Serbia number 323-07-04422/2017-05 and followed the Guidelines for the Care and Use of Laboratory Animals. Two different modes of intensive exercise training were used on rats: traditional endurance training (ETr) and high-intensity interval training (HIITr). ETr and HIITr programs were progressive in nature and programmed after the animals completed an initial graded treadmill exercise test to assess specific work capacity. The exercise protocols included treadmill running at 0% inclination (Rahimi et al., 2015). The rats on exercise ETr protocol ran on a treadmill for 4 weeks, 5 days weekly, with 1 week before the adaptation period (8 m/min speed for 30 min/day). After each week of training protocol, speed was gradually increased from 10 m/min in the second week to 15 m/min in the fifth week (Table 1). The exercise HIITr group ran on treadmill for 4 weeks, 5 days weekly with 1 week before the adaptation period (7 m/min speed for 15 min/day). Before the actual experiment, they just had 5 min of warmup at 8 m/min as the habituation period to the treadmill. Program details for HIITr protocol is presented in Table 2. Table 1. Protocol for endurance training for rats (ETr). Table 2. Protocol for high intensity interval training for rats (HIITr). The hearts of male Wistar albino rats were excised and perfused on a Langendorff apparatus (Experimetria Ltd, 1062 Budapest, Hungary) following treatments. Thirty-six hours after the last physical capacity test, after a short-term ketamine/xylazine narcosis, the animals were killed by cervical dislocation (Schedule 1 of the Animals/Scientific Procedures, Act 1986, UK) and premedicated with heparin as an anticoagulant (Stanojevic et al., 2016). After emergency thoracotomy and rapid cardiac arrest by superfusion with ice-cold isotonic saline, the aortas were rapidly excised, cannulated, and retrogradely perfused under a constant perfusion pressure (CPP). The composition of the non-recirculating Krebs–Henseleit perfusate was as follows (mM): NaCl 118, KCI 4.7, CaCI2 × 2H2O 2.5, MgSO4 × 7H2O 1.7, NaHCO3 25, KH2PO4 1.2, glucose 11, pyruvate 2, equilibrated with 95% O2 plus 5% CO2 and warmed to 37°C (pH 7.4). Immediately after the restoration of a normal heart rhythm, a sensor (transducer BS473-0184, Experimetria Ltd, Budapest, Hungary) was inserted into the left ventricle for continuous monitoring of cardiac function through a created entrance to the left atrium of the heart and damaged mitral valve. The hearts from all groups underwent a 20-min stabilization perfusion period at CPP of 70 cm H2O. CTRL underwent perfusion for 1 h and 30 min without any intervention. In the CTRL group, hearts were subjected to ischemic preconditioning lasting 5 min before global ischemia (perfusion was totally stopped) for 30 min followed by 1 h of reperfusion. Both rat exercise groups (ETr and HIITr) went through the same ischemia/reperfusion injury protocol 36 h after following the exercise protocol. After stabilization, the hearts were under global ischemia for 30 min followed by 1 h of reperfusion. Using the sensor within the left ventricle, the following parameters of myocardial function were determined: 1. Maximum rate of pressure development in the left ventricle (dp/dt max) 2. Minimum rate of pressure development in the left ventricle (dp/dt min) 3. Systolic left ventricular pressure (SLVP) 4. Diastolic left ventricular pressure (DLVP) 5. Heart rate (HR). Coronary flow (CF) was measured flowmetrically and collected at the following intervals: in stabilization (S), in reperfusion at the first, third, fifth, and tenth minute, and 15-min intervals following the 10th minute (R1–R60). The following oxidative stress parameters were determined spectrophotometrically (Specord S-600 Analytik Jena) using collected samples of the coronary venous effluent: 1. The index of lipid peroxidation, measured as thiobarbituric acid reactive substances (TBARS) 2. The level of nitrite (NO2-) 3. The level of the superoxide anion radical (O2-), and 4. The level of hydrogen peroxide (H2O2). The degree of lipid peroxidation in the coronary venous effluent was estimated by measuring TBARS, using 1% thiobarbituric acid in 0.05 NaOH, which was incubated with the coronary effluent at 100°C for 15 min and measured at 530 nm. Krebs–Henseleit solution was used as a blank probe (Ohkawa et al., 1979). Nitric oxide decomposes rapidly to form stable nitrite/nitrate products. The nitrite level (NO2-) was measured and used as an index of nitric oxide (NO) production, using Griess's reagent. A total of 0.5 ml of perfusate was precipitated with 200 μl of 30% sulfo-salicylic acid, vortexed for 30 min, and centrifuged at 3,000 × g. Equal volumes of the supernatant and Griess's reagent, containing 1% sulfanilamide in 5% phosphoric acid/0.1% naphthalene ethylenediamine-dihydrochloride were added and incubated for 10 min in the dark and measured at 543 nm. The nitrite levels were calculated using sodium nitrite as the standard (Green et al., 1982). The level of the superoxide anion radical (O2-) was measured via a nitro blue tetrazolium (NBT) reaction in TRIS buffer with coronary venous effluent, at 530 nm. Krebs–Henseleit solution was used as a blank probe (Auclair and Voisin, 1985). The measurement of the level of hydrogen peroxide (H2O2) was based on the oxidation of phenol red by hydrogen peroxide in a reaction catalyzed by horseradish peroxidase (HRPO) (Pick and Keisari, 1980). Two hundred microliters of perfusate was precipitated using 800 ml of freshly prepared phenol red solution; 10 μl of (1:20) HRPO (made ex tempore) was subsequently added. For the blank probe, an adequate volume of Krebs–Henseleit solution was used instead of coronary venous effluent. The level of H2O2 was measured at 610 nm. Levels of blood lactate were determined using a portable monitor (Lactate Plus, Nova Biomedical, Waltham, MA, USA) and lancet (Owen Mumford, Inc., Marietta, GA, USA). After 5 min of rest, blood was taken from the tail vein, and changes in lactate levels in response to training were calculated as the difference in the sum of lactate concentration after training vs. health control and group exposed to other exercise protocols (Astorino et al., 2019). Values were expressed as the mean ± standard error. Before statistical analysis, all data were checked for normality using the one-sample Kolmogorov–Smirnov test. Biochemical data were evaluated using one-way analysis of variance (ANOVA and the post-hoc Bonferroni test for multiple comparisons). IBM SPSS Statistics 22.0 for Windows was used for statistical analysis of data. By statistical analysis, the results in the group itself were compared especially referring to three points of interest: stabilization point (S), first minute of reperfusion (R1), and last minute of reperfusion (R60). Values of p< 0.05 were considered to be statistically significant, while values of p< 0.01 were considered to be highly statistically significant. In the control group, there was a significant increase in dp/dt max in the first point of reperfusion (R1) in comparison to the stabilization period and last moment of reperfusion (R60). The value of this parameter in R1 was similar to the stabilization period (S) in the HIITr and ETr groups, but the hearts from the HIITr group showed a better response in the other point of reperfusion period (after ischemia) and less fluctuation in this cardiodynamic parameter compared to those in the ETr group (Figure 1). Figure 1. Effects of high intensity interval training (HIITr) and endurance training (ETr) on the value of maximum rate of pressure development in the left ventricle (dp/dt max) (A), minimum rate of pressure development in the left ventricle (dp/dt min) (B), systolic left ventricular pressure (SLVP) (C), diastolic left ventricular pressure (DLVP) (D), heart rate (E), coronary flow (F). α statistical significance at the level of p< 0.05 between HIITr and ETr groups; β statistical significance at the level of p< 0.05 between HIITr and sedentary control (CTRL) groups; γ statistical significance at the level of p< 0.05 between ETr and CTRL groups; Data are presented as means ± SD and analyzed through points of interest: stabilization (S), first minute of reperfusion (R1), last minute of reperfusion (R60). The most prominent changes of dp/dt min were observed at the end of reperfusion (R60) in comparison to the stabilization (S) and first point of reperfusion (R1) in the ETr group, while in the control group at the last point of the recovery period (R60), dp/dt min value was higher compared to the values before ischemia (S). On the other hand, the values of this parameter in the HIITr group were similar at the first and last points of reperfusion to the period of stabilization (Figure 1). At the end of the recovery period (R60) in the control group, the value of SLVP was significantly decreased in comparison to the values in stabilization (S). Also, a rise in values of SLVP was noticed at the first point of reperfusion (R1) compared to the stabilization point (S) in the HIITr and ETr groups, while at the end of the 60-min reperfusion, the value of SLVP in the HIIT group returned to the value detected before ischemia, which was not noticed in the ETr group where the value of SLVP remained increased after the period of reperfusion (Figure 1). A significant increase in the DLVP values in all groups during the period of reperfusion was noticed compared with the stabilization period. Furthermore, at the end of the observed period (R60), the DLVP values in all groups did not return to the value before ischemia (Figure 1). The most significant drop in HR was observed in the HIITr group at the first point of reperfusion (R1) when compared with the stabilization period (S). However, in the remaining periods of reperfusion, the value of HR in this group stayed constant and returned to the same value before ischemia. In the other two groups, control, and ETr, HR values were significantly decreased at the end of the recovery period (R60) in comparison with the values in stabilization (S) (Figure 1). In the control group, the CF value was the same at the first point of reperfusion (R1) compared with the stabilization period (S), while there was a prominent decrease at the last point of reperfusion (R60) when compared with the stabilization period (S). Additionally, in the HIITr group, a rise in CF during the observed points of interest was noticed, while in the ETr group, CF was remarkably decreased in the first point of reperfusion (R1) as well as other points of the observed period (Figure 1). The index of lipid peroxidation in coronary venous effluent did not differ significantly in the control and HIITr group, while in the ETr group, there was a rise in the first minute of reperfusion (R1) compared with the value at the end of the recovery period (R60) (Table 3). Values of TBARS were higher in the CTRL and HIITr groups in comparison with ETr in all points of interest, while there were no