tbuckley/cabot-search huggingface dataset:
COVID-19 survival associates with the immunoglobulin response to the SARS-CoV-2 spike receptor binding domain
Authors: Massimiliano Secchi, Elena Bazzigaluppi, Cristina Brigatti, Ilaria Marzinotto, Cristina Tresoldi, Patrizia Rovere-Querini, Andrea Poli, Antonella Castagna, Gabriella Scarlatti, Alberto Zangrillo, Fabio Ciceri, Lorenzo Piemonti, Vito Lampasona
Journal: Journal of Clinical Investigation (2020)

BACKGROUNDSerological assays are of critical importance to investigate correlates of response and protection in coronavirus disease 2019 (COVID-19), to define previous exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in populations, and to verify the development of an adaptive immune response in infected individuals.METHODSWe studied 509 patients confirmed to have COVID-19 from the San Raffaele Hospital of Milan and 480 samples of prepandemic organ donor sera collected in 2010-2012. Using fluid-phase luciferase immune precipitation (LIPS) assays, we characterized IgG, IgM, and IgA antibodies to the spike receptor binding domain (RBD), S1+S2, nucleocapsid, and ORF6 to ORF10 of SARS-CoV-2, to the HCoV-OC43 and HCoV-HKU1 betacoronaviruses spike S2, and the H1N1Ca2009 flu virus hemagglutinin. Sequential samples at 1 and 3 months after hospital discharge were also tested for SARS-CoV-2 RBD antibodies in 95 patients.RESULTSAntibodies developed rapidly against multiple SARS-CoV-2 antigens in 95% of patients by 4 weeks after symptom onset and IgG to the RBD increased until the third month of follow-up. We observed a major synchronous expansion of antibodies to the HCoV-OC43 and HCoV-HKU1 spike S2. A likely coinfection with influenza was neither linked to a more severe presentation of the disease nor to a worse outcome. Of the measured antibody responses, positivity for IgG against the SARS-CoV-2 spike RBD was predictive of survival.CONCLUSIONThe measurement of antibodies to selected epitopes of SARS-CoV-2 antigens can offer a more accurate assessment of the humoral response in patients and its impact on survival. The presence of partially cross-reactive antibodies with other betacoronaviruses is likely to impact on serological assay specificity and interpretation.TRIAL REGISTRATIONCOVID-19 Patients Characterization, Biobank, Treatment Response and Outcome Predictor (COVID-BioB). ClinicalTrials.gov identifier: NCT04318366.FUNDINGIRCCS Ospedale San Raffaele and Università Vita Salute San Raffaele.
Somatic mutation distributions in cancer genomes vary with three-dimensional chromatin structure
Authors: Kadir C. Akdemir, Victoria T. Le, Justin M. Kim, Sarah Killcoyne, Devin A. King, Ya-Ping Lin, Yanyan Tian, Akira Inoue, Samirkumar B. Amin, Frederick S. Robinson, Manjunath Nimmakayalu, Rafael E. Herrera, Erica J. Lynn, Kin Chan, Sahil Seth, Leszek J. Klimczak, Moritz Gerstung, Dmitry A. Gordenin, John O’Brien, Lei Li, Yonathan Lissanu Deribe, Roel G. Verhaak, Peter J. Campbell, Rebecca Fitzgerald, Ashby J. Morrison, Jesse R. Dixon, P. Andrew Futreal
Journal: Nature Genetics (2020)
Extremely low prevalence of asymptomatic COVID-19 among healthcare workers caring for COVID-19 patients in Israeli hospitals: a cross-sectional study
Authors: Elizabeth Temkin, Elizabeth Temkin, Mitchell J. Schwaber, Ester Solter, Azza Vaturi, Dafna Hen, Carmela Gweta Lugassy, Nava Teitler, Amir Nutman, Bina Rubinovitch, Haim Ben-Zvi, Rana Shbita, Natalia Halel Wolf, Shmuel Benenson, Ilana Gross, Carole Slama, Miriam Ottolenghi, Tamar Gottesman, Shaul Lev, Viktoria Beilin, Evgeny Berkov, Regev Cohen, Talya Finn Fried, Marina Afraimov, Pnina Shitrit, Noga Vered Egozi, Alia Yassin, Hani Laderman, Haya Friedman, Yonit Wiener-Well, Michal Itach Ben-Dor, Debby Ben-David, Orna Schwartz Harar, Malka Yakobov, Shoshana Yashaev, Dror Marchaim, Inna Estrin, Alexandra Bibliv, Hodaya Saadon, Galit Ben Yossef, Yehuda Carmeli
Journal: Clinical Microbiology and Infection (2020)
