tbuckley/cabot-search huggingface dataset:
Reduction in Acute Limb Ischemia With Rivaroxaban Versus Placebo in Peripheral Artery Disease After Lower Extremity Revascularization: Insights From VOYAGER PAD
Authors: Connie N. Hess, E. Sebastian Debus, Mark R. Nehler, Sonia S. Anand, Manesh R. Patel, Michael Szarek, Warren H. Capell, Judith Hsia, Joshua A. Beckman, Marianne Brodmann, Rafael Diaz, Peter Habertheuer, Nicholas J. Leeper, Richard J. Powell, Henrik Sillesen, Eva Muehlhofer, Scott D. Berkowitz, Lloyd P. Haskell, Rupert M. Bauersachs, Marc P. Bonaca
Journal: Circulation (2021)

Patients with peripheral artery disease (PAD) are at heightened risk of acute limb ischemia (ALI), a thrombotic event associated with amputation, disability, and mortality. Previous lower extremity revascularization (LER) is associated with increased ALI risk in chronic PAD. However, the pattern of risk, clinical correlates, and outcomes after ALI early after LER are not well-studied, and effective therapies to reduce ALI post-LER are lacking. The VOYAGER PAD trial (Vascular Outcomes Study of ASA [Acetylsalicylic Acid] Along With Rivaroxaban in Endovascular or Surgical Limb Revascularization for PAD; rNCT02504216) randomized patients with PAD undergoing LER to rivaroxaban 2.5 mg twice daily or placebo on a background of low-dose aspirin. The primary outcome was a composite of ALI, major amputation of vascular cause, myocardial infarction, ischemic stroke, or cardiovascular death. ALI was prospectively ascertained and adjudicated by a blinded committee. The cumulative incidence of ALI was calculated using Kaplan-Meier estimates, and Cox proportional hazards models were used to generate hazard ratios and associated CIs. Analyses were performed as intention-to-treat. Among 6564 patients followed for a median of 2.3 years, 382 (5.8%) had a total of 508 ALI events. In placebo patients, the 3-year cumulative incidence of ALI was 7.8%. After multivariable modeling, previous LER, baseline ankle-brachial index <0.50, surgical LER, and longer target lesion length were associated with increased risk of ALI. Incident ALI was associated with subsequent all-cause mortality (hazard ratio [HR], 2.59 [95% CI, 1.98-3.39]) and major amputation (HR, 24.87 [95% CI, 18.68-33.12]). Rivaroxaban reduced ALI relative to placebo by 33% (absolute risk reduction, 2.6% at 3 years; HR, 0.67 [95% CI, 0.55-0.82]; P=0.0001), with benefit starting early (HR, 0.45 [95% CI, 0.24-0.85]; P=0.0068 at 30 days). Benefit was present for severe ALI (associated with death, amputation, or prolonged hospitalization and intensive care unit stay, HR, 0.58 [95% CI, 0.40-0.83]; P=0.003) and regardless of LER type (surgical versus endovascular revascularization, P interaction=0.42) or clopidogrel use (P interaction=0.59). After LER for symptomatic PAD, ALI is frequent, particularly early after LER, and is associated with poor prognosis. Low-dose rivaroxaban plus aspirin reduces ALI after LER, including ALI events associated with the most severe outcomes. The benefit of rivaroxaban for ALI appears early, continues over time, and is consistent regardless of revascularization approach or clopidogrel use.
Combination therapy of infliximab and thiopurines, but not monotherapy with infliximab or vedolizumab, is associated with attenuated IgA and neutralisation responses to SARS-CoV-2 in inflammatory bowel disease
Authors: Judith Wellens, Matthew Edmans, Uri Obolski, Colleen GC McGregor, Peter Simmonds, Marc Turner, Lisa Jarvis, Donal Skelly, Susanna Dunachie, Eleanor Barnes, David W Eyre, Jean-Frederic Colombel, Serre-Yu Wong, Paul Klenerman, James O Lindsay, Jack Satsangi, Craig P Thompson
Journal: Gut (2021)