statistical differences in levels of this prooxidant marker between the HIITr and CTRL groups. Table 3. Oxidative stress parameters from coronary venous effluent within and between groups. There was a drop in NO2- production in the control group at the last point of recovery period (R60) in comparison with the first period of reperfusion (R1) and stabilization (S). Furthermore, in the ETr group, a higher value of NO2- was noticed in the first minute of reperfusion (R1) when compared with the end of this period (R60). In the HIITr group, the level of NO2- did not vary significantly (Table 3). Notably, higher NO2- values were detected in the HIITr and ETr groups compared with the CTRL during the observed periods, while the levels of this marker did not differ significantly between the two experimental groups. The level of O2- in the control group was significantly increased in the first period of recovery (R1) in comparison with the level before ischemia (S) and at the end of the reperfusion period (R60). However, a rise in the value of O2- in the ETr group was noticed at the end of the observed period (R60) compared with stabilization (S) and the first minute of reperfusion (R1). In the HIITr group, a difference in the level of O2- during the period of interest was also observed, especially at the period of stabilization (S) in comparison with the end of the period of recovery (R60) (Table 3). A pronounced rise in the level of this oxidative stress marker was detected in groups exposed to exercise protocols than in the control group, except the R1 moment when the value of O2- was higher in CTRL compared with the HIITr group. Furthermore, a significantly greater level of this marker was observed in the HIITr group at the stabilization period compared with ETr, until the period of reperfusion when the O2- level was decreased in the HIITr in comparison with the ETr group. In the HIITr group, the level of H2O2 did not differ significantly, while an increase in H2O2 at the stabilization period (S) in control group was noticed in comparison with the end of reperfusion period (R60). Interestingly, in the ETr group, it was a remarked significant difference in the H2O2 level among all points of interest. At the stabilization period (S), H2O2 was increased compared with the first (R1) and the last period of recovery (R60), and, also there was a significant increase in H2O2 at the first period of reperfusion (R1) in comparison with the end of the observed period (R60) (Table 3). Additionally, the level of this marker was lower in the control group compared with the other two groups in all the experimental moments, except the stabilization period when we observed the same trend of H2O2 between the CTRL and HIITr groups. Comparing the impact of the different exercise regimens on the H2O2 value, we detected higher levels of this marker in the ETr group compared with HIITr except the last point of reperfusion when we did not observe any differences in H2O2 value between these two groups. After HIIT, the level of lactate was significantly increased compared with the health control group (p< 0.01) as well as in comparison with ETr (p< 0.05). Moreover, a higher lactate value was observed in the group exposed to physical activity of moderate intensity in comparison with the control group (p< 0.05). Values of lactate levels are demonstrated in Table 4. Table 4. Lactate levels for analyzed groups of rat (Mean values ± SD). Physical activity such as exercise training is commonly regarded as an effective intervention to improve cardiovascular function, and the health benefits of regular physical activity are certainly irrefutable. It has been proved that exercise training is useful to increase cardiorespiratory fitness, a strong indicator of good metabolic health, low morbidity, and low risk of death (Fiuza-Luces et al., 2018; Feng et al., 2019). However, a great health concern has been focused on inappropriate exercise, which might lead to unexpected death especially for CVD individuals (Cobb and Weaver, 1986). In that sense, animal exercise models have been considered a powerful tool for assessing the impact of various exercise procedures, which would be a basis for designing individualized exercise programs in humans. In the present study, through different experiments, we demonstrated numerous positive and beneficial effects of exercise in general. However, our main goal was to show that cardioprotection, via cardiac improvements, can occur with only 15 min of high intensity exercise. Besides, the fact that HIITr has gained great scientific attention, underlying mechanisms for its cardioprotective abilities, still remains unclear. To examine the effects of exercise intensity in providing cardioprotection in an ischemic insult, we created I/R on a rat heart model in vitro after endurance training (ETr) and high intensity interval training (HIITr). Using the Langendorff apparatus, we collected cardiodynamic parameters and coronary flow. The main finding of the present study was that hearts from the HIITr group showed a better response in the reperfusion period (after ischemia) and less fluctuation in almost all observed cardiodynamic parameters, specifically regarding heart rate and coronary flow (Figure 1). Our data are in agreement with previous studies, which showed that short-term HIITr protects the heart against an in vivo I/R injury for at least 7 days following detraining, while there were no statistically significant differences on values of heart rate and mean arterial blood pressure among the experimental group (Rahimi et al., 2015; Kelly et al., 2018). Regarding long-term physical activity, Bowles et al. reported that coronary flow during early reperfusion after global ischemia in the isolated rat heart was greatest in animals that had high-intensity treadmill running compared with a lower intensity regimen (Bowles et al., 1992). This is in line with our finding showing that the value of coronary flow in the HIITr group was in considerable increment in the first point of recovery period (R1) in contrast to the two other groups (Figure 1). The fact that the value of this parameter returned to baseline values at the end of reperfusion (R60) suggests that preconditioning with short-term training preserved coronary vasodilatory response to I/R. On the other hand, Brown et al. pointed out that there were no differences in baseline coronary flow between groups, while after the onset of ischemia, coronary flow, in groups in which hearts underwent short-term training, and the control group, decreased similarly. However, after 45 min of ischemia, coronary flow was significantly higher in experimental than in the control group, and this difference persisted for the duration of the protocol (p< 0.05) (Brown et al., 2003). To evaluate myocardial contractility, we used dp/dt max (Figure 1) as an indirect indicator of inotropic properties of the heart, while dp/dt min (Figure 1) was measured as the rate of relaxation of the heart. Our results regarding dp/dt max show that after both types of training, the value of this parameter in the first point of reperfusion (R1) was similar to that of the stabilization period, but the hearts from the HIITr group showed better response in the other point of reperfusion period compared with those in the ETr group. Relaxing parameter of the myocardium is in accordance with inotropic characteristics, pointing out that HIITr, decreasing the power of contraction, diminishes the relaxation of the myocardium during all periods of recovery. Brown and co-workers found that high-intensity interval exercise does not affect the value of the left ventricule pressure, until 30 min into the reperfusion period when a significant increase in pressure is noticed, compared with the hearts from the control group (Brown et al., 2003). On the contrary, in the present study, it registered an increase of SLVP in the HIITr group already after the first minute of reperfusion, while at the end of the 60-min reperfusion, the value of SLVP returned to those detected before ischemia (Figure 1). Moreover, a rise in DLVP value after both types of exercise protocol during all times of observed period (Figure 1) was noticed, which is again is contrary to a previous study (Brown et al., 2003) where a lower diastolic pressure from 45 min of ischemia through 30 min of reperfusion was detected. In a sedentary group where we applied just I/R protocol, a low and slow response from hearts during reperfusion was noticed. Values at the end of the reperfusion period (R60) were significantly different from those at the beginning (S), especially regarding coronary flow, systolic left ventricular pressure, and dp/dt min. In relation to the percentage change between the points of interest, the hearts from the ETr group had less fluctuation in the examined parameters compared with those of the control group, while the HIITr group incurred even less change than ETr. According to the literature, it has been observed that inotropic properties of exercise activity are based on two different mechanisms. One way is related to favoring mitochondrial function and ATP production, while another mechanism is associated with a more effective function of the sarcoplasmatic reticulum in the sense of Ca2+ release and return into the sarcoplasmatic reticulum. In this way, muscle strength is stronger, and fatigue is reduced (Mahjoub et al., 2019). However, the mechanisms involved in the superiority of HIIT over ET are not clearly elucidated. One of the reasons for the aerobic capacity improvement during HIIT can be clarified through intracellular signaling sequence. Considering that HIIT induced muscular stimulus, AMPK activity in muscle cells increased leading to higher PGC-1α mRNA, protein level, and mRNA of the mitochondrial oxygenation enzyme (Ito et al., 2016). It was suggested that exercise might activate signaling pathways related to mitochondrial biogenesis, which involve phosphorylation of 5′ AMP-activated protein kinase and p38 MAPK, and the increased expression of PGC-1α mRNA. It was also shown that high expression PGC-1α through miR-322 induces improved mitochondrial function (Jeremic et al., 2020). To evaluate the exercise training-induced cardiac growth, the heart weight/body mass ratio of the rats was assessed in the present study. We observed increases in the heart weight to bodyweight ratio in ETr and HIITr compared with that of the control (Table 5), however, without statistical significance. Moreover, a reduction in body weight after both types of exercise protocol was noticed. Previous research (Ghahremani et al., 2018) has also shown a higher heart weight/body mass ratio in the group that underwent a high-intensity interval training, exercising aerobically on a treadmill for 8 weeks and then applying the I/R protocol at the end of the training period, thus proving the effectiveness of the aerobic exercise training protocol on the cardiac muscle. Table 5. Body