tbuckley/cabot-search huggingface dataset:
Regional Variation in Active Surveillance for Low-Risk Prostate Cancer in the US
Authors: Samuel L. Washington, Chang Wook Jeong, Peter E. Lonergan, Annika Herlemann, Scarlett L. Gomez, Peter R. Carroll, Matthew R. Cooperberg
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Active surveillance (AS) is now recognized as the preferred management option for most low-risk prostate cancers to minimize risks of overtreatment. Despite increasing use of AS in the US, wide regional variability has been observed, and these regional variations in contemporary practice have not been well described. <h3>Objective</h3> To explore variations between county and Surveillance, Epidemiology, and End Results (SEER) regions in AS in the US. <h3>Design, Setting, and Participants</h3> A cohort study using the SEER Prostate with Watchful Waiting (WW) database linked to the County Area Health Resource File for detailed county-level demographics and physician distribution data was conducted from January 2010 to December 2015. Analysis was performed in October 2020. A total of 79 825 men with clinically localized, low-risk prostate cancer eligible for AS or WW were included. <h3>Exposures</h3> Multiple patient-, county-, and SEER region–level factors, including age, year of diagnosis, county-level densities of urologists, radiation oncologists, primary care physicians, and SEER registry region. <h3>Main Outcomes and Measures</h3> Use of AS or WW as the initial reported treatment strategy were noted. Hierarchical mixed-effect logistic regression models were used to evaluate clustered random regional variation on use of AS or WW. Temporal trends by year in proportions of initial treatment type, as well as county-level local variation, were also estimated. <h3>Results</h3> Of 79 825 men (mean [SD] age, 62.8 [7.6] years, 11 292 [14.1%] non-Hispanic Black, 7506 [9.4%] Hispanic) with low-risk prostate cancer, the mean annualized percent increase in AS rates from 2010 to 2015 ranged from 6.3% in New Mexico to 81.0% in New Jersey. Differences across SEER regions accounted for 17% of the total variation in AS. Increasing age (51-60 years: odds ratio [OR], 1.33; 95% CI, 1.21-1.46; 61-70 years: OR, 1.86; 95% CI, 1.70-2.04; 71-80 years: OR, 2.26; 95% CI, 2.05-2.50) was associated with greater odds of AS. Hispanic ethnicity (OR, 0.79; 95% CI, 0.74-0.85), T category (OR, 0.79; 95% CI, 0.73-0.84), and Medicaid enrollment (OR, 0.73; 95% CI, 0.66-0.81) were associated with lower odds of AS. Black race, county-level socioeconomic factors (household income, educational level, and city type), and specialist densities were not associated with AS use. <h3>Conclusions and Relevance</h3> In this US cohort study based on the SEER-WW database, although the use of AS increased, considerable practice variation appeared to be associated with geographic location, but use of AS was not associated with Black race, specialty professional density, or socioeconomic factors. This small area variation underlies the broader national trends in AS practice and may inform policies aimed at continuing to affect risk-appropriate care for men throughout the US.
Pulse oximetry may underestimate hypoxaemia in black patients, study finds
Authors: Owen Dyer
Journal: BMJ (2020)

<h3>Background</h3> Single measurements of plasma Aβ are not useful in the diagnostics of Alzheimer9s disease (AD). However, changes in plasma Aβ levels during repeated testing may be helpful in the prediction and evaluation of progression of the incipient AD or mild cognitive impairment. <h3>Objective</h3> To examine the relation of baseline and serial plasma Aβ levels to cognitive change in follow-up. <h3>Methods</h3> 269 subjects (52 cognitively impaired and 217 controls) from a population-based cohort were clinically followed up from 3 to 6 years. Serial plasma samples were available from 70 subjects who were followed up for 3 years and 43 subjects followed for 6 years. The plasma Aβ levels were measured using ELISA. <h3>Results</h3> Subjects who declined cognitively during the follow-up had lower levels of plasma Aβ42 at the baseline. Plasma Aβ42 and the Aβ42/Aβ40 ratio decreased (−2.4 pg/ml for Aβ42 in 6 years) in those who declined in follow-up, whereas Aβ42 and the Aβ42/Aβ40 ratio increased in the subjects who remained cognitively stable or improved in follow-up. Subjects using acetylsalicylic acid, dipyridamole, antidiabetic or anticoagulant drugs as well as subjects with coronary heart disease had higher levels of Aβ40. <h3>Conclusions</h3> Low or decreasing plasma Aβ42 during the follow-up is associated with cognitive decline. Serial measurement of plasma Aβ42 may be useful in the detection of the subjects who are at risk for cognitive decline.
Repeated Evolution of Inactive Pseudonucleases in a Fungal Branch of the Dis3/RNase II Family of Nucleases
Authors: Elizabeth R Ballou, Atlanta G Cook, Edward W J Wallace
Journal: Molecular Biology and Evolution (2020)

