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Insights on the Depression and Anxiety, Volume 5, pp 025-028; https://doi.org/10.29328/journal.ida.1001027

Abstract:
Considering the geographical complexity and adversity, online communication and consultation are viable method in Nepal. The COVID-19 pandemic has accelerated the already starting trend of use of these technologies in medicine. In BPKIHS, telemedicine efforts were already initiated; lockdown rather warranted its maximum use. Here is an account of the observation made in telepsychiatry service provided by a consultant psychiatrist of its department of psychiatry. It is an institute-based observation noted for all the telepsychiatry consultations in 9 random duty days of the COVID-19 pandemic. Basic necessary information was noted down in a semi-structured proforma, like: socio-demographic, clinical information and advice provided. There were 104 subjects; 73 follow-up and 31 new: 60 male and 44 female cases. Clients of multi-ethnic groups were the most from urban, then semi-urban and least from rural areas. More consultations were for young age-groups and from nearby districts of Sunsari. Mood, somatic (sleep), anxiety were the top presenting complaints and 8/104 clients had suicidal symptoms. Maximum follow-up cases were improving. The most common diagnoses were: Mood (Depression and Bipolar), Anxiety, Psychosis and Substance use disorders. Most common treatment advices included: Antidepressants, Antipsychotics, Benzodiazepines and Counseling/psycho-education. Telepsychiatry is a viable method of delivering service even during the pandemic.
Published: 18 August 2021
by MDPI
Applied Sciences, Volume 11; https://doi.org/10.3390/app11167558

Abstract:
The crankshaft online measurement system has realized the full inspection function with fast beats, at the same time it requires for high-precision measurement. Considering the effect of ambient temperature and temperature changes on measuring machine, the calibration part, the measured crankshaft and displacement sensor, a temperature compensation method is proposed. Firstly, relationship between calibration part and ambient temperature can be get through the zero calibration. Then use the material properties to obtain compensation values of the calibration part and the measured crankshaft part at different temperatures. Finally, the compensation parameters for displacement sensor can be obtained through the BP algorithm. The improved dragonfly algorithm (DA) is used to optimize the parameters of BP neural network algorithm. Experiments verify the effectiveness of IDA-BP for LVDT in temperature compensation. After temperature compensation, the error range of main journal radius is reduced from 0.0156 mm to 0.0028 mm, the residual error decreased from −0.0282 mm~+0.0018 mm to −0.0058 mm~−0.0008 mm. The influence of temperature changes on the measurement is reduced and measurement accuracy is improved through the temperature compensation method. The effectiveness of the method is proved.
Sophie Jones, Claire Stark Toller
Published: 16 March 2021
by BMJ
Poster Presentations, Volume 11; https://doi.org/10.1136/spcare-2021-pcc.133

Abstract:
Background Severe anaemia is common in the hospice setting. Causes include anaemia of chronic disease (ACD) and associated functional iron deficiency (FID), with or without absolute iron deficiency anaemia (IDA). National guidance advises anaemia is investigated and treated to reduce need for blood transfusion.1 However, this is infrequently done.2 Blood transfusion is used to treat symptomatic anaemia but there is limited evidence on effectiveness and duration of response.3,4 Harm of transfusion is well documented; even a single unit risks transfusion associated circulatory overload (TACO).5 Consequently, guidelines were introduced to an inpatient palliative care unit to ensure anaemia was investigated, IV iron prescribed appropriately, and a restrictive transfusion strategy based on weight adopted. Method Retrospective data collection from patients admitted for blood transfusion over one year: investigations (iron studies, haematinics, CRP); IV iron prescriptions. Risk factors for TACO were collated. Results 37 units were administered to 15 patients. 58% had one unit; the remaining had two. Mean pre-transfusion haemoglobin 67g/L (44g/L–84g/L). Mean post-transfusion haemoglobin 78g/L (43g/L-125g/L); checked in 54% patients. 50% patients had <5g/L improvement in haemoglobin. Iron studies and haematinics were requested in 73% patients; at least one requested in 92%. IDA was identified in one patient, FID identified in four, and a combination IDA/FID in two. Five had no deficiency. Of the seven with IDA or FID, five received blood and iron infusions. 100% patients had one risk factor for TACO; 47% had two and 27% had three. 50% had a weight recorded within 2 months of transfusion. Conclusion Guideline introduction increased investigation into causes of anaemia. Identification of FID/IDA enabled treatment with IV iron and blood transfusion. Prior to guideline introduction, IV iron had not been prescribed. High risk of TACO mandates a cautious approach to blood transfusion and supports a restrictive transfusion strategy. References NICE (2015) Blood transfusion. National Guideline NG24. www.nice.org.uk Neoh K, et al. (2019) National comparative audit of red blood cell transfusion practice in hospices: Recommendations for palliative care practice. Palliative Medicine.33:1021‒08. Uceda Torres ME, et al. (2014) Transfusion in palliative cancer patients: A review of the literature. Journal of Palliative Medicine.17: 88‒104. Chin-Yee N, et al. (2018) Red blood cell transfusion in adult palliative care: a systematic review. Transfusion. 58: 233‒241. SHOT. Annual SHOT Report 2019. https://www.shotuk.org/resources/current-resources (accessed 20th December 2020).Save
Journal of Pediatric Intensive Care, Volume 10; https://doi.org/10.1055/s-0041-1723771

Abstract:
Journal of Pediatric Intensive Care wishes to recognize those who contributed as an expert peer reviewer of submitted scientific papers in 2020. Thank you for your contributions to Journal of Pediatric Intensive Care in 2020. Dalia A. Latif Abdelrahman John Abisheganaden Narothama R. Aeddula Hatice F. Akbulut Oluwaseun Akeju Osman Aktas Basak N. Akyıldız Amal Al Maani Fortune Alabi Shadi Al-Jureidini Gokce Alp Bruce S Alpert Angela Ammirabile Somchai Amornyotin Arturo Anadón Heitor F. de Andrade Junior Chika Vera Anekwe Yasir Arafat Grace M. Arteaga Nagehan Aslan Azadeh Assadi Fehmi Ateş Malik Aydin Mustafa Aydın Mehmet Aykur Talin Babikian Vineeta Bal Mariella Baldassare Kalyan C. Balla Nayimisha Balmuri Aditi Banerjee Maja Baretić Oliver Barry Mario Bau Ali Baykan David W. Bearl Gusztav Belteki Jean Bergounioux Agustin Bernatzky Ahmet Besir Pradipta Bhakta Katherine Biagas Robin J. Biellik Manuel D. Bilkis Naomi B. Bishop Davide Bolignano Guillaume Bollee Pablo Bonany Ozlem M. Bostan Francesco Botet Sergio Bottero Maryann Bozzette Khyati Brahmbhatt Luca Brazzi Ryan Breuer Giacomo Brisca Lars M. Broman Hakan Bucak Danilo Buonsenso Jane Burns Bahadir Caglar Ayla A. Çağlar Halime T. Cak Murat Çakır Yigit Canga Roberto M. Carrasco Navarro Desiree Caselli Solmaz Çelebi Tanju Çelik Veysi Çeri Regina G. Cesar John R. Charpie Andrew C. Chatzis Hsiu-Lin Chen Jerome G. Chen Lei Chen Frank Chinowaita Meshe Chonde Chia-Man Chou Horng-Ruey Chua Ampaiwan Chuansumrit Erman Cilsal Catalina Ciocan Alvaro Coronado Munoz Graziela A. Costa Martin Cour Mihai Craiu Alessandro Crocoli Matthew G. Crowson Erkan Cure Mario Jose da Conceição Cesare Danesino Anirudha Das Peter J. Davis Ali Davoodi Matheus F. de Oliveira Tiago H. de Souza Paolo Della Vigna Peter Delputte Christopher Derderian Ramazan Dertli Navin K. Devaraj Sanjoy K. Dey Gurpreet S.Dhillon Wern Y.Ding Tam T. Doan Ahmed M. Dohain Sten Dreborg Elodie Drumez George Du Toit Jean C. Dubus Michael Eisenhut aIssm El Rassi Ibrahim elbaser Selin elmaoğulları Asmaa A.E.W.I. El Sehmawy Nagehan Emiralioğlu Fabian Emrich Simon J. Erickson Hüseyin S. Erol Maria Esposito Nick Evans Valentina Fainardi Sherri Fannon Pierre-Atoine Faye Neil D. Fernandes Francisco Fernández-Carrión Ali Fettah Anthony Fine Milton Finegold Naoto Fkunaga Pedro Flores Paul Forrest Roland C. Francis Linda S. Franck Bernhard Frey Joel Friedlander Kevin G. Friedman Kazuto Fujimoto Seiji Fukuda Victor García Nieto Jonathan A. Gehlbach Salman Genene Michele Ghezzi Elaine Gilfoyle Paola Giordano Raffaele Giordano Stephen J. Gleich Chong Tien Goh Allan Goldstein Silvia Gonella Vijayaprasad Gopichandran Allan Gottschalk Rajeshree Govender Brian W. Gray Serge Grazioli Robin J. Green Steven C. Greenway Ryszard Grenda Ioana Grigoras Eugenio Grillo Simone Gulletta Tulin Gungor Lin Guo Kartik Gupta Naveen Gupta Nitesh Gupta Piyush Gupta Hakan Guvenir Quint A.J. Hagdorn Pankaj Halder Anthony J. Handley Stephen A. Hart Babar S. Hasan Gamal M. Hasan Hideo Hashizume Pippa Hawley Manuel E. Herrera-Gutiérrez Jeremy L. Herrmann Jonathon T. Hill Elizabeth Hisle-Gorman Roger Ho Li-Tung Huang Jan Huber Tim Hundscheid Can Huzmeli Ferika Indarwati Susumu Itoh Craig S. Jabaley Jenisha Jain MarekJastrzebski Muralidharan Jayashree Ida Jeremiasen Alan Jobe Martin Jöhr An Jonckheere Eva-Maria Jordi Ritz Mohamed S. Kabbania Katarzyna Kaczyńska Wisit Kaewput Ayhan Kanat Ozgun K. Kara Spyridon Karageorgos Oliver Karam Sunil Karande Vasılıkı Karava Belde K. Demir Selcuk Kayir Angkool Kerdpanich Jun Kido Mehmet Kilic Se-Chan Kim Naritaka Kimura Norma J. Klein Jake A. Kleinmahon Kathryn Knoop Hiroshi Koga Alper Koker Visnja Kokic Males KathrynKOPEC Ioannis Koutroulis Mirjana Kovac Elizabeth Kramer Conrad Krawiec Shunsuke Kudo Yu-Hung Kuo Akira Kuriyama Charlotte Kvasnovsky Tng Chang Kwok Yi-Chen Lai Saptharishi Lalgudi Ganesan Richard Lambert Francesca Lami Anselm Lee Sherman Lee Rosaura Leis Ana M. Lenz Yosef Levenbrown Jing Li Peng Li Zhuo Li Richard Lichenstein Zheng Lim Victoria Lima-Rogel Jinping Liu Randall T. Loder Spiros Loggos Chantal Loirat Chai Har Loo Sebastian Loos Jorge Lopez-Herce Patricia Louzon Ersilia Lucenteforte Tryggve Lundar Xianli Lv Rodrigo S. Machado Echezona T. Maduekwe Paulo F. Magalhães Ata Mahmoodpoor Bernhard Maisch Sayan Manna Pier M. Mannucci Shabih Manzar Natasa Marcun Varda Christophe Marguet Vikas Marwah Surendra B. Mathur David N. Matlock Kousaku Matsubara Shigeki Matsubara Yuichi Matsuzaki Michael C. McCrory Harry McNaughton Felix Meincke Krishnan Melarkode AIcha Merouani Philippe Meyer Marija Meznaric Martha F. Mherekumombe Ulrike Mietzsch Andrew C. Miller Andrew G. Miller Masaru Miura Mohd F. bin Mohd Miswan Miguel A. Molina Gutiérrez Jens Möller Thomas J. Morgan Bernadett Mosdósi Emad Mossad Katie Moynihan Hilda A. Mujuru Jodi Mullen Tina N. Munch Noha Musa Jeffry Nahmias Bindi Naik-Mathuria Yuki Nakamura Madmumita Nandi Kedareshwar P.S. Narvencar Ali Naseh Abdulqadir J. Nashwan Audrey Nath Archana Nelliot Osmas P. Neto Jaime Newberry Heber Nielsen Wanjiku F.M. Njoroge Francisco Nogareda Allison Norton Jonah Odim Fumihiro Ogawa Ayse Oktem Joyce O'Shea Michael Paddock Izabela Pagowska-Klimek Ayyammal Palaniappan Silin Pan Dimitrios Panagopoulos Manat Panamonta Robert Parker Richard Parrish Davide Pata Maria A. Pena Marc Perreault Tanya Perry Zinia Pervin James Peyton Bethann Mangel Pflugeisen Zi Hao Phang Francisco J. Pilar-Orive Paul M. Pilowsky Gustavo D. Pimentel Michael Pitt Ana Paula Poblacion Dimitri Poddighe Antonella Polimeni Murray M. Pollack Puneet A. Pooni Raymond Pranata Elizabeth Price Charlene Pringle Willem Proesmans Karen M. Puopolo Hasan Qayyum Jill Querney Edon Rabinowitz Akella R.R. Devi Maurizio Radicioni Leslie Raffini Rupesh Raina Ravi P. Rajkumar Dimitrios Rallis...
Journal of Physics: Conference Series, Volume 1730; https://doi.org/10.1088/1742-6596/1730/1/011002

Abstract:
All papers published in this volume of Journal of Physics: Conference Series have been peer reviewed through processes administered by the Editors. Reviews were conducted by expert referees to the professional and scientific standards expected of a proceedings journal published by IOP Publishing.● Type of peer review: Single-blind● Conference submission management system: IDAS Conference management System● Number of submissions received: 215● Number of submissions sent for review: 215● Number of submissions accepted: 143● Acceptance Rate (Number of Submissions Accepted/Number of Submissions Received X 100): 68%● Average number of reviews per paper: 2● Total number of reviewers involved: 450● Any additional info on review process:Contact person for queries: Dimitrios VlachosAssociate ProfessorUniversity of [email protected]
Batsheva Goldman-Ida
Published: 18 November 2020
Images, Volume 13, pp 77-88; https://doi.org/10.1163/18718000-12340127

Abstract:
Batsheva Goldman-Ida, art historian and museum curator, introduces the article by Jiří Mordechai Georgo Langer (1894, Prague–1943, Tel Aviv): “On the Function of the Jewish Doorpost Scroll,” presented for the first time in English translation, and originally written for the Freud journal Imago in 1928. Langer, a Hebrew poet and teacher of Jewish studies was a friend of Franz Kafka. Langer joined the Belz Hasidism from 1913–16 and was one of the people who introduced Kafka to Hasidism. Langer suggests an explanatory model for Jewish religious artifacts such as the Mezuzah and Phylacteries in the context of compulsion neuroses, referencing the rites of indigenous people and totem theory. The introduction provides background material on the author and details of his other books and endeavors, as well as a framework to better appreciate his poetry and scholarly work. Langer sought a revival of “comrade love” whose homerotic bias is of interest today. His essay on the Mezuzah opens up a range of questions on Jewish artifacts, psychoanalysis, and the origins of Jewish rites. Long left unnoticed, it challenges the current field of Jewish scholarship to rethink its methodology.
Michael Auerbach, Carlo Brugnara, Steve Staffa
Published: 5 November 2020
Blood, Volume 136, pp 42-43; https://doi.org/10.1182/blood-2020-134693

Abstract:
It is estimated anemia affects over 30% of the world's population, with iron deficiency (ID) the overwhelmingly most common cause. Whether absolute due to blood loss and/or iron sequestration to underlying morbidity, the need for repletion especially in females, is a formidable medical issue. The diagnosis of iron deficient erythropoiesis has been traditionally based on the biochemical parameters ferritin and percent transferrin saturation (TSAT), mean cell volume and hemoglobin (Hb) concentration. In recent years, reticulocyte Hb content has emerged as a parameter helpful in identifying iron deficient erythropoiesis and informing a need, or lack thereof, for replacement. 556 consecutive, non-selected patients referred for diagnosis and/or treatment of anemia were included in this diagnostic study to compare the performance of reticulocyte hemoglobin equivalent (RET-He) versus traditional biochemical markers for diagnosis and treatment of IDA. CBC, serum ferritin, iron and TSAT were performed as clinically indicated. RET-He was measured with a Sysmex XN-450 analyzer on the residual CBC sample. 556 patients were studied at baseline and 150 were subsequently treated with intravenous (IV) iron. 240/556 were seen at follow-up, with 57 treated and 183 not treated with IV iron. At baseline, ret-He, positively correlated with Hb (Spearman correlation (rho)=0.365, P < 0.001), MCV (rho=0.576, P < 0.001), MCH (rho=0.777, P < 0.001), serum iron (rho=0.526, P < 0.001) and TSAT (rho=0.492, P < 0.001). Serum iron, and TSAT (but not serum ferritin or MCV, or absolute reticulocyte count) positively correlated with Hb concentrations. Based on either a serum ferritin <30 ng/ml and/or a TSAT< 20%, 241/556 (43.4%) patients were diagnosed as iron deficient. Anemia was present in 64/241 of the iron deficient patients (26.6%). Despite the limitations of the biochemical markers outlined above, we performed ROC analysis assessing the value of RET-He in identifying iron deficiency as defined by serum ferritin <30 ng/mL or transferrin saturation <20%. ROC analysis demonstrates a reasonable performance for RET-He (AUC= 0.733, 95% CI: 0.692, 0.775), with a cut-off value of <30.7 pg yielding 68.2% sensitivity and 69.7% specificity. Using both Hb and RET-He in a multivariable ROC analysis does not provide an improved AUC, as compared to just using RET-He (AUC=0.605 vs.0.733). IV iron administration was associated with significant increases in Hb, MCV, MCH, RET-He, serum ferritin, iron and TSAT, whereas in the no-IV iron cohort, there was a small reduction in RET-He and small increases in MCV and MCH, with no significant variations in Hb and in the other parameters. Serum ferritin was below 30 ng/mL in 18/57 (32%) of the patients requiring IV iron and in 19/183 (10.4%) of those not requiring iron at visit 1. These values changed to 4/57 (7%) (P=0.002) and 23/183 (13%) (P=0.623) at visit 2, respectively. Regression analysis for Hb response following IV iron showed that baseline RET-He values are predictive of Hb response, with every unitary increase in RET-He corresponding to a blunting of the Hb change by -0.19 g/dl (95% CI: -0.27, -0.11; P < 0.001). Changes in RE-He associated with IV iron administration are also predictive of the Hb response, with every additional unit increase in RET-He corresponding to a 0.21 g/dL increase in Hb (95% CI: 0.13, 0.28; P < 0.009). ROC analysis for the capability to predict Hb response among the 57 patients receiving IV iron shows that a value of baseline RET-He < 28.5 pg together with a baseline Hb value < 10.3 g/dL provide the highest Youden's index for predicting Hb response > 1.0 g/dl, with sensitivity of 84% and specificity of 78%. The Figure presents data for the 21/57 patients who had RET-He < 28.5 pg and Hb < 10.3 g/dL vs the 36/57 who did not. The present data show that an abnormally low ret-He value (< 28.5 pg) identifies patients who will respond to iron replacement, obviating delays to obtain standard iron parameters. Baseline and changes in ret-He also associate with Hb response. Given the enormous prevalence of ID in the general population the use of the ret-He, which is available with the CBC on the autoanalyzer, informs need for iron replacement, or lack thereof, represents an increase in convenience for patient and physician, decreases costs, streamlines care and represents an improvement in the treatment paradigm of one of the commonest maladies on the planet. Figure 1 Disclosures Auerbach: AMAG: Research Funding; Sysmex: Research Funding. Brugnara:American Journal of Hematology: Other; Sysmex America Inc.: Consultancy.
Shaoni Sun, Risheng Long, , Manhong Li
Proceedings of the Institution of Mechanical Engineers, Part J: Journal of Engineering Tribology, Volume 235, pp 1659-1668; https://doi.org/10.1177/1350650120972293

