Refine Search

New Search

Results: 9,696

(searched for: 10.29328/journal.ivs.1001030)
Save to Scifeed
Page of 194
Articles per Page
by
Show export options
  Select all
Published: 30 November 2021
by MDPI
Abstract:
Background: We have conducted a systematic review focusing on the advancements in preclinical molecular imaging to study the delivery and therapeutic efficacy of miRNAs in mouse models of breast cancer. Methods: A systematic review of English articles published in peer-reviewed journals using PubMed, EMBASE, BIOSIS™ and Scopus was performed. Search terms included breast cancer, mouse, mice, microRNA(s) and miRNA(s). Results: From a total of 2073 records, our final data extraction was from 114 manuscripts. The most frequently used murine genetic background was Balb/C (46.7%). The most frequently used model was the IV metastatic model (46.8%), which was obtained via intravenous injection (68.9%) in the tail vein. Bioluminescence was the most used frequently used tool (64%), and was used as a surrogate for tumor growth for efficacy treatment or for the evaluation of tumorigenicity in miRNA-transfected cells (29.9%); for tracking, evaluation of engraftment and for response to therapy in metastatic models (50.6%). Conclusions: This review provides a systematic and focused analysis of all the information available and related to the imaging protocols with which to test miRNA therapy in an in vivo mice model of breast cancer, and has the purpose of providing an important tool to suggest the best preclinical imaging protocol based on available evidence.
Joseph M. Pimbley
The Journal of Derivatives, Volume 29, pp 1-3; https://doi.org/10.3905/jod.2021.29.2.001

Abstract:
As I’ve written and reminded for past two quarters, Frank Fabozzi, editor of The Journal of Portfolio Management, and I are collaborating to create a special issue for The Journal of Derivatives (JOD) with a scheduled publication in May 2022. The issue’s focus will be derivatives in the asset management world. Our authors will be practitioners and the mission will be educational.
Christian A. Smith
Shakespeare's Influence on Karl Marx pp 69-115; https://doi.org/10.4324/9781003095767-3

Abstract:
In this third chapter, a close reading of Marx’s early journalism looks for quotations from and allusions to Shakespeare’s plays. Marx, writing for the Rheinische Zeitung in 1842–3, critiques current events in Prussian-occupied Rhineland. He uses these articles, some of them long investigative pieces that span over five to six instalments, to deploy a Left Hegelian critical method. In doing so, he finds that the Prussian state does not live up to the standards that Hegel assigned to it in his philosophy, and that Hegel’s philosophical method is inadequate for a critique of the actual historical state. Marx uses images and lines from four of Shakespeare’s plays: The Merchant of Venice, King Lear, Henry IV, p1 and Hamlet, among others, as conceptual resources and anchors for his critique of the state. During this short but productive period of his writing life, Marx’s critical method undergoes a fundamental change. Using a dialectical and materialist approach focused on the critique of capitalism and the states that support it, Marx transforms himself into a communist. His use of Shakespeare in his writings is a key component of this change. In this chapter, a model for interpreting unconscious literary allusion is presented. Evidence for it arises from a close reading of Marx’s texts, in light of Freud’s theory of Nachträglichkeit. The term deep allusion is suggested for this concept.
, James Selfe, Michael J. Callaghan
Published: 24 November 2021
Abstract:
Patellofemoral pain (PFP) can cause significant pain leading to limitations in societal participation and physical activity. PFP is usually associated with athletes undergoing intensive physical training, or military recruits; but recent evidence shows that PFP is common in the general population. The relationship of PFP with physical activity is not entirely clear. Our aim is to provide a better estimate of the general population prevalence of PFP and to relate this to the level of physical activity, and demographic characteristics. The Survey instrument for Natural history, Aetiology and Prevalence of Patellofemoral pain Studies (SNAPPS) was developed as a PFP screening tool to be used in the community. The electronic version of the SNAPPS (eSNAPPS) has recently been validated and was used to survey attendees at mass-participation running events. We will use an electronic survey to collect data from a sample of 1100 Rugby League World Cup spectators. The survey will have four sections: i) general and demographic; ii) knee pain (eSNAPPS); iii) level of physical activity; and iv) quality of life in relation to knee pain. The primary analytic approach will be descriptive of PFP prevalence. Secondary analyses will explore the relationships of the presence of PFP and the other variables. We will disseminate this work by publication of peer-reviewed papers in scientific journals, presentations at scientific conferences, and on the dedicated SNAPPS website https://www.snappspfp.com/.
Clinics in Colon and Rectal Surgery, Volume 34, pp 357-358; https://doi.org/10.1055/s-0041-1736546

Abstract:
Anastomotic leak is one of the most, if not the most, worrisome complications in colorectal surgery. The goal of this issue of Clinics in Colon and Rectal Surgery is to provide a comprehensive examination of anastomotic leak. Serving as a timeless guide for maximizing anastomotic outcomes. Each author has thoughtfully compiled an in-depth review of multiple topics related to anastomotic leak an in effort to educate and inform the reader on optimal anastomotic creation and leak management. This edition takes the reader through the journey of anastomotic leak, starting from definitions and risk factors, exploring intraoperative techniques and advancements, treatment of acute and chronic leaks, and finally exploring unique clinical situations such as rectal cancer and J pouch leaks. Unfortunately, despite every best technical effort, excellent training, and perfect planning, all surgeons who perform anastomoses will experience anastomotic leaks at some point in their careers. One of the main difficulties in discussing anastomotic leak is the lack of a universally accepted definition of this complication. This edition starts with an eloquent discussion of the epidemiology, definition, and implications of anastomotic leak by Drs. Ellis and Maykel. After this fundamental clarification is understood, Dr. Favuzza has identified the risk factors known to contribute to anastomotic leak and continued to then discuss the appropriate utilization of proximal diversion and drains. Drs. Man and Hrabe have done an exceptional job illustrating anastomotic construction. They have meticulously detailed the tried-and-true techniques to create sound anastomoses, one of the most important discussions in this edition. Drs. Uppal and Piggazi have discussed the newer technologies to aid in the creation of an anastomosis. These innovations can be used in conjunction with the tried-and-true traditional techniques to help prevent leak. Anastomotic troubleshooting, including utilization of the air leak test, correction of stapler misfires, evaluation of incomplete anastomotic doughnuts, and management of bleeding from the staple line is articulately discussed by Drs. Sell and Francone. When these preventive and proactive measures fail, anastomotic leak does occur. The management of acute and chronic anastomotic leaks is addressed in detail. Drs. Kane and Hedrick provide a review of the management of anastomotic leak in the acute setting, while Dr. Maykel and I have described management of a chronic anastomotic leaks presenting well after their index operation. There are certain exceptional clinical scenarios in which anastomotic leak treatment must consider the underlying disease process. Drs. Jeganathan and Koltun have provided an in-depth review of this complication in the setting of Crohn's disease. Dr. Guyton, Dr. Kearny, and Dr. Holubar have addressed the particular challenges associated with management of anastomotic leak in the setting of an ileal-pouch-anal anastomosis. Drs. Cauley and Kalady have detailed specific anastomotic leak treatments in the setting of rectal cancer, with a particular focus on optimizing oncologic and functional outcomes. Drs. Keller, van Helsdingen, Talboom, and Hompes have provided a brief overview of some specific techniques in the management of anastomotic leak in rectal cancer patients. Finally, the influence of the patient's microbiome on anastomotic leak remains under investigation. The microbiome's effect may counteract all attempts at prevention of anastomotic leak. This theory has been articulated expertly by Drs. Williamson and Alverdy. It was an honor to bring together this illustrious panel of experts to write what I hope will be an everlasting guide for surgeons in their quest to prevent the daunting complication of anastomotic leak. I would like to personally thank all the authors for their contributions to this edition of the journal. Their expertise and sage advice help shed light on the complexities and intricacies of anastomotic leak. First and foremost, I would like to thank my late father, Dr. Rajendra K. Bhama – whose vision for me was always greater than my own. I would also like to thank my mentors, Drs. Muneera Kapadia, James Mezhir (dec.), and John Stewart IV, who helped propel me to the field of colorectal surgery and remain an ongoing source of support. Finally, I especially want to thank Dr. Scott Steele, not only for his vision and leadership, but for his enduring mentorship, encouragement, and support to me in my career as an academic surgeon. Publication Date: 23 November 2021 (online) © 2021. Thieme. All rights reserved. Thieme Medical Publishers, Inc. 333 Seventh Avenue, 18th Floor, New York, NY 10001, USA
Joseph Rivera
Phenomenology and the Horizon of Experience pp 165-190; https://doi.org/10.4324/9781003251477-13

Abstract:
Part IV shall open with a sustained study of Jean-Yves Lacoste’s early work. Of the same generation of Marion, and thus shaped by similar influences (e.g., Heidegger and Husserl and Derrida and Levinas), the work of Lacoste is, however, later chronologically. For this reason Lacoste remains less accessible to the Anglophone world. In the late 1980s his articles begin to appear and in 1990 his first work was released, Note sur le temps, which remains available in French only. In 1994 a major second monograph appeared, Expérience et absolu, and it was translated into English only in 2004. 1 Several other collections of essays and monographs have since been published in French. 2 A couple of monographs released in English have examined his work, and a recent symposium on aspects of his work appeared in the journal Modern Theology. 3 While I will eventually draw on Lacoste’s later phase (in the mid-2000s forward), the present chapter draws heavily on his first two works; both volumes constitute the ground of a distinctively apophatic spirituality formed consciously in the wake of Heidegger’s existentialism, what I shall call a “spiritual life,” a type of liturgical existentialism.
Xi Zhao
Published: 15 November 2021
Abstract:
Object:To explore the correlation between serum vitamin D level and the occurrence and pathological grade of gastric cancer.Data sources:Search the PubMed, Embase, Web of Science, Cochrane,Chinese Journal Full-text Database (CNKI), Wanfang Science and Technology Journal Full-text Database, Chinese Science and Technology Journal Full-text Database (VIP), Chinese Biomedical Literature Database (CBM), All articles about the correlation between serum vitamin D levels and gastric cancer published before July 2021.Results:10 trials with 1159 cases of gastric cancer patients and 33387 cases of normal control patients were analyzed. The serum vitamin D level of the gastric cancer group(15.56±7.46ng/ml) was lower than the control group (17.60±1.61ng/ml), and the difference was statistically significant (MD=-8.28, 95%CI: -14.32~-2.23, P <0.00001). The patients with gastric cancer clinical stage III/IV(16.19±8.04ng/ml) is lower than that of patients with stage I/II (19.61±9.61ng/ml), and the patients with low differentiation of gastric cancer is (17.5± 9.5ng/ml) is lower than that of well or moderately differentiated patients (18.04±7.92ng/ml), and the patients with lymph node metastasis (19.41±8.63ng/ml) is lower than that of patients without lymph node metastasis (20.65± 7.96ng/ml), the difference is statistically significant;Conclusions:Vitamin D levels are negatively correlated with the occurrence of gastric cancer. Vitamin D levels are significantly correlated with different clinical stages, degrees of differentiation and lymph node metastasis, suggesting that low vitamin D levels may be a predictor of poor prognosis in gastric cancer.
Stephen E Gilman, Allison Aiello, Sandro Galea, Chanelle J Howe, Ichiro Kawachi, Gina S Lovasi, Lorraine T Dean, J Michael Oakes, Arjumand Siddiqi, M Maria Glymour
American Journal of Epidemiology; https://doi.org/10.1093/aje/kwab277

Abstract:
Social epidemiology is concerned with how social forces influence population health. Rather than focusing on a single disease (as in cancer or cardiovascular epidemiology) or a single type of exposure (e.g., nutritional epidemiology), social epidemiology encompasses all the social and economic determinants of health, both historical and contemporary. These include features of social and physical environments, the network of relationships in a society, as well as the institutions, politics, policies, norms and cultures that shape all of these forces. This commentary presents the perspective of several editors at the American Journal of Epidemiology with expertise in social epidemiology. We articulate our thinking to encourage submissions to the journal that: (i) expand knowledge of emerging and under-researched social determinants of population health; (ii) advance new empirical evidence on the determinants of health inequities and solutions to advance health equity; (iii) generate evidence to inform the translation of research on social determinants of health into public health impact; (iv) contribute to innovation in methods to improve the rigor and relevance of social epidemiology; and (v) encourage critical self-reflection on the direction, challenges, successes, and failures of the field.
, Christopher M. Durugbo, Odeh R. Al-Jayyousi
Published: 13 November 2021
Cleaner Engineering and Technology; https://doi.org/10.1016/j.clet.2021.100343

Abstract:
The purpose of this article is to review the eco-innovation literature involving manufacturing firms and to offer a comprehensive insight on strategic considerations from a manufacturing context. Applying the systematic review methodology, this review involves 142 journal articles published from 2006 to 2020. Using a thematic analysis, this review finds five main topics for manufacturing research: (i) eco-design and engineering, (ii) firm characteristics and performance, (iii) decision-making behaviour and options, (iv) industrial trends and indicators, and (v) energy intensity and efficiency. Eight main targets also serve as eco-innovation strategies for manufacturing practice: (i) industrial clusters and collaborations strategy, (ii) eco-engineering standards and skills strategy, (iii) green knowledge sharing and sourcing strategy, (iv) energy pricing and costing strategy, (v) innovation incentives and investments strategy, (vi) environmental regulations and protection strategy, (vii) energy structures and systems strategy, (viii) competitive and creative design strategy. Guided by these findings and an awareness of internal, external, and bilateral factors, this review proposes a multi-level strategic framework identifying design, organisational, and regional networks as central to the management of manufacturing eco-innovation. Additionally, premised on network and symbiotic framings for manufacturing eco-innovation, this article sets an agenda for future eco-innovation research involving manufacturing firms.
, Justin Jang Hann Chu
Published: 12 November 2021
Frontiers in Microbiology, Volume 12; https://doi.org/10.3389/fmicb.2021.777257