Co-expression of calcium and hERG potassium channels reduces the incidence of proarrhythmic events
Authors: Sara Ballouz, Melissa M Mangala, Matthew D Perry, Stewart Heitmann, Jesse A Gillis, Adam P Hill, Jamie I Vandenberg
Journal: Cardiovascular Research (2020)

Cardiac electrical activity is extraordinarily robust. However, when it goes wrong it can have fatal consequences. Electrical activity in the heart is controlled by the carefully orchestrated activity of more than a dozen different ion conductances. While there is considerable variability in cardiac ion channel expression levels between individuals, studies in rodents have indicated that there are modules of ion channels whose expression co-vary. The aim of this study was to investigate whether meta-analytic co-expression analysis of large-scale gene expression datasets could identify modules of co-expressed cardiac ion channel genes in human hearts that are of functional importance.Meta-analysis of 3653 public human RNA-seq datasets identified a strong correlation between expression of CACNA1C (L-type calcium current, ICaL) and KCNH2 (rapid delayed rectifier K+ current, IKr), which was also observed in human adult heart tissue samples. In silico modelling suggested that co-expression of CACNA1C and KCNH2 would limit the variability in action potential duration seen with variations in expression of ion channel genes and reduce susceptibility to early afterdepolarizations, a surrogate marker for proarrhythmia. We also found that levels of KCNH2 and CACNA1C expression are correlated in human-induced pluripotent stem cell-derived cardiac myocytes and the levels of CACNA1C and KCNH2 expression were inversely correlated with the magnitude of changes in repolarization duration following inhibition of IKr.Meta-analytic approaches of multiple independent human gene expression datasets can be used to identify gene modules that are important for regulating heart function. Specifically, we have verified that there is co-expression of CACNA1C and KCNH2 ion channel genes in human heart tissue, and in silico analyses suggest that CACNA1C-KCNH2 co-expression increases the robustness of cardiac electrical activity.
Analysis of Survival Benefits of Living Versus Deceased Donor Liver Transplant in High Model for End‐Stage Liver Disease and Hepatorenal Syndrome
Authors: Tiffany Cho‐Lam Wong, James Yan‐Yue Fung, Herbert H. Pang, Calvin Ka‐Lam Leung, Hoi‐Fan Li, Sui‐Ling Sin, Ka‐Wing Ma, Brian Wong‐Hoi She, Jeff Wing‐Chiu Dai, Albert Chi‐Yan Chan, Tan‐To Cheung, Chung‐Mau Lo
Journal: Hepatology (2020)

Background and Aims Previous recommendations suggested living donor liver transplantation (LDLT) should not be considered for patients with Model for End‐Stage Liver Disease (MELD) &gt; 25 and hepatorenal syndrome (HRS). Approach and Results Patients who were listed with MELD &gt; 25 from 2008 to 2017 were analyzed with intention‐to‐treat (ITT) basis retrospectively. Patients who had a potential live donor were analyzed as ITT‐LDLT, whereas those who had none belonged to ITT‐deceased donor liver transplantation (DDLT) group. ITT‐overall survival (OS) was analyzed from the time of listing. Three hundred twenty‐five patients were listed (ITT‐LDLT n = 212, ITT‐DDLT n = 113). The risk of delist/death was lower in the ITT‐LDLT group (43.4% vs. 19.8%, P &lt; 0.001), whereas the transplant rate was higher in the ITT‐LDLT group (78.3% vs. 52.2%, P &lt; 0.001). The 5‐year ITT‐OS was superior in the ITT‐LDLT group (72.6% vs. 49.5%, P &lt; 0.001) for patients with MELD &gt; 25 and patients with both MELD &gt; 25 and HRS (56% vs. 33.8%, P &lt; 0.001). Waitlist mortality was the highest early after listing, and the distinct alteration of slope at survival curve showed that the benefits of ITT‐LDLT occurred within the first month after listing. Perioperative outcomes and 5‐year patient survival were comparable for patients with MELD &gt; 25 (88% vs. 85.4%, P = 0.279) and patients with both MELD &gt; 25 and HRS (77% vs. 76.4%, P = 0.701) after LDLT and DDLT, respectively. The LDLT group has a higher rate of renal recovery by 1 month (77.4% vs. 59.1%, P = 0.003) and 3 months (86.1% vs, 74.5%, P = 0.029), whereas the long‐term estimated glomerular filtration rate (eGFR) was similar between the 2 groups. ITT‐LDLT reduced the hazard of mortality (hazard ratio = 0.387‐0.552) across all MELD strata. Conclusions The ITT‐LDLT reduced waitlist mortality and allowed an earlier access to transplant. LDLT in patients with high MELD/HRS was feasible, and they had similar perioperative outcomes and better renal recovery, whereas the long‐term survival and eGFR were comparable with DDLT. LDLT should be considered for patients with high MELD/HRS, and the application of LDLT should not be restricted with a MELD cutoff.
Changes in Statin Use Among U.S. Adults With Diabetes: A Population-Based Analysis of NHANES 2011–2018
Authors: Abbie D. Leino, Michael P. Dorsch, Corey A. Lester
Journal: Diabetes Care (2020)

OBJECTIVE To evaluate statin use in the U.S. before and after the 2015 American Diabetes Association position statement, which expanded statin therapy recommendations to include all adults 40–75 years old with diabetes. RESEARCH DESIGN AND METHODS The National Health and Nutrition Examination Survey (NHANES) was used to obtain a representative sample. The difference-in-differences technique determined the impact of the recommendation on the proportion of people with diabetes for whom statin therapy was newly recommended. RESULTS Among people with diabetes, the change in statin use in people without atherosclerotic cardiovascular disease (ASCVD) risk factors, controlling for change among people with ASCVD/risk factors, was 6.6% (P = 0.388). In the adjusted analysis, overt ASCVD, age, Black race, health insurance, a place for routine care, and total cholesterol were significantly associated with statin use (P &amp;lt; 0.05). CONCLUSIONS The most recent change in statin recommendations had minimal impact on the proportion of patients receiving a statin.
A 10-Year Cross-Sectional Analysis of Public, Oncologist, and Patient Attitudes About Lung Cancer and Associated Stigma
Authors: Maureen Rigney, Eleni Rapsomaniki, Lisa Carter-Harris, Jennifer C. King
Journal: Journal of Thoracic Oncology (2020)

IntroductionLung cancer stigma negatively impacts the clinical care and outcomes of those diagnosed, resulting in enduring disparities. The objective of this study was to determine whether attitudes toward lung cancer and the stigmatization of people diagnosed have changed over a decade.MethodsA cross-sectional survey was administered to the general public, oncologists, and people with lung cancer 10 years apart (2008 and 2018) using the same instrument and methodology. The measures of stigma agreement ratings on a five-point Likert scale were compared between 2008 and 2018 for all three sample groups.ResultsIn 2018, a total of 1001 members of the general public, 205 oncologists, and 208 people with lung cancer were enrolled. Improvements were noted over the decade, including the availability of more treatment options. Greater disease awareness was also found, with 94% of the public reporting knowledge of lung cancer (versus 82.5% in 2008, p < 0.0001). However, no change was found in the percentage of the public reporting that patients with lung cancer are at least partially to blame for their illness (60.3% in 2018). In 2018, more people with lung cancer agreed there is a stigma associated with lung cancer (72.1 versus 54.5%, p < 0.001) and that those diagnosed are viewed or treated differently by society in general (69.4% versus 50.8%, p < 0.001).ConclusionsThe results reflect recognition of treatment gains and increased visibility of lung cancer but also highlight that stigma remains a significant problem. Of critical importance to the care of those diagnosed was the unexpected increase in stigma reported by the patient population.
