tbuckley/cabot-search huggingface dataset:
Abnormal Liver Tests in COVID‐19: A Retrospective Observational Cohort Study of 1,827 Patients in a Major U.S. Hospital Network
Authors: Melanie A. Hundt, Yanhong Deng, Maria M. Ciarleglio, Michael H. Nathanson, Joseph K. Lim
Journal: Hepatology (2020)

Background and Aims The coronavirus‐19 disease (COVID‐19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 virus, is associated with significant morbidity and mortality attributable to pneumonia, acute respiratory distress syndrome, and multiorgan failure. Liver injury has been reported as a nonpulmonary manifestation of COVID‐19, but characterization of liver test abnormalities and their association with clinical outcomes is incomplete. Approach and Results We conducted a retrospective cohort study of 1,827 patients with confirmed COVID‐19 who were hospitalized within the Yale‐New Haven Health System between March 14, 2020 and April 23, 2020. Clinical characteristics, liver tests (aspartate aminotransferase [AST], alanine aminotransferase [ALT], alkaline phosphatase [ALP], total bilirubin [TBIL], and albumin) at three time points (preinfection baseline, admission, and peak hospitalization), and hospitalization outcomes (severe COVID‐19, intensive care unit [ICU] admission, mechanical ventilation, and death) were analyzed. Abnormal liver tests were commonly observed in hospitalized patients with COVID‐19, both at admission (AST 66.9%, ALT 41.6%, ALP 13.5%, and TBIL 4.3%) and peak hospitalization (AST 83.4%, ALT 61.6%, ALP 22.7%, and TBIL 16.1%). Most patients with abnormal liver tests at admission had minimal elevations 1‐2× the upper limit of normal (ULN; AST 63.7%, ALT 63.5%, ALP 80.0%, and TBIL 75.7%). A significant proportion of these patients had abnormal liver tests prehospitalization (AST 25.9%, ALT 38.0%, ALP 56.8%, and TBIL 44.4%). Multivariate analysis revealed an association between abnormal liver tests and severe COVID‐19, including ICU admission, mechanical ventilation, and death; associations with age, male sex, body mass index, and diabetes mellitus were also observed. Medications used in COVID‐19 treatment (lopinavir/ritonavir, hydroxychloroquine, remdesivir, and tocilizumab) were associated with peak hospitalization liver transaminase elevations &gt;5× ULN. Conclusions Abnormal liver tests occur in most hospitalized patients with COVID‐19 and may be associated with poorer clinical outcomes.
Bart-Pumphrey Syndrome
Authors: Khalil I Al-Hamdi, Anwar Qais Saadoon, Noor H Abduljabbar
Journal: JAMA Dermatology (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Dermatology journal
Should we pursue high obliteration rate or high hemostatic rate in the therapy of gastric varices?
Authors: Gin-Ho Lo
Journal: Endoscopy (2020)

See also:Endoscopic ultrasonography-guided deployment of embolization coils and cyanoacrylate injection in gastric varices versus coiling alone: a randomized trialEndoscopy 2020; 52(04): 268-275DOI: 10.1055/a-1123-9054See also:Reply to Dr. LoEndoscopy 2020; 52(08): 710-710DOI: 10.1055/a-1191-3206
Bovine breed-specific augmented reference graphs facilitate accurate sequence read mapping and unbiased variant discovery
Authors: Danang Crysnanto, Hubert Pausch
Journal: Genome biology (2020)