Abstract The RNase II family of 3′–5′ exoribonucleases is present in all domains of life, and eukaryotic family members Dis3 and Dis3L2 play essential roles in RNA degradation. Ascomycete yeasts contain both Dis3 and inactive RNase II-like “pseudonucleases.” The latter function as RNA-binding proteins that affect cell growth, cytokinesis, and fungal pathogenicity. However, the evolutionary origins of these pseudonucleases are unknown: What sequence of events led to their novel function, and when did these events occur? Here, we show how RNase II pseudonuclease homologs, including Saccharomyces cerevisiae Ssd1, are descended from active Dis3L2 enzymes. During fungal evolution, active site mutations in Dis3L2 homologs have arisen at least four times, in some cases following gene duplication. In contrast, N-terminal cold-shock domains and regulatory features are conserved across diverse dikarya and mucoromycota, suggesting that the nonnuclease function requires these regions. In the basidiomycete pathogenic yeast Cryptococcus neoformans, the single Ssd1/Dis3L2 homolog is required for cytokinesis from polyploid “titan” growth stages. This phenotype of C. neoformans Ssd1/Dis3L2 deletion is consistent with those of inactive fungal pseudonucleases, yet the protein retains an active site sequence signature. We propose that a nuclease-independent function for Dis3L2 arose in an ancestral hyphae-forming fungus. This second function has been conserved across hundreds of millions of years, whereas the RNase activity was lost repeatedly in independent lineages.
Urgent Need for Diagnosis of a Rapidly Growing Right Atrial Mass
Authors: Sneha Thatipelli, Sasan Raissi, Nausheen Akhter
Journal: JAMA Cardiology (2020)

A patient presents with progressive shortness of breath, a productive cough, fatigue, weight loss, and night sweats for several months. A transthoracic echocardiogram revealed a right atrial mass. What would you do next?
Racial and Ethnic Disparities in Germline Genetic Testing of Patients With Young-Onset Colorectal Cancer
Authors: Pooja Dharwadkar, Garrett Greenan, Elena M. Stoffel, Ezra Burstein, Sara Pirzadeh-Miller, Sayoni Lahiri, Caitlin Mauer, Amit G. Singal, Caitlin C. Murphy
Journal: Clinical Gastroenterology and Hepatology (2020)
Pulmonary artery pulsatility index predicts right ventricular myofilament dysfunction in advanced human heart failure
Authors: M. Imran Aslam, Vivek Jani, Brian L. Lin, Brittany Dunkerly‐Eyring, Carissa E. Livingston, Abhinay Ramachandran, Mark J. Ranek, Kenneth C. Bedi, Kenneth B. Margulies, David A. Kass, Steven Hsu
Journal: European Journal of Heart Failure (2020)
Kidney Filtration Markers in Human Saliva: Accuracy and Reproducibility of Novel Salivary Cystatin C Measurements
Authors: Kamyar Kalantar-Zadeh, Manal Beshay, Connie Rhee, Trong D. Nguyen, Maria Ortega, Michael Shlipak, Danh V. Nguyen
Journal: Journal of the American Society of Nephrology (2020)