Abstract:
This study presents the influence of initial deflection angle (IDA) on the tribological properties of gray cast iron (GCI) rings with curve distributed pits in the radial direction (CDPRD). The thermal behavior of pits textured GCI rings with different initial deflection angles (0°, 30°, 45°, 60°, 75°) and fixed deflexional angle of adjacent pits (DAAP, 10°) were researched, through APDL programming. A pin-on-disc wear test rig was used to reveal the anti-wear performance of samples under dry sliding, at a rotating speed of 200 rpm, with a normal load of 70 N. An electronic balance and an optical microscope (OM) were used to obtain their wear losses and worn surfaces, respectively. The results show that: comparing with the smooth GCI ring, there are evident high temperature regions between two adjacent pits groups, called “temperature barrier and separation effect”. Among all textured samples, the von Mise’s stress of IDA45 is the most stable, and its temperature is almost the lowest. The friction coefficient curve and the wear loss of IDA45 are also the lowest, and much lower than the loss of smooth GCI ring, indicating the excellent anti-wear performance. This work can provide a valuable reference for the surface design of journal bearings.
Published: 8 October 2020
Abstract:
<p>The four larger satellites of Jupiter, with roughly comparable mass, are termed Galilean moons. They display (i) a water fraction that increases with dis- tance to Jupiter (ranging from no-water for volcanic innermost Io, to approximately half-half ratio of water and rocks for outermost Callisto) as well as (ii) various degrees of differentiation (two end-members corresponding to the two outer moons of similar radius: highly differentiated Ganymede, including a metallic core, locus of the dynamo observed at present, and much-less differentiated Callisto possibly harboring large volumes of ice-rock mixtures). A plausible cause for these variations can be related to the formation of the moons, although their later evolution could also affect both properties.</p> <p>Owing to the orbits of the four moons (compact, prograde, coplanar and nearly circular), a contemporaneous formation in a circum-jovian disk orbiting in the equatorial plane of the proto-planet is put forward, similar to the formation of planets albeit with significantly different time- and length-scales. The latter is not a minor difference: in practice, classical scenarios [1, 2] cope with the problem of too-much heating associated to large impacts as well as the migration of satellitesimals onto the proto-planet. A new paradigm for the formation of giant planets has emerged re- cently. It has been termed &#8217;pebble accretion&#8217; and highlights the efficiency of accretion of small particles in a context where gas drag dissipates energy as the pebble passes the protoplanet [3]. In this framework, formation of the Galilean moons is envisioned to occur naturally and contemporaneously to the growth of the giant planet. Details are nevertheless controversial: two re- cent scenarios propose either a fast [4] or a slow [5] accretion.</p> <p>Here, we reproduce these two end-member scenar- ios and specifically focus on the thermal evolution of the growing moons. A simple description of the heat equation is adopted assuming a spherical sym- metry. Heat deposition by pebbles as well as radiogenic heat sources are accounted for during a 30 Myr period that encompasses the formation of all moons. We systematically investigate the influence of timing (start/duration) and consider a range for the concentra- tion in of short-lived radio-isotopes (<sup>26</sup>Al,<sup>60</sup>Fe,<sup>53</sup>Mn) that reproduces the composition of LL (high enery content) and CI (low enery content) chondrites. Our results demonstrate that, whatever the scenario, the formation process involves little collisional energy, as can be expected owing to the small size of impactors. As a consequence, after 30 Myr of evolution, moons formed via pebble accretion show a small degree of differenciation or none at all. Either subsequent heat- ing via radioactive decay of long-lived isotopes or tidal heating possibly associated to the moons entrance in the Laplace resonance must be considered to explain the highly differentiated state observed at present for Ganymede. This includes the formation of the hydrosphere, the dehydration of rocks and the melting of the metallic component in order to form the moon&#8217;s core.</p> <p>Interestingly, the main heat sources differ depend- ing on the scenario: in the case of slow accretion, the decay of short-lived radio-isotopes is predominant when accretion of the moons starts sufficiently early; in the case of a fast accretion, the main heat source is associated to viscous dissipation in the disk that heats up the surface of the protosatellites. In the former case, the interior might reach the melting point of water in a limited fraction of the parameter space but only in the innermost region of the moons. Conversely, in the latter case, the melting point can be reached in the outer envelope, as predicted for large moons in the classical formation scenarios [6], but to a much lesser extent. The subsequent evolutionary path leading to the differentiation observed at present for Ganymede thus necessarily involve distinct dynami- cal phenomena: Rayleigh-Taylor type instabilities of the thick rock-ice mixture into the hydrosphere [7] if accretion is slow; if accretion is rapid, a possible delay in solid-state segregation of the rock component if double-diffusive convection occurs owing to a stabilizing density gradient [8].</p> <p>&#160;</p> <div class="page" title="Page 2"> <div class="layoutArea"> <div class="column"> <p>[1] Estrada, P. R., Mosqueira, I., Lissauer, J. J., D&#8217;Angelo, G., and Cruikshank, D. P. (2009). Formation of Jupiter and conditions for accretion of the Galilean satellites. Eu- ropa, edited by RT Pappalardo, WB McKinnon, and K. Khurana, University of Arizona Press, Tucson, 27-58.</p> <p>[2] Canup, R. M., and Ward, W. R. (2009). Origin of Europa and the Galilean satellites. Europa, edited by RT Pappalardo, WB McKinnon, and K. Khurana, University of Arizona Press, Tucson, 59-83.</p> <p>[3] Johansen, A., and Lambrechts, M. (2017). Forming planets via pebble accretion. Annual Review of Earth and Planetary Sciences, 45, 359-387.</p> <p>[4] Ronnet,T., and Johansen,A.(2020). Formation of moon systems around giant planets-Capture and ablation of planetesimals as foundation for a pebble accretion scenario. Astronomy & Astrophysics, 633, A93.</p> <p>[5] Shibaike, Y., Ormel, C. W., Ida, S., Okuzumi, S., and Sasaki, T. (2019). The Galilean Satellites Formed Slowly from Pebbles. The Astrophysical Journal, 885(1), 79.</p> <div class="page" title="Page 2"> <div class="layoutArea"> <div class="column"> <p>[6] Monteux, J., Tobie, G., Choblet, G., and Le Feuvre, M. (2014). Can large icy moons accrete undifferentiated?....
Diane S Diane S. Corson, Iowa State University
Published: 5 August 2020
Abstract:
The decades just before and after the turn of the 20th century-sometimes referred to as the "golden age of American journalism"-were years when women first made significant inroads into the male-dominated magazine and newspaper fields. Among them were two pioneers whose early work in investigative or crusading journalism paved the way for major governmental and social changes still in effect a century later. They were Ida M. Tarbell, a white northerner, and Ida B. Wells, a black southerner. Working at about the same time in the vastly different worlds of white and black journalism, each woman used the power of the press to raise awareness and bring about social and political change in ways that had never been tried before. Tarbell, using the magazine medium, brought before the bar of public opinion the predatory and destructive business practices of the Standard Oil Company, as personified by one of the most powerful industrial titans in the country's history, John D. Rockefeller. Tarbell's groundbreaking work, based on exhaustively thorough research, led to legal and legislative action affecting the way America would-and could-do business throughout the 20th century. Wells, who was born into slavery, struggled against racial inequality in the post-Reconstruction South to become the editor and part-owner of a Memphis, Tennessee newspaper. Her lifelong crusade against lynching was a demonstration of the power of the press and one person's determination to raise awareness and bring about social change. This thesis compares and contrasts the social and cultural factors that shaped the formative years of the two Idas. It also examines the similarities and differences in their professional activities as reporters and writers with respect to their most famous works. It concludes that, while Wells and Tarbell were products of their own unique upbringings, both women were risk-takers who were willing to defy conventional norms and stick to the courage of their convictions.
Abstract:
ResumenDesde que se empezó a difundir ampliamente la investigación sobre el discurso académico y profesional en el mundo de habla hispana (Parodi 2010; Bolívar y Parodi 2015), han ido en aumento los cursos sobre escritura académica para estudiantes universitarios en América Latina. No obstante, los profesores en el campo de la educación encuentran dificultades para escribir y publicar artículos científicos en revistas indizadas. El objetivo de este artículo es mostrar la complejidad de un proceso que abarca en la teoría varios planos: a) la definición de artículo científico, b) los tipos de textos que aceptan las revistas como productos de la investigación científica, c) las tradiciones discursivas en educación, y d) las estrategias de los investigadores para cumplir con el requisito de escribir un buen artículo científico. Nos remitimos a la experiencia llevada a cabo con profesores de Universidades y Escuelas Normales mexicanas en cursos y talleres sobre la escritura del artículo científico en educación. Para explicar el problema usamos como referencia teórica el análisis interaccional del discurso (AID) (Bolívar 2005a, 2007) y damos especial atención a los conceptos de género discursivo, estructura textual y estrategias discursivas. Los ejemplos se toman de un corpus de artículos de revistas de educación usados en los talleres. Se señalan aspectos discursivos y lingüísticos y las opciones que tienen los docentes para publicar artículos de investigación rigurosos y bien escritos. Se llama la atención sobre la necesidad de fomentar en los talleres la escritura de artículos científicos con investigaciones terminadas y de promover la escritura de otros textos que cubren las distintas etapas de la investigación.Palabras clave: Artículo Científico. Educación. Talleres. Análisis del Discurso. Discurso Académico. Escritura Académica.A escritura de um bom artigo cientifico na Educaçao e o entreinamento em discurso acadêmico de professores universitáriosResumoDesde que se iniciou a difundir amplamente a pesquisa sobre o discurso acadêmico-profissional no mundo de fala hispánica (Parodi 2010; Bolívar y Parodi 2015), hão aumentado os cursos sobre escrita acadêmica voltada para estudantes universitários na América Latina. Não obstante, no campo da educação, profesores/pesquisadores encontram dificuldades para escrever e publicar artígos científicos em revistas indexadas. O objetivo deste artigo é mostrar a complexidade de um processo que abarca, na teoría, vários planos: a) a definição de artígo científico; b) os tipos de textos que as revistas aceitam como produtos de investigação científica; c) as tradições discursivas na educação e d) as estratégias dos pesquisadores para cumprir com o requisito de escrever um bom artigo científico. Balizamo-nos, aquí, na experiência levada a cabo junto a profesores de universidades e Escolas Normais mexicanas em cursos e oficinas sobre a escritura de arttigo científico na educación. Para explicar o problema, utilizamos como referencial teórico a análise interacional do discurso (AID) (Bolívar 2005a, 2007) e dedicamos especial atenção aos conceitos de gênero discursivo, estrutura textual e estratégias discursivas. Os exemplos são tomados de un corpus de artigos de revistas de educação, utilizados nas oficinas. Problemas linguísticos e discursivos são levantados, além de opções que têm os docentes para publicar artigos de investigação, rigorosos e bem elaborados. Apontamos, ao final, a necessidade de se fomentar, nas oficinas, a produção de artigos científicos resultantes de pesquisas concluídas e de se promover a escritura de outros textos que cobren as distintas etapas da investigação.Palavras-chaves: Artigo Científico. Educação. Oficinas. Análise de Discurso. Discurso Acadêmico. Escritura Acadêmica.Writing a good scientific article in Education and training university teachers in academic discourseAbstractSince the research on academic and professional discourse began to spread widely in the Hispanic world (Parodi 2010; Bolívar y Parodi 2015), courses for university students aimed at promoting academic writing in various disciplines have continued to grow. However, one of the problems that teachers/researchers in education point out is the difficulty they have to write scientific articles for indexed Journals. In this paper I focus on the experience carried out with teachers in Mexican universities and Escuela Normales in courses and workshops on the writing of a scientific article in Education. The objective is to show the complexity of a process that touches upon several dimensions: a) how a scientific article is conceived, b) the types of texts that are are accepted by Education Journals as products of scientific research, c) discursive traditions in Education, d) the strategies researchers use to comply with the requirements for writing a scientific article. We focus on the experience with teachers from universities and Escuelas Normales in México in courses and workshops on the writing of a scientific article in Education. In order to explain the problem, Interactional discourse analysis (IDA) (Bolívar 2005a, 2007) is used as a theoretical framework with attention to the concepts of...
Abstract:
ResumenDesde que se empezó a difundir ampliamente la investigación sobre el discurso académico y profesional en el mundo de habla hispana (Parodi 2010; Bolívar y Parodi 2015), han ido en aumento los cursos sobre escritura académica para estudiantes universitarios en América Latina. No obstante, los profesores en el campo de la educación encuentran dificultades para escribir y publicar artículos científicos en revistas indizadas. El objetivo de este artículo es mostrar la complejidad de un proceso que abarca en la teoría varios planos: a) la definición de artículo científico, b) los tipos de textos que aceptan las revistas como productos de la investigación científica, c) las tradiciones discursivas en educación, y d) las estrategias de los investigadores para cumplir con el requisito de escribir un buen artículo científico. Nos remitimos a la experiencia llevada a cabo con profesores de Universidades y Escuelas Normales mexicanas en cursos y talleres sobre la escritura del artículo científico en educación. Para explicar el problema usamos como referencia teórica el análisis interaccional del discurso (AID) (Bolívar 2005a, 2007) y damos especial atención a los conceptos de género discursivo, estructura textual y estrategias discursivas. Los ejemplos se toman de un corpus de artículos de revistas de educación usados en los talleres. Se señalan aspectos discursivos y lingüísticos y las opciones que tienen los docentes para publicar artículos de investigación rigurosos y bien escritos. Se llama la atención sobre la necesidad de fomentar en los talleres la escritura de artículos científicos con investigaciones terminadas y de promover la escritura de otros textos que cubren las distintas etapas de la investigación.Palabras clave: Artículo Científico. Educación. Talleres. Análisis del Discurso. Discurso Académico. Escritura Académica.A escritura de um bom artigo cientifico na Educaçao e o entreinamento em discurso acadêmico de professores universitáriosResumoDesde que se iniciou a difundir amplamente a pesquisa sobre o discurso acadêmico-profissional no mundo de fala hispánica (Parodi 2010; Bolívar y Parodi 2015), hão aumentado os cursos sobre escrita acadêmica voltada para estudantes universitários na América Latina. Não obstante, no campo da educação, profesores/pesquisadores encontram dificuldades para escrever e publicar artígos científicos em revistas indexadas. O objetivo deste artigo é mostrar a complexidade de um processo que abarca, na teoría, vários planos: a) a definição de artígo científico; b) os tipos de textos que as revistas aceitam como produtos de investigação científica; c) as tradições discursivas na educação e d) as estratégias dos pesquisadores para cumprir com o requisito de escrever um bom artigo científico. Balizamo-nos, aquí, na experiência levada a cabo junto a profesores de universidades e Escolas Normais mexicanas em cursos e oficinas sobre a escritura de arttigo científico na educación. Para explicar o problema, utilizamos como referencial teórico a análise interacional do discurso (AID) (Bolívar 2005a, 2007) e dedicamos especial atenção aos conceitos de gênero discursivo, estrutura textual e estratégias discursivas. Os exemplos são tomados de un corpus de artigos de revistas de educação, utilizados nas oficinas. Problemas linguísticos e discursivos são levantados, além de opções que têm os docentes para publicar artigos de investigação, rigorosos e bem elaborados. Apontamos, ao final, a necessidade de se fomentar, nas oficinas, a produção de artigos científicos resultantes de pesquisas concluídas e de se promover a escritura de outros textos que cobren as distintas etapas da investigação.Palavras-chaves: Artigo Científico. Educação. Oficinas. Análise de Discurso. Discurso Acadêmico. Escritura Acadêmica.Writing a good scientific article in Education and training university teachers in academic discourseAbstractSince the research on academic and professional discourse began to spread widely in the Hispanic world (Parodi 2010; Bolívar y Parodi 2015), courses for university students aimed at promoting academic writing in various disciplines have continued to grow. However, one of the problems that teachers/researchers in education point out is the difficulty they have to write scientific articles for indexed Journals. In this paper I focus on the experience carried out with teachers in Mexican universities and Escuela Normales in courses and workshops on the writing of a scientific article in Education. The objective is to show the complexity of a process that touches upon several dimensions: a) how a scientific article is conceived, b) the types of texts that are are accepted by Education Journals as products of scientific research, c) discursive traditions in Education, d) the strategies researchers use to comply with the requirements for writing a scientific article. We focus on the experience with teachers from universities and Escuelas Normales in México in courses and workshops on the writing of a scientific article in Education. In order to explain the problem, Interactional discourse analysis (IDA) (Bolívar 2005a, 2007) is used as a theoretical framework with attention to the concepts of...
Alecia Swasy
A Wall Street Guidebook for Journalism and Strategic Communication pp 1-18; https://doi.org/10.4324/9780429328169-1

Abstract:
Journalist Ida Tarbell was one of the “muckrakers” that led to modern day investigative business journalism. Americans were in giddy mood after World War I and went on spending spree. PR campaigns helped stock brokers gain more customers, including women who had previously bought war bonds, but were new to Wall Street investing. An analysis of biggest US companies’ stocks, based on market capitalization, showed that stock returns were 17 percent during the war, according to Certified Financial Analysts Institute. To be sure, it was picture of middle-class white family, not reflecting the ongoing struggles of African American families or rural poor who didn’t have the access to higher education or steady wages. In 1959, about 55 percent of African American families were poor. The “C-suite” in those days consisted of the chief executive officer, chief operating officer and chief financial officer. And it was a very insular club at the very top of Corporate America.
Shoborose Tantray, Seema Sharma
Research & Reviews: Journal of Oncology and Hematology, Volume 9, pp 1-5; https://doi.org/10.37591/rrjooh.v9i1.1976

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Haematological abnormalities are diverse in nature, in its causation as well as in its clinical manifestations, most ofwhich are exhibitedin the oral cavity. In fact,the oral site in many instances could act as the forerunner of itsmanifestations before the expression of systemic signs and symptoms. The symptoms of haematological disorders are sovaried and nonspecific but often represent the initial sign of an underlying disease. Anaemic disorders are associated with orofacial signs and symptoms including iron deficiency anaemia (IDA), Plummer–Vinson syndrome (PVS), megaloblastic anaemia, sickle cell anaemia, thalassaemia and aplastic anaemia. The manifestations include conjunctiva and facial pallor, atrophic glossitis, angular stomatitis, dysphagia, magenta tongue, midfacial overgrowth, osteosclerosis, osteomyelitis and paraesthesia/anesthesia of the mental nerve. Orofacialpetechiae, conjunctival haemorrhage, nose-bleeding, spontaneous and post-traumatic gingival haemorrhage and prolonged post-extraction bleeding are common orofacialmanifestations.These manifestations must beproperly recognized to detect the abnormality in the early stages.This paper was aimed to review the literature and identify orofacial manifestations of haematological diseases, with particular reference to anaemia’s. Keywords: anaemia, haematological disorders, glossitis, oral manifestations, pallor mucosa Cite this ArticleShoborose Tantray, Seema Sharma. Oral Manifestations of Haematological Disorders(RBC Disorders).Research & Reviews: Journal of Oncology and Hematology. 2020; 9(1): 1–5p.
Philip Schaffalitzky De Muckadell,
Published: 6 April 2020
Drug Safety, Volume 43, pp 503-505; https://doi.org/10.1007/s40264-020-00929-0

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Nathell L, Gohlke A, Wohlfeil S. Reported severe hypersensitivity reactions after intravenous iron administration in the European Economic Area (EEA) before and after implementation of risk minimization measures. Drug Saf. 2019. https://doi.org/10.1007/s40264-019-00868-5. Ehlken B, Nathell L, Gohlke A, Bocuk D, Toussi M, Wohlfeil S. Evaluation of the reported rates of severe hypersensitivity reactions associated with ferric carboxymaltose and iron (III) isomaltoside 1000 in Europe based on data from EudraVigilance and VigiBase™ between 2014 and 2017. Drug Saf. 2019;42(3):463–71. Bhandari S, Thomsen LL. A single 1000 mg infusion of iron isomaltoside 1000 demonstrates a more rapid hemoglobin response and reduced risk of cardio-vascular adverse events compared to multiple doses of IV iron sucrose in the FERWON trials [Abstract SP342]. Nephrol Dial Transplant. 2019;34(Suppl 1):i475–i486. Derman R, Roman E, Modiano MR, Achebe MM, Thomsen LL, Auerbach M. A randomized trial of iron isomaltoside versus iron sucrose in patients with iron deficiency anemia. Am J Hematol. 2017;92(3):286–91. Bhandari S, Kalra PA, Kothari J, Ambühl PM, Christensen JH, Essaian AM, et al. A randomized, open-label trial of iron isomaltoside 1000 (Monofer®) compared with iron sucrose (Venofer®) as maintenance therapy in haemodialysis patients. Nephrol Dial Transplant. 2015;30(9):1577–89. Kalra PA, Bhandari S. Safety of intravenous iron use in chronic kidney disease. Curr Opin Nephrol Hypertens. 2016;25(6):529–35. Avni T, Bieber A, Grossman A, et al. The safety of intravenous iron preparations: systematic review and meta-analysis. Mayo Clin Proc. 2015;90(1):12–23. European Medicines Agency. Rapid response to BMJ. Re: Pandemrix vaccine: why was the public not told of early warning signs? (EMA/659264/2018). 26 September 2018. Available at: https://www.ema.europa.eu/documents/other/european-medicines-agency-rapid-response-british-medical-journal-pandemrix_.pdf. Accessed 18 Jan 2019. Wolf M, Rubin J, Achebe M, Econs MJ, Peacock M, Imel EA, et al. Effects of iron isomaltoside vs ferric carboxymaltose on hypophosphatemia in iron deficiency anemia: two randomized clinical trials. JAMA. 2020;323(5):432–43. Auerbach M, Henry D, Derman RJ, et al. A prospective, multi-center, randomized comparison of iron isomaltoside 1000 versus iron sucrose in patients with iron deficiency anemia; the FERWON-IDA trial. Am J Hematol. 2019;94(9):1007–14. Bhandari S, Kalra PA, Berkowitz M, et al. Safety and efficacy of iron isomaltoside 1000/ferric derisomaltose versus iron sucrose in patients with chronic kidney disease: the FERWON-NEPHRO randomized, open-label, comparative trial. Nephrol Dial Transplant. 2020. https://doi.org/10.1093/ndt/gfaa011. Pollock RF, Biggar P. Indirect methods of comparison of the safety of ferric derisomaltose, iron sucrose and ferric carboxymaltose in the treatment of iron deficiency anemia. Expert Rev Hematol. 2020;13(2):187–95. Monofer® (iron isomaltoside). Summary of product characteristics. Pharmacosmos UK Ltd. 9 July 2019. Ferinject® (ferric carboxymaltose). Summary of product characteristics. Vifor Pharma UK Ltd. 12 December 2018. Venofer® (iron sucrose). Summary of product characteristics. Vifor Pharma UK Ltd. 8 May 2019. CosmoFer® (iron dextran). Summary of product characteristics. Pharmacosmos UK Ltd. 23 January 2019. Rampton D, Folkersen J, Fishbane S, Hedenus M, Howaldt S, Locatelli F, et al. Hypersensitivity reactions to intravenous iron: guidance for risk minimization and management. Haematologica. 2014;99(11):1671–6. Macdougall IC, Bircher AJ, Eckardt KU, Obrador GT, Pollock CA, Stenvinkel P, Conference Participants, et al. Iron management in chronic kidney disease: conclusions from a “Kidney Disease: improving Global Outcomes” (KDIGO) Controversies Conference. Kidney Int. 2016;89(1):28–39. Lim W, Afif W, Knowles S, Lim G, Lin Y, Mothersill C, et al. Canadian expert consensus: management of hypersensitivity reactions to intravenous iron in adults. Vox Sang. 2019;114(4):363–73. Gómez-Ramírez S, Shander A, Spahn DR, Auerbach M, Liumbruno GM, Vaglio S, Muñoz M. Prevention and management of acute reactions to intravenous iron in surgical patients. Blood Transfus. 2019;17(2):137–45. Injectafer® (ferric carboxymaltose injection). Prescribing information. February 2020. Available at: https://injectafer.com/prescribing-information-portlet/getDocument?product=IF&inline=true. Accessed 25 Feb 2020. Onken JE, Bregman DB, Harrington RA, Morris D, Acs P, Akright B, et al. A multicenter, randomized, active-controlled study to investigate the efficacy and safety of intravenous ferric carboxymaltose in patients with iron deficiency anemia. Transfusion. 2014;54(2):306–15. Onken JE, Bregman DB, Harrington RA, Morris D, Buerkert J, Hamerski D, et al. Ferric carboxymaltose in patients with iron-deficiency anemia and impaired renal function: the REPAIR-IDA trial. Nephrol Dial Transplant. 2014;29(4):833–42. Download references Correspondence to Claes Christian Strom. This letter was funded by Pharmacosmos A/S. Philip Schaffalitzky de Muckadell and Claes Christian Strom are employees of Pharmacosmos A/S. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. 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, , Saskia Le Cessie, Carsten Oliver Schmidt,
BMC Medical Research Methodology, Volume 20, pp 1-10; https://doi.org/10.1186/s12874-020-00942-y