Abstract:
Editorial on the Research TopicEvolution & Genomic Adaptation of Emerging and Re-emerging RNA Viruses Emerging and re-emerging infectious diseases are defined as diseases caused by unidentified and reappearing pathogens (NIAID, 2018). RNA viruses are mostly responsible for most of such infectious disease outbreaks (Nichol et al., 2000). One of the key reasons is due to genomic alterations such as spontaneous mutation recombination or reassortment which occurs during adaptation and evolution processes (Nichol et al., 2000). When those genomic changes have been accumulated to a certain level or when the changes are on the antigenic or receptor-binding region, the host immune systems are no longer able to recognize the new variants, resulting in global viral outbreaks (De Wit et al., 2016; Nelemans and Kikkert, 2019; Kikkert, 2020). SARS-CoV-2 and its variants has claimed more than 4.56 million lives from December 2019 until the writing of this manuscript. The high mortality rate emphasizes the importance of continuously monitoring these emerging viruses' evolution and genomic adaptation (WHO, 2021). The purpose of this Research Topic serves to provide an open access platform for an international global team of multidisciplinary researchers and scientists to share their findings on the viral genomic feathers and changes, to provide a platform enabling public health officials to warn the global community of potential and existing epidemics and pandemics, and to develop an analytical platform for researchers to evaluate the outbreak risks, to prepare and to control future pandemics (Huang et al., 2021). In this Research Topic, the authors will present their most recent genomic investigations on these viruses. A total of 28 manuscripts including original research and review have been received, of which 15 were eventually accepted for journal publications after rigorous peer review processes. Based on the viruses involved, these 15 articles can be briefly classified into three groups: positive sense single-strand RNA (+ssRNA) viruses; negative-sense single-strand RNA (-ssRNA) viruses; diagnosis and dynamic single-strand RNA Virus-Host interactions. The first group +ssRNA viruses are the Group IV viruses in the Baltimore classification system (Baltimore, 1971; Cann, 2016), including viruses from Coronaviridae, Picornaviridae, Flaviviridae, Togaviridae. Within this group viruses, Coronavirus is the most researched virus in this topic. Three original research articles discussed the SARS-CoV-2 coronaviruses identified in China, Brazil, and Uruguay, respectively. In China, Song et al. isolated SARS-CoV-2 viruses from the Henan Province, which is adjacent to the Hubei Province, the region which has the highest mortality rate due to the SARS-CoV-2 pandemic within China. They analyzed the samples from different locations to estimate the virus's most recent common ancestor (TMRCA) and evolutionary rate. In Brazil, Resende et al. analyzed 190 SARS-CoV-2 viruses isolated from 13 Brazilian states and found the B.1.1.33-like viruses circulating in Brazil might have been transmitted from Europe or domestically erupted a few weeks before regional outbreaks. Their analysis also indicates public health interventions were successful because the median effective reproductive number (Re) dropped by 66%. In Uruguay, Mir et al. investigated the local virus source and the transmission rate(s). Based on the 122 viruses recovered at Brazilian–Uruguayan border area, they found that the SARS-CoV-2 viruses in the Uruguay border were introduced multiple times independently from Brazil (lineage B.1.1.28 and B.1.1.33). The researchers also revealed in their research that the synonymous and non-synonymous single nucleotide polymorphisms (SNP) are the genetic variations responsible to define the lineages. Castonguay et al. completed the fourth SARS-CoV-2 meta-analysis, which systematically tracked the evolutionary trajectory of SARS-CoV-2 over time, identified emerging mutations, and modeled the structural changes and corresponding molecular interactions. The fifth coronavirus is the avian infectious bronchitis virus (IBV). Jiang et al. identified a critical mutation to determine the host tropism alteration, which is a valuable key in understanding why the coronavirus could jump from one host to another. Porcine Epidemic Diarrhea virus (PEDV) is the last coronavirus discussed in this Research Topic. Li et al. isolated a PEDV, which has been detected to contain a unique insertion in the S1 protein binding by the recombination test. They predicted the structure of this new recombinant and proved its biological correlation by showing this strain had higher pathogenicity than the other viruses isolated in the piglet in vivo challenge. Following the Coronaviridae, Picornaviridae is the second most popular virus family within this topic. In two articles, researchers investigated the Norovirus and Coxsackievirus, which are enteroviruses within the family Picornaviridae. Zuo et al. identified the new Norovirus GII.17 variants, which surpassed the predominant GII.4 genotype causing the Kawasaki variant outbreaks in 2014–2015. Serological analysis showed weak cross-protection to these new variants so attention should be taken to prevent future outbreaks. The corresponding mutated amino acids on antigenic sites were also identified. The second study led by Li's team focused on the Norovirus GII.2 clusters, which caused unprecedented endemic outbreaks in 2016–2017. Eight distinct clusters with increased genetic diversity were characterized with an absence of elevated evolutionary rate. Additionally, the selection pressure was detected, suggesting the outbreak was probably not related to an evolutionary adaptation. The second virus in the Picornaviridae, is the Coxsackievirus A16 (CVA16) and was reported by Nhu et al. This molecular...
Samantha Treacy, Steven Martin, Nelum Samarutilake, Tine Van Bortel
Published: 11 November 2021
Health & Justice, Volume 9, pp 1-21; https://doi.org/10.1186/s40352-021-00154-6

Abstract:
Background: Patient and Public Involvement (PPI) in health and social care research is increasingly prevalent and is promoted in policy as a means of improving the validity of research. This also applies to people living in prison and using social care services. Whilst evidence for the effectiveness of PPI was limited and reviews of its application in prisons were not found, the infancy of the evidence base and moral and ethical reasons for involvement mean that PPI continues to be advocated in the community and in prisons. Objectives: To conduct a review of the literature regarding the involvement of people or persons living in prison (PLiP) in health and social care research focused on: (i) aims; (ii) types of involvement; (iii) evaluations and findings; (iv) barriers and solutions; and (v) feasibility of undertaking a systematic review. Methods: A systematic scoping review was undertaken following Arksey and O’Malley’s (International Journal of Social Research Methodology 8: 19-32, 2005) five-stage framework. A comprehensive search was conducted involving ten electronic databases up until December 2020 using patient involvement and context related search terms. A review-specific spreadsheet was created following the PICO formula, and a narrative synthesis approach was taken to answer the research questions. PRISMA guidelines were followed in reporting. Results: 39 papers were selected for inclusion in the review. The majority of these took a ‘participatory’ approach to prisoner involvement, which occurred at most stages during the research process except for more ‘higher’ level research operations (funding applications and project management), and only one study was led by PLiPs. Few studies involved an evaluation of the involvement of PLiP, and this was mostly PLiP or researcher reflections without formal or independent analysis, and largely reported a positive impact. Barriers to the involvement of PLiP coalesced around power differences and prison bureaucracy. Conclusion: Given the very high risk of bias arising from the available ‘evaluations’, it was not possible to derive firm conclusions about the effectiveness of PLiP involvement in the research process. In addition, given the state of the evidence base, it was felt that a systematic review would not be feasible until more evaluations were undertaken using a range of methodologies to develop the field further.
Nehal Lakhani, Meredith McKean, Amita Patnaik, Kristi Manjarrez, Hany Zayed, Michael Chisamore, Stanford Peng, Zelanna Goldberg
Published: 10 November 2021
by BMJ
Journal for ImmunoTherapy of Cancer, Volume 9; https://doi.org/10.1136/jitc-2021-sitc2021.497

Abstract:
Background: Despite successes with checkpoint inhibition (CPI) in a wide range of tumors, most patients demonstrate primary or acquired resistance, thus driving the need for better IO therapy. Research has suggested that CPI therapy exerts much of its benefit via releasing the inhibition of CD28 signaling, which would only be expected to show clinical benefit in the presence of intra-tumoral engagement of CD28 by its ligands CD80/86. ALPN-202, a variant CD80 vIgD-Fc fusion protein, was engineered to provide tumor localizing PD-L1-dependent CD28 agonism, while inhibiting the PD-L1 and CTLA-4 checkpoints. It has demonstrated superiority to CPI-only therapies in vitro and in in vivo tumor models, while also demonstrating additional benefit in combination with targeted PD-1 axis blockade.1 The benefit appeared to be at least additive in tumor models of poorly immunogenic tumors, suggesting the possibility of meaningful clinical benefit where CPI therapeutic efficacy is limited, i.e., ”non-inflamed or cold” tumors. Single agent safety and tolerability of ALPN-202 has been demonstrated along with pharmacodynamic evidence of CD28 engagement with immune checkpoint inhibition.2Methods: An open-label dose escalation and expansion study of ALPN-202 in combination with pembrolizumab in adults with advanced solid tumors or lymphoma was initiated in June 2021 (NCT04920383). Eligibility includes those tumors where single agent PD-(L)1 antagonists are SOC or patients refractory or resistant to standard therapies (including approved CPIs), or those without available standard or curative therapy. The study is a standard 3+3 dose escalation design with two schedules of ALPN-202 in parallel, Q1W and Q3W. Pembrolizumab is given per label at 400 mg IV Q6W. Objectives include evaluation of safety and tolerability, identification of the recommended phase 2 dose, PK, PD, exploratory predictive biomarker analysis (i.e., PD-L1, CD28, CD80 and CD86, as well as immunophenotyping of immune cell populations on treatment) and preliminary anticancer activity of ALPN-202 in combination with pembrolizumab. Disease assessments are evaluated by RECIST v1.1 for solid tumors or by Lugano Classification for lymphoma. Efficacy endpoints include ORR, duration of response and disease control rate. Once the recommended phase 2 dose combination is identified, dose expansion cohorts will be initiated. Approximately 30–35 patients will be enrolled in each tumor type-specific expansion cohort, including histologies that have not been demonstrated to be CPI responsive, as well as those where CPIs are approved SOC. This study is being conducted in collaboration with Merck & Co., Inc., Kenilworth, NJ, USA.Acknowledgements: We thank the patients and their families for their clinical trial participation and the site staff for their work on this trial.Trial Registration: NCT04920383References: Lewis, Katherine, et al. ALPN-202, a Conditional CD28 Costimulator and Dual Checkpoint Inhibitor, Enhances the Activity of Multiple Standard of Care Modalities. Journal for ImmunoTherapy of Cancer 2019;7. Moser, Justin C, et al. First-in-human dose escalation of ALPN-202, a conditional CD28 costimulator and dual checkpoint inhibitor, in advanced malignancies. 2021; 2547–2547. Ethics Approval: All required ethics committees have reviewed and approved the protocol. The first was WCG IRB, Approval number 20211877. All participants provided informed consent before study participation.
Domenico Mallardo, Maria Grazia Vitale, Diana Giannarelli, Giusy Trillò, Assunta Esposito, Mariaelena Capone, Maria Antonietta Isgrò, Gabriele Madonna, Grazia D’Angelo, Lucia Festino, et al.
Published: 10 November 2021
by BMJ
Journal for ImmunoTherapy of Cancer, Volume 9; https://doi.org/10.1136/jitc-2021-sitc2021.024

Abstract:
Background: Nivolumab (nivo) is a monoclonal antibody that targets programmed death-1 (PD-1) molecule and has been approved for the treatment of several solid tumors; in the treatment of adjuvant and metastatic melanoma had better efficacy compared with chemotherapy or ipilimumab (anti-CTLA4).1–4 The classical dosage of nivo tested in the phase III trials was 3 mg/kg every 2 weeks (Q2W). However, in order to make easier the administration, it was introduced the flat dosage at 240mg every 2 weeks (Q2W) or 480mg every 4 weeks (Q4W).5 6 The purpose of this study was to investigate retrospectively the relationships between the different nivo dosages and their serum concentration; in addition, we also investigated possible relationship with the expression of pro/antitumor activity genes.Methods: From July 2016 to December 2018 at INT IRCCS Pascale, Naples, we collected serum and RNA samples from 88 patients with metastatic melanoma at week 12 from the first administration of nivo. All patients have appropriately signed informed consent. The ORR among the 88 patients was 25% (patients baseline characteristics are listed in table 1). Commercial ELISA assay were performed in 96 well plates following the protocol procedures. Gene expression profiling was performed using NanoString® IO360 panels on 37 patients (CR: 4, PR: 10, SD: 11, PD: 12). Statistical analysis was performed through the Student’s t-test and via Spearman’s rho correlation coefficient. Gene profiling analysis was performed via Bonferroni correction.Results: We observed that patients with complete response (CR) have a higher nivo concentration (p=0.003) compared to other groups. No correlation was observed with the most important markers of renal and hepatic function: eGFR, creatinine, AUC, albumin, ALT, AST and gamma GT. Data from gene expression profile shown that patients with CR had a higher expression of anti-tumor and immune activation genes such as: TAPBP, CD47, HDC, IL12RB2 and HLA-DQA1 (P <0.05). Furthermore, genes with pro-tumor or immunosuppressive activity such as MMP9, GOR160, HK2 and LILRA5 (P <0.05) were found to be inversely related with drug concentration while CD1C, a T-cell surface glycoprotein involved in antigen-presenting, it is directly related (p=0.005). Abstract 24 Table 1 Patients clinical parameters Conclusions: In this retrospective study we found that higher serum concentration of nivo was correlated with a better outcome and higher frequency of CR. Moreover, in patients with a CR there was an enhancing of the immune activation with an increase of HLA-DQA, TAPBP and IL12RB2. Further investigations are needed to get additional information.Acknowledgements: The study was supported by the Institutional Project ‘Ricerca Corrente’ of Istituto Nazionale Tumori IRCCS Fondazione ‘G. Pascale’ of Napoli, Italy.References: James Larkin, Vanna Chiarion-Sileni, Rene Gonzalezet al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med 2015 Jul 2;373(1):23–34. Robert C, Long GV, Brady B et al. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med 2015 Jan 22;372(4):320–30. Weber JS, D’Angelo SP, Minor D et al. Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): a randomised, controlled, open-label, phase 3 trial. Lancet Oncol 2015 Apr;16(4):375–8. Weber J, Mandala M, Del Vecchio M, Gogas HJ, Arance AM, Cowey CL, Dalle S,4. Schenker M, Chiarion-Sileni V, Marquez-Rodas I et al. CheckMate 238 Collaborators. Adjuvant nivolumab versus ipilimumab in resected stage III or IV melanoma. N Engl J Med 2017 Nov 9;377(19):1824–1835. Zhao X, Suryawanshi S, Hruska M et al. Assessment of nivolumab benefit-risk profile of a 240-mg flat dose relative to a 3-mg/kg dosing regimen in patients with advanced tumors. Ann Oncol 2017 Aug 1;28(8):2002–2008. Long GV, Tykodi SS, Schneider JG et al. Assessment of nivolumab exposure and clinical safety of 480?mg every 4 weeks flat-dosing schedule in patients with cancer. Ann Oncol 2018 Nov 1;29(11):2208–2213. Ethics Approval: The study was approved by the internal ethics board of the Istituto Nazionale Tumori IRCCS Fondazione ‘G. Pascale’ of Napoli Italy, approval number of registry 33/17 OSS.Consent: Written informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.
Aude De Gassart, Patrick Brune, Maelle Mairesse, Sophie Agaugué, Ryan Swanson, Loui Madakamutil, Carl Walkey, Paul Frohna
Published: 9 November 2021
by BMJ
Journal for ImmunoTherapy of Cancer, Volume 9; https://doi.org/10.1136/jitc-2021-sitc2021.563

