tbuckley/cabot-search huggingface dataset:
A New Vaccine for Chikungunya Virus
Authors: Kenneth A. Stapleford, Mark J. Mulligan
Journal: JAMA (2020)

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C19orf66 is an interferon-induced inhibitor of HCV replication that restricts formation of the viral replication organelle
Authors: Volker Kinast, Agnieszka Plociennikowska, None Anggakusuma, Thilo Bracht, Daniel Todt, Richard J.P. Brown, Tujana Boldanova, Yudi Zhang, Yannick Brüggemann, Martina Friesland, Michael Engelmann, Gabrielle Vieyres, Ruth Broering, Florian W.R. Vondran, Markus H. Heim, Barbara Sitek, Ralf Bartenschlager, Thomas Pietschmann, Eike Steinmann
Journal: Journal of Hepatology (2020)

HCV is a positive-strand RNA virus that primarily infects human hepatocytes. Recent studies have reported that C19orf66 is expressed as an interferon (IFN)-stimulated gene; however, the intrinsic regulation of this gene within the liver as well as its antiviral effects against HCV remain elusive.Expression of C19orf66 was quantified in both liver biopsies and primary human hepatocytes, with or without HCV infection. Mechanistic studies of the potent anti-HCV phenotype mediated by C19orf66 were conducted using state-of-the-art virological, biochemical and genetic approaches, as well as correlative light and electron microscopy and transcriptome and proteome analysis.Upregulation of C19orf66 mRNA was observed in both primary human hepatocytes upon HCV infection and in the livers of patients with chronic hepatitis C (CHC). In addition, pegIFNα/ribavirin therapy induced C19orf66 expression in patients with CHC. Transcriptomic profiling and whole cell proteomics of hepatoma cells ectopically expressing C19orf66 revealed no induction of other antiviral genes. Expression of C19orf66 restricted HCV infection, whereas CRIPSPR/Cas9 mediated knockout of C19orf66 attenuated IFN-mediated suppression of HCV replication. Co-immunoprecipitation followed by mass spectrometry identified a stress granule protein-dominated interactome of C19orf66. Studies with subgenomic HCV replicons and an expression system revealed that C19orf66 expression impairs HCV-induced elevation of phosphatidylinositol-4-phosphate, alters the morphology of the viral replication organelle (termed the membranous web) and thereby targets viral RNA replication.C19orf66 is an IFN-stimulated gene, which is upregulated in hepatocytes within the first hours post IFN treatment or HCV infection in vivo. The encoded protein possesses specific antiviral activity against HCV and targets the formation of the membranous web. Our study identifies C19orf66 as an IFN-inducible restriction factor with a novel antiviral mechanism that specifically targets HCV replication.Interferon-stimulated genes are thought to be important to for antiviral immune responses to HCV. Herein, we analysed C19orf66, an interferon-stimulated gene, which appears to inhibit HCV replication. It prevents the HCV-induced elevation of phosphatidylinositol-4-phosphate and alters the morphology of HCV's replication organelle.
GP who ran medical report “factory” and made dishonest witness statement is struck off by High Court
Authors: Clare Dyer
Journal: BMJ (2020)

A GP who ran a medical report writing “factory” and abused his position of trust as an expert witness has been struck off the UK medical register by the High Court.1

A medical practitioners tribunal decided to suspend Asef Zafar from the register for 12 months last May,2 but the General Medical Council (GMC) and the Professional Standards Authority appealed to the High Court. Allowing the appeal, the two judge court refused Zafar’s application to send the case back to the tribunal to decide again on sanction, concluding that “no reasonable panel . . . could do anything other than direct erasure.”

Zafar had altered part of a medical report at the request of the solicitor for a car accident victim and then …
Hard domains, biased rationalizations, and unanswered empirical questions
Authors: Stephen E Weinberg, Jonathan M Weinberg
Journal: Behavioral and Brain Sciences (2020)

Abstract Cushman raises the intriguing possibility that rationalization accesses/constructs intuitions that are not otherwise cognitively available. However, he substantially over-reaches in arguing that rationalization is mostly right on average, based on claims that the process must have emerged adaptively. The adaptiveness of “bounded rationalization” is domain specific and is unlikely to be adaptive in a large number of important applications.
The Biology of the HIV-1 Latent Reservoir and Implications for Cure Strategies
Authors: Lillian B. Cohn, Nicolas Chomont, Steven G. Deeks
Journal: Cell Host & Microbe (2020)