The effect of immunomodulator and biological therapy for inflammatory bowel disease (IBD) on the immune response to SARS-CoV-2 is of substantial interest to patients and clinicians worldwide.The CLARITY IBD study recently reported attenuated serological responses in IBD patients treated with infliximab in comparison to vedolizumab 1 , with the effect greatest in those on infliximab/thiopurine combination therapy.Independently, the global SECURE-IBD registry highlighted that infliximab/thiopurine
Belzutifan, a Potent HIF2α Inhibitor, in the Pacak–Zhuang Syndrome
Authors: Junne Kamihara, Kayla V. Hamilton, Jessica A. Pollard, Catherine M. Clinton, Jill A. Madden, Jasmine Lin, Alma Imamovic, Catherine B. Wall, Ari J. Wassner, Brent R. Weil, Matthew M. Heeney, Sara O. Vargas, William G. Kaelin, Katherine A. Janeway, Rodolfo F. Perini, Naseem J. Zojwalla, Stephan D. Voss, Steven G. DuBois
Journal: New England Journal of Medicine (2021)

The integration of genomic testing into clinical care enables the use of individualized approaches to the management of rare diseases. We describe the use of belzutifan, a potent and selective small-molecule inhibitor of the protein hypoxia-inducible factor 2α (HIF2α), in a patient with polycythemia and multiple paragangliomas (the Pacak-Zhuang syndrome). The syndrome was caused in this patient by somatic mosaicism for an activating mutation in
The role of generalizability in moral and political psychology
Authors: Elizabeth A Harris, Philip Pärnamets, William J Brady, Claire E Robertson, Jay J Van Bavel
Journal: Behavioral and Brain Sciences (2022)

The aim of the social and behavioral sciences is to understand human behavior across a wide array of contexts. Our theories often make sweeping claims about human nature, assuming that our ancestors or offspring will be prone to the same biases and preferences. Yet we gloss over the fact that our research is often based in a single temporal context with a limited set of stimuli. Political and moral psychology are domains in which the context and stimuli are likely to matter a great deal (Van Bavel, Mende-Siedlecki, Brady, & Reinero, 2016). In response to Yarkoni (see BBS issue), we delve into topics related to political and moral psychology that likely depend on features of the research. These topics include understanding differences between liberals and conservatives, when people are willing to sacrifice someone to save others, the behavior of political leaders, and the dynamics of intergroup conflict.
Abstract MP11: Impact Of Severe Acute Respiratory Syndrome Coronavirus 2 (sars-cov-2) Pandemic On Diabetes Care Among A North Carolina Patient Population
Authors: Michael P Bancks, Meng-Yun Lin, Alain G Bertoni, Wendell Futrell, Zhixiu Liu, Brian Ostasiewski, Brian J Wells, Amresh Hanchate
Journal: Circulation (2022)

Introduction: We assessed whether the coronavirus disease 2019 (COVID-19) pandemic was associated with within-individual delays in diabetes care processes of glycated hemoglobin (HbA1c) testing, retinal exam, and nephropathy evaluation among patients receiving regular care with Wake Forest Baptist Health (WFBH), overall and stratified by clinical factors, race and ethnicity, and socioeconomic status. Methods: We used electronic health record data for 25,323 WFBH adult patients with diabetes (96% type 2; 53% women; mean age ± SD: 63±13 years). We used Current Procedural Terminology codes to identify each diabetes care process occurring between 3/1/2018 and 2/28/2021. Delayed care between serial assessments was defined as a duration of &gt;6 months for HbA1c testing and &gt;12 months for retinal exam and nephropathy evaluation. We used individual-level fixed effects regression to estimate within-person change in outcomes before and after the start of the COVID-19 pandemic (3/1/2020), overall and among subgroups. Results: During the pandemic, there was a 12.7 to 20.6 percentage point increase in the incidence of delayed diabetes care ( Table ). We did not observe clinically meaningful differences in delayed care for any of the diabetes care procedures during the pandemic across socio-demographic subgroups. However, individuals with the highest HbA1c and greatest burden of comorbidities, respectively, had the greatest increase in the incidence of a delayed HbA1c test during the pandemic. Conclusions: The COVID-19 pandemic was associated with an increase in within-individual delays in HbA1c testing, retinal exams, and nephropathy evaluations. Delays were greatest for individuals with the most severe disease and may portend an increase in diabetes complications.
Surveillance to Track Progress Toward Polio Eradication — Worldwide, 2020–2021
Authors: Amanda L. Wilkinson, Ousmane M. Diop, Jaume Jorba, Tracie Gardner, Cynthia J. Snider, Jamal Ahmed
Journal: MMWR Morbidity and Mortality Weekly Report (2022)