Abstract:
Background: γ9δ2 T-cells are attractive mediators of cancer immunotherapy due to their strong cytolytic and pro-inflammatory activities and the positive correlation between tumor infiltration and good prognosis [1,2]. ICT01, a novel anti-BTN3A mAb activating γ9δ2 T-cells, is being evaluated in a Phase 1/2a clinical study (NCT04243499)[3,4]. Previous studies have shown that IL-2 (Proleukin®) promotes γ9δ2 T-cells expansion following ICT01 stimulation, which may be clinically useful given that γ9δ2 T-cells are normally <5% of total T-cells [5]. However, the severe toxicity of IL-2 has limited its widespread use. NL-201 is a de novo alpha-independent IL-2/IL-15 agonist that preferentially stimulates CD8 T and NK cell proliferation at low concentrations, enabling a potentially wider therapeutic index than IL-2, and is being evaluated in a Phase 1 clinical study (NCT04659629)[6,7]. Here, we explore the potential of ICT01 and NL-201 to synergistically stimulate the activation and proliferation of γ9δ2 T-cells.Methods: Flow cytometry was used to assess IL-2R signaling (pSTAT5), and γ9δ2 T-cell activation and expansion after in vitro culture of huPBMCs with ICT01, NL201 or the combination. Tumor cell killing activity was monitored upon co-culture of huPBMCs with tumor cell lines (Incucyte). In vivo pharmacology was performed in NCG mice engrafted with 20x106 huPBMCs and treated with ICT01 (1 mg/kg IV)±NL-201 (1, 3 or 10 µg/kg IV). Immune cells were phenotyped by flow cytometry in blood and organs collected at sacrifice (Day 16).Results: NL-201 is ~100X more potent than IL-2 in triggering IL-2R signaling in γ9δ2 T-cells, without preferential activity on Tregs. NL-201 plus ICT01 induces synergistic expansion of γ9δ2 T-cells, approaching ~50% of T-cells after 8 days versus ~10% with single agents. In addition, the combination of NL-201 and ICT01 promotes γ9δ2 T-cell effector memory differentiation, in contrast to IL-2, which induces primarily central memory phenotype. Importantly, NL-201 enhances ICT01-mediated killing of cancer cells by γ9δ2 T-cells.In mice, a dose-dependent expansion of peripheral γ9δ2 T-cells from ~1–2% at baseline to up to 40% of T-cells was observed in the ICT01+NL-201 combination groups. Consistently, γ9δ2 T-cell number and frequency increase in spleen and lungs of the ICT01+NL-201 treated animals as compared to controls. Expanded γ9δ2 T-cells in the combination groups display an effector memory phenotype, confirming our in vitro results.Conclusions: These results demonstrate the ability of the ICT01+NL-201 combination to synergistically trigger γ9δ2 T-cell activation, expansion and anti-tumor activity and support clinical evaluation of this combination as a novel therapeutic approach for cancer patients.References: Gentles, A. J. et al. The prognostic landscape of genes and infiltrating immune cells across human cancers. Nat Med 21, 938-945, doi:10.1038/nm.3909 (2015). Tosolini, M. et al. Assessment of tumor-infiltrating TCRVgamma9Vdelta2 gammadelta lymphocyte abundance by deconvolution of human cancers microarrays. Oncoimmunology 6, e1284723, doi:10.1080/2162402X.2017.1284723 (2017). Gassart, A. d. et al. 687 Enhancement of anti-tumor immunity by ICT01: a novel g9d2 T cell-activating antibody targeting butyrophilin-3A (BTN3A). Journal for ImmunoTherapy of Cancer 8, A412-A413, doi:10.1136/jitc-2020-SITC2020.0687 (2020). Marabelle, A. et al. 316 EVICTION Study: Preliminary results in solid tumor patients with ICT01, a first-in-class, gamma9 delta2 T cell activating antibody targeting butyrophilin-3A. Journal for ImmunoTherapy of Cancer 8, A194-A195, doi:10.1136/jitc-2020-SITC2020.0316 (2020). Gassart, A. d. et al. 442 ICT01, an anti-BTN3A mAb that activates Vg9Vd2 T cells, plus interleukin-2: a potent and promising combination for cancer immunotherapy. Journal for ImmunoTherapy of Cancer 8, A268-A269, doi:10.1136/jitc-2020-SITC2020.0442 (2020). Walkey, C., Swanson, R., Ulge, U., Silva Manzano, D. A. & Drachman, J. 576 NL-201, a de novo IL-2 and IL-15 agonist, demonstrates enhanced in vivo antitumor activity in combination with multiple cancer immunotherapies. Journal for ImmunoTherapy of Cancer 8, A346-A346, doi:10.1136/jitc-2020-SITC2020.0576 (2020). Walkey, C. D. et al. Abstract 4518: Pre-clinical development of NL-201: A de novo α-independent IL-2/IL-15 agonist. Cancer Research 80, 4518–4518, doi:10.1158/1538-7445.Am2020-4518 (2020). Ethics Approval: All procedures involving animals described in this study have been reviewed and approved by the local ethic committee (CELEAG) and the French Ministry of Research.
David Page, Krystle Collins, Brie Chun, Zhaoyu Sun, Yoshinobu Koguchi, William Redmond, Maritza Martel, Yaping Wu, Nicole Moxon, Staci Mellinger, et al.
Published: 9 November 2021
by BMJ
Journal for ImmunoTherapy of Cancer, Volume 9; https://doi.org/10.1136/jitc-2021-sitc2021.399

Abstract:
Background: It has previously been shown that immune checkpoint blockade (ICB) with anti-programmed death 1/ligand 1 (anti-PD-1/L1) improves survival when combined with chemotherapy in PD-L1-positive first-line triple-negative metastatic breast cancer (MBC). Given the lower efficacy of ICB in hormone receptor positive (HR+) or PD-L1-negative disease, and in later lines of therapy, novel combinations are necessary. Dual ICB with nivolumab (anti-PD-1) and ipilimumab (anti-CTLA-4) has shown success in other solid tumors but has not been extensively studied in MBC. Furthermore, MBCs often express the androgen receptor (AR), which can be targeted to modulate immune response. AR blockade may stimulate thymic production of naïve T-cell clones by modulating the Notch pathway,1 whereas ICB can amplify the immune activity of recent thymic emigrants by blocking PD-1-mediated peripheral tolerance.2Methods: This is an open-label, Simon 2-stage phase II trial investigating the dual ICB (nivolumab 240mg IV q2w; ipilimumab 1mg/kg IV q6w) and AR blockade (bicalutamide, 150mg PO daily) in MBC. Two cohorts will be studied: AR-positive TNBC [ > 1% by IHC, constituting ~50% of TNBCs]; and HR+ MBC (of which the great majority are AR-positive). Eligible patients must have RECIST1.1 measurable disease, Eastern Cooperative Oncology Group performance score 0 or 1, adequate hematological/hepatic function, and received no more than 1 prior course of non-curative chemotherapy. Target accrual is n=15 per arm (stage I), with a maximum of 46 patients per cohort. Current cohort accrual n=15 HR+ and n=5 TNBC. The primary endpoint is week 24 clinical benefit by iRECIST criteria, with success defined as >20% improvement over historical control (30% per EMBRACE clinical trial).3 Safety will be evaluated by CTCAE v4.0. Biomarkers of recent thymic activation will be evaluated via quantitative deep sequencing of T-cell receptors (TcR, ImmunoSEQ assay), TcR excision circles (TRECs), and flow cytometry using markers for recent thymic emigration (CD3+CD45RA+CD45RO-CD31+)Trial Registration: NCT03650894. The trial is open at Providence Cancer Institute (Portland, OR) and Memorial Sloan Kettering Cancer Center (New York, NY).References: Velardi E, Tsai JJ, Holland AM, et al. Sex steroid blockade enhances thympoesis modulating notch signaling. J Exp Med 2014;211(12):2341–49. Thangavelu G, Parkman JC, Ewen CL, et al. Programmed death-1 is required for systemic self-tolerance in newlygenerated T cells during the establishment of immune homeostasis. Journal of autoimmunity 2011;36(3–4):301–12. Kaufman PA, Awada A, Twevles C, et al. Phase III open-label randomized study of eribulin mesylate versus capecitabine in patients with locally advanced or metastatic breast cancer previously treated with an anthracycline and a taxane. J Clin Oncol 2015;33(6):594–601. Ethics Approval: This study was approved by the IRB department and Providence Portland Medical Center, Clinical Trials Department for study NCT03650894.Consent: Written, informed consent is obtained from each participant.
Corrigendum
Hongyan Bi, Hui Guo, Qianfei Wang, Xiao Zhang, Yaming Zhao, Jimei Li, Weiqin Zhao, Houzhen Tuo, Yongbo Zhang
Published: 9 November 2021
Frontiers in Neurology, Volume 12; https://doi.org/10.3389/fneur.2021.792230

Abstract:
A Corrigendum onA Novel Variation in the Mitochondrial Complex I Assembly Factor NDUFAF5 Causes Isolated Bilateral Striatal Necrosis in Childhoodby Bi, H., Guo, H., Wang, Q., Zhang, X., Zhao, Y., Li, J., Zhao, W., Tuo, H., and Zhang, Y. (2021). Front. Neurol. 12:922. doi: 10.3389/fneur.2021.675616 Error in Table On a recent occasion, we realized that in the original article, there was a mistake in Table 1 as published. The citation numbers in the Table 1 referring to the NDUFAF5 mutations in various ethnic groups did not match the given reference order list in the published article. In Table 1, (1) reference 26 should be reference ( 1); (2) reference 27 should be reference 30; (3) reference 28 should be reference (2); (4) reference 12 should be reference 31; (5) reference 29 should be reference 32; and (6) reference 13 should be reference (3). The corrected Table 1 appears below. Table 1. Clinical features of patients with NDUFAF5 variations reported in literature. Missing Citation In the original article References 30, 31, and 32 were not cited/included in the published article. The citation has now been inserted in Table 1, under the section Discussion. New References to be Added in the continuing order: 30. Fang F, Shen Y, Shen DM, Liu ZM, Ding CH, Zhang WC, et al. [Clinical and genetic characteristics of children with Leigh syndrome]. Zhonghua er ke za zhi = Chinese J Pediatr. (2017) 55:205–9. doi: 10.3760/cma.j.issn.0578-1310.2017.03.008 31. Tong W, Wang Y, Lu Y, Ye T, Song C, Xu Y, et al. Whole-exome sequencing helps the diagnosis and treatment in children with neurodevelopmental delay accompanied unexplained dyspnea. Sci Rep. (2018) 8:5214. 32. Gerards M, Sluiter W, van den Bosch BJ, de Wit LE, Calis CM, Frentzen M, et al. Defective complex I assembly due to C20orf7 mutations as a new cause of Leigh syndrome. J Med Genet. (2010) 47:507–12. doi: 10.1136/jmg.2009.067553 The authors apologize for this error and confirm that it 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. 1. Saada A, Edvardson S, Shaag A, Chung WK, Segel R, Miller C, et al. Combined oxphos complex i and iv defect, due to mutated complex i assembly factor c20orf7. J Inherit Metab Dis. (2012) 35:125–31. doi: 10.1007/s10545-011-9348-y PubMed Abstract | CrossRef Full Text | Google Scholar 2. Sugiana C, Pagliarini DJ, McKenzie M, Kirby DM, Salemi R, Abu-Amero KK, et al. Mutation of c20orf7 disrupts complex i assembly and causes lethal neonatal mitochondrial disease. Am J Hum Genet. (2008) 83:468–78. doi: 10.1016/j.ajhg.2008.09.009 PubMed Abstract | CrossRef Full Text | Google Scholar 3. Simon MT, Eftekharian SS, Stover AE, Osborne AF, Braffman BH, Chang RC, et al. Novel mutations in the mitochondrial complex i assembly gene ndufaf5 reveal heterogeneous phenotypes. Mol Genet Metab. (2019) 126:53–63. doi: 10.1016/j.ymgme.2018.11.001 PubMed Abstract | CrossRef Full Text | Google Scholar Keywords: bilateral striatal necrosis, NDUFAF5, mitochondrial complex I deficiency, whole-exome sequencing, novel variation Citation: Bi H, Guo H, Wang Q, Zhang X, Zhao Y, Li J, Zhao W, Tuo H and Zhang Y (2021) Corrigendum: A Novel Variation in the Mitochondrial Complex I Assembly Factor NDUFAF5 Causes Isolated Bilateral Striatal Necrosis in Childhood. Front. Neurol. 12:792230. doi: 10.3389/fneur.2021.792230 Received: 10 October 2021; Accepted: 11 October 2021; Published: 09 November 2021. Approved by: Copyright © 2021 Bi, Guo, Wang, Zhang, Zhao, Li, Zhao, Tuo and Zhang. 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: Hongyan Bi, [email protected]
Martin Wermke, Aurelien Marabelle, Christiane Jungels, Johann De Bono, Norbert Vey, Cécile Vicier, Elena Garralda, Steven Le Gouill, Patricia LoRusso, Stephane Champiat, et al.
Published: 9 November 2021
by BMJ
Journal for ImmunoTherapy of Cancer, Volume 9; https://doi.org/10.1136/jitc-2021-sitc2021.503

Abstract:
Background: We presented EVICTION Trial data from patients with solid tumors that showed microgram doses of ICT01 rapidly activate γ9δ2 T cells that release inflammatory cytokines (e.g., IFNγ) and traffic from the circulation (Abstract #316, SITC 2020). Confirming tumor infiltration of activated γ9δ2 T cells and the subsequent clinical benefit are the next steps in characterizing the therapeutic potential of ICT01.Methods: EVICTION is an ongoing Phase 1/2a, EU and US trial assessing ICT01 monotherapy (IV Q3W) in advanced/refractory solid and hematologic cancers, and ICT01 in combination with pembrolizumab (200mg IV Q3W) in solid tumor patients who failed ≥1 CPI. Pharmacodynamic activity was monitored by immunophenotyping and cytokine level analysis. Tumor biopsies (baseline, Day 28) were used for immunohistochemistry of BTN3A and tumor-infiltrating lymphocytes, and gene expression profiling. Efficacy evaluations were conducted every 8 weeks.Results: ICT01 monotherapy dose escalation (20µg to 200mg IV ICT01 Q3W) in solid tumor patients (Group A, n=32) has been completed, and 3 dose cohorts of ICT01 (700µg, 2 and 7 mg) plus Pembro (Group C, n=12) were completed; both without any DLTs. First-dose fever and chills (Grade 1/2) were the most common AEs that increased in frequency but not severity with dose and did not recur.ICT01 induced trafficking of >95% of circulating γ9δ2 T cells within 30 min post ICT01 (≥2mg), which was sustained for 21 days at doses ≥75mg. Transient, dose-dependent increases in serum cytokines at 30 min (TNFα) or 4h (IFNγ) post-dose were correlated with baseline γ9δ2 T cell counts and with activation and migration of NK and CD8 T cells out of the blood at doses ≥7mg. Higher baseline circulating γ9δ2 T cells and lower TILs were associated with more robust intra-tumoral increases in total γδ(3–34x increase), CD3 (3–55x increase) and CD8 T cells (1.3–66x increase), which demonstrated the potential to transform an immune desert tumor phenotype. Disease control by ITT analysis of RECIST1.1 data was observed in 6/32 (SD) and 4/7 patients (3 SD (bladder, melanoma, NSCLC), 1 PR (bladder)) in Groups A and C, respectively, with 5/6 patients at 7mg in Group C not yet evaluable.Conclusions: These results show a broad antitumor immune response in the blood and tumors comprising γ9δ2, CD8 T cell, and NK cell activation and tumor-infiltration following ICT01 alone and in combination with pembrolizumab. Preliminary efficacy data suggest low-dose ICT01 plus pembrolizumab may be more effective than ICT01 monotherapy for advanced/refractory solid tumors, which requires confirmation.Acknowledgements: Lena Daher for her medical/scientific writing support.Trial Registration www.clinicaltrials.gov NCT04243499; EudraCT Number: 2019-003847-31Ethics Approval: This study was approved by the following Ethics Committees: COMITE DE PROTECTION DES PERSONNES, Sud-Méditerranée V (Gustave Roussy, IPC, Nantes), Comité d’Ethique Institut Jules Bordet, COMITÉ DE ÉTICA DE INVESTIGACIÓN CLÍNICA CON MEDICAMENTOS del Hospital Universitari Vall d’Hebron, Ethikkommission an der TU Dresden, HRA London-Surrey Borders Research Ethics Committee.Consent: Written informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.
David Saltman, Nicole Croteau, Heather Lockyer, Rob Seitz, Frank McMahon, Jeremy Spille, Andrea Dickey, Matthew Varga, Kim McGregor, Tyler Nielsen, et al.
Published: 9 November 2021
by BMJ
Journal for ImmunoTherapy of Cancer, Volume 9; https://doi.org/10.1136/jitc-2021-sitc2021.466