weight, heart weight, and heart weight/body weight ratio for analyzed groups of rat. Physical exercise has many benefits, but it might also have a negative influence on the body, commonly attributed to an imbalance between the levels of antioxidants and reactive oxygen and nitrogen species due to excessive production of free radicals during physical exercise (Bloomer et al., 2005; Finkler et al., 2014). While the most important variable in determining cardioprotection is the exercise intensity (Rankin et al., 2012), a significant focus should also be oriented to the duration of exercise (Kavazis, 2009). Consequently, as oxidative tissue status can be changed as a result of high intensity or moderate duration exercise, we tested oxidative stress markers in coronary venous effluent. Our findings indicate that the HIITr group showed less release of ROS in the reperfusion period than when we observed the ETr and CTRL (Table 3). In both the ETr and CTRL groups, we noticed a greater fluctuation in the release of the superoxide anion radical (O2-) and hydrogen peroxide (H2O2-); however, in HIITr, those changes were minimal. Similar results were observed in the study of Stanojevic D. and co-workers where the levels of O2- and H2O2 were lower in the hearts from both moderately trained and overtrained rats (Stanojevic et al., 2016). Furthermore, superoxide, as a free radical, has a relatively long half-life, and it is primarily formed as an intermediate in biochemical reactions. Although superoxide anion radical is considered as relatively unreactive compared with the other radical species, this molecule can rapidly react with NO forming unusual peroxide, peroxynitrite. Consequently, the concentrations of these molecules in the experimental groups are increased probably because of the possible interaction of O2- with NO, consequently leading to peroxynitrite formation (Radi, 2018). On the other hand, appropriate levels of antioxidant enzymes are of sustainable importance due to their role to inhibit the formation of ROS. Superoxide dismutase prevents the accumulation of O2- by accelerating its dismutation to H2O2 (Steinbacher and Eckl, 2015). We have found that training induced slightly higher values of H2O2 compared with the control group. These results can be explained by the accepted idea that higher H2O2 steady state levels are observed due to overexpression of CuZn-SOD (Teixeira et al., 1998). Through this report, we can conclude that physical activity induces greater antioxidant defense, which is reflected in a higher level of H2O2 as a consequence of neutralization of O2 by SOD. Measuring TBARS is one of the ways to assess the degree of lipid peroxidation, which is one of the adverse redox change consequences. In our study, the value of this pro-oxidative parameter did not differ significantly in the HIITr group, while it a greater fluctuation in the release of TBARS in the ETr group during reperfusion period was noticed. Furthermore, in the HIITr group, lower levels of TBARS were observed in the ETr, which points to the better redox state after short-term training protocol. An additional factor that may contribute to at least some validation of training protocols in terms of aerobic/anaerobic quantification is metabolic stress. Although there are different methods to monitor this factor, one of the possible ways is via measurement of blood lactate concentration. Studies have shown that this parameter may be an index of intramuscular stress and is associated with muscle fatigue and decreased malleability as the response to the training (Spriet et al., 2000; Astorino et al., 2019). Our data showed higher blood lactate level in the HIITr group compared with those in the other groups. Such results arise as a consequence of HIIT due to lack of time for lactate metabolic degradation. Additionally, lactate levels in the ETr group were also increased compared with those in the CTRL group but significantly lower than those in the HIITr group due to lower intensity of physical activity and longer periods of resting between training sessions. These results are in line with previously published data where they showed increased lactate level in HIIT compared with long-distance training concluding that the HIIT regime is more superior for lactate production (Ní Chéilleachair et al., 2017). In the end, it is important to emphasize that all study findings must be observed in light of the fact that the Langendorff model does not take into account the heart rate variability (HRV) and vagus nerve influence as the left anterior descending artery (LAD) ligation model. Another limitation of the study is the absence of results regarding the systemic effects of the two training regimes, which could certainly affect cardiac changes. In summary, although performed on an animal model, this study may help in the better understanding of the differences between the effects of HIITr/ETr training regimes on I/R injury. Therefore, it proves the beneficial impact of HIITr in cardioprotection. Also, our results can be of interest in explaining both exercise protocols' impact on redox status as well as for the possible clinical impact in the design of therapeutic strategies for cardioprotection. However, we were not able to investigate the possible physiological and molecular changes in both exercise protocols, which would be useful in highlighting unknown molecular mechanisms for cardioprotection. Accordingly, our future plans will be directed to reveal the possible expression and role of many molecules as well as the activation of the different pathways during both training regimes included in the reduction of cardiovascular risks. In the present study, we perceived the main functional differences between the two different styles of exercise that require very different time commitments, while both styles created beneficial cardiac adaptations. The main conclusion of this research is that preconditioning with five sessions of HIITr performed over a 5-week period may also be superior in protecting the heart against I/R injury. Given that a “lack of time” is the most often cited reason for not exercising regularly, this represents a more time-efficient training method for improving cardiac function than a more time-consuming ETr. Moreover, it seems that HIITr can encourage oxidative stress within the heart, which can be of interest for the elucidation of the impact of different exercise protocols on cardiac redox homeostasis. The datasets generated for this study are available on request to the corresponding author. This study was carried out in accordance with the recommendations of European Directive for welfare of laboratory animals no: 2010/63/EU and Good Laboratory Practice (GLP) principles. The protocol for the current study was approved by the Ethics committee for experimental animal well-being of the Faculty Of Medical Sciences at the University of Kragujevac, Serbia (No: 01-13340/1). MRan, VZ, IS, and MRav performed the experiments and collected the data. BJ and TT performed the statistical analyses. JB, IM, JJ, OM, and NJ performed the biochemical analyses and collected the biochemical data from the study. VJ and SB designed the study. All authors contributed to the interpretation of the results and the writing of the manuscript. This work was supported by the Ministry of Science and Technical Development of the Republic of Serbia (Grant No. 175043) and the Faculty of Medical Sciences, University of Kragujevac (Junior Projects Nos. 01/15 and No 03/18). The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Astorino, T. A., DeRevere, J. 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Effects of high-intensity interval training on aerobic capacity in cardiac patients: a systematic review with meta-analysis. Biomed Res. Int. 2017:5420840. doi: 10.1155/2017/5420840 PubMed Abstract | CrossRef Full Text | Google Scholar Keywords: endurance training, high intensity interval training, ischemic reperfusion injury, rats, heart Citation: Rankovic M, Jakovljevic V, Bradic J, Jakovljevic B, Zivkovic V, Srejovic I, Bolevich S, Milosavljevic I, Jeremic J, Ravic M, Mijanovic O, Turnic TN and Jeremic N (2021) Effects of High Intensity Interval vs. Endurance Training on Cardiac Parameters in Ischemia/Reperfusion of Male Rats: Focus on Oxidative Stress. Front. Physiol. 12:534127. doi: 10.3389/fphys.2021.534127 Received: 11 February 2020; Accepted: 22 January 2021; Published: 22 February 2021. Edited by: Reviewed by: Copyright © 2021 Rankovic, Jakovljevic, Bradic, Jakovljevic, Zivkovic, Srejovic, Bolevich, Milosavljevic, Jeremic, Ravic, Mijanovic, Turnic and Jeremic. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. *Correspondence: Vladimir Jakovljevic, [email protected]
Yi-Zu Wang, Cheng-Cheng Wu,
Published: 19 February 2021
Neural Plasticity, Volume 2021, pp 1-15; https://doi.org/10.1155/2021/6634644

Abstract:
Background. The prevalence of comorbid pain after spinal cord injury (SCI) is relatively high in clinical observations and has continued to increase over time. Neuropathic pain (70.14%) is the most popular subject in academic journals after SCI. However, studies that used the bibliometric method to analyze comorbid pain after SCI are still lacking. This study is aimed at combining and integrating acquired information to analyze the global trends of research on the comorbidity of pain after SCI in the last three decades (1990–2019). Methods. Systematic works of literature published from 1990 to 2019 were obtained from the Web of Science Core Collection. CiteSpace software was used to analyze the relationship of publication year with the country, institution, journals, authors, references, and keywords. The regression analysis is used to evaluate the percentage of the category increase or decrease over time significantly. IBM SPSS Statistics was used in the statistical analysis. Results. A total of 730 publications were included in the analysis. A remarkable increase in the number of publications was observed in the study period ( P < 0.05 ). A total of 202 academic journals focused on the categories of clinical neurology, neurosciences, and rehabilitation, and the annual growth rate of articles in these three categories was statistically significant ( P < 0.05 ). The USA (356, 48.77%) and the University of Miami (64, 8.77%) were the country and institution with the highest number of publications, respectively. Spinal Cord, which was the main journal for research on pain after SCI, had the most publications (88, 12.05%). Burst keywords showed that the individual, inflammation, and central sensitization with pain after SCI are the research development trends and focus in this research field. Conclusions. Overall, this study provides the latest research direction for pain after SCI. This historical overview of research into pain after SCI will be a useful basis for further research into development trends, focus issues, cooperators, and cooperative institutions.