Association of Secukinumab Treatment With Tuberculosis Reactivation in Patients With Psoriasis, Psoriatic Arthritis, or Ankylosing Spondylitis
Authors: Boni E. Elewski, John W. Baddley, Atul A. Deodhar, Marina Magrey, Phoebe A. Rich, Enrique R. Soriano, Jennifer Soung, Weibin Bao, Dorothy Keininger, Kwaku Marfo, Manmath Patekar, Abhishek Sharma, Abhijit Shete, Mark Gabriel Lebwohl
Journal: JAMA Dermatology (2020)

Approximately one-quarter of the global population have latent tuberculosis infection (LTBI), and tuberculosis (TB) is accountable for more than 1.5 million deaths annually. Methotrexate, cyclosporine, and tumor necrosis factor inhibitors may be associated with increased risk of TB and LTBI reactivation, although data are limited on the risks of TB with use of newer biologics.To assess the association of secukinumab with reporting of active TB development, TB reactivation, and LTBI activation as an adverse event (AE) in patients with psoriasis, psoriatic arthritis, or ankylosing spondylitis.This pooled cohort study pooled data from 28 clinical trials of secukinumab used in psoriasis (17 phase 3 or 3b and 2 phase 4 trials), psoriatic arthritis (5 phase 3 trials), and ankylosing spondylitis (4 phase 3 trials). A search of the Novartis Secukinumab Compound Pool Database was conducted for the 28 trials. All trial participants who had received at least 1 approved subcutaneous dose of secukinumab (150 mg or 300 mg) were included. Before randomization in these trials, patients underwent screening for TB. Patients with active TB were excluded, and patients with LTBI were treated according to local guidelines. Data were analyzed from the start of treatment in the individual studies through December 25, 2018.Reporting of active TB or LTBI as an AE over a 5-year period using exposure-adjusted incidence rates (EAIR; incidence rates per 100 patient-years).A total of 12 319 patients were included, of whom 8819 patients had psoriasis (71.6%; 5930 men [67.2%]; mean [SD] age, of 44.9 [13.5] years), 2523 had psoriatic arthritis (20.5%; 1323 women [52.4%]; mean [SD] age, 48.8 [12.1] years), and 977 had ankylosing spondylitis (7.3%; 658 men [67.3%]; mean [SD] age, 42.3 [11.9] years). In the total population, 684 patients (5.6%) had tested positive for LTBI at screening. Over 5 years, LTBI as an AE during secukinumab treatment was reported in 13 patients (0.1% of 12 319). Of these 13 patients, 6 had a prior positive LTBI test result, and 7 were newly diagnosed as having LTBI. Four of the 7 patients had psoriasis (EAIR, 0.03; 95% CI, 0.01-0.07), 1 had psoriatic arthritis (EAIR, 0.02; 95% CI, 0.00-0.11), and 2 had ankylosing spondylitis (EAIR, 0.08; 95% CI, 0.01-0.28). No cases of active TB were reported.This study found that LTBI reported as an AE after secukinumab treatment was uncommon and appeared to support the use of secukinumab in chronic systemic inflammatory conditions.