Abstract:
Background: Lung cancer is the leading cause of cancer-related deaths worldwide. The advent of ICIs specifically targeting programmed cell death protein-1 (PD-1), or its ligand (PD-L1) represents a major therapeutic advance that is now included in standard of care regimens for non-small-cell-lung cancer (NSCLC). PD-L1 expression measured by immunohistochemistry (IHC) staining is the current gold standard predictive biomarker for immune checkpoint inhibitor (ICI) therapy in NSCLC, however many factors beyond PD-L1 expression alone affect the outcome of ICI therapy. Evaluation of other factors to better inform clinical practice will reduce both the potential for adverse immune-related toxicities and expenditure on ineffective costly therapies while potentially identifying patients otherwise missed by PD-L1 staining. The 27-gene IO assay is a RT-qPCR based gene expression panel1 that was developed to classify the tumor immune microenvironment (TIME). It has been shown to be associated with response to ICI therapy in multiple tumor types including triple negative breast cancer, metastatic urothelial carcinoma, and NSCLC where the association was independent of PD-L1 status in patients treated either with monotherapy or combination therapy.2 Currently, BC Cancer measures PD-L1 status by IHC using the PD-L1 22C3 PharmDx assay and reports the tumor proportional score (TPS) to inform clinical decision. Patients with a TPS ≥ 50% may be eligible for first-line treatment with ICI monotherapy and those with < 50% TPS are eligible for second line or later ICI monotherapy. We established this retrospective study of ICI monotherapy treated NSCLC patients to assess the 27-gene IO assay as an informative biomarker for NSCLC ICI treatment decisions.Methods: This retrospective study is utilizing the BC Cancer Study Database to select approximately 150 patients with stage IIIB or IV NSCLC treated with single-agent ICI therapy across four BC Cancer centers from 2017 forward (figure 1). Patients are selected based on availability of adequate biopsy specimens (FFPE with at least 20% tumor content), availability of PD-L1 IHC results or sufficient tissue to conduct staining, and for whom outcome data is available via chart review. RNA from patient samples is isolated from FFPE biopsies (either primary or metastatic sites) and those that yield ≥50ng RNA will be analyzed by the 27-gene IO assay 1 to derive IO scores (IO positive or IO negative) based on previously defined thresholds.3 The association between patient outcomes on ICI monotherapy and IO scores and PD-L1 IHC will be reported and compared. Abstract 466 Figure 1 Schematic representation of patient workflow for References: Saltman, A, et al. Prostate cancer biomarkers and multiparametric MRI: is there a role for both in prostate cancer management? Ther Adv Urol 2021;13: 1756287221997186. Ranganath HJA, Smith JR, et al. One-year progression-free survival in lung cancer patients treated with immune checkpoint inhibitors is significantly associated with a novel immunomodulatory signature but not PD-L1 staining. in SITC. Journal Immunotherapy Cancer. 2019. Nielsen, TJ, et al. A novel immuno-oncology algorithm measuring tumor microenvironment to predict response to immunotherapies. Heliyon 2021;7(3):e06438. Ethics Approval: The University of British Columba BC Cancer Research Ethics Board Chair, Vice-Chair or second Vice-Chair, has reviewed the above described research project, including associated documentation, and finds the research project acceptable on ethical grounds for research involving human subjects. All participants have provided informed consent before taking part in the study. REB Number H20-02635.
Robin Meng, Benjamin Besse, Melissa Johnson, Jaafar Bennouna, Luca Toschi, Giovanni Abbadessa, Amele Amrate, Miao Zang, Luis Paz Ares
Published: 9 November 2021
by BMJ
Journal for ImmunoTherapy of Cancer, Volume 9; https://doi.org/10.1136/jitc-2021-sitc2021.455

Abstract:
Background: SAR444245 (THOR-707) is a recombinant human IL-2 molecule that includes a PEG moiety irreversibly bound to a novel amino acid via click chemistry to block the alpha-binding domain while retaining near-native affinity for the beta/gamma subunits. In animal models, SAR444245 showed anti-tumor benefits, but with no severe side effects, both as single agent and when combined with anti-PD1 comparing with historical data from aldesleukin. The HAMMER trial, which is the FIH study shows preliminary encouraging clinical results: initial efficacy and safety profile with SAR444245 monotherapy and in combination with pembrolizumab support a non-alpha preferential activity, validating preclinical models. The Pegasus Lung Ph2 study will evaluate the clinical benefit of SAR444245 in combination with other anticancer therapies for the treatment of patients with lung cancer or pleural mesotheliomaMethods: The Pegasus Lung (NCT04914897) will enroll approximately 354 patients in 6 separate cohorts concurrently or sequentially. In cohorts A1 & A2, patients with first line (L) NSCLC will receive SAR444245 + pembrolizumab. In cohort A3, patients with 1L non-squamous NSCLC will receive SAR444245 + pembrolizumab + pemetrexed + carboplatin/cisplatin. In cohort B1 & B2 patients with 2/3L NSCLC who have progressed on a checkpoint inhibitor (CPI)-based therapy will receive SAR444245 + pembrolizumab, or SAR444245 + pembrolizumab + nab-paclitaxel. In cohort C patients with 2/3L CPI naïve mesothelioma will receive SAR444245 + pembrolizumab. SAR444245 is administered IV at a dose of 24 ug/kg Q3W in an outpatient setting until disease progression or completion of 35 cycles. Pembrolizumab is administered at a dose of 200 mg Q3W until PD or completion of 35 cycles. The study primary objective is to determine the antitumor activity of SAR444245 in combination with other anticancer therapies. Secondary objectives include confirmation of dose and safety profile, assess other indicators of antitumor activity, and assess the pharmacokinetic profile and immunogenicity of SAR444245. The study will be conducted in the US, Australia, France, Italy, Japan, Poland, South Korea, Spain, and Taiwan.Acknowledgements: The Pegasus Lung study is sponsored by Sanofi.Trial Registration: NCT04914897Ethics Approval: This study has been approved by applicable ethics committees or institutional review boards. All participants gave informed consent before taking part.Consent: Written informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.
Domenico Mallardo, Claudia Trojaniello, Maria Grazia Vitale, Grazia D’Angelo, Andrew White, Mariaelena Capone, Antonio Sorrentino, Gabriele Madonna, Marilena Tuffanelli, Vito Vanella, et al.
Published: 9 November 2021
by BMJ
Journal for ImmunoTherapy of Cancer, Volume 9; https://doi.org/10.1136/jitc-2021-sitc2021.308

Abstract:
Background: Adjuvant treatment of melanoma patients with immune-checkpoint inhibition (ICI) significantly improved relapse-free survival (RFS).1 In the phase 3 keynote-054 trial showed that pembrolizumab (anti-PD1) administration in adjuvant setting provided a longer RFS (59,8%) than the placebo group (41,4%) at a 3.5-year median follow-up.2 Moreover, 4 years RFS results from the phase 3 checkmate 238 trial, showed a superior efficacy of nivolumab versus ipilimumab in patients with resected AJCC-7 stage III or IV melanoma. RFS rate was of 58% in the nivolumab arm and 45% in the ipilimumab arm.3 Although treatment with ICIs has improved the RFS of melanoma patients in adjuvant setting, there is still a large proportion of patients who do not respond to the treatment and then relapse. The aim of this study was to investigate the molecular mechanisms underlying resistance to anti-PD1 treatment in the adjuvant setting.Methods: From December 2018 to July 2020, n. 121 melanoma patients in stage III or IV NED were treated with anti-PD1s as adjuvant (minimum follow up of 12 months, range 12–30 months). These patients received nivolumab (n=95) or pembrolizumab (n=26). Distant and local metastases was observed in 33 (27%) and 7 (6%) patients, respectively (patients baseline characteristics are listed in table1). Gene expression profiles, using NanoString IO 360 panel, were performed from peripheral blood mononuclear cell (PBMCs), collected retrospectively, from n.73 patients (of which n.26 had relapse). All patients have appropriately signed informed consent. Statistical analysis was performed via Bonferroni correction, P< 0.05 was considered statistically significant for median stratification.Results: At a minimum follow-up of 12 months, the 12-month rate of Relapse-free survival was 72%, confirming the data reported by checkmate 238 trial. In the transcriptomic analysis we observed that in patients with local-regional metastases there was a higher expression of ITGA2 (p<0.05), a gene that promotes malignant tumor aggression by up-regulating PD-L1 expression through STAT3 pathway and the downregulation of DUSP1 (p<0.05) that is linked in promotion of angiogenesis, invasion and metastasis. Moreover, in male group we found a higher expression of HLA-DQB1 and HLA-DQA1 which belonged to HLA class II beta chains. Abstract 308 Table 1 Conclusions: In this preliminary report we found that RFS 1-yr rate is similar to checkmate 238 study, and that patients with local metastasis have a higher expression of genes related to promote PDL1 levels. Further investigations are needed to get additional information.Acknowledgements: The study was supported by the Institutional Project ”Ricerca Corrente” of Istituto Nazionale Tumori IRCCS Fondazione ”G. Pascale” of Napoli, Italy.References: Weber J, Mandala M, Del Vecchio M, et al, CheckMate 238 Collaborators. Adjuvant nivolumab versus ipilimumab in resected stage III or IV melanoma. N Engl J Med 2017 November 9;377(19):1824–1835. Eggermont AMM, Blank CU, Mandalà M, et al. EORTC melanoma group. Adjuvant pembrolizumab versus placebo in resected stage III melanoma (EORTC 1325-MG/KEYNOTE-054): distant metastasis-free survival results from a double-blind, randomised, controlled, phase 3 trial. Lancet Oncol 2021 May;22(5):643–654. Ascierto PA, Del Vecchio M, Mandalá M, et al. Adjuvant nivolumab versus ipilimumab in resected stage IIIB-C and stage IV melanoma (CheckMate 238): 4-year results from a multicentre, double-blind, randomised, controlled, phase 3 trial. Lancet Oncol 2020 November;21(11):1465–1477. Ethics Approval: The study was approved by internal ethics board of the Istituto Nazionale Tumori IRCCS Fondazione ”G. Pascale” of Napoli Italy, approval number of registry 33/17 OSS.Consent: Written informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.
Rakesh Goyal, Nicole Nasrah, Dan Johnson, William Ho
Published: 9 November 2021
by BMJ
Journal for ImmunoTherapy of Cancer, Volume 9; https://doi.org/10.1136/jitc-2021-sitc2021.548

Abstract:
Background: Regulatory T cells (Treg) can dampen antitumor immune responses in the tumor microenvironment (TME) and have been shown to correlate with poor clinical outcome. Translational studies have demonstrated an accumulation of Treg in tumors after treatment with immunotherapies including CAR-T cells and anti-CTLA-4, which could potentially reflect a mechanism of adaptive immune resistance.1–2 CCR4, the receptor for the chemokines CCL17 and CCL22, is the predominant chemokine receptor on human Treg and is responsible for the migration and accumulation of Treg in the TME. Preclinical studies with orally available CCR4 antagonists have demonstrated potent inhibition of Treg migration into tumors, an increase in the intratumoral Teff/Treg ratio, and antitumor efficacy as a single agent and in combination with checkpoint inhibitors, including anti-CTLA-4.3 In a first-in-human trial conducted in healthy volunteers, the oral CCR4 antagonist FLX475 was demonstrated to be well tolerated with outstanding pharmacokinetic and pharmacodynamic properties.4 An ongoing Phase 1/2 clinical trial of FLX475 is examining the safety and preliminary antitumor activity of FLX475 as monotherapy and in combination with pembrolizumab in subjects with several types of advanced cancer.5 Given the preclinical data demonstrating a significant enhancement of the antitumor activity of anti-CTLA-4 when combined with FLX475, a Phase 2 study investigating the combination of FLX475 and ipilimumab is now being conducted in subjects with advanced melanoma.Methods: This clinical trial is a Phase 2, multicenter, open-label, single-arm study to determine the antitumor activity of FLX475 in combination with ipilimumab in subjects with advanced melanoma previously treated with an anti-PD-1 or anti-PD-L1 agent. The primary objectives of the study are to evaluate objective response rate, and the safety and tolerability of this combination. The study will first examine the safety of the combination of the 100 mg PO QD recommended Phase 2 dose of FLX475 and the approved 3 mg/kg IV Q3W dose of ipilimumab as part of a safety run-in phase, prior to examining the degree of antitumor activity in approximately 20 subjects. Evidence of an overall response rate (ORR) notably greater than the expected ORR of ipilimumab monotherapy alone in such subjects, which has been shown to be approximately 14%,6 would provide preliminary clinical evidence in support of the clinical hypothesis that CCR4 blockade by FLX475 can significantly enhance the antitumor activity of an anti-CTLA-4 checkpoint inhibitor.Trial Registration: ClinicalTrials.gov Identifier: NCT04894994References: O’Rourke D, Nasrallah M, Desai A, Melenhorst J, Mansfield K, Morrissette J, Martinez-Lage M, Brem S, Maloney E, Shen A, Isaacs R, Mohan S, Plesa G, Lacey S, Navenot J, Zheng Z, Levine B, Okada H, June C, Brogdon J, Maus M. A single dose of peripherally infused EGFRvIII-directed CAR T cells mediates antigen loss and induces adaptive resistance in patients with recurrent glioblastoma. Sci Transl Med 2017;9:eaaa0984. doi: 10.1126/scitranslmed.aaa0984. Sharma A, Subudhi S, Blando J, Vence L, Wargo J, Allison JP, Ribas A, Sharma P. Anti-CTLA-4 immunotherapy does not deplete FOXP3+ regulatory T cells (Tregs) in human cancers-Response. Clin Cancer Res 2019;25:1233–1238. Marshall L, Marubayashi S, Jorapur A, Jacobson S, Zibinsky M, Robles O, Hu D, Jackson J, Pookot D, Sanchez J, Brovarney M, Wadsworth A, Chian D, Wustrow D, Kassner P, Cutler G, Wong B, Brockstedt D, Talay O. Tumors establish resistance to immunotherapy by regulating Treg recruitment via CCR4. J Immunother Cancer 2020;8:e000764. van Marle S, van Hoogdalem E, Johnson D, Okal A, Kassner P, Wustrow D, Ho W, Smith S. Pharmacokinetics, pharmacodynamics, and safety of FLX475, an orally-available, potent, and selective small-molecule antagonist of CCR4, in healthy volunteers. J Immunother Cancer 2018; 6(Suppl 1):P484(SITC 2018). Powderly J, Chmielowski B, Brahmer J, Piha-Paul S, Bowyer S, LoRusso P, Catenacci D, Wu C, Barve M, Chisamore M, Nasrah N, Johnson D, Ho W. Phase I/II dose-escalation and expansion study of FLX475 alone and in combination with pembrolizumab in advanced cancer. Journal of Clinical Oncology 2020;38(15_suppl): TPS3163 (ASCO 2020). Long G, Mortier L, Schachter J, Middleton M, Neyns B, Sznol M, Zhou H, Ebbinghaus S, Ibrahim N, Arance A, Ribas A, Blank C and Robert C. Society for Melanoma Research 2016 Congress. Pigment Cell & Melanoma Research 2017;30:76–156. Ethics Approval: This study has been approved by the Institutional Review Board at each investigational site.
Se-In Choe, Ronny Ben-Avi, Housne Begum, Kendra Pearce, Meera Mehta, John Agzarian, Christian J Finley, Waël C Hanna, Forough Farrokhyar, Yaron Shargall
European Journal of Cardio-Thoracic Surgery; https://doi.org/10.1093/ejcts/ezab460