Abstract Background The current bovine genomic reference sequence was assembled from a Hereford cow. The resulting linear assembly lacks diversity because it does not contain allelic variation, a drawback of linear references that causes reference allele bias. High nucleotide diversity and the separation of individuals by hundreds of breeds make cattle ideally suited to investigate the optimal composition of variation-aware references. Results We augment the bovine linear reference sequence (ARS-UCD1.2) with variants filtered for allele frequency in dairy (Brown Swiss, Holstein) and dual-purpose (Fleckvieh, Original Braunvieh) cattle breeds to construct either breed-specific or pan-genome reference graphs using the vg toolkit . We find that read mapping is more accurate to variation-aware than linear references if pre-selected variants are used to construct the genome graphs. Graphs that contain random variants do not improve read mapping over the linear reference sequence. Breed-specific augmented and pan-genome graphs enable almost similar mapping accuracy improvements over the linear reference. We construct a whole-genome graph that contains the Hereford-based reference sequence and 14 million alleles that have alternate allele frequency greater than 0.03 in the Brown Swiss cattle breed. Our novel variation-aware reference facilitates accurate read mapping and unbiased sequence variant genotyping for SNPs and Indels. Conclusions We develop the first variation-aware reference graph for an agricultural animal ( 10.5281/zenodo.3759712 ). Our novel reference structure improves sequence read mapping and variant genotyping over the linear reference. Our work is a first step towards the transition from linear to variation-aware reference structures in species with high genetic diversity and many sub-populations.
Availability and Quality of Internet-Based Cardiopulmonary Resuscitation Training Films Featuring Women Experiencing Cardiac Arrest
Authors: Carlos W. Lynes, Lorrel E. Brown Toft
Journal: JAMA Cardiology (2020)

This study examines videos of cardiopulmonary resuscitation on Google and YouTube to discern the number that show women or female manikins and provide information to facilitate attempts to rescue women in cardiac arrest.
Abstract 15808: Using Machine Learning to Predict 30-Day Readmission of Patients Hospitalized With an Acute Myocardial Infarction
Authors: Ashley Francisco, Meagan E Stabler, William Hisey, Todd A Mackenzie, Chad Dorn, Jason Denton, Michael E Matheny, Jeremiah R Brown
Journal: Circulation (2018)

Introduction: Approximately 790,000 Americans have an AMI annually, of which 20% are readmitted within 30 days. This study evaluates novel approaches to improve prediction of readmission after AMI....
Coordinated Circulating T Follicular Helper and Activated B Cell Responses Underlie the Onset of Antibody-Mediated Rejection in Kidney Transplantation
Authors: Kevin Louis, Camila Macedo, Elodie Bailly, Louis Lau, Bala Ramaswami, Marilyn Marrari, Douglas Landsittel, Alexander Chang, Uma Chandran, Paul Fadakar, Masaki Yamada, Geetha Chalasani, Parmjeet Randhawa, Adriana Zeevi, Harinder Singh, Carmen Lefaucheur, Diana Metes
Journal: Journal of the American Society of Nephrology (2020)

Although antibody-mediated rejection (ABMR) has been long recognized as a leading cause of allograft failure after kidney transplantation, the cellular and molecular processes underlying the induction of deleterious donor-specific antibody (DSA) responses remain poorly understood.Using high-dimensional flow cytometry, in vitro assays, and RNA sequencing, we concomitantly investigated the role of T follicular helper (TFH) cells and B cells during ABMR in 105 kidney transplant recipients.There were 54 patients without DSAs; of those with DSAs, ABMR emerged in 20 patients, but not in 31 patients. We identified proliferating populations of circulating TFH cells and activated B cells emerging in blood of patients undergoing ABMR. Although these circulating TFH cells comprised heterogeneous phenotypes, they were dominated by activated (ICOS+PD-1+) and early memory precursor (CCR7+CD127+) subsets, and were enriched for the transcription factors IRF4 and c-Maf. These circulating TFH cells produced large amounts of IL-21 upon stimulation with donor antigen and induced B cells to differentiate into antibody-secreting cells that produced DSAs. Combined analysis of the matched circulating TFH cell and activated B cell RNA-sequencing profiles identified highly coordinated transcriptional programs in circulating TFH cells and B cells among patients with ABMR, which markedly differed from those of patients who did not develop DSAs or ABMR. The timing of expansion of the distinctive circulating TFH cells and activated B cells paralleled emergence of DSAs in blood, and their magnitude was predictive of IgG3 DSA generation, more severe allograft injury, and higher rate of allograft loss.Patients undergoing ABMR may benefit from monitoring and therapeutic targeting of TFH cell-B cell interactions.
Mutations in COPA lead to abnormal trafficking of STING to the Golgi and interferon signaling
Authors: Alice Lepelley, Maria José Martin-Niclós, Melvin Le Bihan, Joseph A. Marsh, Carolina Uggenti, Gillian I. Rice, Vincent Bondet, Darragh Duffy, Jonny Hertzog, Jan Rehwinkel, Serge Amselem, Siham Boulisfane-El Khalifi, Mary Brennan, Edwin Carter, Lucienne Chatenoud, Stéphanie Chhun, Aurore Coulomb l’Hermine, Marine Depp, Marie Legendre, Karen J. Mackenzie, Jonathan Marey, Catherine McDougall, Kathryn J. McKenzie, Thierry Jo Molina, Bénédicte Neven, Luis Seabra, Caroline Thumerelle, Marie Wislez, Nadia Nathan, Nicolas Manel, Yanick J. Crow, Marie-Louise Frémond
Journal: The Journal of Experimental Medicine (2020)