Mushtaq Ahmad, Farial Naima Rahman, Zubaidur Rahman, Zulfikar Ali, Mohammad Ali
Published: 11 February 2021
KYAMC Journal, Volume 11, pp 166-170; https://doi.org/10.3329/kyamcj.v11i4.51990

Abstract:
Background: COVID-19 is an emerging infectious disease which has created a global health emergency status. It is now super spreading in the community of Bangladeshi population causing morbidity and mortality amongst masses. Objectives: The aim of this study is to find out the knowledge, attitude and practices of medical college students and their family members towards the Covid-19. Materials & Methods: This online cross sectional study was conducted from the 15 April to 30 April 2020 during the lockdown period in Bangladesh. Collected data was analyzed by using SPSS IBM version 22.0. Results: A total of 517 responses were obtained. The majority of the population 326 (63.06%) were female and 352 (68.09%) belonged to an age group of 21-30 years. This study has revealed that 412(79.69%) believe COVID-19 affect all age group, 311(60.15%) thinks that it affect the elder people seriously, 215(41.59%) thinks specific treatment is not available for COBID-19, Greater part of respondents 256(49.52%) says COVID-19 infection is preventable, 452(87.43%) gives positive opinion about government lockdown to avoid further spread of infection and 402(77.76%) believes physical distancing is helpful to prevent spread of this disease. Regarding 14 days quarantine period 375(72.53%) give positive answer, 425(82.20%) says COVID-19 affects world economy badly, 298(57.64%) thinks the situation may be controlled soon. Conclusion: Since prevention is better that cure, hence an increasing need of awareness amongst the local population regarding COVID-19 is required. Further extensive survey studies are required in future that can provide supportive data in developing and implementing public health policies regarding COVID-19 pandemic in our country. KYAMC Journal Vol. 11, No.-4, January 2021, Page 166-170
IOP Conference Series: Materials Science and Engineering, Volume 1083; https://doi.org/10.1088/1757-899x/1083/1/011002

Abstract:
All papers published in this volume of IOP Conference Series: Materials Science and Engineering have been peer reviewed through processes administered by the Editors. Reviews were conducted by expert referees to the professional and scientific standards expected of a proceedings journal published by IOP Publishing. The International Scientific Conference “Construction and Architecture: Theory and Practice for the innovation Development” (CATPID-2020 Part II)• Type of peer review: Single-anonymous • Describe criteria used by Reviewers when accepting/declining papers. Was there the opportunity to resubmit articles after revisions? The main criterion used by reviewers is the scientific significance of the submitted materials. The authors had the opportunity to correct the article according to the comments of the reviewers. • Conference submission management system: used own systems • Number of submissions received: 158 submissions were received • Number of submissions sent for review: 146 submissions were sent for review • Number of submissions accepted: 114 submissions were accepted • Acceptance Rate (Number of Submissions Accepted/Number of Submissions Received X 100): 72.2 • Average number of reviews per paper: 2 reviews per paper • Total number of reviewers involved: 18 reviewers were involved • Any additional info on review process (ie plagiarism check system):• Contact person for queries: Professor Batyr Yazyev Don State Technical University, Rostov-on-Don, Russia [email protected]
, Klaus North, Agustín Zubillaga, María Paz Salmador
Published: 28 January 2021
Frontiers in Psychology, Volume 11; https://doi.org/10.3389/fpsyg.2020.587949

Abstract:
Sustainable competitiveness and growth of small- and medium-sized enterprises (SMEs) are increasingly determined by their capability to make use of digital technologies [EU (European Commission), 2018b] and tie into a digital ecosystem (Pelletier and Cloutier, 2019). Surveys (Tarutea and Gatautis, 2014; Bouwman et al., 2019; Shettima and Sharma, 2020) prove that the digitalization has a positive effect on the performance of SMEs. This includes dimensions such as growth, market value, and profitability as well as social and environmental performance and satisfaction; 46% of firms that participated in a survey of the European Digital Transformation Scoreboard report a medium-to-large increase in their annual turnover over the last 3 years following the adoption of technology [EU (European Commission), 2018a]. Many SMEs, however, are lagging behind in digital transition (OECD, 2017). According to a report by the Digital Innovation Hubs Working Group (2018), only 17% of SMEs have successfully integrated digital technologies into their businesses, compared with 54% of large companies. They lack resources and capabilities or suffer from inertia, which hampers opportunities (Cenamora et al., 2019). In the emerging highly interconnected and collaborative forms of value creation, the capacity to connect better to an integrated business network will be important to stay competitive (Rehm and Goel, 2017; EU (European Commission), 2014). SMEs comprise three different categories of enterprises, namely, micro-enterprises, small enterprises, and medium-sized enterprises (see Table 1). To classify firms, the official European definition of SMEs considers three different factors: level of employment, level of turnover, and size of balance sheet. Table 1. Definition of SMEs. According to the EU (European Commission) (2018b) overall, in 2017, SMEs in the EU accounted for 99.8% of all EU-28 nonfinancial business sector enterprises, two–thirds of total EU-28 employment (66.4%), and slightly less than three–fifths (56.8%) of the value added generated by the nonfinancial business sector. Micro-SMEs are by far the most common type of SME, accounting for 93.1% of all enterprises. SMEs are a highly diverse group of enterprises that also condition how they approach digitalization (OECD/UN ECLAC, 2012; Neirotti et al., 2018). For example, approaches differ in case of Industry 4.0 adoption (Matt and Rauch, 2020) or the integration in platform ecologies (Gierlich-Joas et al., 2019). A common denominator, however, is the need to integrate, build, and reconfigure internal and external resources in order to adapt to rapidly changing environments (North and Varvakis, 2016). These dynamic capabilities take the form of skills, processes, procedures, organizational structures, and decisions that motivate and promote the detection (sensing) and capture (seizing) of opportunities in order to reconfigure (transform) their capabilities (Teece, 2007). As several studies show, the development of dynamic capabilities impacts SME performance and growth (He and Wong, 2004; Lubatkin et al., 2006; Macpherson and Holt, 2007; Protogerou et al., 2008; Sunday and Vera, 2018) and is vital for implementing Industry 4.0 approaches (Garbellano and Da Veiga, 2019) and digitalization (Matarazzo et al., 2021). However, currently, there is a limited understanding of how SMEs are approaching digitalization from a dynamic capabilities perspective. Garzoni et al. (2020) introduce a four-level approach of engagement of SMEs in the adoption of digital technologies, namely, digital awareness, digital enquirement, digital collaboration, and digital transformation, hence the need to map adoption and learning paths of these firms. For this mapping, digital maturity models or frameworks can provide guidance (Valdez de Leon, 2016, Williams et al., 2019). The DIGROW digital maturity framework (North et al., 2020) is grounded on the microfoundations of dynamic capabilities (Teece, 2007) and therefore allows to link digitalization to organizational capabilities. Based on this framework, a questionnaire has been built and applied to a sample of 380 SMEs from the Basque region (Spain). In the following section, we describe the framework, the structure of the questionnaire, the data collection process, and the content of the database built as a result of this process. The DIGROW framework of digital maturity (North et al., 2020) aims at companies to assess their digital maturity level, and the capabilities associated with each level of maturity, which could support their digitally enabled growth. The framework is grounded in dynamic capabilities theory. In the explanation of microfoundations of dynamic capabilities, Teece (2007) described his constituent capacities: “For analytical purposes, dynamic capabilities can be disaggregated into the capacity (1) to sense and shape opportunities and threats, (2) to seize opportunities, and (3) to maintain competitiveness through enhancing, combining, protecting and, when necessary, reconfiguring the business enterprise's intangible and tangible assets” (Teece, 2007: 1319). Pavlou and El Sawy (2011), based on their empirical research, proposed four steps of dynamic capabilities development—sensing, learning, integration, and coordination—thus highlighting the importance of managing knowledge and learning to cope with turbulent and disruptive environments (North and Varvakis, 2016). A particular shortcoming in SMEs is that owners and managers are aware of growth potentials; however, they tend to lack an explicit strategy, and if they have one, they do not communicate that strategy to employees (North et al., 2016). Therefore, in the DIGROW framework, an intermediate step is inserted between Teece's “sensing” and “seizing,” the step of strategy development and communication, which is related to Pavlou and El Sawy's (2011) learning and integration. Thus, the “DIGROW” framework considers four capacities: 1. Sensing digitally enabled growth potentials: searching for digitally enabled growth opportunities, understanding and developing digital customer needs, sensing technology-driven opportunities, and use of external sources for digital innovation. 2. Developing a digitally enabled growth strategy and mindset: Digitally enabled growth strategy, digital leadership, digital mindset (attitudes and behaviors), and empowered employees. 3. Seizing digitally enabled growth potentials: Digitally enabled business models, digital market presence, digital customer experience, and agile implementation/deployment of digitalization initiatives. 4. Managing resources for digital transformation: Digital skills and learning, digital processes, digital technology and security, and digital investments. Each of these capacities is assessed at six levels described by an anchor statement. A pretest in selected firms (North et al., 2019) revealed that these six levels would allow a sufficient degree of differentiation. As mentioned above, a self-assessment questionnaire has been developed based on this framework. This is shown in the Appendix. The companies subject to study are small- and medium-sized enterprises (SMEs) from the Basque region in Northern Spain, which, according to the definition of SME proposed by the European Union, comprise between 10 and 249 employees. The questionnaire has been addressed to 7,040 firms in cooperation with regional business associations between July and November 2018 and was answered by the chief executive officer (CEO) or the information technology (IT) manager in each firm. The number of SMEs that responded to the survey amounted to 540 (response rate 7.67%). After only partially completed or invalid questionnaires were eliminated, the final sample consisted of 427 companies. As for company size, 47 firms were micro-enterprises (i.e., <10 employees), 220 were small firms (i.e., between 10 and 49 employees), and 160 were medium-sized firms (i.e., between 50 and 249 employees). Regarding composition of the sample according to industries, 133 firms belong to the manufacturing sector and 24 to commerce, 198 companies are distributed among different types of services (i.e., education, health services, insurance, information services, transport, and professional services), and 25 companies belong to the building sector. Based on the data collected, we built a database in which the structure and content are described in this section. The database is structured in rows and columns. Each row contains the information related to each firm (in total, 427 firms). On the other hand, the columns include the following information: – Industry where the company operates. Industries are codified according to NACE (A21) classification. – Range of employees per company. We consider these data to categorize the firm as a micro-enterprise (range = 0–9 employees), a small company (range = 10–49 employees), or a medium-sized company (range = 50–249 employees). – The level of maturity reported by each firm regarding each question referred to firm's digital capacities (16 questions/capacities in total). We distinguish six maturity levels. Levels 0 and 1 correspond to a low degree of a firm's digital