Abstract:
OBJECTIVES: The large volume of scientific publications and the increasing emphasis on high-quality evidence for clinical decision-making present daily challenges to all clinicians, including thoracic surgeons. The objective of this study was to evaluate the contemporary trend in the level of evidence (LOE) for thoracic surgery clinical research. METHODS: All clinical research articles published between January 2010 and December 2017 in 3 major general thoracic surgery journals were reviewed. Five authors independently reviewed the abstracts of each publication and assigned a LOE to each of them using the 2011 Oxford Centre for Evidence-Based Medicine classification scheme. Data extracted from eligible abstracts included study type, study size, country of primary author and type of study designs. Three auditing processes were conducted to establish working definitions and the process was validated with a research methodologist and 2 senior thoracic surgeons. Intra-class correlation coefficient was calculated to assess inter-rater agreement. Chi-square test and Spearman correlation analysis were then used to compare the LOE between journals and by year of publication. RESULTS: Of 2028 publications reviewed and scored, 29 (1.4%) were graded level I, 75 (3.7%) were graded level II, 471 (23.2%) were graded level III, 1420 (70.2%) were graded level IV and 33 (1.6%) were graded level V (lowest level). Most publications (94.9%) were of lower-level evidence (III–V). There was an overall increasing trend in the lower LOE (P < 0.001). Inter-rater reliability was substantial with 95.5% (95%, confidence interval: 0.95–0.96) level of agreement between reviewers. CONCLUSIONS: General thoracic surgery literature consists mostly of lower LOE studies. The number of lower levels of evidence is dominating the recent publications, potentially indicating a need to increase the commitment to produce and disseminate higher-level evidence in general thoracic surgery.
Shrutii Sarda, Geoffrey Lowman, Michelle Toro, Loni Pickle, Timothy Looney, Fiona Hyland
Published: 5 November 2021
Blood, Volume 138, pp 4002-4002; https://doi.org/10.1182/blood-2021-151154

Abstract:
Background T-cell and B-cell repertoire analysis is used in oncology research, to understand the etiology of complex disease phenotypes, for the identification of biomarkers predictive of disease burden, outcome, and response to treatment, and for research in diagnosis and recurrence monitoring. Key predictors include secondary and tertiary repertoire features not reported by existing sequencing software solutions. For example, due to ongoing somatic hypermutation in mature B-cell receptors, the underlying sequence of a given clone can accumulate base differences and appear as several distinct clones with smaller frequencies, thereby hampering the ability of analysis software to detect its presence as a single dominant clone with the highest frequency. This has particularly detrimental implications for research in disorders such as follicular lymphoma and may require clonal lineage analysis for proper mitigation. Therefore, to aid the downstream analytics of biomarker identification and the study of complex disease, we developed fully automated analysis solutions that directly compute and report several key features (clonal lineage, amongst several others described below) pertinent to this area of research. Results We developed the Oncomine™ TCR Beta-SR, TCR Gamma-SR, BCR IGH-SR and BCR IGKL-SR workflows on Ion Reporter™ to characterize T-cell (β, γ chains) and B-cell (heavy and light (κ, δ) chains) repertoires. These workflows generate output tables and visualizations for primary repertoire features such as detected clones (viz., unique rearrangements in the receptor DNA sequence), their frequencies, as well as their somatic hypermutation levels in the case of B-cells (Figure 1a & 1b) for clonality assessment and rare clone detection. The software also quantifies and reports several secondary and tertiary repertoire features in a sample, such as clonal diversity, evenness of the clonal population, and B-cell lineage groupings useful in identifying related sub-clones. It includes spectratyping format plots to simultaneously assess the above features as a function of v-gene usage and CDR3 length combinations (Figure 1c & 1d), thereby providing users a complete snapshot of the repertoire, and also the capability to quickly determine CDR3 lengths and V-gene usage of highly expanded or mutated clones. A separate CDR3 lengths histogram is included, as well as a heatmap that depicts the distributions/intensity of Variable-Joining gene combinations (Figure 1e & 1f). Furthermore, the TCR workflows also report (i) convergence frequencies (fraction of clones with different nucleotide sequences, but identical amino acid sequences), and (ii) haplotype grouping for an analyzed sample, based on V-gene allele genotyping and clustering (Figure 1g). In addition, the long read Oncomine™ BCR IGH-LR workflow uniquely reports the isotype class for every detected clone, and includes a visualization of total reads, clones and lineages in the sample represented by isotype (Figure 1h). Conclusion The Oncomine™ immune repertoire workflows for T-cell and B-cell receptor sequencing were designed to be of high utility in distinct areas of malignancy research, and we expect them to greatly simplify complex downstream analyses. The unique capabilities of the workflows to automatically report secondary and tertiary repertoire features such as (i) clonal lineages for improved dominant clone detection in blood cancers, (ii) TCR clone convergence for prediction of response to immune checkpoint inhibitors [1,2], (iii) TCR haplotype grouping for evaluation of risk factors for autoimmunity and immune-related adverse events [3], and (iv) isotype classification in BCRs for studying pan-cancer immune evasion mechanisms, demonstrate the clear advantages of using these automated workflows over other existing solutions. For research use only. References 1) Looney TJ et al. (2020) TCR Convergence in Individuals Treated With Immune Checkpoint Inhibition for Cancer. Front. Immunol. 10:2985. 2) Naidus et al. (2021) Early changes in the circulating T cells are associated with clinical outcomes after PD-L1 blockade by durvalumab in advanced NSCLC patients. Cancer Immunology, Immunotherapy 70:2095-2102 3) Looney TJ et al. (2019) Haplotype Analysis of the T-Cell Receptor Beta (TCRB) Locus by Long-amplicon TCRB Repertoire Sequencing. Journal of Immunotherapy and Precision Oncology. 2 (4): 137-143. Figure 1 Figure 1. Disclosures: Sarda: Thermo Fisher Scientific: Current Employment. Lowman: Thermo Fisher Scientific: Current Employment. Toro: Thermo Fisher Scientific: Current Employment. Pickle: Thermo Fisher Scientific: Current Employment. Looney: Thermo Fisher Scientific: Ended employment in the past 24 months; Singular Genomics: Current Employment. Hyland: Thermo Fisher Scientific: Current Employment.
Published: 4 November 2021
by MDPI
Remote Sensing, Volume 13; https://doi.org/10.3390/rs13214439

Abstract:
We conducted a systematic review and inventory of recent research achievements related to spaceborne and aerial Earth Observation (EO) data-driven monitoring in support of soil-related strategic goals for a three-year period (2019–2021). Scaling, resolution, data characteristics, and modelling approaches were summarized, after reviewing 46 peer-reviewed articles in international journals. Inherent limitations associated with an EO-based soil mapping approach that hinder its wider adoption were recognized and divided into four categories: (i) area covered and data to be shared; (ii) thresholds for bare soil detection; (iii) soil surface conditions; and (iv) infrastructure capabilities. Accordingly, we tried to redefine the meaning of what is expected in the next years for EO data-driven topsoil monitoring by performing a thorough analysis driven by the upcoming technological waves. The review concludes that the best practices for the advancement of an EO data-driven soil mapping include: (i) a further leverage of recent artificial intelligence techniques to achieve the desired representativeness and reliability; (ii) a continued effort to share harmonized labelled datasets; (iii) data fusion with in situ sensing systems; (iv) a continued effort to overcome the current limitations in terms of sensor resolution and processing limitations of this wealth of EO data; and (v) political and administrative issues (e.g., funding, sustainability). This paper may help to pave the way for further interdisciplinary research and multi-actor coordination activities and to generate EO-based benefits for policy and economy.
Published: 3 November 2021
by MDPI
Metabolites, Volume 11; https://doi.org/10.3390/metabo11110757

Abstract:
In the era of big and omics data, good organization, management, and description of experimental data are crucial for achieving high-quality datasets. This, in turn, is essential for the export of robust results, to publish reliable papers, make data more easily available, and unlock the huge potential of data reuse. Lately, more and more journals now require authors to share data and metadata according to the FAIR (Findable, Accessible, Interoperable, Reusable) principles. This work aims to provide a step-by-step guideline for the FAIR data and metadata management specific to grapevine and wine science. In detail, the guidelines include recommendations for the organization of data and metadata regarding (i) meaningful information on experimental design and phenotyping, (ii) sample collection, (iii) sample preparation, (iv) chemotype analysis, (v) data analysis (vi) metabolite annotation, and (vii) basic ontologies. We hope that these guidelines will be helpful for the grapevine and wine metabolomics community and that it will benefit from the true potential of data usage in creating new knowledge being revealed.
, S. Ramani Moonesinghe, Paul S. Myles, Michael P.W. Grocott, J. Bartoszko, W.S. Beattie, R. Bellomo, D. Buggy, L. Cabrini, J. Canet, et al.
Published: 2 November 2021
British Journal of Anaesthesia; https://doi.org/10.1016/j.bja.2021.09.027

The publisher has not yet granted permission to display this abstract.
, Matthew S. Fury, Stephen P. Maier, David N. Bernstein, Robert E. Carrier, Jon J.P. Warner
Abstract:
Background: The utilization of outpatient shoulder arthroplasty has been increasing. With increasing pressure to reduce costs, further underscored by the coronavirus (COVID-19) pandemic, many health-care organizations will move toward outpatient interventions to conserve inpatient resources. Although abundant literature has shown the advantages of outpatient total hip arthroplasty (THA) and total knee arthroplasty (TKA), there is a relative paucity describing outpatient shoulder arthroplasty. Thus, the purpose of this study was to summarize the peer-reviewed literature of outpatient shoulder arthroplasty with particular attention to patient selection, patient outcomes, and cost benefits. Methods: The PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Embase databases were queried according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. All articles on outpatient shoulder arthroplasty were included. Data on patient selection, patient outcomes, and cost analyses were recorded. Patient outcomes, including complications, reoperations, and readmissions, were analyzed by weighted average. Results: Twenty-three articles were included for analysis. There were 3 review articles and 20 studies with Level-III or IV evidence as assessed per The Journal of Bone & Joint Surgery Level of Evidence criteria. Patient selection was most often predicated on age <70 years, body mass index (BMI) <35 kg/m2, absence of active cardiopulmonary comorbidities, and presence of home support. Complications and readmissions were not common and either improved or were equivalent to those of inpatient shoulder arthroplasty. Patient satisfaction was high in studies of short-term and intermediate-term follow-up. The proposed cost benefit ranged from $747 to $53,202 with outpatient shoulder arthroplasty. Conclusions: The published literature to date supports outpatient shoulder arthroplasty as an effective, safe, and cost-reducing intervention with proper patient selection. Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Arthroscopy: The Journal of Arthroscopic & Related Surgery, Volume 37; https://doi.org/10.1016/s0749-8063(21)00868-9

The publisher has not yet granted permission to display this abstract.
Nathaniel L. Rawicki, Gregory B. Fasani-Feldberg, Avinesh Agarwalla, , Rajkumar S. Pammal, Justin Lapow, Robert Cristofaro
Journal of Pediatric Orthopaedics; https://doi.org/10.1097/bpo.0000000000001994