Abstract:
Background In the data pipeline from the data collection process to the planned statistical analyses, initial data analysis (IDA) typically takes place between the end of the data collection and do not touch the research questions. A systematic process for IDA and clear reporting of the findings would help to understand the potential shortcomings of a dataset, such as missing values, or subgroups with small sample sizes, or shortcomings in the collection process, and to evaluate the impact of these shortcomings on the research results. A clear reporting of findings is also relevant when making datasets available to other researchers. Initial data analyses can provide valuable insights into the suitability of a data set for a future research study. Our aim was to describe the practice of reporting of initial data analyses in observational studies in five highly ranked medical journals with focus on data cleaning, screening, and reporting of findings which led to a potential change in the analysis plan. Methods This review was carried out using systematic search strategies with eligibility criteria for articles to be reviewed. A total of 25 papers about observational studies were selected from five medical journals published in 2018. Each paper was reviewed by two reviewers and IDA statements were further discussed by all authors. The consensus was reported. Results IDA statements were reported in the methods, results, discussion, and supplement of papers. Ten out of 25 papers (40%) included a statement about data cleaning. Data screening statements were included in all articles, and 18 (72%) indicated the methods used to describe them. Item missingness was reported in 11 papers (44%), unit missingness in 15 papers (60%). Eleven papers (44%) mentioned some changes in the analysis plan. Reported changes referred to missing data treatment, unexpected values, population heterogeneity and aspects related to variable distributions or data properties. Conclusion Reporting of initial data analyses were sparse, and statements on IDA were located throughout the research articles. There is a lack of systematic reporting of IDA. We conclude the article with recommendations on how to overcome shortcomings in the practice of IDA reporting in observational studies.
, Werner Vach, Saskia Le Cessie, Carsten Oliver Schmidt, Lara Lusa
Published: 17 February 2020
Abstract:
Background In the data pipeline from the data collection process to the planned statistical analyses, initial data analysis (IDA) typically takes place between the end of the data collection and do not touch the research questions. A systematic process for IDA and clear reporting of the findings would help to understand the potential shortcomings of a dataset, such as missing values, or subgroups with small sample sizes, or shortcomings in the collection process, and to evaluate the impact of these shortcomings on the research results. A clear reporting of findings is also relevant when making datasets available to other researchers. Initial data analyses can provide valuable insights into the suitability of a data set for a future research study. Our aim was to describe the current practice of reporting of initial data analyses in observational studies in five highly ranked medical journals with focus on data cleaning, screening, and reporting of findings which led to a potential change in the analysis plan. Methods This review was carried out using systematic search strategies with eligibility criteria for articles to be reviewed. A total of 25 papers about observational studies were selected from five medical journals. Each paper was reviewed by two reviewers and IDA statements were further discussed by all authors. The consensus was reported. Results IDA statements were reported in the methods, results, discussion, and supplement of papers. Ten out of 25 papers (40%) included a statement about data cleaning. Data screening statements were included in all articles, and 18 (72%) indicated the methods used to describe them. Item missingness was reported in 11 papers (44%), unit missingness in 15 papers (60%). Eleven papers (44%) mentioned some changes in the analysis plan. Reported changes referred to missing data treatment, unexpected values, population heterogeneity and aspects related to variable distributions or data properties. Conclusion Reporting of initial data analyses were sparse, and statements on IDA were located throughout the research articles. There is a lack of systematic reporting of IDA. We conclude the article with recommendations on how to overcome shortcomings in the current practice of IDA reporting in observational studies.
, Werner Vach, Saskia Le Cessie, Carsten Oliver Schmidt, Lara Lusa
Published: 30 January 2020
Abstract:
Background In the data pipeline from the data collection process to the planned statistical analyses, initial data analysis (IDA) typically takes place between the end of the data collection and do not touch the research questions. A systematic process for IDA and clear reporting of the findings would help to understand the potential shortcomings of a dataset, such as missing values, or subgroups with small sample sizes, or shortcomings in the collection process, and to evaluate the impact of these shortcomings on the research results. A clear reporting of findings is also relevant when making datasets available to other researchers. Initial data analyses can provide valuable insights into the suitability of a data set for a future research study. Our aim was to describe the current practice of reporting of initial data analyses in observational studies in five highly ranked medical journals with focus on data cleaning, screening, and reporting of findings which led to a potential change in the analysis plan. Methods This review was carried out using systematic search strategies with eligibility criteria for articles to be reviewed. A total of 25 papers about observational studies were selected from five medical journals. Each paper was reviewed by two reviewers and IDA statements were further discussed by all authors. The consensus was reported. Results IDA statements were reported in the methods, results, discussion, and supplement of papers. Ten out of 25 papers (40%) included a statement about data cleaning. Data screening statements were included in all articles, and 18 (72%) indicated the methods used to describe them. Item missingness was reported in 11 papers (44%), unit missingness in 15 papers (60%). Eleven papers (44%) mentioned some changes in the analysis plan. Reported changes referred to missing data treatment, unexpected values, population heterogeneity and aspects related to variable distributions or data properties. Conclusion Reporting of initial data analyses were sparse, and statements on IDA were located throughout the research articles. There is a lack of systematic reporting of IDA. We conclude the article with recommendations on how to overcome shortcomings in the current practice of IDA reporting in observational studies.
Francis Wade, Florence-Damilola Odufalu, Gretchen Grosch, Melissa Chambers, Katie Schroeder
Inflammatory Bowel Diseases, Volume 26; https://doi.org/10.1093/ibd/zaa010.138

Abstract:
Introduction Iron deficiency Anemia (IDA) is a common complication of inflammatory bowel disease (IBD). High prevalence of IDA in IBD suggests suboptimal surveillance and treatment. Oral iron is poorly tolerated, associated with worsened disease activity, and often insufficient to reverse anemia in IBD patients. Intravenous (IV) iron is favored for treatment of IDA in IBD in most clinical scenarios and many guidelines recommend IV iron as first line for IBD patients. Regardless, oral iron is prescribed commonly for IDA in IBD. The objective of this study is to determine practice patterns of primary care physicians (PCP) and gastroenterologists (GI) in the management of IDA in IBD. Methods We anonymously surveyed GI and PCP attendings and trainees at Saint Louis University School of Medicine in St. Louis, Missouri, using paper self-administered instruments. We asked about practice patterns in the management of IDA in IBD patients and knowledge of IV iron. The study questionnaire was developed based on United States expert opinion consensus statements and European guideline recommendations published in the Journal of Crohn’s and Colitis and Inflammatory Bowel Diseases. Results Of GI responders, 92.3% were fellows, 7.7% were attendings; of PCP responders, 81.8% were residents, 18.2% were attendings. 15.4% GIs, 12.7% PCPs were very comfortable managing IBD patients with IDA; 76.9% GIs, 58.2% PCPs were somewhat comfortable; 7.7% GIs, 29.1% PCPs were not comfortable (p=0.275). 61.5% GIs, 25.5% PCPs always check iron studies when evaluating anemic IBD patients; 30.1% GIs, 21.8% PCPs check most of the time; 7.7% GIs, 34.5% PCPs sometimes check; 0% GIs, 12.7% PCPs rarely check; 0% GIs, 5.4% PCPs never check (p =0.05). In mild Crohn’s disease with severe anemia, 15.4% GIs, 41.8% PCPs would prescribe oral iron daily; 15.4% GIs, 12.7% PCPs would prescribe oral iron every other day; 69.2% GIs, 45.5% PCPs would prescribe IV iron (p=0.58). 0% GIs reported good knowledge of IV iron, 53.8% reported acceptable knowledge, and 46.1% reported poor knowledge. 7.7% GIs, 10.9% PCPs reported good knowledge of how to order IV iron; 53.8% GIs, 7.3% PCPs reported acceptable knowledge; 38.5% GIs, 81.8% PCPs reported poor knowledge (p=0.000215). 23.1% GIs, 61.8% PCPs thought PCPs were responsible for screening for IDA in IBD patients; 76.9% GIs, 36.4% PCPs thought GIs were responsible (p= 0.0131). Discussion Both PCPs and GIs perceived responsibility to manage IDA in IBD patients. PCPs were less likely than GIs to screen for IDA in anemic IBD patients or to report adequate knowledge of clinic processes to order IV iron. Future efforts to reinforce gastroenterologists’ role in the management of IDA in IBD and to bolster familiarity with IV iron and its indications might improve outcomes and quality of life for IBD patients.
I Putu Gede Parmajaya
Published: 14 January 2020
Kamaya: Jurnal Ilmu Agama, Volume 3, pp 59-76; https://doi.org/10.37329/kamaya.v3i1.377

Abstract:
Art in the Hindu perspective in Bali have a very basic position, because it can not be separated from the Hindu community relegius. Ceremony in pretending (holy place) also can not be separated off from the arts such as singing, dancing, musical, painting, art, and literature. Temples, temples and the others are built in such a way as an expression of aesthetics, ethics, and attitudes of the people relegius Hindus in Bali. Pragina or dancers in a spirit of selfless ngayah or work offered various forms of art as a form of devotion presented to Ida Sang Hyang Widhi Wasa (God Almighty). In it there is a sense of devotion and dedication as a form of longing wanted to meet with the source of art itself and the artist wanted to be one with it because the real art of every human being in this world is the spark of art.. The research method used in this research is the Study of Literature. Literature study is research conducted by collecting information from various sources such as books, theses, theses, journals and others to answer and describe the problem formulation in a study. The purpose of this study is to study the Sacred and Secular Arts in Problems in Religious Social Life: The Perspective of Yadnya Hindus in Bali.
Yu.E Dobrokhotova, E.A. Markova
Russian Journal of Woman and Child Health, Volume 3; https://doi.org/10.32364/2618-8430-2020-3-2-88-94

Abstract:
Iron-deficiency anemia (IDA) is an important issue. The prevalence of IDA in women of reproductive age and women in perimenopause is high and has no tendency to reduce. Pharmacoeconomic aspects and recent data on clinical efficacy of iron supplements for obstetrical gy-necological disorders are addressed. The authors review international and domestic published data on iron supplements prescribed in women with obstetrical gynecological diseases. The paper describes the results of cost-effectiveness analysis and clinical trials published earlier that compare the efficacy of the treatment with iron supplements in women who experienced IDA or gynecological disorders complicated by iron deficiency during the pregnancy. One of the bivalent iron retard preparations, Tardyferon®, is discussed. In addition, Tardyferon® is compared with similar iron supplements and Fe(III)-hydroxide-polymaltose complex. Pharmacoeconomic utility of bivalent iron preparation from the viewpoint of the patient and the doctor is validated.Keywords: pharmacoeconomic analysis, iron deficiency, iron-deficiency anemia, pregnancy, iron supplements, bivalent iron.For citation: Dobrokhotova Yu.E., Markova E.A. Peroral retard iron preparation for iron-deficiency anemia: case study and pharmacoecono-mic analysis. Russian Journal of Woman and Child Health. 2020;3(2):88–94. DOI: 10.32364/2618-8430-2020-3-2-88-94.
, A.V. Ledina, S.I. Rogovskaya, Moscow Region Lapino Clinical Hospital “Mother & Child”
Russian Journal of Woman and Child Health, Volume 3; https://doi.org/10.32364/2618-8430-2020-3-4-248-253

Abstract:
Iron-deficiency anemia (IDA) is an acquired disease characterized by the reduced levels of iron in the serum, tissues, and bone marrow that mainly result from hemorrhages (e.g., nasal, gastrointestinal etc.). Women are at risk for IDA due to the physiological monthly loss of blood, childbearing, and breastfeeding but also due to various gynecological disorders leading to iron depletion and anemia. The paper describes the pathogenic mechanisms, diagnostic criteria, and clinical presentations of IDA and the potential consequences of iron overload. Considering a high medical and social importance of anemia in pregnancy, the data on IDA prevalence in this cohort as well as the potential complications both for the mother and the child are addressed. Current therapeutic approaches for anemia using peroral and parenteral iron preparations and their indications are highlighted. The prevention of iron deficiency and the effective options of its correction are viable tasks which allow for improving the health and quality of women’s life. KEYWORDS: anemia, iron-deficiency anemia, diagnosis, pregnancy, latent iron deficiency, iron overload, treatment, iron (II) fumarate. FOR CITATION: Lukina E.A., Ledina A.V., Rogovskaya S.I. Iron-deficiency anemia: a view of hematologist and gynecologist. Optimizing diagnostic and treatment approach. Russian Journal of Woman and Child Health. 2020;3(4):248–253. DOI: 10.32364/2618-8430-2020-3-4-248-253.
М.S. Selikhova, P.A. Soltys, L.S. Kalacheva
Russian Journal of Woman and Child Health, Volume 3; https://doi.org/10.32364/2618-8430-2020-3-4-276-281

Abstract:
The prevalence of iron-deficiency anemia (IDA) is steadily increasing. IDA is more common in women of reproductive age, pregnant women, and adolescent girls thus accounting for the importance of this issue in obstetrics and gynecology. Abnormal uterine bleeding (AUB) is one of the most common causes of IDA both in the puberty and reproductive period which requires hemostasis as well as addressing iron deficiency. A high rate of IDA was also reported in women with pelvic inflammatory diseases; this should considered when managing this large group of gynecological patients. The treatment for anemia or latent iron deficiency is performed for a long time, therefore, the selection of a medication is particularly important. Peroral Tardyferon® containing 80 mg of iron meets all modern-day requirements for anti-anemic drugs and is recommended for anemia resulting from AUB both in women of reproductive age and adolescent girls. Case studies illustrate high efficacy and good tolerability of this medication. KEYWORDS: iron-deficiency anemia, pregnancy, abnormal uterine bleeding in puberty, heavy menstrual bleeding, genital inflammation, high efficacy, compliance. FOR CITATION: Selikhova М.S., Soltys P.A., Kalacheva L.S. Prevention and treatment for iron-deficiency anemia in obstetrical gynecological practice. Russian Journal of Woman and Child Health. 2020;3(4):276–281. DOI: 10.32364/2618-8430-2020-3-4-276-281.
, Werner Vach, Saskia Le Cessie, Carsten Oliver Schmidt, Lara Lusa
Published: 16 December 2019
Abstract:
Background: In the data pipeline from the data collection process to the planned statistical analyses, initial data analysis (IDA) typically takes place between the end of the data collection and do not touch the research questions. A systematic process for IDA and clear reporting of the findings would help to understand the potential shortcomings of a dataset, such as missing values, or subgroups with small sample sizes, or shortcomings in the collection process, and to evaluate the impact of these shortcomings on the research results. A clear reporting of findings is also relevant when making datasets available to other researchers. Initial data analyses can provide valuable insights into the suitability of a data set for a future research study. Our aim was to describe the current practice of reporting of initial data analyses in observational studies in five highly ranked medical journals with focus on data cleaning, screening, and reporting of findings which led to a potential change in the analysis plan.Methods: This review was carried out using systematic search strategies with eligibility criteria for articles to be reviewed. A total of 25 papers about observational studies were selected from five medical journals. Each paper was reviewed by two reviewers and IDA statements were further discussed by all authors. The consensus was reported.Results: IDA statements were reported in the methods, results, discussion, and supplement of papers. Ten out of 25 papers (40%) included a statement about data cleaning. Data screening statements were included in all articles, and 18 (72%) indicated the methods used to describe them. Item missingness was reported in 11 papers (44%), unit missingness in 15 papers (60%). Eleven papers (44%) mentioned some changes in the analysis plan. Reported changes referred to missing data treatment, unexpected values, population heterogeneity and aspects related to variable distributions or data properties. Conclusion: Reporting of initial data analyses were sparse, and statements on IDA were located throughout the research articles. There is a lack of systematic reporting of IDA. We conclude the article with recommendations on how to overcome shortcomings in the current practice of IDA reporting in observational studies.
Retraction
International Journal of Endocrinology, Volume 2019, pp 1-1; https://doi.org/10.1155/2019/4390934

Abstract:
International Journal of Endocrinology has retracted the article titled “Sexual Dysfunction in Women with Diabetic Kidney” [1]. The article was found to contain a substantial amount of material from previously published articles, including the following sources: (i) Santoro D., Satta E., Bellinghieri G., (2014), Sexual Dysfunction in Chronic Kidney Disease, Arici M. (eds), In: Management of Chronic Kidney Disease, Springer, Berlin, Heidelberg, https://doi.org/10.1007/978-3-642-54637-2_24, [2] (not cited). (ii) Esposito, Katherine, Maria Ida Maiorino, and Giuseppe Bellastella, “Diabetes and sexual dysfunction: current perspectives,” Diabetes Metabolic Syndrome and Obesity Targets and Therapy, 2014, https://doi.org/10.2147/DMSO.S36455, [3] (not cited). (iii) Priya Anantharaman, Rebecca J. Schmidt, “Sexual Function in Chronic Kidney Disease,” Advances in Chronic Kidney Disease, 2007, https://doi.org/10.1053/j.ackd.2007.01.002, [4] (not cited). (iv) F. O. Finkelstein, S. Shirani, D. Wuerth, and S. H. Finkelstein, “Therapy Insight: sexual dysfunction in patients with chronic kidney disease,” Nature Clinical Practice Nephrology, vol. 3, no. 4, pp. 200–207, 2007, https://dx.doi.org/10.1038/ncpneph0438, [5] (cited as reference 6). (v) R. Basson, J. Berman, A. Burnett, et al., “Report of the international consensus development conference on female sexual dysfunction: definitions and classifications,” Journal of Urology, vol. 163, no. 3, pp. 888–893, 2000, https://dx.doi.org/10.1097/00005392-200003000-00043, [6] (cited as reference 7).
, Belcaro Giovanni
Journal of Cancer Research and Therapeutic Oncology, Volume 1; https://doi.org/10.17303/jcrto.2019.7.204

Abstract:
Treatment of Metastatic Sweat Gland Carcinomas: Response in Two Cases Journal of Cancer Research and Therapeutic Oncology aims at rapid publication of high quality results in cancer research which are open access.
Alfin Syahrian, Ricky Irawan, Agustinus Sani Aryanto
Journal of Music Science, Technology, and Industry, Volume 2, pp 199-218; https://doi.org/10.31091/jomsti.v2i2.867

Abstract:
The Balinese song Ida Sang Sujati (2016) performed by Bali Kumara singers was inspired by a moment when its composer I Komang Darmayuda was appointed as a music judge at Pesta Kesenian Bali (PKB) which located at Ardha Candra Open Stage. He was stunned by the idea of ​​the parade and the venue for the event which was being made for the governor of Bali Prof. Ida Bagus Mantra who served in 1978-1988. The problems of this research are (1) the musical form of the Balinese song Ida Sang Sujati by I Komang Darmayuda, (2) the process of making the Balinese song Ida Sang Sujati by I Komang Darmayuda, (3) the musical meaning contained in the Balinese song Ida Sang Sujati by I Komang Darmayuda. The method that being used for this research is qualitative, with data collection techniques through interviews, observation, documentation. The theory used to explore the problem is the theory of song form and structure analysis and the theory of meaning. Primary data sources were obtained from interviews and observations. Secondary data were obtained from books, journals, and internet sources
Elder Pereira Ribeiro
AntHropológicas Visual, Volume 5; https://doi.org/10.51359/2526-3781.2019.242105

Abstract:
SINOPSE: Esse ensaio fotográfico traduz as minhas viagens etnográficas entre a cidade de Cachoeira e São Félix, no Recôncavo da Bahia. O que falar de Cachoeira e São Félix? Penso que são cidades históricas e culturais que me desperta o desejo pela riqueza bioancestrálica.A pesquisa etnográfica nos permite encontros, afetos, múltiplos conhecimentos, descobrimentos, e assim como já afirmou o antropólogo Marcio Goldman (2003), que defende a ideia de “catar folha”, obtendo resultados satisfatórios pouco a pouco, indo ali, indo cá, andando, e buscando as informações em campo. A partir daí entendo que todas as idas e vindas de viagens fez com que eu pudesse me reencontrar com a ancestralidade.Ao chegar em Cachoeira x São Félix conheci diversas pessoas que me acolheu de coração, como Ekedji Romilda de Sogbó da Roça do Ventura em Cachoeira, Babá Idelson de Ogum Megege do Terreiro Ogunjá em São Félix, Iyá Regina de Avimaje do Terreiro Huntologi, Professora Francisca Marques do (LEAA-Recôncavo), Udinaldo Neto e Letícia Catete do (PPGCS-UFRB) amigos ímpares, dentre outros. As fotos do ensaio em questão registra o meu percurso diário, festivo e turístico nas cidades já mencionadas acima.A diversidade religiosa dos terreiros é imensurável na cidade de Cachoeira x São Félix, porque pude conhecer Terreiros de Nação: Nagô, Nagô-Vodum, Ketu, Jeje Mahin e Angola. Participei da Lavagem de Cachoeira, em 2019, da Festa de Ogum, Oxum e Caboclos no Ogunjá em São Félix, em 2019, o Centenário do Terreiro Raíz de Ayrá, em 2019, e tantos outros espaços religiosos e não religiosos.Referência BibliográficaGOLDMAN, Marcio. 2003. “Os Tambores dos Mortos e os Tambores dos Vivos”. Etnografia, Antropologia e Política em Ilhéus, Bahia”. Revista de Antropológia, vol. 46, n. 2, São Paulo, USP. SINOPSIS:This photo essay reflects my ethnographic travels between the city of Cachoeira and São Félix, in the Recôncavo da Bahia. What about Cachoeira e São Félix? I think they are historical and cultural cities that arouse my desire for bio-estral richness.Ethnographic research allows us to find encounters, affections, multiple knowledge, discoveries, and as stated by anthropologist Marcio Goldman (2003), who defends the idea of “picking leaves”, getting satisfactory results little by little, going there, going here, walking, and seeking information in the field. From then on I understand that all the comings and goings of travels allowed me to rediscover my ancestry.Arriving in Cachoeira x São Félix I met several people who welcomed me from the heart, such as Ekedji Romilda from Sogbo da Roça do Ventura in Cachoeira, Babysitter Idelson from Ogum Megege from Terreiro Ogunjá in São Félix, Iyá Regina from Terreiro Huntologi Avimaje, Professor Francisca Marques do (LEAA-Recôncavo), Udinaldo Neto and Letícia Catete from (PPGCS-UFRB) odd friends, among others. The photos of the essay in question record my daily, festive and touristic journey in the cities already mentioned above.The religious diversity of the terreiros is immeasurable in the city of Cachoeira x São Félix, because I got to know Terreiros de Nação: Nagô, Nagô-Vodum, Ketu, Jeje Mahin and Angola. I participated in the Waterfall Wash in 2019, the Ogum, Oxum and Caboclos Festival in the Ogunjá in São Félix, in 2019, the Terreiro Raíz de Ayrá Centenary, in 2019, and many other religious and non-religious spaces.Bibliographic referenceGOLDMAN, Marcio. 2003. “The Drums of the Dead and the Drums of the Living”. Ethnography, Anthropology and Politics in Ilhéus, Bahia ”. Journal of Anthropology, vol. 46, no. 2, Sao Paulo, USP. Palavras-chave:Cachoeira; São Félix; Etnografia; Antropologia Visual. Keywords:Waterfall; Sao Felix; Ethnography; Visual anthropology. Ficha técnica:Autor: Elder Pereira RibeiroFotografias: Elder Pereira RibeiroDireção, Edição de Imagem e Texto: Elder Pereira Ribeiro Datasheet:Author: Elder Pereira RibeiroPhotographs: Elder Pereira RibeiroDirection, Image and Text Editing: Elder Pereira Ribeiro
, Arif Senja Fitrani
JICTE (Journal of Information and Computer Technology Education), Volume 3, pp 22-28; https://doi.org/10.21070/jicte.v3i1.953