Heterozygous missense mutations in coatomer protein subunit α, COPA, cause a syndrome overlapping clinically with type I IFN-mediated disease due to gain-of-function in STING, a key adaptor of IFN signaling. Recently, increased levels of IFN-stimulated genes (ISGs) were described in COPA syndrome. However, the link between COPA mutations and IFN signaling is unknown. We observed elevated levels of ISGs and IFN-α in blood of symptomatic COPA patients. In vitro, both overexpression of mutant COPA and silencing of COPA induced STING-dependent IFN signaling. We detected an interaction between COPA and STING, and mutant COPA was associated with an accumulation of ER-resident STING at the Golgi. Given the known role of the coatomer protein complex I, we speculate that loss of COPA function leads to enhanced type I IFN signaling due to a failure of Golgi-to-ER STING retrieval. These data highlight the importance of the ER–Golgi axis in the control of autoinflammation and inform therapeutic strategies in COPA syndrome.
Nilotinib Versus Nilotinib Combined to Pegylated-Interferon Alfa 2a in First-Line Chronic Phase Chronic Myelogenous Leukemia Patients. Interim Analysis of a Phase III Trial
Authors: Franck Emmanuel Nicolini, Gabriel Etienne, Francoise Huguet, Agnes Guerci-Bresler, Aude Charbonnier, Martine Escoffre-Barbe, Viviane Dubruille, Hyacinthe Johnson-Ansah, Laurence Legros, Valerie Coiteux, Pascale Cony-Makhoul, Pascal Lenain, Lydia Roy, Philippe Rousselot, Denis Guyotat, Jean-Christophe Ianotto, Martine Gardembas, Fabrice Larosa, Denis Caillot, Pascal Turlure, Stephane Courby, Philippe Quittet, Eric Hermet, Shanti Ame, Simona Lapusan, Verane Schwiertz, Stephane Morisset, Madeleine Etienne, Delphine Rea, Stephanie Dulucq, Francois-Xavier Mahon
Journal: Blood (2017)
Current treatments, determinants of use, and survival for patients with hepatoma in the United States from 1998–2002
Authors: A. B. Siegel, R. McBride, D. Hershman, R. S. Brown, J. Emond, A. I. Neugut
Journal: Journal of Clinical Oncology (2006)