Since the Global Polio Eradication Initiative (GPEI) was established in 1988, the number of reported poliomyelitis cases worldwide has declined by approximately 99.99%. By the end of 2021, wild poliovirus (WPV) remained endemic in only two countries (Pakistan and Afghanistan). However, a WPV type 1 (WPV1) case with paralysis onset in 2021, was reported by Malawi a year after the World Health Organization (WHO) African Region (AFR) was certified as WPV-free and circulating vaccine-derived poliovirus (cVDPV) cases were reported from 31 countries during 2020-2021 (1,2). cVDPVs are oral poliovirus vaccine-derived viruses that can emerge after prolonged circulation in populations with low immunity and cause paralysis. The primary means of detecting poliovirus transmission is through surveillance for acute flaccid paralysis (AFP) among persons aged <15 years, with confirmation through stool specimen testing by WHO-accredited laboratories, supplemented by systematic sampling of sewage and testing for the presence of poliovirus (environmental surveillance). The COVID-19 pandemic caused disruptions in polio vaccination and surveillance activities across WHO regions in 2020; during January-September 2020, the number of reported cases of AFP declined and the interval between stool collection and receipt by laboratories increased compared with the same period in 2019 (3). This report summarizes surveillance performance indicators for 2020 and 2021 in 43 priority countries* and updates previous reports (4). In 2021, a total of 32 (74%) priority countries† met two key surveillance performance indicator targets nationally, an improvement from 2020 when only 23 (53%) met both targets; however, substantial national and subnational gaps persist. High-performing poliovirus surveillance is critical to tracking poliovirus transmission. Frequent monitoring of surveillance indicators could help identify gaps, guide improvements, and enhance the overall sensitivity and timelines of poliovirus detection to successfully achieve polio eradication.
18P RATIONALE-307: Safety analysis of patients (pts) receiving tislelizumab (TIS) plus chemotherapy (chemo) vs chemo alone in advanced squamous (sq) NSCLC
Authors: X. Yu, J. Wang, Y. Hu, Y. Sun, J. Zhao, Y. Yu, C. Hu, K. Yang, G. Feng, S.J. Leaw, Y. Yuan, X. Lin, F. Bai, S. Lu
Journal: Annals of Oncology (2022)
Hallmarks of Cancer: New Dimensions
Authors: Douglas Hanahan
Journal: Cancer Discovery (2022)

The hallmarks of cancer conceptualization is a heuristic tool for distilling the vast complexity of cancer phenotypes and genotypes into a provisional set of underlying principles. As knowledge of cancer mechanisms has progressed, other facets of the disease have emerged as potential refinements. Herein, the prospect is raised that phenotypic plasticity and disrupted differentiation is a discrete hallmark capability, and that nonmutational epigenetic reprogramming and polymorphic microbiomes both constitute distinctive enabling characteristics that facilitate the acquisition of hallmark capabilities. Additionally, senescent cells, of varying origins, may be added to the roster of functionally important cell types in the tumor microenvironment. SIGNIFICANCE: Cancer is daunting in the breadth and scope of its diversity, spanning genetics, cell and tissue biology, pathology, and response to therapy. Ever more powerful experimental and computational tools and technologies are providing an avalanche of "big data" about the myriad manifestations of the diseases that cancer encompasses. The integrative concept embodied in the hallmarks of cancer is helping to distill this complexity into an increasingly logical science, and the provisional new dimensions presented in this perspective may add value to that endeavor, to more fully understand mechanisms of cancer development and malignant progression, and apply that knowledge to cancer medicine.
Durability of omicron-neutralising serum activity after mRNA booster immunisation in older adults
Authors: Kanika Vanshylla, Pinkus Tober-Lau, Henning Gruell, Friederike Münn, Ralf Eggeling, Nico Pfeifer, N Han Le, Irmgard Landgraf, Florian Kurth, Leif E Sander, Florian Klein
Journal: The Lancet Infectious Diseases (2022)
Epigenetic Age and the Risk of Incident Atrial Fibrillation
Authors: Jason D. Roberts, Eric Vittinghoff, Ake T. Lu, Alvaro Alonso, Biqi Wang, Colleen M. Sitlani, Pedrum Mohammadi-Shemirani, Myriam Fornage, Jelena Kornej, Jennifer A. Brody, Dan E. Arking, Honghuang Lin, Susan R. Heckbert, Ivana Prokic, Mohsen Ghanbari, Allan C. Skanes, Traci M. Bartz, Marco V. Perez, Kent D. Taylor, Steven A. Lubitz, Patrick T. Ellinor, Kathryn L. Lunetta, James S. Pankow, Guillaume Paré, Nona Sotoodehnia, Emelia J. Benjamin, Steve Horvath, Gregory M. Marcus
Journal: Circulation (2021)