maturity; levels 2 and 3 correspond to a medium degree of a firms' digital maturity; and levels 4 and 5 refer to a high degree of a firm's digital maturity (see the Appendix). These level values are reported in the database and ranged from 0 to 5. The data contained in this database can be analyzed for different purposes. The main purpose is to assess the level of digital maturity of each company. In order to obtain an overall picture of the level of digital maturity, we have carried out a descriptive analysis, in particular, a frequencies analysis. We used the software IBM SPSS (version 26.0). First, a frequency analysis for the whole sample allows us to obtain the number and percentage of companies that rated each one of the levels of digital maturity for each one of the capacities considered. In other words, for each capacity, we could know how many firms attain a particular level of maturity. Based on this, we could conclude if the maturity level achieved by each company regarding each capacity was low, medium, or high. The results of the frequency analysis are as follows: Regarding sensing potential opportunities for digital growth, a high number of companies are able to search and identify growth opportunities (77%), and 28.2% of firms work actively on their identification. Nevertheless, only 24% identify growth opportunities systematically. As far as developing a digitally based growth strategy and mindset is concerned, while many companies understand the relevance of digitalization, they are not able to develop strategies aimed at taking advantage of the growth opportunities opened by digital technologies. Only 18% of companies define a digitally enabled growth strategy, and 15% update their strategy, taking into account different facets of digitally enabled growth. In terms of seizing digitally enabled growth potentials, 31.6% of companies do not have a digitally based business model, while 22% of firms claim to have started to change some components of their business models. Finally, only 14.4% of companies systematically adapt their business models or create new business models to promote a digitally enabled growth. With regard to managing resources for digital transformation, approximately a quarter of firms (26%) consider that investment to develop digital skills is low. And only 6.7% of companies claim to possess the necessary digital skills. On the other hand, almost a quarter of firms (24%) claim to achieve a medium level of investment in digital transformation initiatives, while only 9.5% of companies consider they invest a lot in digitalization. Second, we also run a correlation analysis. Observing the correlation matrix, we find that the highest correlated variables are the following: digitally enabled growth strategy highly correlates with digital leadership (0.76) and a digitally based business model (0.70). Moreover, a digitally based business model correlates with digital market presence (0.70) and digital customer experience (0.72). Digital customer experience also highly correlates with digital skills and learning (0.74). Finally, there is a high correlation between digital skills and learning and agile implementation of digital initiatives (0.72). On the other hand, we run a factor analysis, but this does not show relevant results, since it only discriminates one factor, probably due to the high extant correlation among most of variables (i.e., capacities). Third, we carried out a regression model analysis to explore the relationship between a digitally enabled growth strategy as the dependent variable and digital mindset, digital leadership, and empowered employees as the independent variables (Aramburu et al., 2020). The results of the regression model test show that the relationship between each independent variable and the dependent one is significant in all cases at a significance level of 95% (p< 0.05; see Table 2). Therefore, digital leadership, digital mindset, and the fact of having empowered employees who deploy digital initiatives have a positive and significant influence on digitally enabled growth strategy. In addition, digital leadership is the most relevant capacity influencing digitally enabled growth strategy (β = 0.533), followed by digital mindset (β = 0.287) and empowered employees (β = 0.151). Table 2. Regression model (coefficients and significance). Finally, further analyses have been carried out with the aim of testing the role of firm's size. With this purpose, a mean comparative analysis has been carried out comparing small- and medium-sized companies (i.e., between 50 and 249 employees) and big firms (i.e., between 250 and 500 employees), showing that there is a significant difference according to the size of the firm only in the case of eight capacities included in the framework over a total of 16 (i.e., use of external sources for digital innovation, digital leadership, empowered employees, digitally enabled business models, digital market presence, digital customer experience, agile implementation/deployment of digitalization initiatives, and digital skills and learning). Therefore, we conclude that the firm's size affects digital maturity, but this effect is not extremely relevant. Additional types of data analysis could be carried out. For instance, and considering the data contained in the database, further regression analyses might be carried out in order to explore the relationships among different sets or combinations of capacities. One potential area of interest to explore would be to analyze which factors can influence the digitalization processes, such as digital skills, digital investments, and digitally enabled growth strategy. Another future avenue could be to explore how digitally enabled business models are influenced by the digitally enabled growth strategy, digital investments, and the digital mindset. Finally, a future relevant path for research is opened regarding the impact of coronavirus disease 2019 (Covid-19) in digital transformation of SMEs, in terms of both firms' capabilities and also firms' characteristics (e.g., size and industry). The pandemia is catalyzing digitalization processes in many companies; thus, it would be interesting to explore what is happening in SMEs. To conclude, the database has some limitations, such as it only includes data of SMEs from a particular geographical setting (i.e., Basque region in Spain). Moreover, it only refers to SMEs, not including data of big companies. Regarding the industries represented, the dataset is quite complete since it contains data of SMEs belonging to all industries in the region. Finally, another limitation is that the database does not contain data regarding the companies' performance (i.e., revenues or growth rate). This might be completed in the future collecting additional data about performance. The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/supplementary material. The dataset is available here: http://data.orkestra.deusto.es/es/dataset/digrow-basque-sme. NA has led the writing process of this manuscript. KN has led the development of the digital maturity framework referred to in this paper (i.e., DIGROW framework). AZ has led the data collection process and database building. MPS has contributed to the writing of a part of the article. All authors contributed to the article and approved the submitted version. The research reported in the article has been founded by Orkestra-Basque Institute of Competitiveness (a part of this funding has been provided by the firm Euskaltel). The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor declared a past co-authorship with one of the authors MPS. 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This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. *Correspondence: Nekane Aramburu, [email protected]
Journal of Nusantara Studies (JONUS), Volume 6, pp 199-221; https://doi.org/10.24200/jonus.vol6iss1pp199-221

Abstract:
Background and Purpose: Recent technological advancements and Covid-19 pandemic have prompted more opportunities for online learning. However, there is a dearth of empirical research that is focused on high school students. Therefore, this study aims to obtain a more comprehensive view of ESL learners’ involvement or word contributions in a ‘normal’ face-to-face situation and in a synchronous online text-based environment by relating it to their personality and language proficiency. Methodology: In this study, a quasi-experiment was carried out over four weeks. It involved eight sessions of face-to-face and online discussions with 48 Malaysian high school students who were divided into two matched-sample groups. The participants' feedback was used to support and provide insights on the findings. The quantitative data were analysed using using IBM SPSS statistics 26 software while the participants’ responses to the online feedback session were analysed using open coding and axial coding strategies. Findings: Statistically significant difference was found in learners’ word contributions during face-to-face and online discussions. Apart from the extroverts with high-intermediate language proficiency, the other groups of learners who are either introverts or having lower level language proficiency were found to produce significantly more words in synchronous online text-based discussions. The non-face-to-face context of online forums might have lowered the learners’ level of anxiety and increased their confidence to interact with their peers. Contributions: Learners’ personalities and language proficiency levels should be considered when choosing a discussion setting and when facilitating discussion activities. More support should be provided for the less proficient or introverted learners to express themselves in a face-to-face discussion. Keywords: Personality, Language proficiency, Computer-mediated communication, Synchronous text-based online discussions, Word contributions Cite as: Chew, S. Y., & Ng, L. L. (2021). The influence of personality and language proficiency on ESL learners' word contributions in face-to-face and synchronous online forums. Journal of Nusantara Studies, 6(1), 199-221. http://dx.doi.org/10.24200/jonus.vol6iss1pp199-221
, Domingo Orozco Beltrán, José Antonio Quesada Rico, María Concepción Carratalá Munuera
Published: 26 January 2021
Frontiers in Nutrition, Volume 7; https://doi.org/10.3389/fnut.2020.577797

Abstract:
The worldwide growth of diabetes mellitus (DM) has, in recent years, generated an exponential increase in associated comorbidities such as high blood pressure, cholesterol, and cardiovascular risk (CVR), with an increase in mortality in the population (1). At the same time, the global DM pandemic increased by 75% in recent decades, with a large proportion of affected individuals spanning all age groups from 1988 to 2010 (2). In the Americas, its prevalence has increased from 5 to 8.3% in recent years, particularly in Honduras, where 6% of individuals over 20 years of age have DM (3). As such, DM increases health care costs in low- and middle-income nations (4). Diagnosing diabetes mellitus type 2 (DM2) has changed since the inclusion of glycosylated hemoglobin (HbA1-c), as it is ≥6.5% in DM2. The criterion for fasting glucose is ≥126 mg/dL, whereas glucose at 2 h is ≥200 mg/dL (5). A hyperglycemic state can lead to an underlying prothrombotic environment, an overactivation of the coagulation cascade, fatal thromboembolic complications, and, eventually, increased mortality in DM patients (6). Medical treatment focuses on three pillars: drugs, nutrition, and education (7). The use of metformin acts as a standard pharmacological insulin used by patients to avoid weight gain (8). Nutritional medical therapy (NMT) prioritizes glycemic control and reduces comorbidities (7, 9). The diet promotion program is based on dietary guidelines, with group physical activity proving effective for predicting DM2 sowing but ineffective for long term benefits due to the lack of adherence (10). To this effect, the American Diabetes Association emphasized the need for individualized medical nutritional therapy (IMNT) (11). Carbohydrate counting (CCHO) has been shown to be effective for glycemic control in diabetes mellitus type 1 patients when being intensively treated with insulin (12, 13). Carbohydrate counting considers the actual content of food consumed based on the individual's usual intake and coordinates insulin-glucose utilization so that both curves act as a single exponentially flattened growth curve (14). The resulting weight gain is a consequence of decreased urine sugar loss (15). Few studies have used carbohydrate counting in DM2 in the primary care setting, and although it showed improvements in HbA1c, compression of carbohydrate counting was considered difficult for participants (16). Given the paucity of evidence from randomized controlled clinical trials in Latin American for carbohydrate counting DM2 patients, this work aimed to evaluate the