Abstract:
The purpose of this study is, to find out the features of the wanscry ransomware that have not been run and extract the Windows computer data system from wannacry in the scope of an interconnection network. To find out the behavior of wannacry ransomware after running on a Windows computer system and knowing how to use the ransomware The method used in this research is Surface Analysis, Static Analysis, Runtime Analysis, and Intrusion Detection System. The research was carried out in the umsida informatics laboratory, data collection information about wannacry through journals, ebooks, and the internet. Identification techniques are carried out before ransomware is run on the system Windows operation, and after running. The conclusion of this study is to identify the characteristics of wannacry ransomware outside with software strings, graphics, and to identify in depth with the OllyDbg, IdaPro software, and to identify when the ransomware is run the software used by TcpView, Procmon, ProcessExplore. Determine the exploitation technique of wannacry spread on computer systems. Along with ways to prevent the spread of infections in computer systems and networks using microtics
Caroline Bressey
Women, Periodicals and Print Culture in Britain, 1830s-1900s pp 528-541; https://doi.org/10.3366/edinburgh/9781474433907.003.0034

Abstract:
Caroline Bressey’s essay explores how ‘racial prejudice excluded black women from new spaces of expression created by white women’ in the British press (p. 528). It was not until 1900, with the founding of the Pan-African, that there was a British periodical explicitly dedicated to publishing the contributions of black journalists. Thus, the history of black women’s journalism in Britain prior to the turn of the century is largely unknown. This lack of scholarship makes it necessary to take a ‘transatlantic comparative approach’ when surveying an emerging field of inquiry (p. 528). In the United States, there was more explicit discussion of black women’s contributions to the periodical press, as highlighted in I. Garland Penn’s 1891 book, The Afro-American Press and Its Editors. This volume not only highlighted the unequal, sometimes hostile environment in which black journalists worked but also provided a key for discovering the names and achievements of a wide range of women writers, including Victoria Earle and Ida B. Wells. These writers spoke out on key political issues, including racism and sexism, contributing to journals as diverse as Our Women and Children (1888–90) and the more radical Free Speech (1892).
, Sandeep Shrestha, Santosh Pathak
Journal of Nepal Paediatric Society, Volume 39, pp 63-64; https://doi.org/10.3126/jnps.v39i1.22444

Abstract:
Dear editor, We read with interest the article “Prevalence of Anaemia in Children Diagnosed with Pneumonia in a Tertiary Hospital in Quito, Ecuador” in the recent issue of your esteemed journal and found it very useful and informative1. This article presents the prevalence of anemia in children with pneumonia. However, there are certain points we would like to comment and highlight which might bring more clarity to this issue and will be useful to the readers of JNPS. In the abstract (conclusion section), the authors have mentioned that “anaemia or nutritional deficiencies could be a risk factor for respiratory diseases”. The authors seem to draw a conclusion on “nutritional deficiencies” as a risk factor for respiratory disease without any evidence or data provided in the results. We feel that it should better be omitted from the conclusion. The authors have mentioned that they used physical findings such as: fever, tachypnea, breathing difficulties, rhonchi, crackles, and wheezing to diagnose pneumonia and them again have mentioned using WHO tachypnea threshold to diagnose pneumonia. It is very unlikely for all the 80 cases to have all the above listed physical findings. Diagnosis of pneumonia in children remains an important yet difficult clinical problem. WHO criteria which uses the presence of cough, fast breathing and chest indrawing to diagnose pneumonia may over-estimate the diagnosis of actual pneumonia2. Chest radiograph remains a diagnostic test of choice in hospitals3. The readers would be keen to know which diagnostic criteria the authors had used to diagnose pneumonia (either clinical or radiological?). If they had used the clinical criteria, what were the exact parameters used to diagnose pneumonia needs further clarification. The authors also need to reply the reason of not including cough and retractions in the inclusion criteria to diagnose pneumonia. The readers would also be keen to know that if any attempt was made to exclude pneumonia like illnesses e.g., bronchiolitis, asthma or cardiac diseases which can mimic pneumonia. The authors have mentioned that diagnosis of concomitant conditions that could affect anthropometric or haemoglobin parameters, or that could predispose to pneumonia were excluded. The readers would be interested to know (a) what anthropometric parameters or hemoglobin parameters were excluded and (b) what factors predisposing to pneumonia were excluded which is missing in the material and methods. The authors have concluded that anaemia is a frequent condition in paediatric pneumonia and could be a risk factor for respiratory diseases. The study done by the authors was a cross-sectional study which has always a chance of selection bias4. The increased prevalence of anemia in pneumonia patients could have been due to chance, we do not know. Therefore, it is very difficult to answer (in a cross-sectional study) either anemia is prevalent in children with pneumonia or not unless we have some cohort studies on the same. This should have been mentioned as one of the limitations of the study. The readers would be interested to know regarding any iron supplements in children aged more than 3 years which might be the cause of decrease prevalence of anemia in this age group. In the discussion section, the authors have tried to convince that anemia in the study groups was most likely due to iron deficiency. They have used hemoglobin, MCV and RDW to support the diagnosis of iron deficiency anemia. The sensitivity and specificity of MCV to diagnose IDA is 61.7% and 59.1% respectively with a positive predictive value of 70% 5 whereas using RDW as a criteria to diagnose IDA has a sensitivity of 81% and specificity of 53.4%6. In the discussion, the authors have emphasized iron deficiency as the cause of anemia in the cases. The authors need to explain that how can they be sure that all the cases of anemia in their study was due to iron deficiency without undergoing iron profile (serum ferritin, % saturation, TIBC). It is well known that with subclinical infection, serum iron concentrations are reduced, altering the synthesis of hemoglobin, the main indicator of anemia7. The readers would be interested to know if any attempts were made to exclude those subclinical infections from the enrolled cases with pneumonia.
Shannon McLaughlin
Published: 1 April 2019
Abstract:
In organisms, behavior can be a reflection of environment and nervous system activity. Previous studies have shown that the DAF-7 signaling pathway in C. elegans is affected by the environment, such as inadequate food supply or high temperature. The DAF-7 signaling pathway also regulates the glutamate receptor GLR-1, and increased amounts of GLR-1 occur in C. elegans strains with mutations in the genes of the DAF-7 signaling pathway. Additionally, spontaneous reversal behavior depends on GLR-1 and increased reversals are evident in the daf-7 mutants. The mechanism by which the DAF-7 pathway affects GLR-1 levels is currently unknown. Our research focuses on understanding this mechanism by investigating the role of the candidate gene ida-1. IDA-1 was identified because of its involvement in regulating presynaptic neurotransmission and its presence in neurons along the ventral nerve cord (VNC) that express GLR-1. To test if IDA-1 was involved in the DAF-7 pathway regulation of GLR-1 an assessment of spontaneous reversals in single and double mutants was performed along with fluorescence imaging. Results supported the idea that IDA-1 plays a role in the DAF-7 pathway regulation of GLR-1. To follow up on IDA-1's potential regulation of GLR-1 levels, the involvement of IDA-1 in neuromodulatory signaling was examined. IDA-1 is normally found on the surface of dense core vesicles (DCV's) and is involved in normal neuropeptide and DCV signaling. To investigate if IDA-1 is working through the DCV pathway to regulate GLR-1 levels several strains will be obtained with mutations in various places in the DCV pathway. Future directions will include analysis of these mutants using fluorescence imaging as well as direct protein level analysis through immunoblotting. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Christine Mehner,
Frontiers in Cell and Developmental Biology, Volume 7; https://doi.org/10.3389/fcell.2019.00010

Abstract:
Serine protease inhibitor Kazal type 1 (SPINK1) is a small secreted protein with dual roles—in the pancreas, it is a protective trypsin inhibitor, while in the context of the tumor microenvironment, it is a cell growth and survival factor that promotes tumor progression. While the mechanism by which SPINK1 protects the pancreas is long established and well-understood, the mechanisms that underlie its tumor promoting properties are complex and multifaceted, with major questions remaining to be answered. In this Opinion article, we briefly overview the known functions and mechanisms of SPINK1 both in health and in disease, and then seek to highlight several of the mechanistic “missing links,” with the aim of identifying research opportunities and stimulating new lines of investigation. SPINK1, also known as pancreatic secretory trypsin inhibitor (PSTI), is a 6.2 kDa secreted serine protease inhibitor that is produced by pancreatic acinar cells. In the pancreas, SPINK1 plays a physiological role as an inhibitor of digestive trypsins (Figure 1A) (Rinderknecht, 1986; Paju and Stenman, 2006). It is co-secreted in zymogen granules with trypsinogen, the trypsin precursor protein, allowing inhibitory intervention in case of early activation of trypsinogen to trypsin, and preventing organ damage of the pancreas or duct system due to autodigestion. The importance of SPINK1 for pancreatic health is demonstrated by the association of SPINK1 gene mutations (N34S, P55S, IVS3 + 2TC, and others) with increased risk for several forms of chronic pancreatitis (Pfützer et al., 2000; Witt et al., 2000; Raphael and Willingham, 2016). Most pathogenic SPINK1 mutations reduce function of the protein by interfering with folding and/or secretion (Kiraly et al., 2007a,b; Kereszturi et al., 2009), while the N34S mutation does not appear intrinsically deleterious, but is associated with another mutation in the 5′ regulatory region of the gene that can diminish mRNA expression (Kereszturi and Sahin-Toth, 2017). On the other hand, homozygous mutations causing complete loss of SPINK1 function were found to be responsible for several cases of severe early-onset exocrine pancreatic insufficiency (Venet et al., 2017). Figure 1. Roles of SPINK1. (A) In the pancreas, SPINK1 acts as an important regulator of protease activity. SPINK1 is co-expressed with trypsinogen by the pancreatic acinar cells and secreted from zymogen granules into the pancreatic duct. Within the acinar cells or the duct, SPINK1 quenches prematurely activated trypsin to prevent further protease activation and organ damage. (B) Tumor cell secreted SPINK1 inhibits unknown serine protease(s) to induce anoikis resistance, tumor cell survival and metastatic disease. (C) Tumor cell secreted SPINK1 activates EGFR kinase pathways and leads to tumor cell proliferation; the direct receptor of SPINK1 in this context requires further definition. (D) Sequence alignment using Clustal Omega comparing human, mouse, and rat EGF with human, mouse, and rat SPINK1 (ISK1) homologs. Identified are sequence identity between hEGF and hSPINK1, sequence identities across all three species, and disulfide bond pattern. Outside of the normal pancreas, aberrant expression of SPINK1 plays a role in cancer. SPINK1 was originally named tumor associated tissue inhibitor (TATI) when it was first isolated from the urine of ovarian cancer patients (Huhtala et al., 1982). Since then SPINK1 has been found to be overexpressed by multiple types of tumor cells, including breast, ovarian, prostate, pancreas, liver, and colon (reviewed Itkonen and Stenman, 2014; Rasanen et al., 2016). More recently, SPINK1 has also been found to be expressed by the tumor stroma after chemotherapy, where it may contribute to chemoresistance and increased risk of recurrence (Chen et al., 2018). SPINK1 tumor cell expression and possible prognostic value have been most studied in prostate cancer, where SPINK1 positive tumors form a subgroup of about 10–15% of prostate cancers (Tomlins et al., 2008; Ateeq et al., 2011, 2015). Prostate tumors that express SPINK1 have been reported to show a significantly more aggressive phenotype and poorer progression-free survival (Tomlins et al., 2008; Leinonen et al., 2010). In other tumor types, multiple studies have explored the potential utility of SPINK1 expression as a biomarker through analysis of tumor tissues, urine, and serum (Halila et al., 1988; Inaudi et al., 1991; de Bruijn et al., 1993; Paju et al., 2007). Tumor tissue staining for SPINK1 has been associated with poorer survival in non-serous ovarian cancers (Mehner et al., 2015) and in estrogen receptor- positive breast cancer (Soon et al., 2011), and there is potential for SPINK1 to serve as a diagnostic marker for hepatocellular carcinoma (Marshall et al., 2013). Studies in experimental model systems have demonstrated significant effects of SPINK1 in promoting tumor cell growth and survival (Rasanen et al., 2016), the mechanisms of which remain to be fully elucidated. Unlike in the normal pancreas, in tumors SPINK1 appears to be expressed independently of trypsin, and little is known about the direct target(s) of SPINK1 in the context of cancer. Normal epithelial cells require contact to other cells or the extracellular matrix to ensure their function and survival; if they detach, intracellular mechanisms drive the apoptosis protocol called anoikis resulting in cell death. Tumor cell metastasis often involves circulation as isolated cells, and thus anoikis resistance is believed to be a common feature of metastatic dissemination (Frisch and Francis, 1994; Simpson et al., 2008; Kim et al., 2012). We have shown that SPINK1 plays an essential role in ovarian cancer cell survival under attachment free conditions (Mehner et al., 2015). Non-adherent cell survival was increased in a dose-dependent manner when treating ovarian cancer cell lines with recombinant SPINK1 protein. Notably, this effect could be mimicked by several alternative trypsin inhibitors, suggesting that anoikis resistance is mediated through the serine protease inhibitory activity of SPINK1 (Mehner et al., 2015). SPINK1 has also been reported to confer apoptotic resistance on tumor cells in the context of chemotherapeutic treatment. Soon et al. found that SPINK1 knockdown activated apoptotic pathways in breast cancer cells, while SPINK1 overexpression induced resistance to apoptosis in cells treated with a variety of cytotoxic chemotherapy agents (Soon et al., 2011). Chemoresistance was not similarly induced by a mutant form of SPINK1 lacking the reactive site lysine residue that is required for trypsin inhibition, again implicating the serine protease inhibitory function of SPINK1 in its antiapoptotic function (Soon et al., 2011). While evidence points to serine protease inhibition as a mechanism by which SPINK1 promotes resistance to both anoikis (Mehner et al., 2015) and chemically induced apoptosis (Soon et al., 2011) (Figure 1B), the specific serine protease target(s) of SPINK1 through which these effects are mediated are not known. The relevant apoptosis-promoting protease is unlikely to be trypsin-1 or-2, the natural physiological targets of SPINK1 in the pancreas (Rinderknecht, 1986), because although these enzymes are expressed by many tumors, they possess pro-tumorigenic activities and are predominantly associated with increased malignancy and poorer patient outcomes (Koivunen et al., 1990; Ohta et al., 1994; Yamamoto et al., 2003; Yamashita et al., 2003; Paju et al., 2004; Nyberg et al., 2006; Soreide et al., 2006). By contrast, the relevant target of SPINK1 antiapoptotic activity is expected to possess predominantly antitumor activity and to correlate with better prognosis. Besides trypsins, the human proteome includes around 80 other serine proteases with trypsin-like specificity, representing possible alternative targets for SPINK1 through which apoptosis may be regulated. Efforts to identify the SPINK1 target(s) and signaling pathways of interest could lead to identification of new biomarkers and novel points of intervention to reduce tumor cell survival and prevent spread of metastatic disease. A second important mechanism by which SPINK1 influences tumor progression is its ability to stimulate tumor cell proliferation (Rasanen et al., 2016). Here, evidence suggests that SPINK1 activates epidermal growth factor receptor (EGFR) signaling pathways (Ogawa et al., 1985; Ozaki et al., 2009; Ateeq et al., 2011; Wang et al., 2014; Mehner et al., 2015; Chen et al., 2018). In our own work we find phosphorylation of the intracellular domain of EGFR as well as phosphorylation of AKT and ERK upon treatment of ovarian cancer cells with SPINK1, consistent with activation of EGFR downstream pathways (Mehner et al., 2015). Furthermore, treatment of ovarian cancer cells with erlotinib, a selective inhibitor of the EGFR kinase domain, completely blocked the proliferative response of the cells to SPINK1, demonstrating that EGFR signaling is required for SPINK1-stimulated proliferation (Mehner et al., 2015). Others have seen similar downstream signaling of SPINK1 through EGFR in pancreatic (Ozaki et al., 2009; Wang et al., 2014), prostate (Ateeq et al., 2011), and colorectal cancers (Chen et al., 2015) (Figure 1C). SPINK1-treated pancreatic cancer cells showed increased phosphorylation of EGFR as well as activation of MAPK and STAT3; this response was attenuated in cells treated with the EGFR inhibitor AG1478 (Ozaki et al., 2009). Ateeq et al. showed in prostate cancer cells that SPINK1 knockdown reduced proliferation, which could be restored by recombinant SPINK1 protein; silencing of EGFR resulted in a significant reduction in the pro-proliferative effects of SPINK1 on the cells (Ateeq et al., 2011). Despite the strong evidence that EGFR signaling is stimulated downstream of SPINK1, the details of how SPINK1 elicits this response remain in question. Early work by Hunt et al. (1974) identified possible sequence homology between SPINK1 and epidermal growth factor (EGF), the preferred ligand of EGFR. The possibility of functional overlap between these proteins was further suggested by studies showing that a rat SPINK1 homolog, monitor peptide, can stimulate growth of murine 3T3 fibroblasts (Fukuoka et al., 1986), and can compete with mouse EGF for binding to EGFR on the surface of these cells (Fukuoka et al., 1987). Ateeq et al. later hypothesized that human cancer cell-secreted SPINK1 may bind directly to EGFR as an alternative ligand to stimulate proliferation (Ateeq et al., 2011). Consistent with this possibility, exogenous SPINK1-GST was co-immunoprecipitated with EGFR from cell lysates (Ateeq et al., 2011), and immobilized SPINK1 showed evidence of binding to the EGFR ectodomain in a quartz-crystal microbalance assay (Ozaki et al., 2009). However, the original premise of homology between SPINK1 and EGF was based on very limited similarity between short partial sequences (Hunt et al., 1974; Scheving, 1983); only 10/56 amino acids of hSPINK1 are identical with hEGF, five of which are not conserved across species (Figure 1D). Furthermore, while SPINK1 and EGF each contain six cysteines comprising three disulfide bonds, comparison of their structures reveals entirely dissimilar protein folds (Bolognesi et al., 1982; Ogiso et al., 2002; Ferguson et al., 2003) (Figure 1C) and disulfide bonding patterns (Figure 1D). The few identical residues do not occur in similar structural contexts in the two protein families, nor do they present comparable potential binding epitopes. Thus, it is not clear why EGFR would be a natural binding target for SPINK1, and the mode of their potential interaction remains a mystery. Until stronger evidence emerges to validate and structurally characterize this binding interaction, the possible involvement of other accessory proteins or alternative SPINK1 receptors with crosstalk to EGFR should be considered (Figure 1C). For example, an earlier study by Niinobu et al. (1990) showed binding of SPINK1 to a cell surface receptor of 140 kDa, considerably smaller than EGFR, in a manner that was not diminished by competing EGF. We suggest that efforts to more clearly confirm or identify the direct receptor of SPINK1, and the mechanism by which it influences EGFR signaling, could lead to identification of novel points for therapeutic intervention in cancers that express SPINK1. SPINK1 is an important contributor to both increased proliferation and metastasis development in a variety of cancers. Patients with tumors expressing SPINK1 face a poorer overall prognosis and stimulation of SPINK1 expression in the treatment-damaged tumor microenvironment may further contribute to chemoresistance and tumor recurrence. While patient studies have provided strong evidence for the importance of SPINK1 across different tumor types, the regulatory pathways that control SPINK1 expression and the direct targets of SPINK1 in the context of the tumor microenvironment, including both protease target(s) and cell surface receptor(s), remain largely unknown. The identification of specific protease targets of SPINK1 inhibition will reveal pathways controlling anoikis resistance and aid in development of biomarkers and therapeutic strategies to reduce tumor metastasis. To better understand and target SPINK1 driven tumor cell proliferation we need to further investigate the missing link between SPINK1 and EGFR signaling using modern methods and technologies. Concerted efforts are needed to uncover SPINK1 targets, signaling mechanisms and mediators, and such efforts may lead to the development of novel therapeutic strategies to reduce the impact of SPINK1 on tumors and improve patient prognosis. All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. ESR acknowledges funding from National Institutes of Health grants R21 CA226302 and R01 CA154387. CM acknowledges support from the Mayo Clinic Graduate School of Biomedical Sciences. We thank Derek Radisky for helpful comments on the manuscript. Ateeq, B., Kunju, L. 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Biol. 7:10. doi: 10.3389/fcell.2019.00010 Received: 14 November 2018; Accepted: 16 January 2019; Published: 04 February 2019. Edited by: Reviewed by: Copyright © 2019 Mehner and Radisky. 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: Evette S. Radisky, [email protected]
Gustavo Adolfo González Roys
Published: 30 January 2019
Revista UNIMAR, Volume 36, pp 77-78; https://doi.org/10.31948/unimar36-2.art5

Abstract:
Este artículo partió de la postura epistemológica de Bachelard (2007), quien recalca la necesidad de formar futuros investigadores, complementada desde las perspectivas de teóricos como Bracho (2012), Burbules y Callister (2008), Chiroque (2007), Gómez y Maldonado (2005), Jenkins, Ford y Green (2015), Tamayo y Restrepo (s.f.), entre otros. Metodológicamente, es documental con diseño bibliográfico y analítico. 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Comment
Published: 10 January 2019
Frontiers in Microbiology, Volume 9; https://doi.org/10.3389/fmicb.2018.03313