4138 Background: Multiple case series have described the use of current therapies for hepatocellular carcinoma (HCC), but recent estimates of treatment utilization in the general population and the impact of various treatments on survival are not known. Methods: We first identified 2898 adults diagnosed with HCC with known tumor size and stage in the Surveillance, Epidemiology, and End-Results Program (SEER), from 1998–2002. Treatment was categorized as transplant, resection, ablation, or none of these. We created a second data set of 1856 HCC patients who were potentially operable, as defined by SEER. We used these patients to construct Kaplan-Meier survival curves and adjusted Cox proportional hazards models. Results: The median age of the larger cohort at HCC diagnosis was 62 (range:18–96). Approximately 42% were white, 32% Asian, 16% Hispanic, and 10% African American. Overall, 10% received a transplant, 18% resection, 8% ablation, and 65% none of these. Only 5% of African Americans with HCC received a transplant, versus 12% of whites, 10% of Hispanics, and 8% of Asians. Asians were most likely to receive resection (24%) and ablation (9%), and least likely to have non-surgical treatment (60%). Using the restricted cohort, improved survival in the multivariate analysis was seen with later year of diagnosis, younger age, female sex, Asian race, smaller tumor size, lower tumor grade, and localized disease. Treatment was highly correlated with survival. This was greatest in the transplanted group (1, 3, and 5-year survivals 93%, 79%, and 71%), followed by resection (70%, 45%, and 29%), and ablation (71%, 33%, and 18%). The non-surgical group had poor survival (33%, 9%, and 0%). Conclusions: Transplantation yields excellent survival on a population scale, similar to reported series, and resection gives relatively good outcomes as well. Asians are more likely to be resected and ablated than other groups. They also had better survival than other groups, perhaps due to underlying etiology of HCC (hepatitis B) and better preserved liver function. No significant financial relationships to disclose.
Performance of Gene Expression Profile Tests for Prognosis in Patients With Localized Cutaneous Melanoma
Authors: Michael A. Marchetti, Daniel G. Coit, Stephen W. Dusza, Ashley Yu, LaToya McLean, Yinin Hu, Japbani K. Nanda, Konstantina Matsoukas, Silvia E. Mancebo, Edmund K. Bartlett
Journal: JAMA Dermatology (2020)

The performance of prognostic gene expression profile (GEP) tests for cutaneous melanoma is poorly characterized.
Covid-19: Excess deaths point to hidden toll in South Africa as cases surge
Authors: Owen Dyer
Journal: BMJ (2020)

Covid-19: Excess deaths point to hidden toll in South Africa as cases surge Owen DyerSouth Africa seems close to the peak of its infection curve after an alarming month long surge in which the country of 59 million leapt from 18th to 5th in the world for total cases, which now stand at 459 761.
EZH2: a novel target for cancer treatment
Authors: Ran Duan, Wenfang Du, Weijian Guo
Journal: Journal of Hematology & Oncology (2020)

Abstract Enhancer of zeste homolog 2 (EZH2) is enzymatic catalytic subunit of polycomb repressive complex 2 (PRC2) that can alter downstream target genes expression by trimethylation of Lys-27 in histone 3 (H3K27me3). EZH2 could also regulate gene expression in ways besides H3K27me3. Functions of EZH2 in cells proliferation, apoptosis, and senescence have been identified. Its important roles in the pathophysiology of cancer are now widely concerned. Therefore, targeting EZH2 for cancer therapy is a hot research topic now and different types of EZH2 inhibitors have been developed. In this review, we summarize the structure and action modes of EZH2, focusing on up-to-date findings regarding the role of EZH2 in cancer initiation, progression, metastasis, metabolism, drug resistance, and immunity regulation. Furtherly, we highlight the advance of targeting EZH2 therapies in experiments and clinical studies.
Additional measures for bedside endoscope cleaning to prevent contaminated splash during COVID-19 pandemic
Authors: Rungsun Rerknimitr, Roy Soetikno, Thawee Ratanachu-Ek, Kasenee Tiankanon, Pradermchai Kongkam, Wiriyaporn Ridtitid
Journal: Endoscopy (2020)

See also: ESGE and ESGENA Position Statement on gastrointestinal endoscopy and the COVID-19 pandemicEndoscopy 2020; 52(06): 483-490DOI: 10.1055/a-1155-6229
Evolutionary History of Endogenous Human Herpesvirus 6 Reflects Human Migration out of Africa
Authors: Amr Aswad, Giulia Aimola, Darren Wight, Pavitra Roychoudhury, Cosima Zimmermann, Joshua Hill, Dirk Lassner, Hong Xie, Meei-Li Huang, Nicholas F Parrish, Heinz-Peter Schultheiss, Cristina Venturini, Susanne Lager, Gordon C S Smith, D Stephen Charnock-Jones, Judith Breuer, Alexander L Greninger, Benedikt B Kaufer
Journal: Molecular Biology and Evolution (2020)