effectiveness of this medical nutritional treatment, which minimizes the risk of developing comorbidities and public spending on health care. The present work was a double-blind randomized controlled clinical trial. The allocation of the University School Hospital of Honduras was random. The study design was submitted and approved by the Biomedical Research Ethics Committee (IRB N°419-CGPGFCM/UNAH/2017) of the National Autonomous University of Honduras, on June 9, 2017. The doctors and nutritionists assigned to this study took an online ethics course titled “Human Subjects Research, IRB, Behavioral and Educational Focus” via the Collaborative Institutional Training program. As such, they were in compliance with the CONSORT checklist (17), which states the information to be included when reporting a randomized clinical trial. The study was carried out at the National Autonomous University of Honduras. The University School Hospital of Honduras has a specialized unit for the comprehensive care of DM patients and has recently created facilities conducive to the interdisciplinary medical-nutritional approach named “Model Center for Training and Comprehensive Care in Diabetes.” It has become the most prominent medical center in Honduras. The working group was made up of the clinical epidemiology unit and the endocrinology unit belonging to the University School Hospital of Honduras. The director of the Model Center for Training and Comprehensive Care in Diabetes selected two doctors to adjust drug treatments and two nutritionists to apply and follow up with the carbohydrate (CCHO) count and current dietary recommendations (RDC). The working groups were trained separately for the application of nutritional medical therapies. The randomization of the participants was carried out by the head of the clinical epidemiology service. using the “random” function in Microsoft Excel. Participants with a DM2 diagnosis were selected based on clinical records, glycosylated hemoglobin ≥7% (not older than 6 months), aged between 18 and 65 years, insulin use between 1 and 10 years, no use of sulfonylureas, body mass index (BMI) <35 kg/m2, and waist–hip ratio ≥0.90 in men and ≥0.85 in women. Patients excluded were those who had been clinically diagnosed as having cancer, chronic respiratory disease, pregnancy, cognitive impairment (e.g., dementia, amnesia, delirium), macroangiopathy (e.g., ischemic heart disease, stroke, peripheral vascular disease), microangiopathy (e.g., proliferative retinopathy or maculopathy, kidney failure grade IIb, III, or IV), amputations, temporary staff of the institution, and those with insulin use over 10 years. In 2016, the diabetic population of the University School Hospital of Honduras was 4,247 patients. In this study, 400 eligible patients in the endocrinology unit were selected. A mean value of 8.33% glycosylated hemoglobin was considered a regular value (11). For the sample size, we assumed risks foreseen in the current dietary recommendations of the control group (10%). The risk value of making an error was the conventional alpha of 5% (bilateral hypothesis) and beta of 20%. Participants (n = 62), per medical nutritional treatment, were adjusted for 15% loss and resulted in 71 participants per carbohydrate counting group for the current dietary recommendations. Figure 1 shows the flow chart of the selection process. The sample chosen was made up of participants registered with the endocrinology unit. In total, 400 participants were eligible, 258 participants did not meet the inclusion criteria, 142 participants were randomized, and only women decided to participate. During allocation, ten patients with glycosylated hemoglobin values ≤ 7% at the start did not receive allocated intervention. This left a total of 132 patients who met our inclusion criteria. During the 6-month follow-up, three participants were excluded because they had been diagnosed with cancer, chronic renal failure, and Zika, respectively. A total of 9.2% (n = 13) participants were excluded from the analysis. In total, 48.1% (n = 62) of participants remained on the carbohydrate counting diet, whereas 51.9% (n = 67) of participants followed their current dietary recommendations. Figure 1. Flow chart of the selection process. Participants adjusted to the insulin dose prescribed in the drug treatments (13, 14). The calorie requirements based on total energy expenditure were obtained (18). A reduction of 250 kcal/day to allow for adherence to treatment was applied. The nutritional medical therapy was delivered with a list of foods that contained the weight of carbohydrates and insulin (UI) dose, which was adapted to local culinary habits (forms of preparation and ways in which the food was cooked). Moreover, the nutritional medical therapy was adapted to the Central American food pattern (19). Participants were issued a brochure by the Honduran Ministry of Health to help better manage their diabetes mellitus type 2 (20). The brochure details glycemic index, fat content, and food preparation style but does not estimate caloric requirements nor provide food caloric adjustments. Participants in both nutritional medical therapy groups (i.e., carbohydrate counting and current dietary recommendations) took part in 30-min sessions in which they observed photographs that showed food portions, food fiber, types, and cooking techniques. Biochemical glucose, glycosylated hemoglobin, and anthropometric (i.e., weight, height, body mass index, waist circumference, hip circumference, and blood pressure) parameters were evaluated at 6 and 12 months of individualized nutritional therapy. Glucose, however, was evaluated monthly. At each visit, doubts were cleared up, and concepts were reinforced for each nutritional medical therapy. For both nutritional medical therapies the glucose (mg/dL) and glycosylated hemoglobin (%) blood parameters were collected the day of the appointment and analyzed at the University School Hospital of Honduras's clinical laboratory. Participants attended these sessions on an empty stomach and without having previously smoked for 8 h. The 3-mL blood samples obtained using venipuncture were stored in anti-clotting tubes labeled with the code of each participant. They were centrifuged with a Z-29 digital macro-centrifuge kit at a speed of 2,500–3,000 rpm for 5 to 10 min to separate the serum from the clot. They were incubated at 65–85°F ± 5°F (17–30°C ± 2.8°C) per h. Glucose and HbA1c values were analyzed using Siemens Dimension RxLMax equipment (Siemens Healthcare Germany 2010). HbA1c determination was performed using the ascendant/enzymatic endpoint method, with FlexR reagent cartridge reagents. On the same day of the biochemical measurements, we recorded the weight, height, waist–hip size, and blood pressure of participants in accordance with recommendations (21). They were weighed (kg) with precision class I equipment (seca 803). Height (recorded in cm) was measured using a stadiometer (seca 213). Body mass index was calculated in accordance with the standard formula (kg/m2) (22). Blood pressure (mmHg) was measured three times at an interval of 1 min between each measurement (23) using a digital automatic blood pressure monitor (OMRON M6 (HEM-7001-E (V); precision ± 3 mmHg). Therefore, we obtained the values with the means of the second and third measurements of systolic (SBP, mmHg) and diastolic blood pressure (DBP, mmHg). Waists and hips (cm) were measured with a flexible tape measurer (SECA 201). Pressure was avoided on the tissues. Central obesity, waist circumference (≥80 cm), and waist–hip ratio (≥0.85) were defined in accordance with World Health Organization (WHO) criteria (24). The results of each dietary treatment were expressed as mean ± standard error of the mean. The normality of the data was verified using the Kolmogorov-Smirnov test. The uniformity and variance were verified using the Bartlett test. An unpaired Student t-test was performed. Pearson correlations were analyzed to verify the association between HbA1c and anthropometric indicators. The data to compare experimental stages were processed using the Friedman test. Over time, we adjusted the mixed linear multivariate model for HbA1c, taking into account the possible effect of the explanatory variables. A stepwise variable selection process was carried out based on the AIC (Akaike Information Criterion), until the optimal model was reached. The optimal model is shown, with the coefficients, standard error, degrees of freedom, and the t-value and p-value associated with each coefficient of the fixed effects. The standard deviation and the correlation of the random effects (time) are also shown. We used SPSS software version 22 (IBM (International Business Machine), New York, USA) and the nlme package. The R statistical program was used for mixed models. Table 1 shows the effect of carbohydrate counting and current dietary recommendations on anthropometric and biochemical values at 0, 6, and 12 months of treatment. Significant differences were observed between treatment for diastolic blood pressure, body mass index, waist, glycosylated hemoglobin, insulin units, and metformin doses. Diastolic blood pressure was reduced in CCHO from 82.73 to 77.05 mmHg (p = 0.001), while RDC did not obtain a reduction (p = 0.747). Changes in diastolic blood pressure values were observed between groups from 6 months of nutritional medical therapy with statistical significance at 12 months (77.03 mmHg CCHO vs. 80.87 mmHg RDC p = 0.019). Body mass index varied over time, with its highest efficacy at 12 months of CCHO (30.74 to 29.74 in CCHO vs. 31.21 to 32.06 in RDC p< 0.001). Table 1. Effect of medical nutritional treatment vis-à-vis anthropometric and biochemical markers. Participants' waists achieved reductions of 1.143 cm at 6 months for CCHO and RDC (p = 0.02); however, at 12 months, waists began showing a marked trend, with a reduction of 1.23 cm in CCHO (p< 0.01). As a biochemical indicator, glycosylated hemoglobin showed an intergroup reduction at 6 and 12 months (p = 0.05). The intergroup (p< 0.01) compared with the RDC showed an increase in its values at 6 and 12 months (0.69%). The insulin and metformin values for the CCHO behaved with a reduction of administered units for the pharmacologic insulin intergroup (6.85, p< 0.001). Moreover, there was a decrease of 354.79 mg metformin at 12 months of nutritional medical therapy with a p< 0.001 difference between groups. Table 2 shows a linear regression between HbA1c, BMI, waist, hip, glucose, insulin, and metformin. The βi coefficient associated with each variable shows the average change in HbA1c by a one-unit increase in the model variable. In this way, in the RDC group, hemoglobin decreased by 0.12 (β of time factor 2) and 0.45 units (β of time factor 3) when passing from the basal level at 6 and 12 months, respectively. In the CCHO group, the average decrease was 0.62 (0.12 + 0.50) and 0.95 (0.45 + 0.50) units at 6 and 12 months, respectively. The significant reduction occurred at 12 months (p-value < 0.001), not at 6 months (p-value 0.169). The model presented a good fit. There was no lack of normality or homoscedasticity. Table 2. Linear mixed multivariate model of intercept and two random slopes. DM2 patients who counted carbohydrates showed effective gains regarding the main anthropometric and biochemical indicators during 30-min monthly sessions for 12 months. Table 1 shows that this individualized nutritional therapy presents beneficial effects to improve the state of health to prevent cardiovascular risk, which exponentially impacts quality of life. This potential decrease in cardiovascular risk is measured by a significant reduction of diastolic blood pressure (5.5 mmHg) at 6 and 12 months of treatment. The DASH sodium trial showed positive effects in blood pressure after 4 weeks of nutritional medical therapy with sodium reduction from 12 to 6 g, and a decrease of 10 mmHg in 5 weeks (25). Intra-abdominal fat produces certain proteins and hormones such as adipocin, angiotensinogen, and cortisol, all of which cause inflammatory processes that lead to high blood pressure (26). However, for this reduction to be effective, it is necessary for declines to coexist in other indicators, such as body mass index and waist. As suggested by the American Diabetes Association, no studies have demonstrated the efficacy of DM2 patients counting carbohydrates in an individualized medical nutritional treatment. The present work reduced body mass index in participants, who transitioned from obese to overweight. These reductions depended on the time between groups, i.e., 6 and 12 months (p = 0.028) and (p< 0.001), waist (4.08 cm) (p = 0.026), and hip (2.23 cm) at 12 months. As such, cardiovascular risk (26, 27) decreased. Our study corroborated what has been mentioned by other authors on the relationship between weight gain at the expense of visceral adipose tissue. Further, we noticed an increase in systolic