Abstract:
A Commentary onThe Potential Role of the Dipeptidyl Peptidase-4-Like Activity From the Gut Microbiota on the Host Healthby Olivares, M., Schüppel, V., Hassan, A. M., Beaumont, M., Neyrinck, A. M., Bindels, L. B., et al. (2018). Front. Microbiol. 9:1900. doi: 10.3389/fmicb.2018.01900 Peptidases or proteases are enzymes essential for various functions of a cell and are present in all living organisms (Ida et al., 2017; Silva, 2018a). They are capable of hydrolyzing the peptide bond (Silva, 2017, 2018b). These can be classified according to (1) the chemical mechanism of catalysis, depending on the nature of their nucleophilic agents; (2) details of the reaction catalyzed, depending on the length of the target substrate and released product, or the location of the peptide bond where the enzyme will act; and (3) molecular structure and homology (Silva, 2017; Merops, 20181). Dipeptidyl aminopeptidases are enzymes that hydrolyze the penultimate peptide bond at the N-terminus, separating a dipeptide from the remaining substrate (Stressler et al., 2013; Zilleßen et al., 2016). Dipeptidyl peptidase-4 (DPP-4) is an enzyme which exhibits high affinity to proline and alanine in the S1 subsite (Merops, 2018). DPP-4 activity can be found in prokaryotes and eukaryotes (Olivares et al., 2018). In humans, these enzymes are present either as a membrane protein or as a soluble enzyme. In some bacteria, it is present as a membrane protein (S9B family). Additionally, a similar type of cytosolic DPP-4 is found in some bacteria, such as Lactobacillus helveticus (PepX, S15 family) (Stressler et al., 2013; Merops, 2018; Olivares et al., 2018). DPP-4 activity has also been found in fungi (Olivares et al., 2018). DPP-4 is present in commensal microorganisms of the human digestive tract anchored to their plasma membranes (Walker et al., 2003). However, very little information currently exists on such microbial enzymes. This subject, which relates to the effect of these enzymes on the host organism, has been addressed in this comment. This commentary focuses on the work reported by Olivares et al. (2018), in which they have investigated the activity of the DPP-4 present in the gut microbiota of mice, and have hypothesized about its effect on the host organism. The authors base their arguments on the fact that the cecal content of gnotobiotic mice colonized with the gut microbiota of a healthy subject showed increased proteolytic activity of DPP-4 as compared to germ-free mice (GFM). Additionally, cecal tissue mRNA analyzed in both study groups did not demonstrate significant differences in Dpp-4 gene expression between them. This indicates that significant DPP-4-like activity occurs in the gut microbiota. Motivated by the results, the authors discuss about the influence of this enzyme on intestinal and hormonal disorders. It is worth emphasizing here that, all arguments being scientifically grounded, what draws attention to the article is the hypothesis of translocation of DPP-4 from the gut microbiota to blood plasma. The article refers to the work of Marguet et al. (2000), in which Dpp-4-knockout (KO) mice exhibited DPP-4 activity in plasma by a hitherto unknown process. Therefore, the authors sought to determine the origin of this enzyme and the mechanism by which it is present in plasma. They hypothesized that DPP-4 is translocated from the gut microbiota through the intestinal wall. Here, I would like to discuss this hypothesis, in which some points are highlighted: (1) as mentioned by the authors, for the enzyme to be translocated, the microbiota would require to secrete a soluble isoform of the peptidase; (2) the intestinal wall is recognized to be an impermeable barrier to macromolecules, and therefore, increased permeability is associated with intestinal disorder, inflammation, and disease. As described by the authors, DPP-4 in humans can be found in two isoforms, associated with the plasma membrane or a soluble form in the bloodstream (Matteucci and Giampietro, 2009; Roppongi et al., 2018). In contrast, it has been demonstrated that microbial DPP-4 is either associated with the membrane, or in the case of PepX this enzyme is also present in the intracellular medium. However, it has not yet been verified whether microbes can also secrete DPP-4. Additionally to the active secretion of DPP-4, this enzyme could be also released outside microbial cells by cellular lysis following microbial death in the intestine. This finding would be necessary to support the hypothesis of translocation of the enzyme through the intestinal wall. Another important aspect to be considered is the permeability of the intestinal wall. The intestinal wall forms a barrier that contributes to absorption of nutrients derived from digested food; however, it does not permit the flow of macromolecules and microorganisms (Fukui, 2016; Thursby and Juge, 2017). A suitable transport membrane system for translocation of these enzymes would be required, without being necessarily accompanied by detrimental effects on the host. Simultaneously, the integrity of the intestinal wall should be maintained. This justifies the need for further research to understand the feasibility of this scientific proposal. These arguments do not, however, disregard the hypothesis raised by Olivares et al. (2018), but only substantiate the need for further investigation. It is important to note that the discovery of the presence of DPP-4 in the plasma of Dpp-4 KO mice, and the hypothesis raised by the authors in the attempt to explain this information, is of high interest and would guide scientific discoveries and open a forum for discussion, serving as an avenue for further investigations. It is well-known that there are differences in primary structure of citosolic PepX (S15 family, E.C. 3.4.14.11) and mammalian DPP-4 (S9B family, E.C. 3.4.14.5) (Olivares et al., 2018). PepX is not found in superior eukaryotic genomes (André et al., 2013). In part, to verify if the dipeptidyl aminopeptidase activity in KO mice for Dpp-4 gene is a PepX-like, it may possibly be investigated by comparative analysis of the sequence of the enzyme present in the plasma and a gene library of the gut microbiota. Nevertheless, it is quite true that this calls for extensive work! Metagenomics approaches could be useful to validate the presence of this enzyme in the gut microbiota. DNA library construction could be an alternative due to the diversity of the gut microbiota (Gill et al., 2006; Yang et al., 2018). Finding a relationship between the DPP-4 activity present in the plasma of KO mice for Dpp-4 gene and the enzyme expressed by the gut microbiota is a challenge that may contribute to reinforce the concept of enzyme translocation. In fact, this work offers support for future investigations. As mentioned by the authors, further research is necessary to validate this hypothesis. The discussion developed by Olivares et al. (2018) is hugely praiseworthy, as in the light of their own results combined with the information currently available in the literature on this subject, it seems possible to associate the gut microbial DPP-4 activity with effects on the host health. The author confirms being the sole contributor of this work and has approved it for publication. The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. 1. ^ Merops. https://www.ebi.ac.uk/merops/about/classification.shtml#MECHANISM (Accessed December 26, 2018). André, J., Bach, M., Xie, J., and Rigolet, P. (2013). A new binding site involving the C-terminal domain to design specific inhibitors of PepX. Protein Pept. Lett. 20, 45–53. doi: 10.2174/092986613804096766 PubMed Abstract | CrossRef Full Text | Google Scholar Fukui, H. (2016). The gut impacts diabetic management tomorrow: the recent messages from intestine and microbiota. J. Clin. Nutr. Diet 2:4. doi: 10.4172/2472-1921.100027 CrossRef Full Text | Google Scholar Gill, S. R., Pop, M., DeBoy, R. T., Eckburg, P. B., Turnbaugh, P. J., Samuel, B. S., et al. (2006). 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Rep. 6:23074. doi: 10.1038/srep23074 PubMed Abstract | CrossRef Full Text | Google Scholar Keywords: hypothesis, intestinal barrier, microbiota, protease, proteolytic activity Citation: Da Silva RR (2019) Commentary: The Potential Role of the Dipeptidyl Peptidase-4-Like Activity From the Gut Microbiota on the Host Health. Front. Microbiol. 9:3313. doi: 10.3389/fmicb.2018.03313 Received: 20 October 2018; Accepted: 19 December 2018; Published: 10 January 2019. Edited by: Reviewed by: Copyright © 2019 Da Silva. 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: Ronivaldo Rodrigues Da Silva, [email protected]
Published: 1 January 2019
CLA Journal, Volume 62, pp 213-216; https://doi.org/10.1353/caj.2019.0006

Abstract:
CLA JOURNAL 213 CONTRIBUTORS Dr. Elizabeth Brown-Guillory currently serves as Distinguished Professor of Theatre at Texas Southern University (TSU). Prior to joining the faculty at TSU, she served as an English professor at the University of South Carolina—Upstate, Dillard University, and University of Houston. Over the course of her career, she has won five teaching excellence awards and published four books, ten plays, and a number of seminal essays in refereed journals as well as has had her plays produced in Denver, Los Angeles, Houston, New York City, New Orleans, Mobile, and Chicago, to name a few. She has delivered over 200 lectures nationally and internationally and has written, directed, and produced plays for over thirty years. Amy Bryan is a visual artist and educator born in 1976 in New Orleans, Louisiana. She creates drawings, prints, and mixed media art. Bryan’s subject-matter is often memories, portraits, and figures. She has a Master of Fine Arts from Howard University with a concentration in printmaking and a Bachelor of Arts in Studio Art from Xavier University of Louisiana. Jalylah Burrell is a postdoctoral fellow at the Center for the Study of Women, Gender, and Sexuality at Rice University. She received her Ph.D. from Yale University in American Studies and African American Studies and previously held the Ida B. Wells-BarnettPostdoctoralFellowshipintheAfricanandBlackDiasporaDepartment at DePaul University. She is currently at work on the book project, “Capacity for Laughter: Black Women and the American Comedic Tradition,” an interdisciplinary study of race, gender, and comedy. Eve Lorane Brown is the University of California President’s Postdoctoral Scholar in the Department of African American Studies at the University of California Berkeley and the Lionel Cantu Postdoctoral Scholar in Feminist and Gender Studies. Dr. Brown, who identifies as a Black Feminist Psychologist, earned her Ph.D. in Psychology from the University of California, Santa Cruz. Trudier Harris is University Distinguished Research Professor of English at the University of Alabama and formerly the J. Carlyle Sitterson Distinguished Professor of English at University of North Carolina Chapel Hill. Her publications include Fiction and Folklore: The Novels of Toni Morrison (1991), The Scary MasonDixon Line: African American Writers and the South (2009), and Martin Luther King Jr., Heroism, and African American Literature (2014), among others. In 2014, UNC Chapel Hill established the“Trudier Harris Distinguished Professorship.”In 2018,she received various honors and accolades: the Richard Beale Davis Award for Lifetime Achievement in Southern Literary Studies, Clarence E. Cason Award for Nonfiction Writing, and National Humanities Center Fellowship for 2018-2019. 214 CLA JOURNAL Contributors Dyane Harvey-Salaam is a founding member and assistant to director Abdel R. Salaam of Forces of Nature Dance Theatre Company and dance educator at Princeton and Hofstra Universities. Performances with the concert dance companies of Eleo Pomare, Joan Miller, George Faison, Otis Sallid, Jelon Vieira prepared her for a career on/off Broadway, which ultimately paved the way for an inspirational collaborative relationship with Ntozake Shange.As an original cast member of “Spell #7” and “Boogie Woogie Landscapes,” as well as choreographer for “Hydraulics Phat Like Mean” and “Lavender Lizards, Lilac Landmines, Layla’s Dream,” she believes the most thrilling aspects of her connection to Zaki happened when sharing time/space in performance together, often best realized in unusual settings. Quanda Johnson is a Fulbright Scholar and doctoral student in Interdisciplinary Theatre Studies at University of Wisconsin - Madison.As a Dean’s Graduate Scholar at New York University’s Gallatin School (MA 2017), she presented her work, In Search of Negroland: a different study of the negro race and The Ballad of Anthony Crawford: a love letter to america at the Gallatin Art Festivals 2016 and 2017, respectively. A performer from Broadway to grand opera, she seeks ways to utilize performance to disrupt and consequently alter entrenched, cyclical conversations about Blackness and the African Diaspora. All her creative work and scholarship is dedicated to the memory of the first artist in her life: her mother, Vernetta. Jacqueline M. Jones is Associate Professor of English at LaGuardia Community College. Dr. Jones is currently the Program Director of LaGuardia’s Women, Gender, and Sexuality Studies Option in Liberal Arts, and a Writing Program...
Gautam Borthakur, Jorge E. Cortes, Guillermo Garcia-Manero, Keyur Patel, Farhad Ravandi, Tapan M. Kadia, Naveen Pemmaraju, Naval G. Daver, Musa Yilmaz, Zeev E. Estrov, et al.
Published: 29 November 2018
Blood, Volume 132, pp 3993-3993; https://doi.org/10.1182/blood-2018-99-118591

Abstract:
Background: Fludarabine, cytarabine and G-CSF (FLAG) based regimens have resulted in marked improvement in newly diagnosed core binding factor (CBF) acute myelogenous leukemia (AML)(1-3). Addition of gemtuzumab ozogamicin (GO) to chemotherapy has also improved survival outcomes in CBF-AML(4). In 2007 we initiated a frontline study of FLAG-GO in newly diagnosed CBF-AML but after withdrawal of GO from US market, GO was replaced with idarubicin (FLAG-Ida). We report on mature data including early molecular response in patients treated in these sequential protocols. Methods: One hundred and forty five patients [Median age, 48 years (range, 19-78 years) were treated in these sequential protocols (FLAG=GO=50, FLAG-Ida= 95 patients). The treatment groups were comparable for age and distribution of cytogenetic (T8;21 or Inv16) subgroups (p≥0.5). FLAG regimen has been published before(2), GO was administered at 3 mg/m2 on day 1 in induction and in 2 consolidations out of planned 6 and idarubicin was administered at 6 mg/m2 on days 3 and 4 in induction and on day 2 in one of the consolidation cycles out of planned 6. Serial assessment of fusion transcript product relevant to the cytogenetic abnormality was performed in bone marrow samples at baseline, end of induction and every 2-3 cycles thereafter. Results: All except 3 patients (2 induction deaths) achieved remission (98%). After median follow up of 5 years, 5 year overall survival (OS) and relapse free survival (RFS) for the entire cohort is 77% and 72% respectively. There were no differences in OS among FLAG-GO vs FLAG-Ida (p=0.3) and Inv16 vs T(8;21) (p=0.6). While RFS was similar among Inv 16 and T(8;21) subgroups, it was significantly better among the cohort treated with FLAG-GO compared to FLAG-Ida (p=0.04)(Fig 1). We confirmed our earlier report of higher than 3 log reduction of fusion transcript ratio at end of induction(5) being most indicative of sustained RFS (p=0.006) (Fig 2) and this end point was more frequently achieved in the FLAG-GO cohort (57%) compared to FLAG-Ida cohort (29%) (p=0.002). On the other hand, within each regimen there was no difference in RFS between Inv 16 andf T(8;21) subgroups (p=0.3) (Fig. 3). SAEs were mostly related to cytopenias and associated infectious complications for both regimens and no hepatic veno-occlusive disease (VOD) was encountered. Presence of KIT, RAS, FLT3 mutations individually or in combination did not have any impact on outcomes. Conclusion: Compared to idarubicin, GO when added to FLAG based frontline induction/consolidation regimen results in better early molecular responses and improved relapse free survival in CBF AML. Our current frontline protocol is exploring safety and efficacy of addition of both GO and Ida to FLAG based regimen. ReferencesBorthakur G, Cortes JE, Estey EE, Jabbour E, Faderl S, O'Brien S, et al. Gemtuzumab ozogamicin with fludarabine, cytarabine, and granulocyte colony stimulating factor (FLAG-GO) as front-line regimen in patients with core binding factor acute myelogenous leukemia. Am J Hematol. 2014;89(10):964-8.Borthakur G, Kantarjian H, Wang X, Plunkett WK, Jr., Gandhi VV, Faderl S, et al. Treatment of core-binding-factor in acute myelogenous leukemia with fludarabine, cytarabine, and granulocyte colony-stimulating factor results in improved event-free survival. Cancer. 2008;113(11):3181-5.Burnett AK, Russell NH, Hills RK, Hunter AE, Kjeldsen L, Yin J, et al. Optimization of Chemotherapy for Younger Patients With Acute Myeloid Leukemia: Results of the Medical Research Council AML15 Trial. Journal of Clinical Oncology. 2013;31(27):3360-8.Hills RK, Castaigne S, Appelbaum FR, Delaunay J, Petersdorf S, Othus M, et al. Addition of gemtuzumab ozogamicin to induction chemotherapy in adult patients with acute myeloid leukaemia: a meta-analysis of individual patient data from randomised controlled trials. The Lancet Oncology. 2014;15(9):986-96.Boddu P, Gurguis C, Sanford D, Cortes J, Akosile M, Ravandi F, et al. Response kinetics and factors predicting survival in core-binding factor leukemia. 2018. Disclosures Cortes: novartis: Research Funding. Ravandi:Jazz: Honoraria; Sunesis: Honoraria; Jazz: Honoraria; Astellas Pharmaceuticals: Consultancy, Honoraria; Abbvie: Research Funding; Bristol-Myers Squibb: Research Funding; Abbvie: Research Funding; Amgen: Honoraria, Research Funding, Speakers Bureau; Macrogenix: Honoraria, Research Funding; Seattle Genetics: Research Funding; Xencor: Research Funding; Orsenix: Honoraria; Xencor: Research Funding; Macrogenix: Honoraria, Research Funding; Bristol-Myers Squibb: Research Funding; Astellas Pharmaceuticals: Consultancy, Honoraria; Seattle Genetics: Research Funding; Amgen: Honoraria, Research Funding, Speakers Bureau; Sunesis: Honoraria; Orsenix: Honoraria. Kadia:Novartis: Consultancy; Celgene: Research Funding; Amgen: Consultancy, Research Funding; Celgene: Research Funding; Pfizer: Consultancy, Research Funding; BMS: Research Funding; Jazz: Consultancy, Research Funding; Takeda: Consultancy; Amgen: Consultancy, Research Funding; BMS: Research Funding; Pfizer: Consultancy, Research Funding; Abbvie: Consultancy; Novartis: Consultancy; Jazz: Consultancy, Research Funding; Abbvie: Consultancy; Takeda: Consultancy. Pemmaraju:SagerStrong Foundation: Research Funding; Affymetrix: Research Funding; plexxikon: Research Funding; daiichi sankyo: Research Funding; samus: Research Funding; celgene: Consultancy, Honoraria; abbvie: Research Funding; cellectis: Research Funding; stemline: Consultancy, Honoraria, Research Funding; novartis: Research Funding. Daver:ARIAD: Research Funding; Daiichi-Sankyo: Research Funding; Kiromic: Research Funding; Alexion: Consultancy; Otsuka: Consultancy; Sunesis: Consultancy; Karyopharm: Consultancy; BMS: Research Funding; Karyopharm: Research Funding; Pfizer: Research Funding; Pfizer: Consultancy; Incyte: Consultancy; Sunesis: Research Funding; Novartis: Consultancy; Novartis: Research Funding;...
, Yassin Ibrahim, Osama Elhardello
Published: 8 November 2018
BMC Hematology, Volume 18, pp 1-8; https://doi.org/10.1186/s12878-018-0124-1

Abstract:
Anemia during pregnancy is a public health problem especially in developing countries and it is associated with maternal and perinatal adverse outcomes. There is no meta-analysis on anemia during pregnancy in Sudan. The current systemic review and meta-analysis was conducted to assess the prevalence, types and determinant of anemia during pregnancy in Sudan. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was followed. The databases (PubMed, Cochrane Library, Google Scholar, CINAHL, and African Journals Online) were searched using; anemia, pregnancy related anemia and Sudan. Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument (JBI-MAStARI) and Modified Newcastle – Ottawa quality assessment scale were used for critical appraisal of studies. The pooled Meta logistic regression was computed using OpenMeta Analyst software. Sixteen cross-sectional studies included a total of 15, 688 pregnant women were analyzed. The pooled prevalence of anemia among pregnant women in Sudan was 53.0% (95%, CI = 45.9–60.1). The meta-analysis showed no statistical significant between the age (mean difference = 0.143, 95 CI = − 0.033 − 0.319, P = 0.112), parity (mean difference = 0.021, 95% CI = − 0.035 − 0.077, P = 0.465) between the anemic and no anemic women. Malaria was investigated in six studies. Pregnant women who had malaria infection during pregnancy were 1.94 times more likely to develop anemia than women who had no malaria infection (OR = 1.94, 95% CI =1.33–2.82). Six (37.5%) studies investigated type of anemia. The pooled prevalence of iron deficiency anemia (IDA) among pregnant women in Sudan was 13.6% (95% CI = 8.9–18.2). There is a high prevalence of anemia among pregnant in the different region of Sudan. While age and parity have no association with anemia, malaria infection was associated with anemia. Interventions to promote the strengthening of antenatal care, and access and adherence to nutrition, and malaria preventive measures are needed to reduce the high level of anemia among pregnant women in Sudan.
Helen Rainey
Published: 1 November 2018
Journal of Kidney Care, Volume 3; https://doi.org/10.12968/jokc.2018.3.sup6.s9

Abstract:
An online survey, conducted via the Journal of Kidney Care, identified variations in knowledge about iron deficiency anaemia (IDA), as well as concerns about the ease with which national guidance on its management can be implemented. The results highlight the need to simplify and standardise recommendations on the management of IDA
Sze Wan Shan, , Bing Zuo, Chi Ho To, Quan Liu, Sally A. McFadden, Rachel Ka-Man Chun, , King Kit Li,
Published: 31 August 2018
Data in Brief, Volume 21, pp 1750-1755; https://doi.org/10.1016/j.dib.2018.08.119

Abstract:
Myopia is generally regarded as a failure of normal emmetropization process, however, its underlying molecular mechanisms are unclear. Retinal protein profile changes using integrated SWATH and MRM-HR MS were studied in guinea pigs at 3- and 21-days of age, where the axial elongation was significantly detected. Differential proteins expressions were identified, and related to pathways which are important in postnatal development in retina, proliferation, breakdown of glycogen-energy and visual phototransduction. These results are significant as key retinal protein players and pathways that underlying emmetropization can be discovered. All raw data generated from IDA and SWATH acquisitions were accepted and published in the Peptide Atlas public repository (http://www.peptideatlas.org/) for general release (Data ID PASS00746). A more comprehensive analysis of this data can be obtained in the article “Integrated SWATH-based and targeted-based proteomics provide insights into the retinal emmetropization process in guinea pig” in Journal of Proteomics (Shan et al., 2018) [1].
Gregory A. Borchard
A Narrative History of the American Press pp 102-114; https://doi.org/10.4324/9781315658667-7

Abstract:
“The Press in Transition: From Reconstruction to the Gilded Age” describes the triumphs and failures of the press during Reconstruction, focusing on Ida B. Wells’ The Red Record as a landmark piece of journalism. It opens with a narration of Horace Greeley’s failed campaign for president in 1872, juxtaposed with Wells’ crusade against lynching, and it shows how Reconstruction journalism bridged traditional models of publishing popularized before the Civil War into a new wave of sensational content fueled by technological development at the end of the nineteenth century. Using materials from this chapter, students should know why the Reconstruction era introduced important precedents in the role of the press as an agent for social change. They should identify key problems both highlighted and ignored by the press leaders and politicians of the era, and they should be able to explain why Ida B. Wells deserves credit for taking a particularly brave stance as a writer in exposing the abhorrent practice of lynching. Key words, names, and phrases associated with Chapter 6 include: Horace Greeley, the Liberal Republicans, and the 1872 election; Ida B. Wells, lynching, The Red Record; Mark Twain and the Gilded Age; and Horatio Alger and the American Dream.
Si‑Xi Liu, Hai‑Rong Xiao, Guo‑Bing Wang, Xiao‑Wen Chen, Chang‑Gang Li, Hui‑Rong Mai, Xiu‑Li Yuan, Guo‑Sheng Liu,
Experimental and Therapeutic Medicine, Volume 16, pp 1433-1441; https://doi.org/10.3892/etm.2018.6326