Abstract:
Background: Academic conferences such as the annual Pediatric Orthopaedic Society of North America (POSNA) meeting provide opportunities to present up-to-date scientific work that can influence clinical decision making. This study reviewed 4 years of abstracts presented at POSNA to assess trends in poster and podium presentation publication rates and associated metrics and the impact of academic presentations on the pediatric orthopaedic literature. Methods: All abstracts presented at POSNA annual meetings from 2013 to 2016 were analyzed for presentation type, subspeciality, level of evidence, study design, peer-reviewed publication within 4 years of presentation, 1-year publication rates, journal impact factors, number of authors, and citations of the final publication. χ2, analysis of variance, and t tests were conducted to measure independence of variables. Statistical significance was indicated at P<0.05. Results: A total of 1135 abstracts were included with 676 published in peer-reviewed journals by August 2020 and 38 excluded because of publication before presentation. The number of accepted abstracts increased yearly. Total of 58.2% of POSNA abstracts were published and 42.5% had the same first author on the final manuscript. Average journal impact factor was 2.60±1.30 with a mean 14.3±16.0 citations. Podium presentations were significantly more likely to be published than poster presentations (63.1% vs. 51.2%, P<0.001) and in higher-impact factor journals. Level I evidence abstracts were published in journals with an average 1.663 higher impact factor than level V evidence abstracts, with no significant difference between overall publication rate and study type (P=0.69) or level of evidence (P=0.95) for podium presentations. The Journal of Pediatric Orthopaedics accepted the most abstracts, 38.4% overall, with 64.1% of acceptances resulting from podium presentations and no difference in time to publication based on subspecialty. Conclusions: The overall publication rate for POSNA abstracts has increased 8.7% from prior analysis. Podium presentations are more likely than poster presentations to be published, overall and in higher-impact journals, and are cited more frequently. Level of Evidence: Level IV—descriptive retrospective epidemiological study.
, , Ruben Juhl Jensen, Susanne Frevert, Mats Håkan Lindh, Mikkel Taudorf, Klaus Brasso, Lars Lönn, Martin Andreas Røder
Published: 1 November 2021
by BMJ
Abstract:
Introduction: Postembolisation syndrome (PES) is the most common side effect of vascular embolisation of solid organs. Although prophylactic corticosteroids are known to reduce the incidence and severity of PES, no trials investigating their efficacy have been conducted in men undergoing prostatic artery embolisation (PAE). We postulate that steroids can have a similar effect in reducing PES after PAE. This paper describes the rationale and detailed protocol for a randomised controlled trial evaluating the efficacy of dexamethasone (DEXA) in reducing PES after PAE.Methods and analysis: In this single-centre, randomised, double-blind, placebo-controlled trial, we will enrol 60 individuals undergoing PAE for benign prostatic hyperplasia. Participants will be randomised to receive IV DEXA (24 mg) or placebo (saline). The primary outcomes will be postprocedural fever, pain and quality of life. The secondary outcomes will include postprocedural nausea, postprocedural medicine usage, laboratory parameters (C reactive protein, prostate-specific antigen) and early PAE results.Ethics and dissemination: Ethics approval was obtained from the Danish Committee on Health Research Ethics in the Capital Region (H-20025910). The results from this trial will be disseminated through publication in peer-reviewed journals and national and international presentations.Trial registration number: Clinicaltrials.gov identifier: NCT04588857; EudraCT number: 2020-000915-53.
, , Michaela Brown, Ashley P Jones, Helen Hickey, , , , , Dannii Clayton, et al.
Health Technology Assessment, Volume 25, pp 1-128; https://doi.org/10.3310/hta25650

Abstract:
Background: People with cystic fibrosis are susceptible to pulmonary infection with Pseudomonas aeruginosa. This may become chronic and lead to increased mortality and morbidity. If treatment is commenced promptly, infection may be eradicated through prolonged antibiotic treatment. Objective: To compare the clinical effectiveness, cost-effectiveness and safety of two eradication regimens. Design: This was a Phase IV, multicentre, parallel-group, randomised controlled trial. Setting: Seventy UK and two Italian cystic fibrosis centres. Participants: Participants were individuals with cystic fibrosis aged > 28 days old who had never had a P. aeruginosa infection or who had been infection free for 1 year. Interventions: Fourteen days of intravenous ceftazidime and tobramycin or 3 months of oral ciprofloxacin. Inhaled colistimethate sodium was included in both regimens over 3 months. Consenting patients were randomly allocated to either treatment arm in a 1 : 1 ratio using simple block randomisation with random variable block length. Main outcome measures: The primary outcome was eradication of P. aeruginosa at 3 months and remaining free of infection to 15 months. Secondary outcomes included time to reoccurrence, spirometry, anthropometrics, pulmonary exacerbations and hospitalisations. Primary analysis used intention to treat (powered for superiority). Safety analysis included patients who had received at least one dose of any of the study drugs. Cost-effectiveness analysis explored the cost per successful eradication and the cost per quality-adjusted life-year. Results: Between 5 October 2010 and 27 January 2017, 286 patients were randomised: 137 patients to intravenous antibiotics and 149 patients to oral antibiotics. The numbers of participants achieving the primary outcome were 55 out of 125 (44%) in the intravenous group and 68 out of 130 (52%) in the oral group. Participants randomised to the intravenous group were less likely to achieve the primary outcome; although the difference between groups was not statistically significant, the clinically important difference that the trial aimed to detect was not contained within the confidence interval (relative risk 0.84, 95% confidence interval 0.65 to 1.09; p = 0.184). Significantly fewer patients in the intravenous group (40/129, 31%) than in the oral group (61/136, 44.9%) were hospitalised in the 12 months following eradication treatment (relative risk 0.69, 95% confidence interval 0.5 to 0.95; p = 0.02). There were no clinically important differences in other secondary outcomes. There were 32 serious adverse events in 24 participants [intravenous: 10/126 (7.9%); oral: 14/146 (9.6%)]. Oral therapy led to reductions in costs compared with intravenous therapy (–£5938.50, 95% confidence interval –£7190.30 to –£4686.70). Intravenous therapy usually necessitated hospital admission, which accounted for a large part of this cost. Limitations: Only 15 out of the 286 participants recruited were adults – partly because of the smaller number of adult centres participating in the trial. The possibility that the trial participants may be different from the rest of the cystic fibrosis population and may have had a better clinical status, and so be more likely to agree to the uncertainty of trial participation, cannot be ruled out. Conclusions: Intravenous antibiotics did not achieve sustained eradication of P. aeruginosa in a greater proportion of cystic fibrosis patients. Although there were fewer hospitalisations in the intravenous group during follow-up, this confers no advantage over the oral therapy group, as intravenous eradication frequently requires hospitalisation. These results do not support the use of intravenous antibiotics to eradicate P. aeruginosa in cystic fibrosis. Future work: Future research studies should combine long-term follow-up with regimens to reduce reoccurrence after eradication. Trial registration: Current Controlled Trials ISRCTN02734162 and EudraCT 2009-012575-10. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 65. See the NIHR Journals Library website for further project information.
Mei Qiu, Li-Min Zhao
Frontiers in Cardiovascular Medicine, Volume 8; https://doi.org/10.3389/fcvm.2021.778284

Abstract:
A Commentary onCardiovascular Outcome in Patients Treated With SGLT2 Inhibitors for Heart Failure: A Meta-Analysisby Gager, G. M, Gelbenegger, G., Jilma, B., von Lewinski, D., Sourij, H., Eyileten, C., Filipiak, K., Postula, M., Siller-Matula, J. M. (2021). Front. Cardiovasc. Med. 8:691907. doi: 10.3389/fcvm.2021.691907 In the meta-analysis of Gager et al. (1) recently published in the journal Frontiers in Cardiovascular Medicine, the authors identified that sodium-glucose co-transporter-2 (SGLT2) inhibitors could reduce heart failure (HF) events and all-cause mortality in patients with HF and that the benefit of this drug class on the primary endpoint (i.e., a composite of hospitalization for HF HHF) or cardiovascular mortality (CVM) was consistent across relevant HF subgroups defined by the following clinically important factors: the status of type 2 diabetes at baseline, type of HF (according to left ventricular ejection fraction, LVEF), cause of HF, specific SGLT2 inhibitors, gender, age, estimated glomerular filtration rate (eGFR), body mass index, and concomitant medications. However, Gager et al. (1) failed to evaluate the effect of SGLT2 inhibitors in several subgroups defined by three other clinically important factors: race, region, and baseline New York Heart Association (NYHA) class. Hence, we aimed to conduct another meta-analysis to examine whether these factors affect the efficacy of gliflozins in patients with HF or not. Moreover, Gager et al. in their meta-analysis (1), failed to include the latest EMPEROR-Preserved trial (2) assessing empagliflozin in patients with HF with an LVEF of > 40%. Since that trial (2) provided the new data in the subgroup of HF with mildly reduced LVEF (HFmrEF) and the subgroup of HF with preserved LVEF (HFpEF), we repeated the subgroup analysis according to LVEF by adding these new data, although this subgroup analysis had been performed in the meta-analysis of Gager et al. (1). We only included in this meta-analysis large cardiovascular outcome trials (CVOTs) that compared the HF outcomes of SGLT2 inhibitors with those of placebo in patients with HF. The only endpoint of interest for this meta-analysis was the composite HF outcome, which was defined as a composite of HHF or CVM. Embase and PubMed were searched (from inception to August 31st, 2021), using the following retrieval terms: “heart failure,” “HFpEF,” “HF with reduced LVEF (HFrEF),” “SGLT2 inhibitors,” “empagliflozin,” “canagliflozin,” “ertugliflozin,” “dapagliflozin,” “sotagliflozin,” and “randomized controlled trial.” Finally, we included four CVOTs (2–5) focusing on assessing gliflozins in patients with HF. We extracted trial-level survival data (i.e., hazard ratios, HRs, and 95% confidence intervals, CIs) in various subgroups of interest from included trials, and, based on them, performed a random-effects meta-analysis. Subgroup analyses were conducted according to the following four factors: region (Asia, Latin America, North America, and Europe), race (White, Asian, and Black), baseline NYHA class (Class II and Class III or IV), and LVEF at baseline (LVEF ≤ 40%, i.e., HFrEF, LVEF > 40 to <50%, i.e., HFmrEF, and LVEF ≥ 50%, i.e., HFpEF). Subgroup differences were examined by Cochran's Q test, with P< 0.05 indicating statistical significance. We completed data analyses using Stata (version 16.0). Compared with placebo, SGLT2 inhibitors reduced the composite HF outcome by 40% in patients with HF enrolled in Asia (HR.6, 95% CI 0.50–0.73), 17% in those enrolled in Europe (HR 0.83, 95% CI 0.74–0.93), 26% in those enrolled in Latin America (HR 0.74, 95% CI 0.64–0.85), and 30% in those enrolled in North America (HR 0.7, 95% CI 0.58–0.84); and yielded more reductions in those enrolled in Asia than in the other three continents (Psubgroup = 0.03; Figure 1A). SGLT2 inhibitors yielded more reductions in that outcome in Asian patients (38% reduction, HR 0.62, 95% CI 0.52–0.74) and Black patients (36% reduction, HR 0.64, 95% CI 0.47–0.87) than in White patients (21% reduction, HR 0.79, 95% CI 0.72–0.88), with a significant subgroup difference (Psubgroup = 0.04; Figure 1B). SGLT2 inhibitors yielded more reductions in that outcome in patients with NYHA class II (31% reduction, HR 0.69, 95% CI 0.63–0.76) than NYHA classes III–IV (14% reduction, HR 0.86, 95% CI 0.77–0.97), with a significant subgroup difference (Psubgroup< 0.01; Figure 1C). SGLT2 inhibitors reduced that outcome by 24% (HR 0.76, 95% CI 0.69–0.82) whether in patients with HFmrEF, patients with HFrEF patients, or patients with HFpEF patients (Psubgroup = 0.53; Figure 1D). Figure 1. Forest plots illustrating the effect of SGLT2 inhibitors on composite HF outcome in patients with HF by four important factors. (A) Effects of SGLT2 inhibitors on composite HF outcome in HF patients by Regions. (B) Effects of SGLT2 inhibitors on composite HF outcome in HF patients by Race. (C) Effects of SGLT2 inhibitors on composite HF outcome in HF patients by Baseline NYHA class. (D) Effects of SGLT2 inhibitors on composite HF outcome in HF patients by LVEF at baseline. SGLT2, sodium-glucose co-transporter-2; HF, heart failure; CI, confidence interval; NYHA, New York Heart Association; LVEF, left ventricular ejection fraction; Composite HF outcome: defined as a composite of hospitalization for HF or cardiovascular mortality. The meta-analysis of Gager et al. (1) confirmed the consistent efficacy of SGLT2 inhibitors on the composite HF outcome (i.e., a composite of HHF/CVM) in various HF subgroups defined by...
Published: 26 October 2021
by MDPI
in J
J, Volume 4, pp 664-697; https://doi.org/10.3390/j4040048

Abstract:
Current technological advancements have allowed robots to be successfully employed in the healthcare sector. However, the recently acquired ability of social robots to process social information and act according to it has potentially made them very well suited to support or conduct psychological interventions. The present paper carried out a systematic review of the available literature regarding social-robot-based interventions in psychological domains using preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. The inclusion criteria were: (i) publication date until 2020; (ii) being an empirical study, master thesis, or project report; (iii) written in English or Italian languages (the two languages spoken by the authors); (iv) published in a scholarly peer-reviewed journal or conference proceedings, or were Ph.D. or master’s theses; and (v) assessed “social robot”-based intervention in psychological domains. Overall, the review showed that three main areas may benefit from social-robot-based interventions: social skills, mood, and wellbeing (e.g., stress and anxiety levels). Interestingly, social robots seemed to have a performance comparable to, and sometimes even better than, human operators. The main, but not exclusive, target of robot-based interventions in the psychological field was children with autism spectrum disorder (ASD). As evidence is, however, still limited and in an embryonic state, deeper investigations are needed to assess the full potential of social robots for the purposes of psychological intervention. This is relevant, considering the role that social robots could have in overcoming barriers to access psychological assessment and therapies.
Published: 21 October 2021
by MDPI
Sustainability, Volume 13; https://doi.org/10.3390/su132111646

Abstract:
The emerging demand for sustainable development and the need for efficient use of resources across the built environment have stirred research efforts globally. The construction sector is often regarded as one of the major world consumers of resources, so many international establishments are trying to create a sustainable environment through adaptive reuse of existing building stocks, a concept which has been receiving momentous recognition by reason of its richly diversified applicability for circular economy. Thus, profound knowledge of the topic and research trends is requisite to promote scholarship. For this analysis, the global research developments in adaptive reuse are assessed according to published documents, co-authorship, geographical distribution and keyword- co-occurrences. From the Scopus directory, 227 journal articles published from 2006 to 2021 were retrieved. Results showed that from 2006, published documents rose by 221 articles. About 29% of the publications were from Italy and the United Kingdom. Among the articles, 110 were from the subject area of environmental science (48.5%), while the subject area of engineering represents 104 publications (45.8%). Recent progress in adaptive reuse in building and construction includes, but not limited to: (i) component and materials reuse and technology, (ii) life cycle assessment, (iii) economic assessment and multi-criteria decision making and (iv) regulatory policies and stakeholders’ analysis. The findings are important to furnish all relevant personnel in the academic and industries with a broad perception of the status and potential emerging trends on the adaptive reuse of buildings.
Aisha Alhammadi, Wafa Alnaqbi, , ,
ECS Meeting Abstracts, pp 604-604; https://doi.org/10.1149/ma2021-0212604mtgabs