Antiretroviral therapy (ART) inhibits HIV replication but is not curative. During ART, the integrated HIV genome persists indefinitely within CD4+ T cells and perhaps other cells. Here, we describe the mechanisms thought to contribute to its persistence during treatment and highlight findings from numerous recent studies describing the importance of cell proliferation in that process. Continued progress elucidating the biology will enhance our ability to develop effective curative interventions.
New effects of caffeine on corticotropin‐releasing hormone (CRH)‐induced stress along the intrafollicular classical hypothalamic–pituitary–adrenal (HPA) axis (CRH‐R1/2, IP<sub>3</sub>‐R, ACTH, MC‐R2) and the neurogenic non‐HPA axis (substance P, p75<sup>NTR</sup>and TrkA) in<i>ex vivo</i>human male androgenetic scalp hair follicles
Authors: T.W. Fischer, A. Bergmann, N. Kruse, K. Kleszczynski, C. Skobowiat, A.T. Slominski, R. Paus
Journal: British Journal of Dermatology (2020)

Human hair is highly responsive to stress, and human scalp hair follicles (HFs) contain a peripheral neuroendocrine equivalent of the systemic hypothalamic–pituitary–adrenal (HPA) stress axis. Androgenetic alopecia (AGA) is supposed to be aggravated by stress. We used corticotropin‐releasing hormone (CRH), which triggers the HPA axis, to induce a stress response in human ex vivo male AGA HFs. Caffeine is known to reverse testosterone‐mediated hair growth inhibition in the same hair organ culture model. To investigate whether caffeine would antagonize CRH‐mediated stress in these HFs. HFs from balding vertex area scalp biopsies of men affected by AGA were incubated with CRH (10−7 mol L−1) with or without caffeine (0·001% or 0·005%). Compared to controls, CRH significantly enhanced the expression of catagen‐inducing transforming growth factor‐β2 (TGF‐β2) (P < 0·001), CRH receptors 1 and 2 (CRH‐R1/2) (P < 0·01), adrenocorticotropic hormone (ACTH) (P < 0·001) and melanocortin receptor 2 (MC‐R2) (P < 0·001), and additional stress‐associated parameters, substance P and p75 neurotrophin receptor (p75NTR). CRH inhibited matrix keratinocyte proliferation and expression of anagen‐promoting insulin‐like growth factor‐1 (IGF‐1) and the pro‐proliferative nerve growth factor receptor NGF‐tyrosine kinase receptor A (TrkA). Caffeine significantly counteracted all described stress effects and additionally enhanced inositol trisphosphate receptor (IP3‐R), for the first time detected in human HFs. These findings provide the first evidence in ex vivo human AGA HFs that the stress mediator CRH induces not only a complex intrafollicular HPA response, but also a non‐HPA‐related stress response. Moreover, we show that these effects can be effectively antagonized by caffeine. Thus, these data strongly support the hypothesis that stress can impair human hair physiology and induce hair loss, and that caffeine may effectively counteract stress‐induced hair damage and possibly prevent stress‐induced hair loss.
Rational rationalization and System 2
Authors: Wim De Neys
Journal: Behavioral and Brain Sciences (2020)

Abstract In this commentary, I highlight the relevance of Cushman's target article for the popular dual-process framework of thinking. I point to the problematic characterization of rationalization in traditional dual-process models and suggest that in line with recent advances, Cushman's rational rationalization account offers a way out of the rationalization paradox.
A Multicenter Open Label Phase II Study of Pomalidomide, Cyclophosphamide and Dexamethasone in Relapse Multiple Myeloma Patients Initially Treated with Lenalidomide, Bortezomib and Dexamethasone
Authors: Laurent Garderet, Frederique Kuhnowski, jean Yves Mary, Murielle Roussel, Martine Escoffre-Barbe, Ingrid Lafon, Thierry Facon, Lionel Karlin, Aurore Perrot, Philippe Moreau, Gerald Marit, Anne-Marie Stoppa, Jean-Pierre Marolleau, Carine Chaleteix, Mourad Tiab, Carla Araujo, Pascal Lenain, Margaret Macro, Eric Voog, Lofti Benboubker, Olivier Allangba, Eric Jourdan, Mohamad Mohty, Herve Avet Loiseau, Claire Mathiot, Michel Attal
Journal: Blood (2017)
The Mental Health Consequences of COVID-19 and Physical Distancing
Authors: Sandro Galea, Raina M. Merchant, Nicole Lurie
Journal: JAMA Internal Medicine (2020)