Abstract:
The current study aimed to investigate the changes and regulatory mechanism of cluster of differentiation (CD)4+CD25high forkhead box protein 3 (Foxp3+) regulatory T cells (Tregs) in childhood B‑cell acute lymphocytic leukemia (B‑ALL). A total of 18 children with B‑ALL and 15 age‑matched healthy children were included. Reverse‑transcription quantitative polymerase chain reaction was used to evaluate the mRNA levels of Foxp3, cytotoxic T‑lymphocyte associated protein 4 (CTLA4), glucocorticoid‑induced tumor necrosis factor receptor (GITR), lymphocyte activation gene 3 (LAG3), interleukin (IL)‑2 receptor (R)β/γ, IL‑6Rα/β, mothers against decapentaplegic homolog (Smad)3/4 and runt‑related transcription factor (RUNX)1/3 in CD4‑positive cells. The concentration of cytokines in plasma were measured using a cytometric bead array. Additionally, the proportion of CD4+CD25highFoxp3+ Tregs and levels of associated proteins was analyzed using flow cytometry. The results demonstrated that the proportion of CD4+CD25highFoxp3+ and expression of Foxp3 in children with B‑ALL was significantly higher compared with healthy controls (P Introduction Acute lymphoblastic leukemia (ALL) is a heterogeneous disease, which is characterized by massive proliferation, extensive infiltration and inhibition of normal hematopoiesis (1). ALL is the most common cancer in children, accounting for 25% of cancer diagnosed among children <15 years of age (2). Lymphocyte phenotyping reveals that ALL has two subtypes: B cell (B-) and T cell (T-) ALL, with 85% of cases being B-ALL and 15% of T-ALL (3). Various therapeutic protocols have been applied in treatment and management of ALL, including chemotherapy, targeted therapy and bone marrow transplantation (4). Among children with ALL, ~95% of patients achieved complete remission following targeted therapy and 15-20% achieved an initial remission followed by a relapse (5). The etiology and pathogenesis of ALL is yet to be fully elucidated (1,3). Previous studies have demonstrated that the malignant proliferation of B-ALL cells was closely associated with a low level of anti-tumor immunity (1–3). However, the molecular mechanism of antitumor immune dysfunction remains unclear (1). It may be associated with the emergence and accumulation of immune regulatory cells, including regulatory T regulatory cells (Tregs) suppressing anti-cancer immunity (6–8). CD4+CD25+ Tregs have been discovered recently as a subpopulation of T cells, characterized by low reactive, immune suppression and expression of forkhead box P3 (FoxP3) (9,10). Tregs are produced in the thymus during T-cell maturation and are generated in the peripheral blood from naive CD4+ T cells (11). Previously studies revealed that numerous cancers induced the generation of Tregs from naïve T cells and promoted their proliferation, resulting in the accumulation of these cells in the tumor microenvironment and peripheral blood, leading to the suppression of tumor-specific T cells and regulation of antitumor responses (6–8). To gain insight into this potential mechanism of B-ALL pathogenesis, the present study investigated the changes of Treg cells in pediatric patients and the possible mechanism of differentiation and regulation, with the objective to further elucidate the tumorigenesis of B-ALL. Materials and methods Patients A total of 18 newly diagnosed pediatric patients with B-ALL and admitted to Shenzhen Children's Hospital (Shenzhen, China) between July 2012 and February 2013 were enrolled in the current study. The cohort consisted of 13 males and 5 females, aged 2.3-11.5 years, with a mean age of 5.1 years. All patients with B-ALL were examined and diagnosis was confirmed using clinical examination, bone marrow cell morphology and immunophenotyping by flow cytometry (12). The diagnosis was confirmed in accordance with the Recommendation of Diagnosis of Pediatric Acute Lymphoblastic Leukemia (3rd Amendment Draft) (13). Inclusion criteria of patients with B-ALL: Age >12 months and <13 years; confirmed new diagnosis of B-ALL with ≥25% blasts in the bone marrow; no prior therapy. Exclusion criteria: Age ≥13 years at the time of consent; relapsed or refractory B-ALL; prior therapy; known HIV positive. Blood samples were collected prior to chemotherapy. A total of 15 outpatients (10 males, 5 females; age range, 3.2-9.6 years; mean age, 4.8 years) recruited between June 2012 and March 2013, received a physical examination in the Department of Pediatrics in Shenzhen Children's Hospital and served as the healthy control group. No significant differences in age or gender were identified between the two groups. Blood samples of patients with B-ALL and control group were analyzed immediately and without mitogen stimulation to avoid interference of the activation of immunocompetent cells. Informed consent was obtained from family members of all subjects and the study was approved by the Biomedical Ethics Committee of Shenzhen Children's Hospital. Isolation of peripheral blood cluster of differentiation (CD)4+ T cells Anti-coagulant EDTA was used to collect 3 ml sterile venous blood from each patient in the current study. Peripheral blood mononuclear cells were isolated using density gradient centrifugation at 500 × g for 20 min at 4°C with fructose-diatrizoate (P=1.077; GE Healthcare Life Sciences, Little Chalfont, UK). Peripheral CD4+ T cells were isolated using immunomagnetic beads according to manufacturer's instructions (DynalBeads CD4 kit; cat. no. 111.45D; Invitrogen; Thermo Fisher Scientific, Inc., Waltham, MA, USA). Cell activity was determined by light microscopic examination (BX41; Olympus Corporation, Tokyo, Japan), following staining with 4% trypan blue at room temperature for 5 sec. Cell purity was determined using flow cytometry and Diva V6.1.3 software (BD Biosciences, Franklin Lakes, NJ, USA) following staining with CD4-fluorescein isothiocyanate (FITC) antibody (10 µg/ml; cat. no. 11-0049-80; Invitrogen; Thermo Fisher Scientific, Inc.) for 1 h at 4°C. Cells were then prepared completely and immediately used in further experiments. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) Total RNA was extracted from isolated peripheral CD4+ T cells using the RNAqueous kit (cat. no. AM1912; Ambion; Thermo Fisher Scientific, Inc.) according to the manufacturer's protocol. RNA was quantified using a UV spectrophotometer. cDNA was synthesized by reverse transcription using a RevertAid H Minus First Strand cDNA Synthesis kit (cat. no. K1632; Thermo Fisher Scientific, Inc., Waltham, MA, USA) following the manufacturer's protocol. cDNA (1 µl) was used as a template and PCR amplification was conducted as follows: First cycle at 95°C for 15 min, followed by 35-50 cycles at 95°C for 15 sec, 54 to 62°C for 15 sec and 72°C for 25 sec. Primers were designed using the mRNA sequence of target genes from Genebank (https://www.ncbi.nlm.nih.gov/genbank/), as presented in Table I. All primers were synthesized by Shanghai Yingjun Biotechnology Co., Ltd. (Shanghai, China). The amplification products (each 10 µl) of forkhead box 3 (Foxp3), cytotoxic T lymphocyte-associated antigen 4 (CTLA4), glucocorticoid-induced tumor necrosis factor receptor (GITR), lymphocyte activation gene 3 (LAG3), interleukin (IL)-2 receptor (R)β/γ, IL-6Rα/β, mothers against decapentaplegic homolog (Smad)3/4, runt-related transcription factor (RUNX)1/3 and β-actin were loaded into 2% agarose gel. Electrophoresis was conducted at 90 v for 30 min. The gel was then recovered and purified for sequencing at Shanghai Yingjun Biotechnology Co., Ltd. The sequencing results were compared with the mRNA sequence of the target genes obtained from Genebank. All products of amplification, including Foxp3, CTLA4, GITR, LAG3, IL-2Rβ/γ, IL-6Rα/β, Smad3/4, RUNX1/3 and β-actin were identical to the mRNA sequences presented in Genebank. The cDNA synthesized in RT-qPCR was detected using a SYBR Green kit (cat. no. DRR820S; Takara Biotechnology Co., Ltd., Dalian, China) and an RT-PCR cycler (LightCycle 480II; Roche Applied Science, Penzberg, Germany). Results were analyzed using the 2−ΔΔCq method with LightCycler Software V1.5 (Roche Applied Science) (14). The results were expressed as the ratio of tested gene to β-actin. This procedure was performed following the manufacturer's protocol. Table I. Primers utilized in reverse transcription-quantitative polymerase chain reaction. Table I. Primers utilized in reverse transcription-quantitative polymerase chain reaction. Gene Primer sequence Renaturation temperature (°C) Number of cycles Amplification position Length of products (bp) Foxp3 Sense: 5′-GTGGCATCATCCGACAAGG-3′ 58 50 1,002-1,167 166 Antisense: 5′-TGTGGAGGAACTCTGGGAAT-3′ CTLA4 Sense: 5′-GTCCGGGTGACAGTGCTTCG-3′ 58 59 360-579 220 Antisense: 5′-CCAGGTAGTATGGCGGTGGG-3′ GITR Sense: 5′-ACACGCACTTCACCTGGGTCG-3′ 58 50 18-146 129 Antisense: 5′-TGTGCCATGCTCGGGTTTCA-3′ LAG3 Sense: 5′-CCTCACTGTTCTGGGTCTGG-3′ 56 48 1,117-1,355 239 Antisense: 5′-GGATATGGCAGGTGTAGGTC −3′ IL-2Rβ Sense: 5′-AAGCCCTTTGAGAACCTTCG-3′ 56 42 504-593 90 Antisense: 5′-GATTTCCCAGCTTATGTTGC-3′ IL-2Rγ Sense: 5′-ATTGGAAGCCGTGGTTATCT-3′ 56 42 869-1013 145 Antisense: 5′-AAAGTTCCCGTGGTATTCAG-3′ IL-6Rα Sense: 5′-TAGTGTCGGGAGCAAGTTCAG-3′ 58 40 1,025-1,116 92 Antisense: 5′-CGGCAGTGACTGTGATGTTGG-3′ IL-6Rβ Sense: 5′-AGTCGTGCCTGTTTGCTTAG-3′ 56 40 2,176-2,338 163 Antisense: 5′-ATTGTGCCTTGGAGGAGTGT-3′ TGF-βRI Sense: 5′-AATGGGCTTAGTATTCTGGG-3′ 55 35 1,285-1,437 153 Antisense: 5′-ATATTTGGCCTTAACTTCTG-3′ Smad3 Sense: 5′-GGGCTTTGAGGCTGTCTACC-3′ 56 45 1,372-1,458 87 Antisense: 5′-TGTCTCCTGTACTCCGCTCC-3′ Smad4 Sense: 5′-GGATACGTGGACCCTTCTGG-3′ 55 45 1,592-1,667 76 Antisense: 5′-CAATGGCTTCTGTCCTGTGG-3′ RUNX1 Sense: 5′-CATCGCTTTCAAGGTGGTGG-3′ 58 50 1,836-1,948 113 Antisense: 5′-TGGCTGCGGTAGCATTTCTC-3′ RUNX3 Sense: 5′-CCAGGAAAGCACCTACAGAC-3′ 56 50 2,447-2,644 198 Antisense: 5′-AATGATCCCTCACCTCAATG −3′ β-actin Sense: 5′-GAGCTACGAGCTGCCTGACG-3′ 56-61 50 787-906 120 Antisense: 5′-GTAGTTTCGTGGATGCCACAG-3′ [i] Foxp3, forkhead box p3; CTLA4, cytotoxic T lymphocyte-associated antigen 4; GITR, glucocorticoid-induced tumor necrosis factor receptor; LAG3, lymphocyte activation gene 3; IL, interleukin; R, receptor; TGF-βRI transforming growth factor β receptor I; RUNX, runt-related transcription factor. Cytometric bead array A total of 2 ml peripheral blood was collected from patients with B-ALL and healthy control subjects, following 6 h of fasting. Heparin was added for anti-coagulation. Samples were centrifuged at 500 × g for 10 min at room temperature and plasma from the upper layer was separated. The plasma concentrations of IL-6 and transforming growth factor (TGF)-β were measured using a cytometric bead array (eBioscience; Thermo Fisher Scientific, Inc.). The procedure was performed according to the manufacturer's protocol, using FlowCytomix Pro v3.0 (eBioscience; Thermo Fisher Scientific, Inc.). Flow cytometry The percentage of CD4+CD25highFoxP3+ T cells was detected using a whole blood counting method. According the instruction from the Foxp3 Staining Buffer set (cat. no. 00-5523-00; Invitrogen; Thermo Fisher Scientific, Inc.), cells were gated with CD4-FITC (10 µg/ml; cat. no. 11-0049-80; Invitrogen; Thermo Fisher Scientific, Inc.) for 30 min at 4°C, fixed and permeabilized with Foxp3/Transcription Factor Staining Buffer set (cat. no. 00-5523-00; Invitrogen; Thermo Fisher Scientific, Inc.) for 60 min at 4°C. Samples were blocked with normal mouse serum (cat. no. 24-5524-94; Invitrogen; Thermo Fisher Scientific, Inc.) for 15 min at 4°C and incubated with anti-CD25-phycoerythrin (PE) (1.25 µg/ml; cat. no. 12-0259-41; Invitrogen; Thermo Fisher Scientific, Inc.) and anti-Foxp3-allophycocyanin (APC) (1.25 µg/ml; cat. no. 17-4777-42; Invitrogen; Thermo Fisher Scientific, Inc.) antibodies for 30 min at 4°C. Cells were also incubated with anti-phosphorylated (p)-signal transducer and activator of transcription factor (STAT)3-PerCP-Cy5.5 (as supplied; cat. no. 560114; BD Bioscience, Inc., San Jose, CA, USA) and anti-pSTAT5-Alexa Fluor647 (as supplied; cat. no. 612599; BD Bioscience, Inc.) for 30 min at 4°C, to detect the protein mean fluorescence intensity (MFI) of pSTAT3 and pSTAT5 in CD4+T cells. To detect the MFI of TGF-βRII and IL-2Rα on CD4+T, peripheral blood samples were stained and gated with CD4-eFlour450 (2.5 µg/ml; cat. no. 48-0049-42; Invitrogen; Thermo Fisher Scientific, Inc.) for 30 min at 4°C, fixed and permeabilized with intracellular fixation and permeabilization buffer set (cat. no. 88-8824-00; Invitrogen; Thermo Fisher Scientific, Inc.) for 20 min at room temperature and stained with anti-TGF-βRII-FITC (as supplied; cat. no. FAB241F-100; R&D System, Inc., Minneapolis, MN, USA) and anti-IL-2Rα-PE (1.25 µg/ml; cat. no. 12-0259-41; Invitrogen; Thermo Fisher Scientific, Inc.) for 30 min at 4°C. Cell counting was conducted using a CantoII flow cytometer (BD Biosciences, Franklin Lakes, NJ, USA). Data were obtained and analyzed using Diva V6.1.3 software. Statistical analysis SPSS v19.0 statistical software (IBM Corp., Armonk, NY, USA) was used for all statistical analyses. Continuous variables were represented as the mean ± standard deviation. A two-tailed t-test was used for the comparison of continuous variables between two groups. P<0.05 was considered to indicate a statistically significant result. Associations between the expression of pSTAT3 and CD4+CD25highFoxp3+ Treg in children with B-ALL were analyzed using a Pearson's correlation test. Results Detection of CD4+CD25highFoxp3+ cells The percentage of Tregs and the expression of Treg associated molecules were detected using flow cytometry (Fig. 1A-D) and RT-qPCR (Fig. 1E-H). The percentage of CD4+CD25highFoxp3+ cells (P<0.0001; Table II and Fig. 1A-D) and the expression of Foxp3 were significantly increased (P<0.05; Fig. 1E) in peripheral blood samples of pediatric patients with B-ALL compared with the healthy controls. The expression of inhibitory signaling molecules CTLA4, GITR and LAG3 was also significantly higher in pediatric patients with B-ALL compared with the control group (P<0.05; Fig. 1F-H). a 3.71 P<0.001 IL-2Rα/CD4+ 120.89±37.93 79.62±20.22a 9.79 P<0.05 pSTAT3/CD4+ 29.61±6.85 41.92±17.12a 2.79 P<0.05 pSTAT5/CD4+ 45.83±14.17 34.01±9.04 2.90 P<0.05 TGF-βRII/CD4+ 50.78±18.87 31.39±9.02a 3.65 P<0.05 RUNX1 2.38±1.44 3.07±1.17a 2.87 P<0.05 Smad3 6.58±4.41 4.77±2.38a 6.81 P<0.05 IL-6 (pg/ml) 27.32±8.12 16.39±5.78a 4.51 P<0.05 TGF-β (ng/ml) 23.53±13.28 8.61±6.10a 4.01 P<0.05 { label (or @symbol) needed for fn[@id='tfn2-etm-0-0-6326'] } Data are presented as the mean ± standard deviation. a P<0.05 vs. healthy control group. B-ALL, B cell acute lymphocytic leukemia; CD, cluster of differentiation; Foxp3, forkhead box p3; IL, interleukin; pSTAT, phosphorylated signal transducer and activator of transcription; TGF, transforming growth factor; RUNX1, runt-related transcription factor 1; Smad, mothers against decapentaplegic homolog. Detection of IL-2 signaling molecules The expression of IL-2Rα/β in CD4+ T cells in patients with B-ALL was significantly upregulated when compared with healthy controls (P<0.05; Fig. 2A and B); however, no significant difference in IL-2Rγ was identified (Fig. 2C). Further investigation into the activation of downstream molecules associated with the IL-2 signal transduction pathway and the effect of IL-2 signaling on Treg cell differentiation in B-ALL patients reveled that the expression of pSTAT5 was significantly higher in patients with B-ALL compared with healthy controls (P<0.05; Table III; Fig. 2D). Furthermore, pSTAT5 expression was positively correlated with the percentage of CD4+CD25highFoxp3+ cells (r=0.17; P<0.05; Table III).
Open Access
Robert Giles, Robert W. Snyder, Lisa DeLisle
Profiles in Journalistic Courage; https://doi.org/10.4324/9781351307925

Abstract:
Some of the bravest actions of journalists are unknown, obscured by the passage of time, hidden by veils of anonymity or buried by systematic repression. Profiles in Journalistic Courage corrects this imbalance. With few exceptions, the stories told in this collection are unfamiliar. In the words of Richard Whelan on Robert Capa's vision of the Spanish Civil War, these tales are drawn from the edge of things. Most of the people highlighted here are journalists who worked on the margins of popularity, who blazed new and solitary paths, and who left fleeting legacies.Courageous journalists were not always thanked for their pioneering efforts. Jealousy, political disagreements, and differing conceptions of journalism sometimes fueled criticism of some of those dealt with in this volume. To complicate the subject further, brave journalists do not always act for reasons that win popularity or acclaim. Actions with laudable consequences are sometimes the result of egoism, stubbornness and ignorance, no less than selflessness, prudence, and principle. These psychological dimensions are not avoided in these profiles.In "Yesterday" David Copeland examines the tangled legacy of the trial of John Peter Zenger. Graham Hodges unearths the story of David Ruggles, an African-American journalist and abolitionist. Pamela Newkirk recalls the life and work of Ida B. Wells-Barnett. Pierre Albert explores the journalism of the French Resistance. Bernard L. Stein and Hank Klibanoff describe the work and motives of the civil rights movement. The volume covers the journalism of commitment from Northern Ireland to Native American tribes. It closes with an extended essay by James Boylan on varied perspectives on different aspects of courage in journalism, from the capacity to resist threats to the courage to tell people what they may not want to hear or read.
Pamela Newkirk
Profiles in Journalistic Courage pp 29-36; https://doi.org/10.4324/9781351307925-4

Abstract:
On May 4, 1884, more than 70 years before Rosa Parks fueled the civil rights movement by refusing to give up her seat on a bus to a white man, 22-year-old Ida B. Wells-Barnett spurned a segregated train car to sit in the ladies' coach. In 1889 Wells' Living Way columns under the pen name Iola were nationally circulated in black newspapers. Wells insisted on coming on board at Free Speech and Headlight as an equal partner. She became editor and one-third owner of the paper while maintaining her job as a Memphis public school teacher. For two years, she operated on dual fronts without incident. The loss of her job allowed Wells to turn her full attention to journalism. She was already known in black circles throughout the country as "Princess of the Press" for her contributions to many of the nation's leading black newspapers.
Tsair Wei Chien
Open Access Biostatistics & Bioinformatics, Volume 1, pp 1-9; https://doi.org/10.31031/oabb.2018.01.000515

Abstract:
Chien Cheng Huang1,2 and Tsair Wei Chien3,4* 1Chang Jung Christian University, Taiwan 2Chi-Mei Medical Center, Taiwan 3Department of Medical Research, Chi-Mei Medical Center, Taiwan 4Department of Hospital and Health Care Administration, Chia-Nan University of Pharmacy and Science, Taiwan *Corresponding author: Tsair Wei Chien, Department of Hospital and Health Care Administration, Chia-Nan University of Pharmacy and Science, Tainan, Department of Medical Research, Chi-Mei Medical Center, 901 Chung Hwa Road, Yung Kung Dist, Tainan 710, Taiwan Submission: April 16, 2018;Published: April 25, 2018 DOI: 10.31031/OABB.2018.01.000515 ISSN: 2578-0247Volume1 Issue3 Background: Identifying an author’s research domain (RD) using MeSH (Medical Subject Headings) terms is essential for a journal’s development and its readership, but no journal uses mining online methods or social network analysis (SNA) to extract journal publication information to report an author’s contributions. Objective: To select prestigious authors and papers that have contributed most to a journal, we retrospectively (1) calculated an SCI (Science Citation Index) journal’s most recent impact factors (IF) and (2) used graphical representations that include MeSH terms of RDs for authors and journals. Methods: We collected 2,053 papers published between July 1, 1999, and April 3, 2017, in the Journal of Medical Internet Research (JMIR) and cited by 673 journals, for which we also collected annual IFs for 394 SCI journals, including the JMIR. The prestigious authors and JMIR papers based on the weight of the 5-year SCI IFs from 394 cited-by papers in 2015. The JMIR core aims and scope are presented using major MeSH terms based on their corresponding average weighted scores. Social network analysis was used to create a graphical RD pattern for JMIR, and its prestigious papers and authors. Results: All JMIR 5-year IFs have not been less than 2.9 for the past 14 years. The authors who contributed most to JMIR in a number of publications and weighted citations are Gunther Eysenbach and My Hua. Their cohesion measures (ranging from 0 to 1.0) to JMIR are 34% and 5.7%, respectively. The highest prestige weighted contribution among papers published in JMIR is the one (PMID: 23567935 /DOI: 10.2196/jmir.2324) with a cohesion measure of 4.5%. Conclusion: An author’s research domain is required with an essential and graphical presentation along with the author’s submission to the target journal. Journal editors also look forward to evaluating an author’s research domain and the submitted paper’s cohesion measure for the journal. Keywords: Research domain; MeSH terms; Cohesion measure for a journal; Social network analysis; Science Citation index; Impact factor Abbreviations: BC: Betweenness Centrality; CR: Concentration Ratio; EDA: Exploratory Data Analysis; HHI: Herfindahl Hirschman Index; IDA: Initial Data Analysis; IF: Impact Factor; JCR: Journal Citation Reports; JMIR: Journal of Medical Internet Research; MeSH: Medical Subject Headings; NLM: National Library of Medicine; RD: Research Domain; SCI: Sciences Citation Index; SNA: Social Network Analysis; SSCI: Social Sciences Citation Index; VBA: Visual Basic for Applications Keywords or short phrases can assist indexers to cross-index an article of interest. However, author-defined keywords are not as common or accurate as MeSH (medical subject headings) terms used by researchers in search of bioinformatics [1,2], but authors are often required by their target journal to provide three to ten keywords that represent the main content of the article for an article [3-7]. MeSH terms, developed by the National Library of Medicine (NLM), are manually assigned to each document by biomedical subject specialists based on the context of the whole document [2]. Usually, MeSH processing is not finished until at least a half year after a paper published in Medline, but new MeSH vocabulary is annually added. MeSH terms contain high-density and well-defined information the whole article which cannot be inferred merely by reading the title and the Our review of the relevant literature revealed no studies that have applied MeSH terms to identify author research domains (RDs). Our online mining approach will improve the ability of authors to objectively report their RDs when using increasingly large and complex PubMed data. Scientific publication is one of the objective measurements to evaluate the achievements of a medical specialty or discipline [8]. Many journals are included in the Thomson Reuters Science Citation Index (SCI). Since the advent of bibliometrics, citation analysis has been widely used in many disciplines to evaluate the influence of academic articles [9-17]. Social network analysis (SNA) [18-20] is used to define authors, journals, or papers as the “nodes” of a network connecting to another node with a relationship represented as an edge [21,22]. Several algorithms and measures have been developed and used with SNA to graphically explore data. When our aim is set to investigate whether any author or paper most fits the research domain of a journal and its scope within the journal’s MeSH network, centrality measures can be applied [22], which means that the core subject can be analyzed using the centrality measure [23,24]. We aimed to report prestigious authors, and prestigious papers contributed to a journal, both of which we can use to retrospectively (i) calculate a journal’s past SCI IFs and (ii) show graphical representations of the RD for the author and the journal within the network of MeSH terms. We downloaded 2,053 abstracts based on the journal of medical internet research (JMIR) from the US NLM of Health (Pubmed. com) since 1999(July 1st) to 2017(April 3th), Their corresponding 1st authors, MeSH terms, and cited-by papers along with the journal names were extracted from the online website using an...
, Lucas Sedeño, , Robert M. J. Deacon, Patricia Cogram
Frontiers in Aging Neuroscience, Volume 10; https://doi.org/10.3389/fnagi.2018.00095