Abstract:
Two-dimensional (2D) nanomaterials have captured a great deal of attention recently, with most of the focus on improving the functionality of devices. Molybdenum disulfide (MoS2) is a type of transition metal dichalcogenide (TMD) with an indirect band gap. However, a 2D monolayer of MoS2 has a direct band gap [1]. 2D films of MoS2 have a multitude of features such as high strength, flexibility and has better quantum yield than bulk MoS2 [2]. 2D films of MoS2 can be widely used in various devices for their electronic, optical, and catalytic properties [3]. In this work MoS2 nanoflakes were prepared and studied using atomic force microscopy (AFM) microscopy. The initial bulk MoS2 was in two forms, powder and crystal, which were used to prepare the nanoparticles and flakes respectively. The preparation of the nanoparticles was done by dispersing 0.5 g of MoS2 powder in 50 mL NMP (N-Methyl-2-Pyrrolidone) followed by sonicating the mixture for 6 hours using an ultra probe-sonicator at 10 s / 2 s duty cycle in an ice bath, and then centrifuging at 1500 rpm for 60 min to filter the unexfoliated particles and at 7500 rpm for 30 min to remove the insoluble impurities. This caused the MoS2 nanoparticles to precipitate on the wall of the centrifuge tube and after filtering, the nanoparticles were deposited via drop casting on a Si wafer. The preparation procedure for the MoS2 nano flakes was by a simple exfoliation technique which uses scotch tape. Part of the bulk MoS2 crystal is placed on the sticky part of the tape and the tape is then folded on the MoS2 piece with the scotch tape surrounding the crystal on the top and bottom. The tape is then separated from each other, which results in exfoliation of the MoS2 into flakes. The more the steps are repeated of this process, the thinner the flakes are. The flakes on the tape were transferred to a Si wafer. The achieved MoS2 nanoflakes on Si wafer were then imaged using AFM microscopy and conductive measurements. The AFM images was done to identify the distribution of the flakes and nanoparticles. AFM images showed clear flakes on the Si wafer at which they were distributed randomly over the surface. Furthermore, conductive AFM was employed to obtain the IV curve over the flake and obtain the electrical properties of the flakes, where forward and reverses scanning was done that showed hysteresis loop. The hysteresis observed showed good gap in the loop indicating high voltage difference that is useful for devices such as non-volatile memory, perovskite solar cells, modulators and many other electronics. References [1] E. Zhang, W. Wang, C. Zhang, Y. Jin, G. Zhu, Q. Sun, D. W. Zhang, P. Zhou, and F. Xiu, "Tunable Charge-Trap Memory Based on Few-Layer MoS2," ACS Nano, vol. 9, no. 1, pp. 612–619, Dec. 2014. [2] R. Ganatra and Q. Zhang, "Few-Layer MoS2: A Promising Layered Semiconductor," ACS Nano, vol. 8, no. 5, pp. 4074–4099, 2014. [3] L. Muscuso, S. Cravanzola, F. Cesano, D. Scarano, and A. Zecchina, "Optical, Vibrational, and Structural Properties of MoS2Nanoparticles Obtained by Exfoliation and Fragmentation via Ultrasound Cavitation in Isopropyl Alcohol," The Journal of Physical Chemistry C, vol. 119, no. 7, pp. 3791–3801, 2015.
Donald Adams, Paige L McDonald, Elaine Sullo, Alexander B Merkle, Timothy Nunez, , Stacy A Shackelford, Mark W Bowyer, Philip van der Wees
Published: 19 October 2021
by BMJ
Trauma Surgery & Acute Care Open, Volume 6; https://doi.org/10.1136/tsaco-2021-000811

Abstract:
The management of non-compressible torso hemorrhage in military austere/remote environments is a leading cause of potentially preventable death in the prehospital/battlefield environment that has not shown a decrease in mortality in 26 years. Numerous conceptual innovations to manage non-compressible torso hemorrhage have been developed without proven effectiveness in this setting. This scoping review aims to assess the current literature to define non-compressible torso hemorrhage in civilian and military austere/remote environments, assess current innovations and the effectiveness of these innovations, assess the current knowledge gaps and potential future innovations in the management of non-compressible torso hemorrhage in civilian and military austere/remote environments, and assess the translational health science perspective of the current literature and its potential effect on public health. The Joanna Briggs Institute for evidence synthesis will guide this scoping review to completion. A nine-step development process, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews checklist, will be used to enhance the methodological and reporting quality of this scoping review. The Participant, Concept, Context framework will broaden this scoping review’s reach in developing a comprehensive search strategy. Thirty years will be explored to assess all relevant literature to ensure a thorough search. Two researchers will explore all the discovered literature and develop consensus on the selected literature included in this scoping review. The article will undergo review and data extraction for data analysis. The knowledge to action framework will guide the knowledge synthesis and creation of this scoping review. A narrative synthesis will systematically review and synthesize the collected literature to produce and explain a broad conclusion of the selected literature. Lastly, a consultation exercise in the form of qualitative interviews will be conducted to assess the thematic analysis results and validate the result of this scoping review. This scoping review will require Institutional Review Board approval for the expert consultation in the form of qualitative interviews. Consultants’ identifying information will remain confidential. The collected and analyzed data from this scoping review will identify gaps in the literature to create an evidence-informed protocol for the management of non-compressible torso hemorrhage of the abdomen in civilian and military austere/remote environments. The results of this scoping review will be distributed in peer-reviewed journals and educational, medical presentations. Scoping Review Protocol, Level IV.
, Xiangyi Ma, Wenwen Wang, Minli Zhang, Zhiying Yu, Wei Zhang, Li Hong, Zhiying Li, Lin Li, Xin Du, et al.
Published: 18 October 2021
by BMJ
Abstract:
Introduction Leiomyoma recurrence is a major concern for long-term myomectomy management, especially for multiple leiomyomas. Gonadotropin-releasing hormone agonist (GnRHa) is one of the most effective medications to reduce the volume of fibroids and the uterus. However, its role in preventing recurrence after conservative surgery remains unclear. At present, there is no randomised clinical trial determining the efficacy of GnRHa treatment for preventing multiple leiomyomas recurrence after myomectomy. Methods and analysis We are conducting a phase IV randomised controlled trial in women aged 18–45 undergoing myomectomy for multiple leiomyomas. After surgery, women whose pathological result confirms multiple leiomyomas are randomised in a 1:1 ratio into an observation or GnRHa group. The primary outcome is the recurrence of either clinical symptoms or fibroids on imaging. Patients will be assessed for adverse events during the follow-up. Ethics and dissemination The study was approved by the Medical Ethics Committee of the Tongji Hospital Affiliated with the Tongji Medical College of Huazhong University of Science and Technology (TJ-IRB20180311) according to the submitted study protocol (V.1.0, 10 November 2017) and informed consent (V.1.0, 10 November 2017). The results will be presented at domestic and international conferences and published in peer-reviewed journals. Trial registration number ChiCTR-IPR-17012992.
Igor V. Evdokimov, Vologda State Dairy Farming Academy Named After N.V. Vereshchagin, Aleksandr P. Dobrynin, Nelli A. Armeeva, Cherepovets State University
Lesnoy Zhurnal (Forestry Journal) pp 201-209; https://doi.org/10.37482/0536-1036-2021-5-201-209

Abstract:
Common juniper (Juniperus communis L.) is one of the most widespread undergrowth species in the forests of Russia. It has not only important silvicultural significance but is also widely used in economic activities. Numerous works of Russian and foreign authors are devoted to its study. The article shows the results of geobotanical and forest inventory studies of a unique area of pine plantation in the Kirillovskiy district of the Vologda region. In the second understorey of which tree-form common juniper grows. The stand was classified as high-density (relative fullness – 0.85) and low quality (quality class – V–IV). The total stock of trunk wood on the site is 280 m3/ha, including the stock of juniper wood – 28 m3/ha. The average diameter of juniper trunks is 14 cm, the average height is 11 m and the age is 180 yrs. This is several times higher than its usual parameters in other forests. A significant number of specimens of juniper (50 pcs/ha) are in the stage of drying out or have already died and represent dead wood of different years. The number of small and medium-sized juniper undergrowth is 1.5 ths pcs/ha or 62.5 % of the growing. Undergrowth of European spruce, downy birch and black alder is also found. The existing undergrowth is assessed as promising, but Scots pine undergrowth is missing. The ground cover is dominated by green and sphagnum mosses as well as shrubs of the Ericaceae and Vacciniaceae families. The study of such objects, extremely rare not only in the north of the European part of Russia, but also everywhere, is of great practical importance. It is also important for understanding the biology of the only representative of the Cupressaceae family that naturally grows here. The tree-form juniper in the pine plantation has survived and reached a size not typical for this species due to the inaccessibility of the site, the lack of fires and forest felling. Such forest areas should be identified, protected, and subjected to stationary research. For citation: Evdokimov I.V., Dobrynin A.P., Armeeva N.A. Tree Form of Juniper (Juniperus communis L.) in the Forests of the Vologda Region. Lesnoy Zhurnal [Russian Forestry Journal], 2021, no. 5, pp. 201–209. DOI: 10.37482/0536-1036-2021-5-201-209
Helen Elizabeth Noble, Felipe Vega Rivera, Lacey LaGrone
Published: 11 October 2021
by BMJ
Trauma Surgery & Acute Care Open, Volume 6; https://doi.org/10.1136/tsaco-2021-000774

Abstract:
Background We aimed to understand how surgical trauma providers in the Americas acquire answers to clinical questions and what barriers and facilitators they face in efforts to practice according to recommendations for common surgical cases. We hypothesized that increased English proficiency and country income improved providers’ acquisition and application of clinical knowledge. Methods A 23-question survey evaluated reported confidence in interpretation of evidence, perceived language fluency, and access to and application of recommendations on sepsis and appendicitis. Electronic surveys were distributed across the Americas to Pan American Trauma Society members. Results 108 participants from 21 countries completed this survey. 59% had ≥21 years of provider experience. 38% reported their English reading comprehension as less than or equal to “limited working proficiency.” 44% endorsed using Google Translate; 35% reported they did not need translation tools to evaluate medical literature. 59% felt uncertainty regarding clinical care at least weekly. 65% reported inability to answer their clinical questions at least once per month. 86% felt confident in their ability to interpret and apply evidence for their practice. To answer clinical questions, participants listed guidelines (76%), full-text peer-reviewed journal articles (61%), and meta-analyses (49%) as their most used resources. 25% answered all five clinical questions correctly, whereas 43% answered three or fewer correctly. 79% felt they had adequate access to resources to answer the five clinical questions. When controlling for individual demographic characteristics, decreased age (p<0.01) and increased country income level (p=0.03) positively impacted correct answers to questions. Discussion Uncertainties in clinical care are unavoidable. Language, age, and country income level impacted provider acquisition and application of knowledge relevant to select clinical scenarios. These findings highlight disparities in access and training and add urgency to the movement for improved dissemination and implementation approaches for evidence-based practice in surgery. Level of evidence IV.
Philosophy, Ethics, and Humanities in Medicine, Volume 16, pp 1-14; https://doi.org/10.1186/s13010-021-00108-8

Abstract:
Background Many indigenous people have died or been harmed because of inadequately monitored research. Strong regulations in Human Research Ethics (HRE) are required to address these injustices and to ensure that peoples’ participation in health research is safe. Indigenous peoples advocate that research that respects indigenous principles can contribute to addressing their health inequities. This scoping literature review aims to analyze existing peer reviewed and grey literature to explore how indigenous values and principles from countries of Oceania are incorporated into HRE and the governance of research involving human participants. Methods A scoping literature review framework was used for this study. A search for peer reviewed and grey literature from Google, bibliographies, and electronic databases such as SCOPUS, SPRINGER, Medline (Ovid) and JBI Database of Systematic Reviews was conducted, limited to the years 2002–2020. Sixty (60) documents that focused on indigenous knowledge from Oceania region and HRE were included, from which key findings and themes were synthesized. Results Charting the data showed that more than half the eligible documents were peer-reviewed journal articles (54%). Other sources included: International Declarations on Human Research (8%); book chapters (8%); government documents (8%); HRE Guidelines or protocols (13%); news articles (7%) and PhD thesis (2%). The literature was from Australia, Cook Islands, Guam, New Zealand, Fiji, Samoa, Tonga and Vanuatu, some of which focused specifically on HREs in the Pacific Region. Issues emerging from the literature were grouped into five themes (i) indigenous and cultural principles of HRE; (ii) informed consent in indigenous settings in Oceania; (iii) vulnerability and minority status of indigenous populations exploited for research; (iv) research ethics governance for Oceania indigenous peoples; and (v) research ethics committees in Oceania. Respect, relationship building, and trust were priority indigenous HRE principles that encompass the principles of partnership, capacity building, reciprocity, and equality. Relationship building and trust imply the equal distribution of benefits for indigenous population and researchers. Conclusion Indigenous principles of HRE identified were interconnected and interdependent. Recommendations were to incorporate indigenous principles of research in HRE regulations and processes of all countries with indigenous populations. This is especially pertinent for emerging national research committees in LMIC countries, including Fiji and Tonga. Relationship building among researchers and indigenous populations is key to successful research with indigenous populations. HRE principles important for relationship building include respect that is reciprocal among researchers and indigenous people. Elements of the principle of respect highlighted are empathy, collaboration, sharing of benefits, reciprocity, appreciation, empowerment, protection, safety and awareness of culture and languages. Indigenous ontology from the Oceania region involves spirituality, connectedness to land, religious beliefs and a participatory approach to HRE and should be respected in research. An ethical governance mechanism of HRE is one that incorporates indigenous principles and applications for the purpose of maximizing the protection of the dignity and rights of indigenous peoples of Oceania.
Gregorio Hernandez Zendejas, , Andrew Phelps, Gabriel Planas, Marco Sanchez
Published: 7 October 2021
Aesthetic Plastic Surgery pp 1-10; https://doi.org/10.1007/s00266-021-02600-0