The Need for Prevention and Early InterventionSince the first case of novel coronavirus disease 2019 (COVID-19) was diagnosed in December 2019, it has swept across the world and galvanized global action.This has brought unprecedented efforts to institute the practice of physical distancing (called in most cases "social distancing") in countries all over the world, resulting in changes in national behavioral patterns and shutdowns of usual day-to-day functioning.While these steps may be critical to mitigate the spread of this disease, they will undoubtedly have consequences for mental health and well-being in both the short and long term.These consequences are of sufficient importance that immediate efforts focused on prevention and direct intervention are needed to address the impact of the outbreak on individual and population level mental health.The sparse literature on the mental health consequences of epidemics relates more to the sequelae of the disease itself (eg, mothers of children with congenital Zika syndrome) than to social distancing.However, largescale disasters, whether traumatic (eg, the World Trade Center attacks or mass shootings), natural (eg, hurricanes), or environmental (eg, Deepwater Horizon oil spill), are almost always accompanied by increases in depression, posttraumatic stress disorder (PTSD), substance use disorder, a broad range of other mental and behavioral disorders, domestic violence, and child abuse. 1 For example, 5% of the population affected by Hurricane Ike in 2008 met the criteria for major depressive disorder in the month after the hurricane; 1 out of 10 adults in New York City showed signs of the disorder in the month following the 9/11 attacks. 2,3And almost 25% of New Yorkers reported increased alcohol use after the attacks. 4Communities affected by the Deepwater Horizon oil spill showed signs of clinically significant depression and anxiety. 5The SARS epidemic was also associated with increases in PTSD, stress, and psychological distress in patients and clinicians. 6For such events, the impact on mental health can occur in the immediate aftermath and then persist over long time periods.In the context of the COVID-19 pandemic, it appears likely that there will be substantial increases in anxiety and depression, substance use, loneliness, and domestic violence; and with schools closed, there is a very real possibility of an epidemic of child abuse.This concern is so significant that the UK has issued psychological first aid guidance from Mental Health UK. 7 While the literature is not clear about the science of population level prevention, it leads us to conclude that 3 steps, taken now, can help us proactively prepare for the inevitable increase in mental health conditions and associated sequelae that are the consequences of this pandemic.
Artificial Intelligence to Detect Papilledema from Ocular Fundus Photographs
Authors: Dan Milea, Raymond P. Najjar, Zhubo Jiang, Daniel Ting, Caroline Vasseneix, Xinxing Xu, Masoud Aghsaei Fard, Pedro Fonseca, Kavin Vanikieti, Wolf A. Lagrèze, Chiara La Morgia, Carol Y. Cheung, Steffen Hamann, Christophe Chiquet, Nicolae Sanda, Hui Yang, Luis J. Mejico, Marie-Bénédicte Rougier, Richard Kho, Thi H.C. Tran, Shweta Singhal, Philippe Gohier, Catherine Clermont-Vignal, Ching-Yu Cheng, Jost B. Jonas, Patrick Yu-Wai-Man, Clare L. Fraser, John J. Chen, Selvakumar Ambika, Neil R. Miller, Yong Liu, Nancy J. Newman, Tien Y. Wong, Valérie Biousse
Journal: New England Journal of Medicine (2020)

Nonophthalmologist physicians do not confidently perform direct ophthalmoscopy. The use of artificial intelligence to detect papilledema and other optic-disk abnormalities from fundus photographs has not been well studied.We trained, validated, and externally tested a deep-learning system to classify optic disks as being normal or having papilledema or other abnormalities from 15,846 retrospectively collected ocular fundus photographs that had been obtained with pharmacologic pupillary dilation and various digital cameras in persons from multiple ethnic populations. Of these photographs, 14,341 from 19 sites in 11 countries were used for training and validation, and 1505 photographs from 5 other sites were used for external testing. Performance at classifying the optic-disk appearance was evaluated by calculating the area under the receiver-operating-characteristic curve (AUC), sensitivity, and specificity, as compared with a reference standard of clinical diagnoses by neuro-ophthalmologists.The training and validation data sets from 6779 patients included 14,341 photographs: 9156 of normal disks, 2148 of disks with papilledema, and 3037 of disks with other abnormalities. The percentage classified as being normal ranged across sites from 9.8 to 100%; the percentage classified as having papilledema ranged across sites from zero to 59.5%. In the validation set, the system discriminated disks with papilledema from normal disks and disks with nonpapilledema abnormalities with an AUC of 0.99 (95% confidence interval [CI], 0.98 to 0.99) and normal from abnormal disks with an AUC of 0.99 (95% CI, 0.99 to 0.99). In the external-testing data set of 1505 photographs, the system had an AUC for the detection of papilledema of 0.96 (95% CI, 0.95 to 0.97), a sensitivity of 96.4% (95% CI, 93.9 to 98.3), and a specificity of 84.7% (95% CI, 82.3 to 87.1).A deep-learning system using fundus photographs with pharmacologically dilated pupils differentiated among optic disks with papilledema, normal disks, and disks with nonpapilledema abnormalities. (Funded by the Singapore National Medical Research Council and the SingHealth Duke-NUS Ophthalmology and Visual Sciences Academic Clinical Program.).
Restructuring Structural Heart Disease Practice During the COVID-19 Pandemic
Authors: Christine J. Chung, Tamim M. Nazif, Mariusz Wolbinski, Emad Hakemi, Mark Lebehn, Russell Brandwein, Carolina Pinheiro Rezende, James Doolittle, Leroy Rabbani, Nir Uriel, Allan Schwartz, Angelo Biviano, Elaine Wan, Lisa Hathaway, Rebecca Hahn, Omar Khalique, Nadira Hamid, Vivian Ng, Amisha Patel, Torsten Vahl, Ajay Kirtane, Vinayak Bapat, Isaac George, Martin B. Leon, Susheel K. Kodali
Journal: Journal of the American College of Cardiology (2020)
Notes from the Field: Seasonal Human Influenza A(H3N2) and Influenza A(H1N1)pdm09 Reassortant Infection — Idaho, 2019
Authors: Randi Pedersen, Vonnita Barton, Jennifer Tripp, Lenee Blanton, John Barnes, Christine Hahn
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