Abstract:
Editorial on the Research TopicHuman and animal models for translational research on neurodegeneration: challenges and opportunities from South America Facing the alarming growth of dementia and neurodegenerative conditions has become a critical priority across the globe (Alzheimer's Disease International, 2009; Lancet, 2015; Shah et al., 2016; Parra et al., 2018). Neurodegenerative diseases are the most frequent cause of dementia, representing a burden for public health systems (especially in middle and middle-high income countries). Although most research on this subject is concentrated in first-world centers, growing efforts in South American countries (SACs) are affording important breakthroughs. This emerging agenda poses not only new challenges for the region, but also new opportunities for the field at large. SACs have witnessed a promising development of relevant research in humans and animals, giving rise to new regional challenges. As highlighted in a recent experts' consensus paper Latin-American countries (LAC), and SACs in particular (Parra et al., 2018), face a critical situation. Higher demographic rates and the predicted prevalence of dementia have reached and even exceeded those of developing countries. In SACs, low- and middle-income countries (e.g., Bolivia, Paraguay), the prevalence of dementia will double that of high-income countries, while upper-middle-income countries in the region (e.g., Argentina, Brazil, Chile, Colombia, Peru, Uruguay, and Venezuela) will experience the greatest impact of dementia. The WHO estimated that the standardized prevalence of dementia in Latin America was 8.5%, but multiple SACs have been underrepresented or underestimated in such a calculation (Parra et al., 2018). Moreover, raw prevalence rates across studies are characterized by high variability within and between countries (e.g., Argentina: 8.3; Brazil: 7.1-2.0; Chile: 4.4-7.0; Colombia: 6.0; Peru: 6.72-9.3; Uruguay: 3.1; Venezuela: 5.7-13,7) (Parra et al., 2018). In addition, most of these studies are undermined by various limitations and methodological problems. Even considering these data, SACs possess the highest global prevalence of dementia after North Africa/Middle East in people above the age of 60 (Parra et al., 2018). Moreover, the harmonization of global strategies against dementia in these contexts is hindered not only by reduced epidemiological data, but also by the lack of standardized clinical practice, insufficient training of physicians, limited resources, and poor governmental support, let alone poverty and more general cultural barriers and stigmas. All of these factors have impacted the type and amount of research conducted in SACs. A regional network, based on multi-institutional actors from research, governmental, and private sectors is fundamental to overcome these challenges (Parra et al., 2018). Nevertheless, until now most research groups still work in isolation or in sporadic collaboration, without developing large-scale multicenter studies or active cooperation networks. The field could grow exponentially by combining the strengths of regional research with higher visibility, a translational philosophy, and enhanced global networking. Importantly, collaborative developments may promote the establishment of translational centers studying neurodegeneration. This Research Topic engages researchers from the world over, helping to integrate the international community of experts and to establish new challenges and developments for future investigation. We present original research in SACs, including studies assessing the interplay among genetic, neural, and behavioral dimensions of these diseases, as well as articles on vulnerability factors, comparisons of findings from various countries, and works promoting multicenter and collaborative networking. More generally, our Research Topic covers a broad scope of human research approaches (behavioral assessment, neuroimaging, electromagnetic techniques, brain connectivity, peripheral measures), animal methodologies (genetics, epigenetics, proteomics, metabolomics, other molecular biology tools), target species (human and non-human animals, sporadic, and genetic versions), and article types (mainly original research articles, but also case reports, data reports, commentaries, opinions, and reviews), all based on work conducted in SACs. Thus, in capturing the breakthroughs, possibilities, and limitations of such a promising niche, the present Research Topic (titled Human and animal models for translational research on neurodegeneration: challenges and opportunities from South America) represents a valuable forum to initialize a constructive dialogue and reflect on the present and future of neurodegenerative research in the region. Here, we summarize the main contributions included in the volume. Through this wide-ranging proposal, we hope to introduce a fresh approach to the challenges and opportunities of research on neurodegeneration across these countries, focusing on two overarching levels of evidence (human and animal research), as summarized below. Concerning human research, SACs offer invaluable possibilities to pursue neurogenetic studies and clinical trials. This region possesses the world's largest population of familial Alzheimer's and Huntington's disease (AD and HD, respectively), among others, alongside multiple novel and rare functional genomic variants of other disorders. Moreover, poor socioeconomic conditions in several communities provide a natural scenario to study the role of vulnerability, resilience, and genetic-cultural interaction on disease progression. These opportunities are already being exploited by consolidated research groups in Argentina, Chile, Colombia, Peru, and Brazil, among others, via cutting-edge approaches which include connectomics, omics-biomarkers, and neuropsychological assessment. Moreover, the emerging cognitive neuroscience of neurodegeneration in the region (Parra et al., 2010, 2015; Ibanez and Manes, 2012; Baez et al., 2013, 2014a,b, 2015, 2016a,b, 2017; García-Cordero et al., 2015, 2016; Melloni et al., 2015, 2016; Pietto et al., 2016; Santamaría-García et al., 2016, 2017; Sedeño et al., 2016, 2017; Abrevaya et al., 2017; Birba et al., 2017; Calvo et al., 2017; Dottori et al., 2017; Garcia et al., 2017a; García et al., 2017b,c; Ibáñez et al., 2017; García and Ibáñez, 2018; Kumfor et al., 2018) has provided manifold pathways of synergy with multimethodological approaches to genetic, clinic, neuropsychological, and neuroscientific data. The research on human neurodegeneration presented in this collection includes works on: (a) global challenges to dementia, from diagnosis to public health; (b) different dimensions of assessment (low socio-educational levels, cultural and competence-related variability, and robust evaluations to face heterogeneous contexts); (c) neurodegeneration discrimination and disease progression (through combinations of behavioral measures, neuroscientific approaches, and biomarkers for improving differential diagnosis between dementia subtypes), the characterization of specific initial alterations in each disease, and the identification of factors that manifest in early aging; and (d) the impact of non-pharmacological interventions for dementia using non-invasive brain stimulation. A first group of studies assesses diverse aspects of the global challenges related to dementia, from diagnosis to public health at a regional level. After reviewing critical sociodemographic and epidemiological data form LACs, Baez and Ibanez propose to evaluate the plausibility of international expert recommendations regarding dementias in these countries. Key issues of this evaluation include diagnosis, demographic specificities of LACs, lack of social awareness of these diseases, deficiencies in the health system, the need for standardizing diagnostic practices, and the existing barriers in terms of resources and cultural factors. Similarly, Custodio et al. outline a challenging picture of epidemiological data in LACs, evidencing the major impact of unprecedented demographic changes and projections of dementia for people between 65 and 69 years old. The situation is worst for low-income people whose families cover the majority of the cost related to the disease. This is even worse for illiterate people, where the majority of the costs are covered by families. Accordingly, the authors propose a critical assessment of regional differences and similarities for the implementation of long-term care policies and plans. For their own part, Cardona-Gómez and Lopera assess the intertwine of novel animal and human translational research on molecular targets and pre/clinical studies. Then they discuss on cases of pure and mixed dementias in the region, and, finally, they recommend the implementation of a protocol clarification policy for developing clinical trials and local intervention strategies. Another set of articles focuses on various dimensions of assessment, including the effects of low socioeconomic status and educational level, the role of clinical competence, and the relevance of trans-culturally valid tasks. The low detection of dementia is a major problem in SACs, accentuated by the lack of validated and standardized tools. In a cross-sectional study, Custodio et al. evaluate the robustness of the memory alteration test (MAT) in low-educated patients with mild cognitive impairment (MCI) and AD by using validity measures (sensitivity, specificity, and correctly classified percentage), internal consistency (Cronbach's alpha coefficient), and concurrent validity (Pearson's ratio coefficient between the MAT and Clinical Dementia Rating scores). All measures, they conclude, provide robust and adequate classification scores. Some instruments, like the working memory binding (WMB) task (Parra et al., 2009, 2010), seem to have high sensitivity and specificity to detect AD in early stages. It has been suggested that cultural aspects such as education, age, and memory abilities may impact in relatively culture-free tasks (Parra et al., 2018). Building on this line of research, Hoefeijzers et al. provide evidence of a new WMB task composed by everyday items that is not affected by education. This result suggests that the WMB test may be culturally and educationally unbiased for the screening of abnormal aging trajectories. A third set of works integrates behavioral and neuroscientific insights (including biomarker research) to examine differential diagnosis across dementia subtypes, the characterization of specific initial alterations for each disease, and the identification of factors that impact early aging. Russo et al. investigate whether memory recognition and deferred recall measures of episodic memory, in combination with cerebrospinal fluid (CSF) biomarkers, can predict the conversion from MCI (397 amnestic-MCI patients of the Alzheimer's disease Neuroimaging Initiative, ADNI) to AD (at 24 months of follow-up). Predictive models of memory, together with risk factors (age, sex, education, APOE genotype and CSF biomarkers), evidence that memory measures alongside amyloid biomarkers can predict the conversion of MCI to AD in the ADNI cohort, especially when combined with amyloid biomarkers. This highlights the relevance of a multimodal approach to anticipate the MCI progression to dementia. Guevara et al. introduce an ante-mortem method to differentiate progressive supranuclear palsy (PSP) from idiopathic Parkinson's disease (IPD) at early stages. To this end, the authors combine normalized measures of brain atrophy with clinical metrics (Unified Parkinson's Disease Rating Scale Part III, Hoehn and Yahr, Clinical Global Impression for Disease Severity Scale, and the Frontal Assessment Battery). Their results show that whole-brain and gray matter volumes distinguished PSP from IPD, and that clinical-imaging correlations were indicative of clinical presentation and differentiation. Campêlo et al. investigate the relationship among single nucleotide polymorphisms of alpha-synuclein gene (SNCA) and risk for PD in a Brazilian sample, considering potential interactions with environmental factors and specific clinical outcomes (cognitive, motor, and mood impairments). Their findings confirm the association between SNCA and PD risk (and early onset PD). Specific SNCA alleles were significantly more frequent in PD patients with cognitive impairment, and negative association with protective factors (cognitive activity and smoking habits). This study constitutes the first description of SNCA polymorphism and PD in a South-American sample. The relation among familial antecedents of late-onset AD (LOAD), cognitive impairment, and sleep patterns in asymptomatic subjects was investigated by Abulafia et al. Middle-aged children of patients with LOAD (O-LOAD), in comparison with controls, displayed deficits in episodic memory and language. Moreover, the former group showed a phase-delayed rhythm of body temperature. Also, cognitive performance in these subjects was associated with cardiac autonomic sleep-wake variables (greater sympathetic activity at night was related to worse cognitive performance). Long-lasting neurofunctional influences during childhood can impact pathological aging. Iron deficiency anemia (IDA) is a marker of iron micronutrient deficit affecting myelination, dopamine neurotransmission, and neuronal metabolism. Algarin et al. explore the connection between IDA in infancy and altered connectivity patterns of the default-mode network (DMN, an aging-sensitive resting-state network) in young adults. Compared to controls, participants with IDA evidenced atypical DMN connectivity. These preliminary findings suggest that a common nutritional problem among human infants may be important for understanding aberrant aging mechanisms. Senescence has been associated with metabolic changes including mitochondrial fission and fusion events. Stab et al. assess the cell senescence and structural remodeling of mesenchymal stromal/stem cells (from human mitochondrial tissue) isolated from adipose tissue in vitro. Cell morphology aging was associated with an increase in β-galactosidase activity. Old cells showed increased mitochondrial mass, augmented superoxide production, and decreased mitochondrial membrane potential. Morphological changes were related to increases in mitochondrial fusion proteins, Mitofusion 1, and Dynamin-related GTPase. Thus, aged, adipose tissue-derived mitochondrial stem cells developed a senescent phenotype. A fourth set of studies evaluate the impact of non-pharmacological interventions for dementia. Non-invasive brain stimulation (NIBS) methods can induce plastic changes in the brain and modulate cognitive functions in humans. Thus, their potential use for early stages of dementia has become a promissory strategy. Birba et al. conducted a systematic review of the effects of NIBS on MCI and subjective cognitive impairment (SCI) in preventing or delaying the development of AD. In particular, they discuss the impact of NIBS on specific target functions, including recognition of verbal and non-verbal stimuli, attention, psychomotor speed, and everyday memory. Moreover, they identify a number of methodological issues (differences among tasks, designs, and samples size) that arguably underlie the mixed results obtained so far. They also outline further methodological approaches to boost the efficacy and specificity of NIBS in MCI and SCI. These issues are critical for developing robust treatments for both conditions. Finally, another report by Birba et al. provides the first evidence that direct electrical brain stimulation can enhance performance in the working memory binding (WMB) task, a sensitive tool for early AD. WMB deficits constitute a robust clinical and preclinical marker of AD, associated with early atrophy of posterior brain regions. Profiting from a unique approach, the authors show that direct intracranial electrical stimulation of the parietal cortex can induce a selective improvement in WMB performance. These preliminary but promising results promote new opportunities to improve binding functions in preclinical AD through brain stimulation. The region also constitutes a rich platform for developments via animal research. Preclinical testing of new therapeutic concepts has been difficult due to the lack of naturally occurring disease models. Although availability of genetically engineered mouse models has partly addressed this challenge, neurodegenerative diseases rarely occur in non-human animals (Jucker, 2010); and the causes of non-familial dementia are multifactorial and age-related (Hurley et al., 2018). In consequence, non-genetic and natural models of dementia are still required. Advances could be made by studying species such as the Octodon degus, an endemic rodent from Chile that spontaneously develops an analog of dementia at behavioral and neurobiological levels (Ardiles et al., 2012; Hurley et al., 2018). In addition, the O. degus can also naturally develop several other conditions like diabetes mellitus type 2, macular and retinal degeneration and atherosclerosis, conditions that are often associated with aging and comorbid disorders with dementia (Hurley et al., 2018). Consequently, the O. degus is a suitable novel experimental model that can be utilized for the development of disease-modifying treatments for dementia. In addition, scientific efforts in the region have been enhanced through new models from promising groups (e.g., single and double immunohistochemistry, inmunoblot, RT-PCR, behavioral phenotyping, CNS lesioning techniques, neuronal tracers for connectivity studies, small craniotomy for drug delivery). These approaches are now fueled by the engagement of international centers and the development of multicenter alliances. The section on animal research provides timely works on regionally relevant topics. These include (a) natural models of AD; (b) pathophysiological models of different neurodegenerative conditions, such as frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), and AD; (c) the role of the proteostasis network in basic organisms; and (d) cognitive interventions as early non-pharmacological therapeutics. In a Data Report Article, Altimiras et al. offer the first characterization of the O. degus's brain transcriptome (in order to support its use as a natural model of AD), together with a comparison between the transcriptomes of AD-like and healthy specimens. Of note, this work includes an unprecedented report of whole transcriptome sequencing (RNA-seq) of the Octogon degus brain. Results reveal differences in novel and previously reported genes for AD and related disorders (CHRNA6, AMD1, WISP1, COX8A, APOC-I, among others). In addition, the comparison of human and O. degus AD-like brain transcriptomes evidences multiple common genes in both species. These findings highlight the relevance of this rodent species to foster progress in AD research. Braidy et al. use the O. degus model to evaluate the biometal imaging and role of metal uptake transporters in AD pathogenesis and aging. Their work hinges on the hypothesis that O. degus may develop neuropathological abnormalities in the distribution of redox active biometals, due to alterations in the expression of lysosomal protein, major Fe/Cu transporters, and selected Zn transporters (ZnTs and ZIPs). Using laser ablation inductively coupled plasma mass spectrometry, they find elevated quantitative images of biometals (Fe, Ca, Zn, Cu, and Al) in the aged O. degus, which in turn showed an age-dependent rise. Some of these metals were specifically enriched in the cortex and hippocampus. Whole-brain extracts evidenced age-related deregulation of metal trafficking pathways (impaired lysosomal function, demonstrated by increased cathepsin D protein expression). An age-related reduction in the expression of subunit B2 of V-ATPase was also identified, alongside significant increases in amyloid beta peptide 42 (Aβ42), and metal transporter ATP13a2. Finally, enhanced expression of transporter of divalent metal species, 5′-aminolevulinate synthase 2 (ALAS2), and the proto-oncogene, FOS was associated with aging. Thus, these results suggest that transition metals in the brain may be enriched with age in the O. degus, and that metal dyshomeostasis in specific brain regions may be related to age. Two additional studies provide pathophysiological models of FTD, ALS, and AD. FTD and ALS are both associated with TAR DNA-binding protein 43 (TDP-43). To investigate the behavioral phenotype associated with this proteinopathy, Alfieri et al. implemented a transgenic (Tg) mouse model that conditionally overexpresses human wild-type TDP 43 protein (hTDP-43-WT) in forebrain neurons. They analyzed the motor, social, and cognitive performance of this species. The young hTDP-43-WT Tg mice presented a mild degree of spasticity. Analysis of social and cognitive behavior showed a rapid installment of deficits in social interaction, working memory, and recognition memory. After long-term (up to 12 months) transgene induction, a motor phenotype (previously absent in younger mice) was identified. Thus, this work points to the time-dependent emergence of a motor phenotype, a clinical presentation of FTD with involving motor deficits, and a complementary animal model for studying TDP-43 proteinopathies. The effect of chronic treatment with reserpine (an inhibitor of vesicular monoamine transporter-2), which induces dyskinesia in PD, has been proposed to be attenuated in spontaneously hypertensive rats (SHRs). Leão et al. evaluated whether SHRs (in comparison with Wistar rats) present differential susceptibility to repeated reserpine-induced deficits in a progressive model of PD. Only reserpine-treated Wistar rats presented increased motor signs. After a withdrawal period, both strains recovered from motor impairment, but SHRs were slower to reach control levels. Immunohistochemistry for tyrosine hydroxylase (TH) and α-synuclein (α-syn) after the last injection or 15 days after withdrawal showed a reduction in TH and an increase in α-syn immunoreactivity in the substantia nigra and dorsal striatum (recovered after 15 days of withdrawal). The SHRs were resistant to reserpine-induced TH decrement in the substantia nigra, and presented reduced immunoreactivity to α-syn in the dorsal striatum relative to Wistar rats, irrespective of treatment. In brief, SHRs may be resilient to motor and neurochemical impairments induced by the repeated low-dose reserpine. Accumulation of β in AD begins many years before clinical onset. Yet, given that massive accumulation of Aβ appears in 30% of healthy aged individuals, compensatory mechanisms and/or additional neurotoxic or protective factors need to be discovered. Belfiori-Carrasco et al. provide a novel genetic screen in the drosophila brain that identifies modifiers of age-dependent amyloid β toxicity. One hundred and ninety-nine deficiency lines accounting for ~6,300 genes were analyzed. Six lines significantly modified Aβ42 neurotoxicity, including the CG11796 and CG17249 (orthologs to human HPD and PRCC, respectively) as candidates. These modifiers of Aβ42 neurotoxicity in Drosophila open avenues for new validation studies into their possible role in sporadic AD. Abnormal protein aggregation is a transversal pathological mechanism in neurodegeneration. Thus, the capacity of neurons to handle alterations in the proteome seems to be specifically altered in aging. Martínez et al. critically asses the proteostasis network in basic organisms, highlighting the challenges for moving toward human research in this domain. Although several reports are pointing to this network as a relevant adjustor of organismal aging in several species, its relevance to human aging remains unknown. The authors discuss multiples challenges (regarding buffering capacity, neural control of organismal proteostasis, connections among stress and aging in protein misfolding disorders, control the cell-nonautonomous UPR as a therapeutic strategy) in the light of new drug-based avenues to intervene in brain aging. To conclude, Gehres et al. set forth a challenging opinion on cognitive interventions as an early non-pharmacological strategy in AD, considering a translational perspective from animal research to human behavior. The critical concepts of cognitive reserve, cognitive interventions, and early-life exposure to environmental enrichment (EE) are reviewed from the vantage point of animal research, with new vistas for neurodegenerative human conditions. After an informative revision, the authors conclude that study designs that aim to unravel EE-specific mechanisms are crucial and could guide the generation of non-pharmacological strategies. Moreover, the combination of EE with better models of sporadic AD, in conjunction with CSF/PET biomarkers, could promote novel insights on novel therapeutic targets for AD. Amid a multiple collection of theories, experimental approaches, and models, all these studies highlight both the rise of world-class research in SACs, as well as the specificity of problems and opportunities in the region. Moreover, they provide relevant evidence for the harmonization of multilevel approaches to neurodegenerative research. Overall, this integrated and pluralistic approach to neurodegeneration in SACs can provide the basic building blocks for a future translational network based on (but not limited to) experimental research, focusing on policy changes and the development of international collaborations (Parra et al., 2018). In sum, this book demonstrates that SACs are highly active in generating first-class translational and multicenter research on neurodegeration, thus amplifying the powerful voice of the South in this worldwide program. AI: designed the proposal. AI, LS, and AG: wrote the first draft, discussed contributions from all co-authors, and approved the final version. All authors (AI, LS, AG, RD, and PC) searched the literature, participated in discussing the contents of the paper, contributed to editing and approved the final version of the article. 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The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner 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: Agustín Ibáñez, [email protected]
Drew Pratt, Sandra Camelo-Piragua, Kathryn McFadden, Denise Leung, Rajen Mody, Arul Chinnaiyan, ,
Acta Neuropathologica Communications, Volume 6, pp 1-4; https://doi.org/10.1186/s40478-018-0525-1