Fundus-controlled perimetry (microperimetry): Application as outcome measure in clinical trials
Authors: Maximilian Pfau, Jasleen Kaur Jolly, Zhichao Wu, Jonathan Denniss, Eleonora M. Lad, Robyn H. Guymer, Monika Fleckenstein, Frank G. Holz, Steffen Schmitz-Valckenberg
Journal: Progress in Retinal and Eye Research (2020)

Fundus-controlled perimetry (FCP, also called 'microperimetry') allows for spatially-resolved mapping of visual sensitivity and measurement of fixation stability, both in clinical practice as well as research. The accurate spatial characterization of visual function enabled by FCP can provide insightful information about disease severity and progression not reflected by best-corrected visual acuity in a large range of disorders. This is especially important for monitoring of retinal diseases that initially spare the central retina in earlier disease stages. Improved intra- and inter-session retest-variability through fundus-tracking and precise point-wise follow-up examinations even in patients with unstable fixation represent key advantages of these technique. The design of disease-specific test patterns and protocols reduces the burden of extensive and time-consuming FCP testing, permitting a more meaningful and focused application. Recent developments also allow for photoreceptor-specific testing through implementation of dark-adapted chromatic and photopic testing. A detailed understanding of the variety of available devices and test settings is a key prerequisite for the design and optimization of FCP protocols in future natural history studies and clinical trials. Accordingly, this review describes the theoretical and technical background of FCP, its prior application in clinical and research settings, data that qualify the application of FCP as an outcome measure in clinical trials as well as ongoing and future developments.
Interferon Regulatory Factors 3 and 7 Regulate Vein Graft Remodeling via Tumor Necrosis Factor Induced Macrophage Accumulation
Authors: K.H. Simons, M.R. de Vries, E.A. Peters, J.F. Hamming, J.W. Jukema, P.H. Quax
Journal: Circulation (2016)
A Man With a Sixth Wave in Electrocardiogram Results
Authors: Arshi Naz, Sajjad A. Khan, Rahman Shah
Journal: JAMA Internal Medicine (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 Internal Medicine 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 Internal Medicine journal
PCSK9 (Proprotein Convertase Subtilisin/Kexin 9) Enhances Platelet Activation, Thrombosis, and Myocardial Infarct Expansion by Binding to Platelet CD36
Authors: Zhiyong Qi, Liang Hu, Jianjun Zhang, Wenlong Yang, Xin Liu, Daile Jia, Zhifeng Yao, Lin Chang, Guanxing Pan, Haoxuan Zhong, Xinping Luo, Kang Yao, Aijun Sun, Juying Qian, Zhongren Ding, Junbo Ge
Journal: Circulation (2020)

PCSK9 (proprotein convertase subtilisin/kexin 9), mainly secreted by the liver and released into the blood, elevates plasma low-density lipoprotein cholesterol by degrading low-density lipoprotein receptor. Pleiotropic effects of PCSK9 beyond lipid metabolism have been shown. However, the direct effects of PCSK9 on platelet activation and thrombosis, and the underlying mechanisms, as well, still remain unclear.We detected the direct effects of PCSK9 on agonist-induced platelet aggregation, dense granule ATP release, integrin αIIbβ3 activation, α-granule release, spreading, and clot retraction. These studies were complemented by in vivo analysis of FeCl3-injured mouse mesenteric arteriole thrombosis. We also investigated the underlying mechanisms. Using the myocardial infarction (MI) model, we explored the effects of PCSK9 on microvascular obstruction and infarct expansion post-MI.PCSK9 directly enhances agonist-induced platelet aggregation, dense granule ATP release, integrin αIIbβ3 activation, P-selectin release from α-granules, spreading, and clot retraction. In line, PCSK9 enhances in vivo thrombosis in a FeCl3-injured mesenteric arteriole thrombosis mouse model, whereas PCSK9 inhibitor evolocumab ameliorates its enhancing effects. Mechanism studies revealed that PCSK9 binds to platelet CD36 and thus activates Src kinase and MAPK (mitogen-activated protein kinase)-extracellular signal-regulated kinase 5 and c-Jun N-terminal kinase, increases the generation of reactive oxygen species, and activates the p38MAPK/cytosolic phospholipase A2/cyclooxygenase-1/thromboxane A2 signaling pathways downstream of CD36 to enhance platelet activation, as well. Using CD36 knockout mice, we showed that the enhancing effects of PCSK9 on platelet activation are CD36 dependent. It is important to note that aspirin consistently abolishes the enhancing effects of PCSK9 on platelet activation and in vivo thrombosis. Last, we showed that PCSK9 activating platelet CD36 aggravates microvascular obstruction and promotes MI expansion post-MI.PCSK9 in plasma directly enhances platelet activation and in vivo thrombosis, and MI expansion post-MI, as well, by binding to platelet CD36 and thus activating the downstream signaling pathways. PCSK9 inhibitors or aspirin abolish the enhancing effects of PCSK9, supporting the use of aspirin in patients with high plasma PCSK9 levels in addition to PCSK9 inhibitors to prevent thrombotic complications.