§ This new reassortant virus was identified and investigated in March 2019.Despite the delay in presenting the results of this investigation, the recommendation for continued surveillance of emerging influenza viruses has particular relevance at this time.
Compassionate Use of Remdesivir for Patients with Severe Covid-19
Authors: Jonathan Grein, Norio Ohmagari, Daniel Shin, George Diaz, Erika Asperges, Antonella Castagna, Torsten Feldt, Gary Green, Margaret L Green, François-Xavier Lescure, Emanuele Nicastri, Rentaro Oda, Kikuo Yo, Eugenia Quiros-Roldan, Alex Studemeister, John Redinski, Seema Ahmed, Jorge Bernett, Daniel Chelliah, Danny Chen, Shingo Chihara, Stuart H Cohen, Jennifer Cunningham, Antonella D'Arminio Monforte, Saad Ismail, Hideaki Kato, Giuseppe Lapadula, Erwan L'Her, Toshitaka Maeno, Sumit Majumder, Marco Massari, Marta Mora-Rillo, Yoshikazu Mutoh, Duc Nguyen, Ewa Verweij, Alexander Zoufaly, Anu O Osinusi, Adam DeZure, Yang Zhao, Lijie Zhong, Anand Chokkalingam, Emon Elboudwarej, Laura Telep, Leighann Timbs, Ilana Henne, Scott Sellers, Huyen Cao, Susanna K Tan, Lucinda Winterbourne, Polly Desai, Robertino Mera, Anuj Gaggar, Robert P Myers, Diana M Brainard, Richard Childs, Timothy Flanigan
Journal: New England Journal of Medicine (2020)

Remdesivir, a nucleotide analogue prodrug that inhibits viral RNA polymerases, has shown in vitro activity against SARS-CoV-2. We provided remdesivir on a compassionate-use basis to patients hospitalized with Covid-19, the illness caused by infection with SARS-CoV-2. Patients were those with confirmed SARS-CoV-2 infection who had an oxygen saturation of 94% or less while they were breathing ambient air or who were receiving oxygen support. Patients received a 10-day course of remdesivir, consisting of 200 mg administered intravenously on day 1, followed by 100 mg daily for the remaining 9 days of treatment. This report is based on data from patients who received remdesivir during the period from January 25, 2020, through March 7, 2020, and have clinical data for at least 1 subsequent day. Of the 61 patients who received at least one dose of remdesivir, data from 8 could not be analyzed (including 7 patients with no post-treatment data and 1 with a dosing error). Of the 53 patients whose data were analyzed, 22 were in the United States, 22 in Europe or Canada, and 9 in Japan. At baseline, 30 patients (57%) were receiving mechanical ventilation and 4 (8%) were receiving extracorporeal membrane oxygenation. During a median follow-up of 18 days, 36 patients (68%) had an improvement in oxygen-support class, including 17 of 30 patients (57%) receiving mechanical ventilation who were extubated. A total of 25 patients (47%) were discharged, and 7 patients (13%) died; mortality was 18% (6 of 34) among patients receiving invasive ventilation and 5% (1 of 19) among those not receiving invasive ventilation. In this cohort of patients hospitalized for severe Covid-19 who were treated with compassionate-use remdesivir, clinical improvement was observed in 36 of 53 patients (68%). Measurement of efficacy will require ongoing randomized, placebo-controlled trials of remdesivir therapy. (Funded by Gilead Sciences.).
Abstract 16534: Physical Functioning And Quality Of Life In Different Congenital Heart Defects: Comparative Analysis In 3,589 Patients From 15 Countries
Authors: Philip Moons, Koen Luyckx, Corina Thomet, Werner Budts, Junko Enomoto, Maayke A Sluman, Chun-Wei Lu, Jamie L Jackson, Paul Khairy, Stephen Cook, Shanthi Chidambarathanu, Luis E Alday, Katrine Eriksen, Mikael G Dellborg, Malin Berghammer, Bengt Johansson, Andrew Mackie, Samuel Menahem, Maryanne Caruana, Gruschen Veldtman, Alexandra Soufi, Susan M Fernandes, Kamila White, Edward Callus, Shelby Kutty, Fouke Ombelet, Silke Apers, Adrienne Kovacs
Journal: Circulation (2019)