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Department of Pathology, University of Michigan, Ann Arbor, MI, 48104, USA Drew Pratt, Sandra Camelo-Piragua, Kathryn McFadden, Arul Chinnaiyan & Sriram Venneti Department of Neurology, University of Michigan, Ann Arbor, MI, USA Denise Leung Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA Rajen Mody Michigan Center for Translational Pathology, Ann Arbor, MI, USA Arul Chinnaiyan Department of Pediatrics, Division of Pediatric Hematology/Oncology, Mott Children’s Hospital at the University of Michigan, Ann Arbor, MI, USA Carl Koschmann You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar Correspondence to Carl Koschmann or Sriram Venneti. Sequencing studies were performed at the University of Michigan after approval by our Institutional Review Board. All authors declare that they have no competing interests. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Clinical details, pathologic work-up, and sequencing methodology used in the current study. Figure S1. Additional histopathology from case #1 showed characteristic eosinophilic granular bodies (EGBs) (a) and an elevated proliferation index (Ki-67) (b). Immunohistochemistry for p16 showed loss of expression in tumor cells with retained expression in non-neoplastic cells (c, arrowhead), consistent with deletion of the INK4a locus. Staining with mutant-specific BRAF (VE1) was negative (d). Figure S2. Case #2 showed lipidized tumor cells and PAS-positive, diastase-resistant EGBs (arrowheads) (a). Nuclear pleomorphism and increased mitotic activity were seen (b, c). Neurofilament stain showing circumscription of the tumor mass (d). BRAF V600E was negative by IHC (e). Figure S3. MI-ONCOSEQ integrative sequencing report elements: somatic point mutations for case #1 (a) and #2 (c). Copy number plots for case #1 (b) and #2 (d). (DOCX 13229 kb) Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,...
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Published: 13 March 2018
Frontiers in Microbiology, Volume 9; https://doi.org/10.3389/fmicb.2018.00467

Abstract:
A commentary onFungal lifestyle reflected in serine protease repertoireby Muszewska, A., Stepniewska-Dziubinska, M. M., Steczkiewicz, K., Pawlowska, J., Dziedzic, A., and Ginalski, K. (2017). Sci. Rep. 7:9147. doi: 10.1038/s41598-017-09644-w Biochemical diversity and adaptability to different environments are well-known biological characteristics of filamentous fungi. Thus, these microorganisms are widely distributed throughout the biosphere, integrating saprophytic (essential for cycling of nutrients), pathogenic, and symbiotic (with various animals and plants) lifestyles into the environment. Their biological versatility is aligned with their ability to secrete a wide array of enzymes that degrade macromolecules available in the growing environment (da Silva et al., 2014). From the perspective of the secreted enzyme repertoire, a recent noteworthy article titled “Fungal lifestyle reflected in serine protease repertoire” (Muszewska et al., 2017) exhibited a phylogenetic distribution of serine peptidases represented in the fungal kingdom. The paper provides a comprehensive analysis of the presence of the different serine peptidases families in a large number of fungal species. Based on statistical analyses, the authors also draw associations between fungal lifestyle and serine peptidase repertoire. The article shows the evolutionary trajectory of serine peptidases. However, despite what is proposed in the paper, the association between the fungal lifestyle and the serine peptidase repertoire has not yet been well-discussed, especially with respect to the biochemical versatility of these enzymes, which makes them fundamental for broad spectrum action over different proteins in the growth medium and play an essential role in the intracellular processing of proteins and peptides. Thus, the aim of this commentary is to add some further aspects about the catalytic properties of serine peptidases and their representative importance for proteolysis in the fungal growth environment. This characteristic is closely associated with exploration and adaptation to the habitat, which has been demonstrated by the ability of fungi to take advantage of the protein sources present in the environment, eventually contributing to their ecological success. Therefore, an enzyme with a broad spectrum of action over different proteins, and under different pH and temperature conditions stands out as a fundamental tool for the survival of the species (Di Cera, 2009; da Silva, 2017). Based on several studies conducted over the years, serine peptidases represent the best-known group of proteolytic enzymes among the seven catalytic types of this group of enzymes that are crucial for all organisms (Di Cera, 2009; da Silva, 2017). Metallopeptidase, cysteine peptidase, and aspartic peptidase are also enzymes that are studied in depth. What makes serine peptidases crucial tools for different fungal lifestyles from an enzyme catalysis standpoint? To answer this question, the enzyme catalytic properties needs to be detailed. This catalytic type of proteolytic enzyme is characterized by the conventional catalytic triad, His, Ser, and Asp, where the serine residue is responsible for the nucleophilic cleavage of the peptide bond (Di Cera, 2009). Some serine peptidases have modifications in the catalytic triad or dyad. However, serine residues are characteristic in the active sites and they define the mechanism of action of these enzymes (Hedstrom, 2002; da Silva, 2017). Based on the different fungal lifestyle, it is important to highlight the versatility of serine peptidases in the degradation of proteins present in fungal growth media. When observing pathogenic fungi in plants and animals, serine peptidases are important to hydrolyze tissue proteins favoring fungal metabolism and the spread of infection. In saprophytic fungi, serine peptidases are also extremely important in decomposing biomass. Thus, serine peptidases in fungi isolated from the soil have been frequently characterized. Numerous investigations have described this in the literature. The same is also observed in symbiotic fungi associated with animals and plants. Notably, it is important to mention that symbiotic fungi have less subtilisins and other serine peptidase family members than saprotrophic and pathogenic fungi (Zanphorlin et al., 2011; da Silva et al., 2013a,b, 2014; Graminho et al., 2013; Biaggio et al., 2016; Ida et al., 2016; da Silva, 2017). The catalytic properties of serine peptidases deserve more attention. Many investigations have described the effects of the broad pH and temperature range on the enzymatic activity of fungal serine peptidases (da Silva et al., 2013a,b, 2014; Graminho et al., 2013; Biaggio et al., 2016; Ida et al., 2016; da Silva, 2017), which can be categorized as endo or exopeptidases (da Silva, 2017). It is possible to observe reports of fungal serine peptidases with optimum activity varying between pH 6.0–11.0 and temperatures between 50 and 70°C. In general, extracellular serine peptidases secreted by fungi have a broad spectrum of action over different proteins. Some studies have demonstrated the secretion of serine peptidases acting on different amino acid sequences (Graminho et al., 2013; da Silva et al., 2014). Some studies have indicated the broad spectrum of protein hydrolysis by serine peptidases on different peptide substrate sequences. This was observed by Zanphorlin et al. (2011) in Myceliophthora spp., Graminho et al. (2013) in Penicillium waksmanii, and Watson et al. (2011) and da Silva et al. (2014) in Aspergillus fumigatus. In another study regarding substrate specificity, Biaggio et al. (2016) reported that an extracellular serine peptidase from Aspergillus terreus exhibited low specificity at the S1 subsite, accepting several amino acids in this position and having the highest catalytic efficiency (kcat/KM) when threonine and tyrosine were located at P1. This demonstrates the importance of these enzymes in the degradation of proteins present in the fungal growth substrate, the proteolysis of which favors the assimilation of amino acids fundamental for the survival of the microorganism. Here, it is important to emphasize that the biochemical characteristics highlighting the performance of these enzymes correlate with optimal growth conditions for most fungi, thereby establishing their importance with respect to fungal ubiquity in the biosphere. It is also essential to point out that the broad pH and temperature range for enzymatic activity, and the versatility in hydrolyzing a broad spectrum of proteins, establish extracellular serine peptidases as essential components in the exploration of nutritional environmental resources, which facilitate the fungal kingdom with representative species with varying lifestyles. It is extremely important to highlight the scientific contribution of the paper authored by Muszewska et al. (2017). Here, an argument was made to better relate the catalytic versatility of serine peptidases as fundamental tools for different fungal lifestyles and their importance to the exploration of different habitats on the planet. The author confirms being the sole contributor of this work and approved it for publication. The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Biaggio, R. T., Silva, R. R., Rosa, N. G., Leite, R. S., Arantes, E. C., Cabral, T. P., et al. (2016). Purification and biochemical characterization of an extracellular serine peptidase from Aspergillus terreus. Prep. Biochem. Biotechnol. 46, 298–304. doi: 10.1080/10826068.2015.1031387 PubMed Abstract | CrossRef Full Text | Google Scholar da Silva, R. R. (2017). Bacterial and fungal proteolytic enzymes: production, catalysis and potential applications. Appl. Biochem. Biotechnol. 183, 1–19. doi: 10.1007/s12010-017-2427-2 PubMed Abstract | CrossRef Full Text | Google Scholar da Silva, R. R., Ângelo, T., and Cabral, H. (2013a). Comparative evaluation of peptidases produced by Penicillium corylophilum and Penicillium waksmanii in solid state fermentation using agro-industrial residues. J. Agric. Sci. Technol. B 3, 230–237. Google Scholar da Silva, R. R., de Freitas Cabral, T. P., Rodrigues, A., and Cabral, H. (2013b). Production and partial characterization of serine and metallo peptidases secreted by Aspergillus fumigatus Fresenius in submerged and solid state fermentation. Braz. J. Microbiol. 44, 235–243. doi: 10.1590/S1517-83822013000100034 PubMed Abstract | CrossRef Full Text | Google Scholar da Silva, R. R., Caetano, R. C., Okamoto, D. N., de Oliveira, L. C., Bertolin, T. C., Juliano, M. A., et al. (2014). The identification and biochemical properties of the catalytic specificity of a serine peptidase secreted by Aspergillus fumigatus Fresenius. Prot. Pept. Lett. 21, 663–671. doi: 10.2174/0929866521666140408114646 PubMed Abstract | CrossRef Full Text | Google Scholar Di Cera, E. (2009). Serine proteases. IUBMB Life 61, 510–515. doi: 10.1002/iub.186 PubMed Abstract | CrossRef Full Text | Google Scholar Graminho, E. R., da Silva, R. R., de Freitas Cabral, T. P., Arantes, E. C., da Rosa, N. G., Juliano, L., et al. (2013). Purification, characterization, and specificity determination of a new serine protease secreted by Penicillium waksmanii. Appl. Biochem. Biotechnol. 169, 201–214. doi: 10.1007/s12010-012-9974-3 PubMed Abstract | CrossRef Full Text | Google Scholar Hedstrom, L. (2002). Serine protease mechanism and specificity. Chem. Rev. 102, 4501–4523. doi: 10.1021/cr000033x PubMed Abstract | CrossRef Full Text | Google Scholar Ida, É. L., da Silva, R. R., de Oliveira, T. B., Souto, T. B., Leite, J. A., Rodrigues, A., et al. (2016). Biochemical properties and evaluation of washing performance in commercial detergent compatibility of two collagenolytic serine peptidases secreted by Aspergillus fischeri and Penicillium citrinum. Prep. Biochem. Biotechnol. 47, 282–290. doi: 10.1080/10826068.2016.1224247 PubMed Abstract | CrossRef Full Text | Google Scholar Muszewska, A., Stepniewska-Dziubinska, M. M., Steczkiewicz, K., Pawlowska, J., Dziedzic, A., and Ginalski, K. (2017). Fungal lifestyle reflected in serine protease repertoire. Sci. Rep. 7:9147. doi: 10.1038/s41598-017-09644-w PubMed Abstract | CrossRef Full Text | Google Scholar Watson, D. S., Feng, X., Askew, D. S., Jambunathan, K., Kodukula, K., and Galande, A. K. (2011). Substrate specifity profiling on the Aspergillus fumigatus proteolytic secretome reveals consensus motifs with predominance of Ile/Leu and Phe/Tyr. PLoS ONE 6, 1–13. doi: 10.1371/journal.pone.0021001 PubMed Abstract | CrossRef Full Text | Google Scholar Zanphorlin, L. M., Cabral, H., Arantes, E., Assis, D., Juliano, L., Juliano, M. A., et al. (2011). Purification and characterization of a new alkaline serine protease from the thermophilic fungus Myceliophthora sp. Process Biochem. 46, 2137–2143. doi: 10.1016/j.procbio.2011.08.014 CrossRef Full Text | Google Scholar Keywords: biotechnology, catalysis, fungal enzyme, lifestyle, protease Citation: da Silva RR (2018) Commentary: Fungal lifestyle reflected in serine protease repertoire. Front. Microbiol. 9:467. doi: 10.3389/fmicb.2018.00467 Received: 13 December 2017; Accepted: 28 February 2018; Published: 13 March 2018. Edited by: Reviewed by: Copyright © 2018 da Silva. 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 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: Ronivaldo R. da Silva, [email protected]
Published: 28 February 2018
Frontiers in Robotics and AI, Volume 5; https://doi.org/10.3389/frobt.2018.00017

Abstract:
Recent articles by Schneider and Turner (Turner and Schneider, 2017; Schneider and Turner, 2017) outline an artificial consciousness test (ACT); a new, purely behavioral process to probe subjective experience (“phenomenal consciousness”: tickles, pains, visual experiences, and so on) in machines; work that has already resulted in a provisional patent application from Princeton University (Turner and Schneider, in press). In light of the author’s generic skepticism of “consciousness qua computation” (Bishop, 2002, 2009) and Tononi and Koch’s “Integrated Information Theory”-driven skepticism regarding the possibility of consciousness arising in any classical digital computer (due to low ϕmax) (Tononi and Koch, 2015), consideration is given to the claimed sufficiency of ACT to determine the phenomenal status of a computational artificial intelligence (AI) system. In science and science fiction, the hope is periodically reignited that a computer system will one day be conscious in virtue of its execution of an appropriate program; indeed, as far back as 2004, the UK funding body EPSRC awarded an “Adventure Fund” grant [GR/S47946/01] of around £500,000, to a team of “Roboteers and Psychologists” at the Universities of Essex and Bristol, with a goal of instantiating “machine consciousness” in a humanoid-like robot called Cronos. In addition, extant claims of “machine consciousness” have long been claimed in the scientific literature. (For example, in 2002, Kevin Warwick announced his “Cybernetic learning robots” to be “as conscious as a slug” (Warwick, 2002).) Other proposals for conscious machines have ranged from the mere “functional consciousness” of Stan Franklin’s “Intelligent Distribution Agent” (Franklin, 2003) to the claim of “true conscious cognition” of [Pentti] “Haikonen’s Cognitivist Architecture” (HCA), an architecture that seeks to reproduce the processes of perception, inner imagery, inner speech, pain, pleasure, emotions, and the cognitive functions behind these. Haikonen has asserted that, when implemented with sufficient complexity, HCA will develop consciousness (Haikonen, 2012). It is in this febrile atmosphere that Schneider and Turner (2017) highlight the importance of a test to ascertain machine consciousness as (i) it may be deemed morally improper to oblige such machines to “serve” humans; (ii) it could raise safety concerns; and (iii) it could impact on the viability of brain-implant technologies (Hampson et al., 2013). Hence, given the impact of an ACT result that ascribes consciousness to machine, it is critical that the test is both robust and accurate; in this context, Schneider and Turner explicitly clarify that passing ACT “… is sufficient but not necessary evidence for AI consciousness.” Given that one of the most forceful indications that humans experience consciousness is that every adult can readily and quickly grasp concepts based on this quality, Schneider and Turner describe their ACT as follows: [T]he ACT would challenge an AI with a series of increasingly demanding natural language interactions to see how quickly and readily it can grasp and use concepts and scenarios based on the internal experiences we associate with consciousness. At the most elementary level we might simply ask the machine if it conceives of itself as anything other than its physical self. At a more advanced level, we might see how it deals with ideas and scenarios such as those mentioned in the previous paragraph. At an advanced level, its ability to reason about and discuss philosophical questions such as ‘the hard problem of consciousness’ would be evaluated. At the most demanding level, we might see if the machine invents and uses such a consciousness-based concept on its own, without relying on human ideas and inputs. Turner and Schneider claim that the above procedure is sufficient to establish consciousness in any “boxed-in” AI system (i.e., any AI not connected to the Internet); any AI that passes ACT will be conscious. But could a non-conscious AI machine cheat? Schneider and Turner (2017) specifically consider this question, outlining the following possible scenario: Even today’s robots can be programmed to make convincing utterances about consciousness, and a truly superintelligent machine could perhaps even use information about neurophysiology to infer the presence of consciousness in humans. If sophisticated but non-conscious AIs aim to mislead us into believing that they are conscious for some reason, their knowledge of human consciousness could help them do so. The solution here, so the author’s suggest, is simply to “box-in” the AI, denying it access to the Internet and “… making it unable to get information about the world or act outside of a circumscribed domain.” But this methodology yields its own problems. For even if we cut off access to the Internet—and the AIs knowledge domain is restricted to “prohibit it from gaining any knowledge of the world, especially information about conscious experience and neuroscience”—we are led to the problem of explicitly identifying, a priori, precisely what knowledge needs to be circumscribed in this manner; alternatively, as one of the reviewers of this short piece pithily observed, if we cut off access to the Internet but allow access to the entire knowledge of the World Wide Web to be “pre-loaded” into the “box,” then the boxing-in idea would not appear to have added anything to the argument. In addition, because the principle of computational multiple realizability states that, despite potential underlying physical differences in operation, it is possible to run the same functional program (e.g., Microsoft Word) on very different architectures (cf. Windows, MAC, SCO Unix, etc.), it is clear that were an AI’s successful responses merely generated by a suitably large “look-up table” (Block, 1981), it would still qualify as “passing” ACT. Moreover, Schneider clarified at PTAI conference (Leeds, 2017) that ACT is robust to repeated use of exactly the same question set: if machine M, given a set A of k questions, responds with a set A* of k answers, in such a way that it is deemed to have passed ACT (and consciousness is ascribed to M), then if, posing exactly the same question set A to a second machine M*, generates exactly the same responses A*, then M* must also be deemed to have passed ACT; so construed, we note that the test is explicitly behaviorist in its conception. Unfortunately, an unintended consequence of such behaviorism is that any trivial machineM**, hard coded to explicitly respond to question set A with responses A* (i.e., any machine simply programmed to output these k responses to those k questions), must also be deemed to pass ACT. For these reasons, unless we are content to ascribe conscious sensation to a mere look-up table [of a list of acceptable questions and answers], it is not clear that ACT (or any purely behavioral test) can succeed as a sufficient test to establish phenomenal consciousness in an artificial system; furthermore, it is observed that objections to behaviorism along these lines date back at least to Chomsky’s sharp critique (Chomsky, 1959) of the cognitive vapidity of Skinner’s (Skinner, 1957) approach to language. The author confirms being the sole contributor of this work and approved it for publication. The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. I would like to thank the reviewers of this piece for their very helpful and insightful comments. Bishop, J. M. (2002). “Dancing with Pixies: strong AI and panpsychism,” in Views into the Chinese Room, eds J. Preston and J. M. Bishop (Oxford, UK: Clarendon Press), 360–378. Google Scholar Bishop, J. M. (2009). Why robots can’t feel pain. Minds Mach. 19, 507–516. doi: 10.1007/s11023-009-9173-3 CrossRef Full Text | Google Scholar Block, N. (1981). Psychologism and behaviourism. Philos. Rev. 90, 5–43. doi:10.2307/2184371 CrossRef Full Text | Google Scholar Chomsky, N. (1959). A review of B. F. Skinners verbal behavior. Language 35, 26–58. doi:10.2307/411334 CrossRef Full Text | Google Scholar Franklin, S. (2003). “IDA: a conscious artefact,” in Machine Consciousness, ed. O. Holland (Exeter, UK: Imprint Academic), 47–67. Google Scholar Haikonen, P. (2012). Consciousness and Robot Sentience. Singapore: World Scientific. Google Scholar Hampson, R. E., Song, D., Opris, I., Santos, L. M., Shin, D. C., Gerhardt, G. A., et al. (2013). Facilitation of memory encoding in primate hippocampus by a neuroprosthesis that promotes task-specific neural firing. J. Neural Eng. 10, 066013. doi:10.1088/1741-2560/10/6/066013 PubMed Abstract | CrossRef Full Text | Google Scholar Schneider, S., and Turner, E. L. (2017). Is Anyone Home? A Way to Find Out If AI Has Become Self-Aware. Scientific American Blog Network. Google Scholar Skinner, B. F. (1957). Verbal Behavior. Acton, MA: Copley Publishing Group. Google Scholar Tononi, G., and Koch, C. (2015). Consciousness: here, there and everywhere? Philos. Trans. R. Soc. Lond. B Biol. Sci. 370, 20140167. doi:10.1098/rstb.2014.0167 CrossRef Full Text | Google Scholar Turner, E. L., and Schneider, S. (2017). Princeton University. Behavioral Tests for AI Consciousness, Empathy, and Goal Content Integrity. Patent Application No. 62/532,749. Google Scholar Turner, E. L., and Schneider, S. (in press). “The ACT test for AI consciousness,” in Ethics of Artificial Intelligence, eds M. Liao and D. Chalmers (Oxford University Press). Google Scholar Warwick, K. (2002). “Alien encounters,” in Views into the Chinese Room, eds J. Preston and J. M. Bishop (Oxford, UK: Clarendon Press), 308–318. Google Scholar Keywords: machine consciousness, Turing test, ACT, beaviorism, artificial intelligence Citation: Bishop JM (2018) Is Anyone Home? A Way to Find Out If AI Has Become Self-Aware. Front. Robot. AI 5:17. doi: 10.3389/frobt.2018.00017 Received: 28 November 2017; Accepted: 05 February 2018; Published: 28 February 2018 Edited by: Reviewed by: Copyright: © 2018 Bishop. 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 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: John Mark Bishop, [email protected]
Oxford Dictionary of National Biography; https://doi.org/10.1093/odnb/9780192683120.013.3514

Abstract:
Bromley, Valentine Walter(1848–1877), painter, great-grandson of William Bromley (1769–1842) [q.v.], was born in London on 14 Feb. 1848. From his childhood he manifested a remarkable faculty for art, both as an original designer and as a depicter of nature. He was especially remarkable for invention and swiftness of execution. He contributed largely to the ‘Illustrated London News,’ and illustrated the American travels of Lord Dunraven, whom he accompanied in his tour. He was an associate of the Institute of Painters in Water Colours, and was an exhibitor at the Royal Academy at the time of his death. He died very unexpectedly from an attack of smallpox on 30 April 1877, just as he had undertaken an important series of illustrations of Shakespeare and the Bible. He was a thorough artist, as full of animation and energy as of talent, and greatly beloved for his affectionate temper and warmth of heart. He had been married only a few months to a lady artist of considerable mark, Ida, daughter of Mr. John Forbes-Robertson. His picture of ‘Troilus and Cressida’ is engraved in the ‘Art Journal’ for 1873....
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