blood pressure (25–27), where a reduction in these indicators had an impact on the reduction cardiovascular risk (28–30). Carbohydrate counting at 12 months had the potential to normalize and improve these indicators, as well as reduce cardiovascular risk by improving the life expectancy for individuals. Another important point to highlight in the evolution of this disease and its impact on quality of life are the biochemical indicators of glucose and glycosylated hemoglobin. In this study, it is shown that carbohydrate counting at 12 months achieved comprehension and adherence (31, 32), as well as a reduction in both indicators. A prospective study showed that severe visceral, parenchymal, and generalized adiposity are accompanied by inflammatory, neurohormonal, vascular, and metabolic responses that converge in cardiac and renal damage. Hypertension and diabetes mellitus are pathologies that amplify and perpetuate cardiovascular risk (33). Fasting glucose decreased by 8.72 mg / dL. Yet without statistical differences over time, glycosylated hemoglobin reflected a marked reduction of 1.34% over time (p< 0.001). Associated with these indicators, decreases in 12-month insulin and metformin doses of 6.86 IU and 354.79 mg (p = 0.003). Further, we found that p = 0.001 for insulin and p< 0.001 for metformin between groups. These results demonstrate that carbohydrate counting affected not only the aforementioned benefits but also health expenses at the individual level. From a public health perspective, metformin reduced body weight by 2.1 kg compared to individuals who only receive drug treatment with insulin (8). However, this result was inconsistent with the data of the present study, as the current dietary recommendations did not improve any of the previously mentioned indicators. Likewise, in accordance with the American Diabetes Association, which considers carbohydrate counting the standard goal when managing diabetes mellitus type 1, we emphasized individualized nutritional therapy for stability and improvement of glycemic control in the prevention of vascular complications with HbA1c values <8% (5, 11). The present work achieved a glycosylated hemoglobin value of 8.20%, where it was clearly demonstrated that carbohydrate counting was effective for DM2 patients at 12 months. Moreover, it improved all indicators associated with cardiovascular risk. Insulin is necessary to metabolize carbohydrates, proteins, fats, and maintain a certain euglycemia after meals. The main goal of insulin treatment is to mimic the physiological pattern of insulin secretion for better glycemic control (34). To maintain basal metabolism and limit liver glucose production between meals, 0.5–1 unit/h of insulin is needed. One unit of insulin is released for every 10 g of carbohydrate in the postprandial phase of insulin secretion (the meal-stimulated phase), which causes the diffusion of ingested nutrients (mainly glucose) to the periphery (35). A healthy patient's insulin secretion normally takes place 5 min after food intake. However, for DM2 patients, the first phase of insulin secretion is completely absent. The second phase, which in healthy patients lasts 1 to 2 h until blood glucose is normalized, is reduced by 50% in DM2 (33). In accordance with the data found in this paper, there is an association between the variable HbA1c and the values of insulin. Therefore, this indicator can be said to reduce the pharmacological dose and have a beneficial effect on individual health, given that cardiovascular risk is the main cause of death. Intervention programs for physical lifestyle changes, such as weight loss, are proven to be ineffective (10). Therefore, individualized medical nutritional treatment and drug treatments could be key to preventing and reducing mortality rates for DM2 patients (11, 36). Past studies have shown the negative effects of weight gain with respect to indicators of arterial pressure and cardiovascular risk, among other effects (37). Herein, we observed anthropometric indicators for current dietary recommendations in accordance with similar studies where the increase in pressure was positively impacted by weight, central fat, body mass index, and basal metabolic rate (38). Another study that examined women in middle age correlated diastolic pressure positively with weight, visceral adipose tissue, and other indicators (26, 39). These results coincided with the data found in current dietary recommendations, which clearly shows that these factors negatively impact cardiovascular risk. For DM patients, individualized medical nutritional treatment, i.e., carbohydrate counting, improved patients' reduction of their cardiovascular risk measured via anthropometric indicators: body mass index (p< 0.001) diastolic pressure (p = 0.019), waist (p< 0.001), biochemical/glycosylated hemoglobin (p< 0.001), and glucose (p< 0.001). A decrease in the pharmacological dose of insulin (p = 0.001) and metformin (p = 0.001) was demonstrated. Our findings should be considered in light of the benefits of metabolic enhancement and its cardiovascular implications. The nutritional education received at each 30-min meeting allowed individuals to understand the method. The portion graphs and equivalent food measurements, as well as the adaptation of the method to the Central American diet, allowed participants to attend monthly scheduled appointments. From a social and health perspective, implementing the model for DM2 patients will not only impact the quality of life (i.e., less expenditure on drugs such as insulin and metformin), but it will also create a lower rate of long-term complications. The non-digitization of medical records and low educational levels of participants prevented a deeper understanding of the study's purpose, delaying the start of sampling. There were no methodological limitations during the development of this study. Future studies should replicate the present work at a local multicenter level and regional level and assess the similarities of data with the present work. Future studies should also insist on the importance of the nutritionist's role in primary health care centers in order to make possible the use of the method in the most needed regions. The original contributions presented in the study are included in the article/supplementary materials, further inquiries can be directed to the corresponding author/s. The study design was submitted and approved by the Biomedical Research Ethics Committee (CEIB), (IRB 419-CGPGFCM/UNAH/2017) of the National Autonomous University of Honduras (UNAH). The patients/participants provided their written informed consent to participate in this study. All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Model Center for Training and Comprehensive Care in Diabetes (CMCAID), Hospital Autonomous University School of Honduras (HEUAH). Dr. Alejandra Ramos, Dr. Concepción Zúniga. 1. Leon BM, Maddox TM. 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(2016) 28:2933–7. doi: 10.1589/jpts.282933 PubMed Abstract | CrossRef Full Text | Google Scholar Keywords: diabetes mellitus 2, medical nutritional treatment, blood indicators of health, body indicators, hypoglycemia Citation: Di Iorio AB, Orozco Beltrán D, Quesada JAR and Carratalá Munuera MC (2021) The Adaptation of the Carbohydrate Counting Method Affects HbA1c and Improves Anthropometric Indicators in Patients With Diabetes Mellitus 2. Front. Nutr. 7:577797. doi: 10.3389/fnut.2020.577797 Received: 30 June 2020; Accepted: 05 November 2020; Published: 26 January 2021. Edited by: Reviewed by: Copyright © 2021 Di Iorio, Orozco Beltrán, Quesada Rico and Carratalá Munuera. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. *Correspondence: Adriana Beatriz Di Iorio, [email protected]
, Yew Soon Ong, Huajin Tang, Will Neil Browne
Published: 22 January 2021
Frontiers in Neuroscience, Volume 15; https://doi.org/10.3389/fnins.2021.619090

Abstract:
Editorial on the Research TopicCognitive Multitasking – Towards Augmented Intelligence The original inspiration of artificial intelligence (AI) was to build autonomous systems that were capable of demonstrating humanlike behaviors. However, modern AI systems have begun to far exceed humanly achievable performance levels in areas such as image processing, complex optimization, and unmanned systems, due to the present-day data deluge, accompanied by subtle algorithmic enhancements in machine learning algorithms. This is occurring across a variety of domains, where prominent examples include IBM Watson winning Jeopardy! and Google DeepMind's AlphaGo beating the world's leading Go player. However, the AI future need not be limited to a human imitating standpoint. Instead, it may be more beneficial to build AI systems that are able to excel at that which humans have not evolved to do or to even consider. Humans have not evolved to process multiple distinct situations within short timespans (i.e., in the order of a few seconds) – as interleaving more than one task usually entails a considerable switching cost during which the brain must readjust from one task to the other. Machines, on the other hand, are largely free from any such switching bottlenecks. Thus, machines can move more fluidly between tasks. Furthermore, when related tasks are bundled together, it may also be possible to seamlessly transfer or share the learned knowledge among them. As a result, while an AI attempts to solve some complex task, several other simpler ones may be unconsciously solved. Moreover, knowledge learned unconsciously in one task may be harnessed for intentional use in another application. This special issue aims to explore deeply the issues faced in cognitive multitasking. Emphasis is placed on computational models and algorithms, as well as new hardware advances, that shall enable machines to be developed as consummate multitask problem-solvers. Following a rigorous peer review process, 11 papers have been accepted to be included in the special issue. The first paper, “Multi-Task Learning Based Network Embedding” by Wang et al. presents a multi-task learning-based network embedding approach for network representation learning. The first task is designed to preserve the high-order proximity between pairwise nodes, while the second task is to preserve the low-order proximity in the one-hop area of each node. Comprehensive empirical studies on multi-label classification, link prediction, and visualization in five real-world networks, including social network, citation network, and language network, have been conducted to evaluate the performance of the proposed method over existing state-of-the-art approaches. In the second paper entitled “High Cognitive Flexibility Learners Perform Better in Probabilistic Rule Learning,” Feng et al. analyze how cognitive flexibility of human being, as assessed by the number-letter task, is associated with the learning process of a probabilistic rule task. This paper concludes that further research should be conducted to explore the internal process of learning differences between high and low flexibility learners by using other technologies across multiple modes. To improve the convergence speed, a two-level transfer learning method has been proposed by Ma et al. in their paper “A Two-Level Transfer Learning Algorithm for Evolutionary Multitasking.” The proposed method intends to use the correlation and similarity among the paired tasks to improve the efficiency and effectiveness of a multifactorial evolutionary algorithm. The forth paper, “A Preliminary Study of Knowledge Transfer in Multi-Classification Using Gene Expression Programming” by Wei and Zhong. embarks a preliminary study on evolutionary multitasking optimization with gene expression programming for multi-classification. Experimental studies on 10 high-dimensional datasets show that knowledge transfer among separate binary classifiers under the proposed multitasking method can enhance multi-classification performance when compared to existing approaches. To learn good representations of node in graphs or network, Xie et al. proposed a multi-task representation learning architecture coupled with the task of supervised node classification for graph classification and an end-to-end multi-task network representation learning framework with multi-task loss function for network embedding, in “A Multi-Task Representation Learning Architecture for Enhanced Graph Classification” and “Multi-Task Network Representation Learning,” respectively. In the seventh paper entitled “Droplet-Transmitted Infection Risk Ranking Based on Close Proximity Interaction,” to identify people who are potentially-infected by droplet-transmitted diseases, Guo et al. present a multi-tasking framework to model the principle of Close Proximity Interaction and thus infer the infection risk of individuals. Experimental studies in different scenarios, including indoor office, bus station and bus compartment, hospital, show that the proposed