Background: Invasive phlebotomy followed by laborious blood specimen processing is the only reliable approach to assess routinely measured kidney filtration markers including cystatin C (CysC)  Non-invasive testing of these markers is urgently needed particularly during the COVID-19 pandemic to enhance social-distancing  Methods: We developed novel Enhanced Enzyme and Immunoassay-based Lateral Flow (ELF) assays to measure concentrations of CysC in human saliva  Highly selective binding reagents were screened for optimum specificity, followed by applying sample treatment steps to mitigate sample to sample variability using healthy donor saliva samples spiked with known levels of the filtration markers  Standard calibration curves (SCCs) for each marker was developed with nonlinear 4-parameter logistic curve fitting to triplicate measurements at each spiked concentration level  Accuracy/fit of the SCC was assessed using the coefficient of determination (R2)  Intra-assay repeatability was assessed using coefficient of variation (CV) and studies of inter-assay repeatability over time (over ∼8 days) examined reproducibility of whole experimental protocol  Results: SCC fitted to relative optical intensities (ratio of test to control lines vs  spiked CysC (0-14 ng/ml) was excellent (R2=0 991) and provided accurate estimates of spiked/ true CysC levels (R2=0 994)  Assessment of intra-assay variation showed that repeatability is very good with CV <10% throughout the dynamic range of measurements  Assessment of inter-assay variation (measurements over 8 days) showed that reproducibility is acceptable with CV <13% throughout most of the dynamic range  Preliminary assessment of long-term reproducibility (stability) out to 258 days indicated similar performance  [figure] Conclusions: We demonstrated feasibility of CysC measurements in human saliva samples with acceptable ELF assay characteristics including accuracy, repeatability, reproducibility, and long-term stability  Validation studies are ongoing to optimize the saliva testing framework for kidney function markers
Polo-like Kinase-1 and Aurora Kinase A As Novel Therapeutic Targets in Neoplastic Mast Cells
Authors: Manuela Mancini, Cecilia Monaldi, Sara De Santis, Cristina Papayannidis, Michela Rondoni, Maria Chiara Abbenante, Luana Bavaro, Margherita Martelli, Roberta Zanotti, Livio Pagano, Michele Cavo, Peter Valent, Giovanni Martinelli, Simona Soverini
Journal: Blood (2017)
Antibody Status and Incidence of SARS-CoV-2 Infection in Health Care Workers
Authors: Sheila F Lumley, Denise O'Donnell, Nicole E Stoesser, Philippa C Matthews, Alison Howarth, Stephanie B Hatch, Brian D Marsden, Stuart Cox, Tim James, Fiona Warren, Liam J Peck, Thomas G Ritter, Zoe de Toledo, Laura Warren, David Axten, Richard J Cornall, E Yvonne Jones, David I Stuart, Gavin Screaton, Daniel Ebner, Sarah Hoosdally, Meera Chand, Derrick W Crook, Anne-Marie O'Donnell, Christopher P Conlon, Koen B Pouwels, A Sarah Walker, Tim E A Peto, Susan Hopkins, Timothy M Walker, Katie Jeffery, David W Eyre
Journal: New England Journal of Medicine (2020)

BackgroundThe relationship between the presence of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the risk of subsequent reinfection remains unclear.MethodsWe investigated the incidence of SARS-CoV-2 infection confirmed by polymerase chain reaction (PCR) in seropositive and seronegative health care workers attending testing of asymptomatic and symptomatic staff at Oxford University Hospitals in the United Kingdom. Baseline antibody status was determined by anti-spike (primary analysis) and anti-nucleocapsid IgG assays, and staff members were followed for up to 31 weeks. We estimated the relative incidence of PCR-positive test results and new symptomatic infection according to antibody status, adjusting for age, participant-reported gender, and changes in incidence over time.ResultsA total of 12,541 health care workers participated and had anti-spike IgG measured; 11,364 were followed up after negative antibody results and 1265 after positive results, including 88 in whom seroconversion occurred during follow-up. A total of 223 anti-spike–seronegative health care workers had a positive PCR test (1.09 per 10,000 days at risk), 100 during screening while they were asymptomatic and 123 while symptomatic, whereas 2 anti-spike–seropositive health care workers had a positive PCR test (0.13 per 10,000 days at risk), and both workers were asymptomatic when tested (adjusted incidence rate ratio, 0.11; 95% confidence interval, 0.03 to 0.44; P=0.002). There were no symptomatic infections in workers with anti-spike antibodies. Rate ratios were similar when the anti-nucleocapsid IgG assay was used alone or in combination with the anti-spike IgG assay to determine baseline status.ConclusionsThe presence of anti-spike or anti-nucleocapsid IgG antibodies was associated with a substantially reduced risk of SARS-CoV-2 reinfection in the ensuing 6 months. (Funded by the U.K. Government Department of Health and Social Care and others.) Quick Take Incidence of SARS-CoV-2 Infection in Health Care Workers by Antibody Status 2m 35s
Endoscopic resection of a choledochocele
Authors: Vincenzo Giorgio Mirante, Paolo Cecinato, Simone Grillo, Giuliana Sereni, Matteo Lucarini, Marina Beltrami, Romano Sassatelli
Journal: Endoscopy (2020)