Background: The most prominent risk factor for atrial fibrillation (AF) is chronological age; however, underlying mechanisms are unexplained. Algorithms using epigenetic modifications to the human genome effectively predict chronological age. Chronological and epigenetic predicted ages may diverge in a phenomenon referred to as epigenetic age acceleration (EAA), which may reflect accelerated biological aging. We sought to evaluate for associations between epigenetic age measures and incident AF. Methods: Measures for 4 epigenetic clocks (Horvath, Hannum, DNA methylation [DNAm] PhenoAge, and DNAm GrimAge) and an epigenetic predictor of PAI-1 (plasminogen activator inhibitor-1) levels (ie, DNAm PAI-1) were determined for study participants from 3 population-based cohort studies. Cox models evaluated for associations with incident AF and results were combined via random-effects meta-analyses. Two-sample summary-level Mendelian randomization analyses evaluated for associations between genetic instruments of the EAA measures and AF. Results: Among 5600 participants (mean age, 65.5 years; female, 60.1%; Black, 50.7%), there were 905 incident AF cases during a mean follow-up of 12.9 years. Unadjusted analyses revealed all 4 epigenetic clocks and the DNAm PAI-1 predictor were associated with statistically significant higher hazards of incident AF, though the magnitudes of their point estimates were smaller relative to the associations observed for chronological age. The pooled EAA estimates for each epigenetic measure, with the exception of Horvath EAA, were associated with incident AF in models adjusted for chronological age, race, sex, and smoking variables. After multivariable adjustment for additional known AF risk factors that could also potentially function as mediators, pooled EAA measures for 2 clocks remained statistically significant. Five-year increases in EAA measures for DNAm GrimAge and DNAm PhenoAge were associated with 19% (adjusted hazard ratio [HR], 1.19 [95% CI, 1.09–1.31]; P &lt;0.01) and 15% (adjusted HR, 1.15 [95% CI, 1.05–1.25]; P &lt;0.01) higher hazards of incident AF, respectively. Mendelian randomization analyses for the 5 EAA measures did not reveal statistically significant associations with AF. Conclusions: Our study identified adjusted associations between EAA measures and incident AF, suggesting that biological aging plays an important role independent of chronological age, though a potential underlying causal relationship remains unclear. These aging processes may be modifiable and not constrained by the immutable factor of time.
Primary Hyperoxaluria
Authors: Xiaotong Xie, Xiaoliang Zhang
Journal: New England Journal of Medicine (2022)

A 40-year-old man with end-stage kidney disease and calcium oxalate nephrolithiasis presented to the emergency department with joint pain. A workup was notable for nephrocalcinosis on imaging; dense, metaphyseal bands on radiography of the hands; and calcium deposition in the cornea and skin. A diagnosis of primary hyperoxaluria was made by means of genetic testing.
HIV among migrants in precarious circumstances in the EU and European Economic Area
Authors: Christiana Nöstlinger, Theo Cosaert, Ella Van Landeghem, Jef Vanhamel, Gary Jones, Dominik Zenner, Jantine Jacobi, Teymur Noori, Anastasia Pharris, Alyna Smith, Rosalie Hayes, Elena Val, Elisabeth Waagensen, Elena Vovc, Sarita Sehgal, Marie Laga, Henk Van Renterghem
Journal: The Lancet HIV (2022)
Epigenetic Alterations and Mechanisms That Drive Resistance to Targeted Cancer Therapies
Authors: Narendra Wajapeyee, Romi Gupta
Journal: Cancer Research (2021)

Cancer is a complex disease and cancer cells typically harbor multiple genetic and epigenetic alterations. Large-scale sequencing of patient-derived cancer samples has identified several druggable driver oncogenes. Many of these oncogenes can be pharmacologically targeted to provide effective therapies for breast cancer, leukemia, lung cancer, melanoma, lymphoma, and other cancer types. Initial responses to these agents can be robust in many cancer types and some patients with cancer experience sustained tumor inhibition. However, resistance to these targeted therapeutics frequently emerges, either from intrinsic or acquired mechanisms, posing a major clinical hurdle for effective treatment. Several resistance mechanisms, both cell autonomous and cell nonautonomous, have been identified in different cancer types. Here we describe how alterations of the transcriptome, transcription factors, DNA, and chromatin regulatory proteins confer resistance to targeted therapeutic agents. We also elaborate on how these studies have identified underlying epigenetic factors that drive drug resistance and oncogenic pathways, with direct implications for the prevention and treatment of drug-resistant cancer.
Quincke’s Sign of Janeway Lesion in Infective Endocarditis
Authors: Hyun Jin Cho, Jae Hyeon Yu
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