Abstract:
Background A new technique in plastic surgery termed Osteogenesis Modulation is described. This technique uses a surgically implanted, battery-operated medical device to deliver customized electrical pulses to produce mandibular bone growth. This device was designed to be a temporary, nonpermanent implant. The purpose of this study was to review both the safety and efficacy of Osteogenesis Modulation. Methods This study comprises two phases. Phase I involved experimental technology development and animal experiments. Phase II included technology development for clinical use and a clinical trial. In Phase II, four patients with a diagnosis of mandibular hypoplasia and microgenia underwent surgical implantation of the novel medical device over the chin bone. Once a satisfactory change of contour of mandibular bone was achieved, the devices were removed. In all patients, the devices were left in place for 12 months, then surgically removed under local anesthesia. Preoperative and long-term postoperative cephalometric controls were done. Results In all patients, symmetrical mandibular bone growth was observed with good-to-excellent aesthetic results. The overall follow-up period was 39 months. Cephalometric controls taken 3 to 6 months after the device removal showed an average increase in mandible length of 5.26mm (range, 2.83–7.60mm) Conclusions Preliminary clinical results suggest that Osteogenesis Modulation is a safe, minimally invasive, and effective alternative treatment for the correction of mandibular hypoplasia in selected cases. Level of Evidence IV This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.
Atilla Soran, Serdar Ozbas, Lutfi Dogan, , Efe Sezgin
Published: 7 October 2021
Abstract:
We read the article entitled “Locoregional therapy in de novo metastatic breast cancer: systematic review and meta-analysis, written by Reinhorn D et al. in The Breast Journal 58 (2021) 173–181 [[1]Reinhorn D. Mutai R. Yerushalmi R. Moore A. Amir E. Goldvaser H. Locoregional therapy in de novo metastatic breast cancer: systemic review and meta-analysis.Breast. 2021 Aug; 58: 173-181https://doi.org/10.1016/j.breast.2021.05.003Abstract Full Text Full Text PDF Scopus (1) Google Scholar]. We found this meta-analysis presentation quite interesting, but it has many points that needs to be cleared.1This meta-analysis includes a not finished (early terminated because of poor recruitments; ABSCG-28 POSITIVE) trial;aIt has only 90 patients' data; 35% of (90/254) of estimated sample size.b21% (n = 9) has R1 resection margins. Studies showed that primary breast surgery group has survival benefit when R0 margin resection is achieved.c40% T3-T4 tumors (not equally distributed in Arms A and B);dNo visceral only met (all either bone or visceral + bone);eNot all the breast conserving surgery (BCS) patients received RT to breast; all BCS patients in the MF07-01 Study patients in the surgery group received RT; standard clinical practice is RT in patients who underwent BCS.2This meta-analysis includes “A randomized phase III trial of systemic therapy plus early local therapy versus systemic therapy alone in women with de novo stage IV breast cancer: A trial of the ECOG-ACRIN Research Group (E2108) presented by Khan et al. at the plenary session of ASCO 2020 virtual meeting earlier than expected. ECOG-ACRIN 2108 (Eastern Cooperative Oncology Group-American College of Radiology Imaging Network - NCT01242800)”aThis study has not been published yet.bAlthough 125 patients were randomized to the early LRT group; only 109 were treated surgically.cSurgical margin remained positive in approximately 20% of the early LRT group.dDetails of the extent of surgery for axilla and radiation volumes are not available.eThe distribution of patients with locally advanced disease is not specified; 44% of patients have skin involvement, skin nodules and fascia invasion; 48% of them have T4 and/or N2/N3 diseases.f38% of patients had only bone metastases but subgroup analysis was not performed.gNo organ-specific comparison was made between the groups.hThe patients with 0 months follow-up were included in the analysis.3.Several meta-analyses including one just published including 4 RCTs and 2 prospective trails [[2]Yu Y. Hong H. Wang Y. Fu T. Chen Y. Zhao J. et al.Clinical evidence for locoregional surgery of the primary tumor in patients with de novo stage IV breast cancer.Ann Surg Oncol. 2021 Sep; 28: 5059-5070https://doi.org/10.1245/s10434-021-09650-3Crossref Scopus (0) Google Scholar], and large real-life data collections such as Surveillance, Epidemiology, and End Results (SEER), National Cancer Database (NCDB), and the Epidemiological Strategy and Medical Economic (ESME) data have showed the survival benefit of LRT. The discrepancy between the current meta-analysis and literature with either meta-analyses or a huge number of patients in big data registries should be explained by the authors as they are the ones stating no survival benefit with LRT.
Published: 7 October 2021
by MDPI
Sensors, Volume 21; https://doi.org/10.3390/s21196654

Abstract:
The research presented in this manuscript proposes a novel Harris Hawks optimization algorithm with practical application for evolving convolutional neural network architecture to classify various grades of brain tumor using magnetic resonance imaging. The proposed improved Harris Hawks optimization method, which belongs to the group of swarm intelligence metaheuristics, further improves the exploration and exploitation abilities of the basic algorithm by incorporating a chaotic population initialization and local search, along with a replacement strategy based on the quasi-reflection-based learning procedure. The proposed method was first evaluated on 10 recent CEC2019 benchmarks and the achieved results are compared with the ones generated by the basic algorithm, as well as with results of other state-of-the-art approaches that were tested under the same experimental conditions. In subsequent empirical research, the proposed method was adapted and applied for a practical challenge of convolutional neural network design. The evolved network structures were validated against two datasets that contain images of a healthy brain and brain with tumors. The first dataset comprises well-known IXI and cancer imagining archive images, while the second dataset consists of axial T1-weighted brain tumor images, as proposed in one recently published study in the Q1 journal. After performing data augmentation, the first dataset encompasses 8.000 healthy and 8.000 brain tumor images with grades I, II, III, and IV and the second dataset includes 4.908 images with Glioma, Meningioma, and Pituitary, with 1.636 images belonging to each tumor class. The swarm intelligence-driven convolutional neural network approach was evaluated and compared to other, similar methods and achieved a superior performance. The obtained accuracy was over 95% in all conducted experiments. Based on the established results, it is reasonable to conclude that the proposed approach could be used to develop networks that can assist doctors in diagnostics and help in the early detection of brain tumors.
Shobiroh Ulfa Kurniyawati, Andi Prastowo
Jurnal Teknologi Pendidikan (JTP), Volume 14, pp 88-94; https://doi.org/10.24114/jtp.v14i2.26121

Abstract:
Abstrak : Penelitian ini bertujuan untuk mengetahui apakah model pembelajaran simulasi berbasis TIK dapat memberikan kontribusi terhadap kemampuan berpikir logis siswa kelas IV SD/ MI dalam pembelajaran matematika ?. Penelitian ini dilatarbelakangi oleh rendahnya kemampuan berpikir logis siswa dalam pembelajaran matematika serta persepsi siswa terhadap pembelajaran matematika yang sulit dipahami dan menakutkan, sehingga dihadirkan sebuah inovasi dengan memanfaatkan model simulasi berbasis TIK. Metodologi yang digunakan dalam penelitian ini adalah metode kualitatif deskriptif dengan desain penelitian kepustakaan (library research), sedangkan teknik pengumpulan data dilakukan dengan mencari berbagai dokumentasi dari beberapa jurnal yang relevan dengan penelitian ini, kemudian dianalisis dan diambil kesimpulan. Jurnal yang digunakan adalah terbitan sepuluh tahu terakhir yaitu mulai tahun 2010-2020. Hasil peneltian ini menunjukkan bahwa model simulasi berbasis TIK yang diterapkan dalam pembelajaran dapat memberikan kontribusi terhadap kemampuan berpikir logis siswa, dengan kata lain model pembelajaran simulasi berbasis TIK dapat menumbuhkan kemampuan berpikir logis siswa kelas IV SD/ MI. Hal ini dapat dilihat dari analisis 33 artikel yang relevan dengan penelitian ini, sehingga dapat dipakai dalam menentukan kesimpulanKata Kunci : simulasi, tik, berpikir logisAbstract :This study aims to determine Whether the ICT-based simulation learning model can contribute to the logical thinking skills of grade IV SD/ MI students in mathematics learning. This research is motivated by the low ability of students to think logically in mathematics learning and students’ perceptions of learning mathematics which is difficult to understand and scary, so that an innovation is presented by utilizing an ICT-based simulation model. The methodology used in this research is descriptive qualitative method with library research desaign, while the data collection technique is done by looking for various documentation from several journal relevant to this research, then analyzed and conclusions drawn. The journal used are those of the last ten years, starting from 2010-2020. The results of this study indicate that the ICT-based simulation model applied in learning can contribute to student’s logical thinking skills, in other words, the ICT-based simulation learning model can foster logical thinking skills in grade IV SD/ MI students. This can be seen from the analysis of 33 articles relevant to this research, so that it can be used in determining conclusions.Keywords : simulation, ict, logical thinking
Khairulhafiy Muhammad Ruzairi, Balqis Syahirah Jamaludin, ,
Lecture Notes in Mechanical Engineering pp 661-680; https://doi.org/10.1007/978-981-16-4115-2_54

The publisher has not yet granted permission to display this abstract.
Journal of Nuclear Engineering and Radiation Science; https://doi.org/10.1115/1.4052641

Abstract:
This Special Issue of the ASME Journal of Nuclear Engineering and Radiation Science includes 2 editorials and 25 technical papers presenting main achievements of the Horizon-2020 European Union ESFR-SMART project (European Sodium Fast Reactor Safety Measures Assessment and Research Tools) supported by the EURATOM grant and launched in September 2017. ESFR-SMART gathers a consortium of 19 organizations (see Figure 1): Research centres, industries, universities, Technical and Scientific Support Organizations as well as Small to Medium Enterprise aiming at enhancing further the safety of Generation-IV Sodium Fast Reactors (SFRs) and, in particular, of the commercial-size European Sodium Fast Reactor (ESFR) in accordance with the European Sustainable Nuclear Industrial Initiative (ESNII) roadmap.
Fast Facts for the Operating Room Nurse; https://doi.org/10.1891/9780826156112.ap01

Abstract:
Focus PreviousNext Bibliography Add to Favorites Download PDF Permissions Share Close Share this chapter Copy linkShare via emailShare via: Close table of contents chapter information Contents SearchSearch Copyright Foreword Preface Acknowledgments Introduction I: Personal and Patient Preparation 1: Surgical Attire 2: Preoperative Considerations 3: Patient Positioning 4: Surgical Skin Preparation 5: Draping the Patient for Surgery II: Environment and Processing Considerations 6: Operating Room Environment Requirements 7: Sterile Technique 8: Sterilization and Central Processing 9: Surgical Supplies III: Surgical Basics 10: Basic Surgical Procedures 11: Surgical Instrumentation 12: Electrosurgery 13: Surgical Energy and Stapling Devices 14: Surgical Dressings IV: Additional Operating Room Considerations 15: Medications 16: Anesthesia 17: Complications and Emergencies in the Operating Room 18: Emergency Preparedness for Disaster 19: Legal Aspects of Operating Room Practice 20: Lifelong Learning Bibliography DOI: 10.1891/9780826156112.ap01 American Association of Tissue Banks. (2017). Standards for tissue banking (14th ed.). McLean, VA: Author.Google ScholarAmerican Heart Association. (2020). Advanced cardiovascular life support provider manual (16th ed.). South Deerfield, MA: Channing L. Bete.Google ScholarAmerican Institute of Architects. (2018). Guidelines for design and construction of hospital and health care facilities. Dallas, TX: Facility Guidelines Institute.Google ScholarAmerican Society of Anesthesiologists, House of Delegates. (1999, October 13). Continuum of depth of sedation—Definition of general anesthesia and levels of sedation/analgesia (last amended October 15, 2014). Retrieved from http://www.asahq.orgGoogle ScholarAmerican Society of Anesthesiologists Task Force on Prevention of Perioperative Peripheral Neuropathies. (2011). Practice advisory for the prevention of perioperative peripheral neuropathies: An updated report. Anesthesiology, 114(4), 741–754.Google ScholarAmerican Society of Anesthesiologists Task Force on Sedation and Analgesia by Non-Anesthesiologists. (2002). Practice guidelines for sedation and analgesia by non-anesthesiologists. Anesthesiology, 96(4), 1004–1117.Google ScholarAmerican Society of Health-System Pharmacists. (2015). ASHP guidelines on outsourcing sterile compounding services. American Journal of Health-System Pharmacy, 72, 1664–1675.Google ScholarAnderson, D. J. (2014). Prevention of surgical site infection: Beyond SCIP. AORN Journal, 99(2), 315–319.Google ScholarStandard, A.N.S.I., and A.A.M.I. ST79. “Comprehensive guide to steam sterilization and sterility assurance in health care facilities.”. Association for the Advancement of Medical Instrumentation/American National Standards Institute (2017).Google ScholarAssociation for the Advancement of Medical Instrumentation. (2015). Sterilization, Part 1: Sterilization in health care facilities Volume 1. Annapolis Junction, MD: Advancing Safety in Medical Technology Publications.Google ScholarAssociation of Operating Room Nurses. (2021).Guidelines for Perioperative Practice 2021. Denver: CO: AORNGoogle ScholarAssociation of periOperative Registered Nurses. (2021). AORN comprehensive surgical checklist. Retrieved from http://www.aorn.org/guidelines/clinical-resources/tool-kits/correct-site-surgery-tool-kit/aorn-comprehensive-surgical-checklistGoogle ScholarAssociation of periOperative Registered Nurses. (n.d.). AORN safe patient handling pocket reference guide. Retrieved from https://www.aorn.org/-/media/aorn/guidelines/tool-kits/safe-patient-handling/safe-patient-handling-pocket-reference-guide.pdf?la=en&hash=54A3288EDE43FF121FF94AC4257960CAD67B68C5Google ScholarAssociation of Surgical Technologists. (2010). AST standards of practice for ionizing radiation exposure in the perioperative setting. Retrieved from http://www.ast.org/uploadedFiles/Main_Site/Content/About_Us/Standard%20Ionizing%20Radiation%20Exposure.pdfGoogle ScholarBarash, P. G., Cullen, B. F., & Stoelting, R. K. (2015). Clinical anesthesia (7th ed.). Philadelphia, PA: Lippincott Williams & Wilkins.Google ScholarBashaw, M. A. (2016). Guideline implementation: Processing flexible endoscopes. AORN Journal, 104(3), 225–236.Google ScholarBhatt, A., Mittal, S., & Gopinath, K. S. (2016). Safety considerations for Health care Workers involved in Cytoreductive Surgery and Perioperative chemotherapy. Indian Journal of Surgical Oncology, 7(2), 249–257.Google ScholarBouyer-Ferullo, S. (2013). Preventing perioperative peripheral nerve injuries. AORN Journal, 97(1), 110–124.e9. doi:10.1016/j.aorn.2012.10.013Google ScholarBurcharth, J., & Rosenberg, J. (2013). Animal derived products may conflict with religious patients’ beliefs. BMC Medical Ethics, 14(1), 48.Google ScholarCenters for Disease Control and Prevention. (2016). Guidance for the selection and use of personal protective equipment (PPE) in healthcare setting. Retrieved from http://www.cdc.gov/HAI/prevent/ppe.htmlGoogle ScholarCenters for Disease Control and Prevention. (2017). Guidelines for preventing surgical site infections. Retrieved from https://www.cdc.gov/infectioncontrol/guidelines/ssi/index.htmlGoogle ScholarCherry, B., & Jacob, S. R. (2016). Contemporary nursing: Issues, trends, & management (7th ed.). St. Louis, MO: Elsevier Health Sciences.Google ScholarCovidien. (2013). Principles of electrosurgery. Retrieved from http://www.asit.org/assets/documents/Prinicpals_in_electrosurgery.pdfGoogle ScholarCriscitelli, T. (2016). Caring for patients with chronic wounds: Safety considerations during the surgical experience. Association of operating room nurses. AORN Journal, 104(1), 67.Google ScholarDavis, P. J., & Cladis, F. P. (2016). Smith’s anesthesia for infants and children (9th ed.). New York, NY: Elsevier.Google ScholarFalk, S. A., & Fleisher, L. A. (2020). Overview of anesthesia. In S. B. Jones (Ed.)...
Page of 194
Articles per Page
by
Show export options
  Select all
Back to Top Top