Choledochal cysts are uncommon congenital dilatations of the extrahepatic and/or intrahepatic biliary system. Several serious complications of choledochal cysts have been described, including malignancy. According to Todani et al., choledochal cysts are classified into five types [1]. Type III, or choledochocele, is a cystic dilatation of the intra-ampullary portion of the common bile duct (CBD). Compared with other choledochal cysts, the choledochocele has a very low rate of malignant transformation [2]. Therefore, the choledochocele can be treated with sphincterotomy or endoscopic papillectomy [3] [4]. Here we report a case of a 17-year-old man admitted to our hospital with acute mild pancreatitis.
Senescent cells as promising targets to tackle age-related diseases
Authors: Eva Prašnikar, Jure Borišek, Andrej Perdih
Journal: Ageing Research Reviews (2020)

As the world's population progressively ages, the burden on the socio-economic and health systems is escalating, demanding sustainable and lasting solutions. Cellular senescence, one of the hallmarks of ageing, is a state of irreversible cell cycle arrest that occurs in response to various genotoxic stressors and is considered an important factor in the development of many age-related diseases and therefore a potential therapeutic target. Here, the role of senescent cells in age-related diseases is discussed, focusing on their formation and main characteristics. The mechanisms leading to senescent cells are presented, including replicative and premature senescence as well as senescence that occurs in various physiological processes, such as wound healing. The second part comprises a comprehensive description of various biomarkers currently used for the detection of senescent cells along with the investigated therapeutic approaches, namely senolytics, senomorphics and the clearance of senescent cells by the immune system. Potential delivery systems suitable for such therapies and model organisms to study senescence are also briefly examined. This in-depth overview of cellular senescence contributes to a deeper understanding of a rapidly evolving area aimed to tackle the age-related diseases in a more mechanistic way, as well as highlights future research opportunities.
Fusogenic oncolytic vaccinia virus enhances systemic antitumor immune response by modulating the tumor microenvironment
Authors: Motomu Nakatake, Nozomi Kuwano, Emi Kaitsurumaru, Hajime Kurosaki, Takafumi Nakamura
Journal: Molecular Therapy (2020)

Oncolytic viruses induce antitumor immunity following direct viral oncolysis. However, their therapeutic effects are limited in distant untreated tumors because their antitumor function depends on indirect antitumor immunity. Here, we generated a novel fusogenic oncolytic vaccinia virus (FUVAC) and compared its antitumor activity with that of its parental non-fusogenic virus. Compared with the parent, FUVAC exerted the cytopathic effect and induced immunogenic cell death in human and murine cancer cells more efficiently. In a bilateral tumor-bearing syngeneic mouse model, FUVAC administration significantly inhibited tumor growth in both treated and untreated tumors. However, its antitumor effects were completely suppressed by CD8+ T cell depletion. Notably, FUVAC reduced the number of tumor-associated immune-suppressive cells in treated tumors, but not in untreated tumors. Mice treated with FUVAC before an immune checkpoint inhibitor (ICI) treatment achieved complete response (CR) in both treated and untreated tumors, whereas ICI alone did not show antitumor activity. Mice achieving CR rejected rechallenge with the same tumor cells, suggesting establishment of a long-term tumor-specific immune memory. Thus, FUVAC improves the tumor immune microenvironment and enhances systemic antitumor immunity, suggesting that, alone and in combination with ICI, it is a novel immune modulator for overcoming oncolytic virus-resistant tumors.
Abstract 13155: Risk of ASCVD and Non-ASCVD Hospitalizations for Triglycerides Across CKD Stages Among 2 Million US Veterans
Authors: Melissa Soohoo, Jui-Ting Hsiung, Christina Park, Maria Marroquin, Hamid Moradi, Csaba Kovesdy, Kamyar Kalantar-Zadeh, Elani Streja
Journal: Circulation (2019)

Introduction: High triglycerides (TG) are a risk factor for atherosclerotic cardiovascular disease (ASCVD). Studies in Chronic kidney disease (CKD) patients have shown TG-mortality associations wer...
Bilateral Temporal Pole Involvement in Adult-Onset X-Linked Adrenoleukodystrophy
Authors: Mao Liu, Jing Zhang, Min Zhang
Journal: JAMA Neurology (2020)