method can achieve consistent results when compared to manual analysis very efficiently. The eighth paper, “A Privacy-Preserving Multi-Task Learning Framework for Face Detection, Landmark Localization, Pose Estimation, and Gender Recognition” by Zhang et al. introduce a privacy-preserving multi-task learning approach to address the privacy issue existing in the training data for face processing tasks. The proposed method utilizes the differential private stochastic gradient descent algorithm to optimize the end-to-end multi-task model and weighs the loss functions of multiple tasks to improve learning efficiency and prediction accuracy. To improve the performance of multi-task optimization, Xu et al. present new transfer sparks in fireworks algorithm for multitasking. For each task to be optimized, transfer sparks are generated with adaptive length and promising direction vector to transfer useful genetic information between different tasks while the optimization progresses online. The efficacy of the proposed method has been validated on the multi-task optimization benchmarks against existing state-of-the-art evolutionary multitasking approaches. In the 10th paper entitled “Electroencephalographic Workload Indicators During Teleoperation of an Unmanned Aerial Vehicle Shepherding a Swarm of Unmanned Ground Vehicles in Contested Environments,” Rojas et al. try to identify the electroencephalographic (EEG) indicators that can be used for the objective assessment of cognitive workload in a multitasking setting and as a foundational step toward a human-autonomy augmented cognition system. Last but not the least, Howard et al. in their paper “BrainOS: A Novel Artificial Brain-Alike Automatic Machine Learning Framework,” explores some of the principles of the brain that seem to be responsible for its autonomous, problem-adaptive nature. The presented BrainOS is an automatic approach for selecting the appropriate model based on three factors, which are (a) input at hand, (b) prior experience, which is a history of results of prior problem solving attempts), and (c) world knowledge that represented in the symbolic way and used as a means to explain its approach. Preliminary studies of BrainOS show that it can deal with complex problems, such as natural language processing. As can be observed, in the 11 accepted papers, the second and tenth paper focus on psychology and neuroscience in cognitive multitasking, while the other papers concentrate on the multi-task optimization and learning algorithm designs. The human brain possesses the most remarkable ability to perform multiple tasks with apparent simultaneity, and leverages the experiences in solving one task to help the decision making in another task. These accepted papers have first illustrated the explorations of intelligent systems and algorithms that mimic beyond the human brain in efficient multitasking. Secondly, it can also be observed in these papers that the rapid increase in the variety, volume and complexity of real-world problems, the opportunity, tendency, and (even) the need to multitask is unprecedented. The guest editors would like to thank all the authors who submitted their work to the special issue, and all reviewers for their hard work in completing timely and constructive reviews. Special thanks also go to the Editor-in-Chiefs and members of the editorial team for their support during the editing process of this Special Issue. LF was the corresponding guest editor. All the authors are the guest editors of this special issue. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Keywords: cognitive multitasking, multitask learning, transfer optimization, evolutionary multitasking, guest editorial Citation: Feng L, Ong YS, Tang H and Browne WN (2021) Editorial: Cognitive Multitasking – Towards Augmented Intelligence. Front. Neurosci. 15:619090. doi: 10.3389/fnins.2021.619090 Received: 19 October 2020; Accepted: 04 January 2021; Published: 22 January 2021. Edited and reviewed by: Mehdi Khamassi, Centre National de la Recherche Scientifique (CNRS), France Copyright © 2021 Feng, Ong, Tang and Browne. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. *Correspondence: Liang Feng, [email protected]
Shihua H. Wang, Ashok K. Shetty, Kunlin Jin,
Frontiers in Cell and Developmental Biology, Volume 8; https://doi.org/10.3389/fcell.2020.627414

Abstract:
There is no effective therapy for COVID-19 currently. Until an efficient vaccine is developed, therapeutic strategies that facilitate faster recovery in COVID-19 patients developing life-threatening complications are urgently needed. From this perspective, mesenchymal stem/stromal cells (MSCs) that have been used in the clinic for moderating the immune system in graft vs. host disease (GVHD) (Fisher et al., 2019), type 2 diabetes (Path et al., 2019), autoimmune diseases (Weiss and Dahlke, 2019), spinal cord injury (Shende and Subedi, 2017), and several other diseases deserve consideration for treating COVID-19. Importantly, MSCs lack angiotensin-converting enzyme-2 (ACE2) receptor, which is a receptor widely distributed on the surface of human cells, and required for the entry of coronavirus into host cells. Such property ensures that injected MSCs can accomplish immunomodulatory effects without being destroyed by the virus. Our clinical trial, which is also the first published report, showed that the intravenous injection of human umbilical cord-derived MSCs eased the cytokine storm syndrome (CSS) and significantly improved the outcome in severe COVID-19 patients (Leng et al., 2020), suggesting the promise of MSC therapy for saving lives of COVID-19 patients developing severe complications. Although we repeatedly emphasize that studies in a larger cohort of patients are urgently needed to validate this promising therapeutic intervention, some businesses are taking advantage of our findings and offer cell therapy for COVID-19 patients, using types of cells that might not have been tested vigorously for safety and efficacy in FDA-approved clinical trials. This unethical commercial use of MSCs is criticized by Leigh Turner in his article entitled “Preying on Public Fears and Anxieties in a Pandemic: Businesses Selling Unproven and Unlicensed Stem Cell Treatments for COVID-19” published in Cell Stem Cell (Turner, 2020), which we read with great interest and are inspired to write this opinion paper. We strongly agree that such businesses could pose significant risks to patients and detract efforts to advance evidence-based stem cell therapy for COVID-19. We must emphasize that there are no approved MSC-based approaches for the prevention or treatment of COVID-19 patients, although several FDA-approved clinical trials are ongoing at present. Furthermore, we would like to suggest some guidelines from regulatory agencies that might stop such businesses from selling stem cell therapy to COVID-19 patients. Such guidelines should: (1) require companies to provide detailed scientific information on the safety and efficacy of mesenchymal stem/stromal cells in preclinical trials; clear criteria of MSCs manufacture and quality control; scientific rationale of organizing a clinical trial using stem cell therapy for patients; the qualifications of the principal investigators and all the medical staff; registered information in clinical trial https://clinicaltrials.gov/. (2) promote central or local government to establish an independent stem cell therapy committee that could update latest research outcomes or provide professional suggestions for patients. (3) encourage the public to report unproven stem cell therapy to the state administration so that the illegal company could be punished. The objective of these guidelines is to help patients and their caretakers to enroll only in randomized clinical trials conducted in renowned hospitals with approvals from the local Institutional Review Board (IRB) and the Federal Drug Administration (FDA). We think generating and implementing a new policy or law at the national level could stop such cell treatment to COVID-19 patients. Besides, the social platform, including media, should publicize and educate the public regarding dangers associated with cell treatment offered by businesses that are not FDA-compliant. In addition to MSCs, some businesses are also selling MSC-derived extracellular vehicles (EVs) for COVID-19 therapy. EVs, nanosized vesicles secreted by virtually all cells for intercellular communication, carry a cargo comprising cytokines, growth factors, lipids, and microRNAs (Robbins and Morelli, 2014; Phinney and Pittenger, 2017; Kalluri and LeBleu, 2020). Studies in disease models have suggested that stem cell-derived EVs exert similar effects as their parental cells (Yanez-Mo et al., 2015; Kim et al., 2016). Because the therapeutic effects of MSCs have been attributed mainly to their secretome with a significant portion of which is disseminated through EVs (Rani et al., 2015; Keshtkar et al., 2018). MSC-derived EVs could be exploited for cell-free therapy. Compared to MSCs, EVs released from them have unique advantages such as more accessible storage and higher biosafety. However, the disadvantages include that MSCs could home to sites of injury or inflammation and change their secretome depending on the local microenvironment. Importantly, MSCs are relatively large cells with an estimated average size of around 30 μm in suspension (ranging from 16 to 53 μm) (Furlani et al., 2009; Leibacher and Henschler, 2016). This large size makes them easily trapped in lungs after intravenous administration, which might be a hurdle for the treatment of other diseases but a benefit for COVID-19 as lung is the major target organ of coronavirus. So, this specific and preferential pulmonary localization after administration is an advantage of MSCs compared to EVs in terms of treating COVID-19 or other lung diseases. On the other hand, the targeted delivery of EVs to intended tissues after an intravenous administration is currently challenging to achieve. More importantly, the cargo of EVs is determined by the status of parental MSCs as well as culture conditions (Figure 1), which do not change after interactions with the local microenvironment. Figure 1. EV cargos are determined by the status of parental MSCs and would not change after the injection, while MSCs could alter secretome after homing to sites of injury or inflammation due to their ability for plasticity depending on the microenvironment they come across. A very recent article reported the safety and efficacy of allogeneic bone marrow MSC-derived EVs in severe COVID-19 patients who were already on hydroxychloroquine and azithromycin treatment. The study was a prospective, non-randomized, open-label, investigation in which 24 SARS-CoV-2 PCR positive patients at a single hospital center received MSC-derived EVs (Sengupta et al., 2020). Although such EV treatment did result in 71% of patients recovering from COVID-19, it was unclear whether the recovery could be attributed to EVs as the study lacked a matching control group and the protein or the microRNA composition of EVs employed was not reported in the study. One should be extremely cautious with clinical trials using EVs as their cargo determines the functional effects. Therefore, before MSC-derived EVs can be used in a clinical setting, standardized protocols for scaled-up production, isolation, functional evaluation, and batch-to-batch consistency need to be developed. These require a rigorous characterization of the composition of EVs generated in different batches using proteomics and small-RNA sequencing, the release criteria, and the biological properties. Also, the efficacy of EVs needs to be validated in animal models. While the MSC-derived EVs have the potential to replace MSC therapy for many conditions (Kim et al., 2016, 2020; Long et al., 2017), EV therapy does not seem ready in a short time. In summary, we would like to emphasize that well-controlled, rationally designed clinical trials based on reliable scientific data are needed for both MSCs and MSCs-derived EVs for combating COVID-19. 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Biological properties of extracellular vesicles and their physiological functions. J Extracell. Vesicl. 4:27066. doi: 10.3402/jev.v4.27066 PubMed Abstract | CrossRef Full Text | Google Scholar Keywords: mesenchymal stem cell, COVID-19, therapy, extracellular vesicle, exosome Citation: Wang SH, Shetty AK, Jin K and Chunhua Zhao R (2021) Combating COVID-19 With Mesenchymal Stem/Stromal Cell Therapy: Promise and Challenges. Front. Cell Dev. Biol. 8:627414. doi: 10.3389/fcell.2020.627414 Received: 09 November 2020; Accepted: 09 December 2020; Published: 05 January 2021. Edited by: Reviewed by: Copyright © 2021 Wang, Shetty, Jin and Chunhua Zhao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. *Correspondence: Robert Chunhua Zhao, [email protected]
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