"Quincke’s Sign of Janeway Lesion in Infective Endocarditis." American Journal of Respiratory and Critical Care Medicine, 205(10), pp. e51–e52
Leveraging Allele-Specific Expression for Therapeutic Response Gene Discovery in Glioblastoma
Authors: Arko Sen, Briana C. Prager, Cuiqing Zhong, Donglim Park, Zhe Zhu, Ryan C. Gimple, Qiulian Wu, Jean A. Bernatchez, Sungjun Beck, Alex E. Clark, Jair L. Siqueira-Neto, Jeremy N. Rich, Graham McVicker
Journal: Cancer Research (2021)

Abstract Glioblastoma is the most prevalent primary malignant brain tumor in adults and is characterized by poor prognosis and universal tumor recurrence. Effective glioblastoma treatments are lacking, in part due to somatic mutations and epigenetic reprogramming that alter gene expression and confer drug resistance. To investigate recurrently dysregulated genes in glioblastoma, we interrogated allele-specific expression (ASE), the difference in expression between two alleles of a gene, in glioblastoma stem cells (GSC) derived from 43 patients. A total of 118 genes were found with recurrent ASE preferentially in GSCs compared with normal tissues. These genes were enriched for apoptotic regulators, including schlafen family member 11 (SLFN11). Loss of SLFN11 gene expression was associated with aberrant promoter methylation and conferred resistance to chemotherapy and PARP inhibition. Conversely, low SLFN11 expression rendered GSCs susceptible to the oncolytic flavivirus Zika. This discovery effort based upon ASE revealed novel points of vulnerability in GSCs, suggesting a potential alternative treatment strategy for chemotherapy-resistant glioblastoma. Significance: Assessing allele-specific expression reveals genes with recurrent cis-regulatory changes that are enriched in glioblastoma stem cells, including SLFN11, which modulates chemotherapy resistance and susceptibility to the oncolytic Zika virus.
Effect of Bedside Compared With Outside the Room Patient Case Presentation on Patients' Knowledge About Their Medical Care
Authors: Sabina Hunziker
Journal: Annals of Internal Medicine (2022)

LettersJanuary 2022Effect of Bedside Compared With Outside the Room Patient Case Presentation on Patients' Knowledge About Their Medical CareSabina Hunziker, MDSabina Hunziker, MDUniversity Hospital Basel and University of Basel, Basel, SwitzerlandSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L21-0687 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:We agree with the points raised by Dr. Sall and colleagues. We also strongly believe that physicians presenting at the bedside need to be skilled in the use of medical language to avoid confusion and misunderstandings—which was one of the main conclusions of our study.Our trial did not include specific protocol to follow during bedside rounds. However, most involved care teams and physicians have had specific training during medical school and many years of experience in physician–patient interaction. Thus, the overall standard regarding general communication techniques among health care teams in Switzerland is high. Still, we agree ... Author, Article, and Disclosure InformationAffiliations: University Hospital Basel and University of Basel, Basel, SwitzerlandDisclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M21-0909. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoEffect of Bedside Compared With Outside the Room Patient Case Presentation on Patients' Knowledge About Their Medical Care Christoph Becker , Martina Gamp , Philipp Schuetz , Katharina Beck , Alessia Vincent , Seraina Hochstrasser , Kerstin Metzger , Madlaina Widmer , Emanuel Thommen , Beat Mueller , Christoph A. Fux , Jörg D. Leuppi , Rainer Schaefert , Wolf Langewitz , Marten Trendelenburg , Tobias Breidthardt , Jens Eckstein , Michael Osthoff , Stefano Bassetti , Sabina Hunziker , and Effect of Bedside Compared With Outside the Room Patient Case Presentation on Patients' Knowledge About Their Medical Care Dana Sall , Benjamin Kinnear , Matthew Kelleher , and Eric J. Warm Metrics Cited byHealth information sharing on social media: quality assessment of short videos about chronic kidney disease January 2022Volume 175, Issue 1Page: W1 ePublished: 18 January 2022 Issue Published: January 2022 Copyright & PermissionsCopyright © 2022 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Risk of acute respiratory infection and acute cardiovascular events following acute respiratory infection among adults with increased cardiovascular risk in England between 2008 and 2018: a retrospective, population-based cohort study
Authors: Jennifer A Davidson, Amitava Banerjee, Liam Smeeth, Helen I McDonald, Daniel Grint, Emily Herrett, Harriet Forbes, Richard Pebody, Charlotte Warren-Gash
Journal: The Lancet Digital Health (2021)