Objectives: Higher complexity of congenital heart defects (CHD) is found to be associated with poorer physical functioning and quality of life (QOL). Within complexity categories, there may be a la...
Multifunctional PVCL nanogels with redox-responsiveness enable enhanced MR imaging and ultrasound-promoted tumor chemotherapy
Authors: Fang Xu, Jianzhi Zhu, Lizhou Lin, Changchang Zhang, Wenjie Sun, Yu Fan, Fangfang Yin, Jan C. M. van Hest, Han Wang, Lianfang Du, Xiangyang Shi
Journal: Theranostics (2020)

Development of versatile nanoplatforms that simultaneously integrate therapeutic and diagnostic features for stimuli-responsive delivery to tumors remains a great challenge. In this work, we report a novel intelligent redox-responsive hybrid nanosystem composed of MnO2 nanoparticles (NPs) and doxorubicin (DOX) co-loaded within poly(N-vinylcaprolactam) nanogels (PVCL NGs) for magnetic resonance (MR) imaging-guided and ultrasound-targeted microbubble destruction (UTMD)-promoted tumor chemotherapy. Methods: PVCL NGs were first synthesized via a precipitation polymerization method, decorated with amines using ethylenediamine, and loaded with MnO2 NPs through oxidation with permanganate and DOX via physical encapsulation and Mn-N coordination bonding. The as-prepared DOX/MnO2@PVCL NGs were well characterized. UTMD-promoted cellular uptake and therapeutic efficacy of the hybrid NGs were assessed in vitro, and a xenografted tumor model was used to test the NGs for MR imaging and UTMD-promoted tumor therapy in vivo.Results: The as-prepared DOX/MnO2@PVCL NGs with a size of 106.8 nm display excellent colloidal stability, favorable biocompatibility, and redox-responsiveness to the reductive intracellular environment and tumor tissues having a relatively high glutathione (GSH) concentration that can trigger the synchronous release of Mn2+ for enhanced T1-weighted MR imaging and DOX for enhanced cancer chemotherapy. Moreover, the DOX/MnO2@PVCL NGs upon the UTMD-promotion exhibit a significantly enhanced tumor growth inhibition effect toward subcutaneous B16 melanoma owing to the UTMD-improved cellular internalization and tumor penetration. Conclusion: Our work thereby proposes a promising theranostic nanoplatform for stimuli-responsive T1-weighted MR imaging-guided tumor chemotherapy.
m6A-binding proteins: the emerging crucial performers in epigenetics
Authors: Yanchun Zhao, Yuanfei Shi, Huafei Shen, Wanzhuo Xie
Journal: Journal of Hematology & Oncology (2020)

Abstract N 6 -methyladenosine (m 6 A) is a well-known post-transcriptional modification that is the most common type of methylation in eukaryotic mRNAs. The regulation of m 6 A is dynamic and reversible, which is erected by m 6 A methyltransferases (“writers”) and removed by m 6 A demethylases (“erasers”). Notably, the effects on targeted mRNAs resulted by m 6 A predominantly depend on the functions of different m 6 A-binding proteins (“readers”) including YT521-B homology (YTH) domain family, heterogeneous nuclear ribonucleoproteins (HNRNPs), and insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs). Indeed, m 6 A readers not only participate in multiple procedures of RNA metabolism, but also are involved in a variety of biological processes. In this review, we summarized the specific functions and underlying mechanisms of m 6 A-binding proteins in tumorigenesis, hematopoiesis, virus replication, immune response, and adipogenesis.