Human herpesvirus 6A and 6B (HHV-6) can integrate into the germline, and as a result, ∼70 million people harbor the genome of one of these viruses in every cell of their body. Until now, it has been largely unknown if 1) these integrations are ancient, 2) if they still occur, and 3) whether circulating virus strains differ from integrated ones. Here, we used next-generation sequencing and mining of public human genome data sets to generate the largest and most diverse collection of circulating and integrated HHV-6 genomes studied to date. In genomes of geographically dispersed, only distantly related people, we identified clades of integrated viruses that originated from a single ancestral event, confirming this with fluorescent in situ hybridization to directly observe the integration locus. In contrast to HHV-6B, circulating and integrated HHV-6A sequences form distinct clades, arguing against ongoing integration of circulating HHV-6A or "reactivation" of integrated HHV-6A. Taken together, our study provides the first comprehensive picture of the evolution of HHV-6, and reveals that integration of heritable HHV-6 has occurred since the time of, if not before, human migrations out of Africa.
Phase 1 Trial of a Therapeutic Anti–Yellow Fever Virus Human Antibody
Authors: Jenny G. Low, Justin H.J. Ng, Eugenia Z. Ong, Shirin Kalimuddin, Limin Wijaya, Yvonne F.Z. Chan, Dorothy H.L. Ng, Hwee-Cheng Tan, Anjali Baglody, Yok-Hian Chionh, Debbie C.P. Lee, Yadunanda Budigi, Ram Sasisekharan, Eng-Eong Ooi
Journal: New England Journal of Medicine (2020)

Insufficient vaccine doses and the lack of therapeutic agents for yellow fever put global health at risk, should this virus emerge from sub-Saharan Africa and South America.In phase 1a of this clinical trial, we assessed the safety, side-effect profile, and pharmacokinetics of TY014, a fully human IgG1 anti-yellow fever virus monoclonal antibody. In a double-blind, phase 1b clinical trial, we assessed the efficacy of TY014, as compared with placebo, in abrogating viremia related to the administration of live yellow fever vaccine (YF17D-204; Stamaril). The primary safety outcomes were adverse events reported 1 hour after the infusion and throughout the trial. The primary efficacy outcome was the dose of TY014 at which 100% of the participants tested negative for viremia within 48 hours after infusion.A total of 27 healthy participants were enrolled in phase 1a, and 10 participants in phase 1b. During phase 1a, TY014 dose escalation to a maximum of 20 mg per kilogram of body weight occurred in 22 participants. During phases 1a and 1b, adverse events within 1 hour after infusion occurred in 1 of 27 participants who received TY014 and in none of the 10 participants who received placebo. At least one adverse event occurred during the trial in 22 participants who received TY014 and in 8 who received placebo. The mean half-life of TY014 was approximately 12.8 days. At 48 hours after the infusion, none of the 5 participants who received the starting dose of TY014 of 2 mg per kilogram had detectable YF17D-204 viremia; these participants remained aviremic throughout the trial. Viremia was observed at 48 hours after the infusion in 2 of 5 participants who received placebo and at 72 hours in 2 more placebo recipients. Symptoms associated with yellow fever vaccine were less frequent in the TY014 group than in the placebo group.This phase 1 trial of TY014 did not identify worrisome safety signals and suggested potential clinical benefit, which requires further assessment in a phase 2 trial. (Funded by Tysana; ClinicalTrials.gov number, NCT03776786.).
Progress Toward Hepatitis B Control — South-East Asia Region, 2016–2019
Authors: Hardeep S. Sandhu, Sigrun Roesel, Mohammad Sharifuzzaman, Supamit Chunsuttiwat, Rania A. Tohme
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

In 2015, the World Health Organization (WHO) South-East Asia Region (SEAR)* reported an estimated 40 million persons living with chronic hepatitis B virus (HBV) infection and 285,000 deaths from complications of chronic infection, cirrhosis, and hepatocellular carcinoma (1). Most chronic HBV infections, indicated by the presence of hepatitis B surface antigen (HBsAg) on serologic testing, are acquired in infancy through perinatal or early childhood transmission (2). To prevent perinatal and childhood infections, WHO recommends that all infants receive at least 3 doses of hepatitis B vaccine (HepB), including a timely birth dose (HepB-BD)