Association Between Time to Colonoscopy After Positive Fecal Testing and Colorectal Cancer Outcomes: A Systematic Review
Authors: Nauzer Forbes, Robert J. Hilsden, Myriam Martel, Yibing Ruan, Catherine Dube, Alaa Rostom, Risa Shorr, Charles Menard, Darren R. Brenner, Alan N. Barkun, Steven J. Heitman
Journal: Clinical Gastroenterology and Hepatology (2020)

Colonoscopy is required following a positive fecal screening test for colorectal cancer (CRC). It remains unclear to what extent time to colonoscopy is associated with CRC-related outcomes. We performed a systematic review to elucidate this relationship.An electronic search was performed through April 2020 for studies reporting associations between time from positive fecal testing to colonoscopy and outcomes including CRC incidence (primary outcome), CRC stage at diagnosis, and/or CRC-specific mortality. Our primary objective was to quantify these relationships following positive fecal immunochemical testing (FIT). Two authors independently performed screening, abstraction, and risk of bias assessments.From 1,612 initial studies, 8 were included in the systematic review, with 5 reporting outcomes for FIT. Although meta-analysis was not possible, consistent trends between longer time delays and worse outcomes were apparent in all studies. Colonoscopy performed beyond 9 months from positive FIT compared to within 1 month was significantly associated with a higher incidence of CRC, with adjusted odds ratios (AORs) of 1.75 and 1.48 in the two largest studies. These studies also reported significant associations between colonoscopy performed beyond 9 months and higher incidence of advanced stage CRC (stage III or IV) at diagnosis, with AORs of 2.79 and 1.55, respectively.Colonoscopy for positive FIT should not be delayed beyond 9 months. Given the additional time required for urgent referrals and surgical planning for CRC, colonoscopy should ideally be performed well in advance of 9 months following a positive FIT.
Microchromosomes Exhibit Distinct Features of Vertebrate Chromosome Structure and Function with Underappreciated Ramifications for Genome Evolution
Authors: Blair W Perry, Drew R Schield, Richard H Adams, Todd A Castoe
Journal: Molecular Biology and Evolution (2020)

Abstract Microchromosomes are common yet poorly understood components of many vertebrate genomes. Recent studies have revealed that microchromosomes contain a high density of genes and possess other distinct characteristics compared with macrochromosomes. Whether distinctive characteristics of microchromosomes extend to features of genome structure and organization, however, remains an open question. Here, we analyze Hi-C sequencing data from multiple vertebrate lineages and show that microchromosomes exhibit consistently high degrees of interchromosomal interaction (particularly with other microchromosomes), appear to be colocalized to a common central nuclear territory, and are comprised of a higher proportion of open chromatin than macrochromosomes. These findings highlight an unappreciated level of diversity in vertebrate genome structure and function, and raise important questions regarding the evolutionary origins and ramifications of microchromosomes and the genes that they house.