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Comprehensive mapping of immune tolerance yields a regulatory TNF receptor 2 signature in a murine model of successful Fel d 1‐specific immunotherapy using high‐dose CpG adjuvant
Authors: Cathy Leonard, Guillem Montamat, Caroline Davril, Olivia Domingues, Oliver Hunewald, Dominique Revets, Coralie Guerin, Simon Blank, Justine Heckendorn, Gauthier Jardon, François Hentges, Markus Ollert
Journal: Allergy (2020)

The prevalence of allergy to cat is expanding worldwide. Allergen-specific immunotherapy (AIT) has advantages over symptomatic pharmacotherapy and promises long-lasting disease control in allergic patients. However, there is still a need to improve cat AIT regarding efficacy, safety, and adherence to the treatment. Here, we aim to boost immune tolerance to the major cat allergen Fel d 1 by increasing the anti-inflammatory activity of AIT with the established immunomodulatory adjuvant CpG, but at a higher dose than previously used in AIT.Together with CpG, we used endotoxin-free Fel d 1 as therapeutic allergen throughout the study in a BALB/c model of allergy to Fel d 1, thus mimicking the conditions of human AIT trials. Multidimensional immune phenotyping including mass cytometry (CyTOF) was applied to analyze AIT-specific immune signatures.We show that AIT with high-dose CpG in combination with endotoxin-free Fel d 1 reverts all major hallmarks of allergy. High-dimensional CyTOF analysis of the immune cell signatures initiating and sustaining the AIT effect indicates the simultaneous engagement of both, the pDC-Treg and B-cell axis, with the emergence of a systemic GATA3+ FoxP3hi biTreg population. The regulatory immune signature also suggests the involvement of the anti-inflammatory TNF/TNFR2 signaling cascade in NK and B cells at an early stage and in Tregs later during AIT.Our results highlight the potential of CpG adjuvant in a novel formulation to be further exploited for inducing allergen-specific tolerance in patients with cat allergy or other allergic diseases.
scLM: Automatic Detection of Consensus Gene Clusters Across Multiple Single-Cell Datasets
Authors: Qianqian Song, Jing Su, Lance D. Miller, Wei Zhang
Journal: Genomics Proteomics & Bioinformatics (2020)

Abstract In gene expression profiling studies, including single-cell RNAsequencing (scRNA-seq) analyses, the identification and characterization of co-expressed genes provides critical information on cell identity and function. Gene co-expression clustering in scRNA-seq data presents certain challenges. We show that commonly used methods for single-cell data are not capable of identifying co-expressed genes accurately, and produce results that substantially limit biological expectations of co-expressed genes. Herein, we present single-cell Latent-variable Model (scLM), a gene co-clustering algorithm tailored to single-cell data that performs well at detecting gene clusters with significant biologic context. Importantly, scLM can simultaneously cluster multiple single-cell datasets, i.e., consensus clustering, enabling users to leverage single-cell data from multiple sources for novel comparative analysis. scLM takes raw count data as input and preserves biological variation without being influenced by batch effects from multiple datasets. Results from both simulation data and experimental data demonstrate that scLM outperforms the existing methods with considerably improved accuracy. To illustrate the biological insights of scLM, we apply it to our in-house and public experimental scRNA-seq datasets. scLM identifies novel functional gene modules and refines cell states, which facilitates mechanism discovery and understanding of complex biosystems such as cancers. A user-friendly R package with all the key features of the scLM method is available at https://github.com/QSong-github/scLM.
A Sickle-Cell Patient Displaced by the Pandemic: Is a Request for Opioids Legitimate, or Sign of a Deeper Problems?
Authors: Leah Eisenberg
Journal: The American Journal of Bioethics (2020)

"A Sickle-Cell Patient Displaced by the Pandemic: Is a Request for Opioids Legitimate, or Sign of a Deeper Problems?." The American Journal of Bioethics, 21(1), pp. 69–70
Association of County-Level Vulnerability, Patient-Level Race/Ethnicity, and Receipt of Surgery for Early-Stage Hepatocellular Carcinoma
Authors: Rosevine A. Azap, J. Madison Hyer, Adrian Diaz, Anghela Z. Paredes, Timothy M. Pawlik
Journal: JAMA Surgery (2020)

This study assesses the association and interaction of county-level social vulnerability index with patient-level race/ethnicity compared with the probability of undergoing resection/transplant for early-stage hepatocellular carcinoma.