tbuckley/cabot-search huggingface dataset:
Molecular identification of Cryptococcus gattii from cerebrospinal fluid using single-cell sequencing: A case study
Authors: Min Chen, Nan Hong, Shan Hu, Peng Wang, HongZhi Guan, Meng Xiao, Xinlin Zhu, Abdullah M.S. Al-Hatmi, Zhe Zhou, Lei Gao, Teun Boekhout, Jianping Xu, Yingchun Xu, Wanqing Liao, Ying Yang
Journal: Journal of Infection (2020)

A 31-year-old man presented with cryptococcal meningitis (CM) without typical clinical characteristics, but with abnormal walking, difficult leg lifting and frequent falling. He was admitted to Peking Union Medical College Hospital. After multiple tests failed to identify the pathogen, single-cell sequencing (scS) was used to test the cerebrospinal fluid (CSF). Comparing the sequence obtained from single-cell sequencing with the reference database, it was found that the infection was caused by Cryptococcus gattii sensu stricto (AFLP4/VGI genotype). Cryptococcus is difficult to cultivate from complex body fluids. The etiological agent of this patient was identified and the patient was treated. This is the first case in which scS was used to detect and identify fungal pathogen after conventional testing failed to identify the cause of the disease. This report demonstrates that the scS approach can be used to generate fungal genome sequences directly from the CSF of a CM patient. The scS technology could become a powerful tool to precise detect microscopically visible but uncultured pathogens in clinical samples.
Correction to: microRNA-124 inhibits bone metastasis of breast cancer by repressing Interleukin-11
Authors: Wei-Luo Cai, Wen-Ding Huang, Bo Li, Tian-Rui Chen, Zhen-Xi Li, Cheng-Long Zhao, Heng-Yu Li, Yan-Mei Wu, Wang-Jun Yan, Jian-Ru Xiao
Journal: Molecular Cancer (2020)

An amendment to this paper has been published and can be accessed via the original article.
Getting back on track: control of covid-19 outbreaks in the community
Authors: Peter Roderick, Alison Macfarlane, Allyson M Pollock
Journal: BMJ (2020)

Peter Roderick , Alison Macfarlane, and Allyson M Pollock argue there's still time to change tack on the UK's ad hoc system for covid-19 tracking, testing, and contact tracing Historically, England's system of communicable disease control has relied on close cooperation between local health services and authorities. General practitioners, NHS and public health laboratories, and local public health officers play key roles, backed by legal notification requirements. That local system has gradually been eroded over several decades. (box 1) But instead of prioritising and rebuilding this system at the start of this epidemic, the government has created a separate system which steers patients away from GPs, avoids local authorities, and relies on commercial companies and laboratories to track, test, and contact trace. The ad hoc parallel system in England has three components: Box 1 ### Erosion of local communicable disease control in England At its height, local communicable disease control was supported by more than 60 national, regional, and local public health laboratories. The service was strengthened from 1977-2002 by the creation of the Communicable Disease Surveillance Centre in Colindale. Erosion began after NHS reorganisation in 1974 and continued when the Public Health Laboratory Service Board was abolished in 2003 and its local laboratories transferred to NHS trusts, at the same time as communicable disease control was centralised in the Health Protection Agency. In 2012, the Health and Social Care Act abolished locally based bodies in England and carved public health functions out of the NHS. Public Health England was set up as an executive agency to fulfil the government's duty to protect the public from disease, with only nine laboratories and eight regional centres. Local authorities were charged with improving public health. Each local authority was required, acting jointly with the secretary of state, to appoint a director of public health, with responsibility for exercising the authority's public health functions. … RETURN TO TEXT
Abstract 17133: Spatio-temporal Pattern Of Rv And Lv T-tubule Dysregulation In A Model Of Ischemic Heart Failure
Authors: Michael Ibrahim, Elizabeth Li, Ann Gaffey, Samuel T Kim, Jennifer Chung, Pavan Atluri
Journal: Circulation (2019)

Introduction: Transverse (t)-tubules provide a critical means for intra-cellular coordinated contractility upon activation of the cell membrane during each heart beat. Dysregulation of t-tubule str...
Effect on Patient Safety of a Resident Physician Schedule without 24-Hour Shifts
Authors: Christopher P. Landrigan, Shadab A. Rahman, Jason P. Sullivan, Eric Vittinghoff, Laura K. Barger, Amy L. Sanderson, Kenneth P. Wright, Conor S. O’Brien, Salim Qadri, Melissa A. St. Hilaire, Ann C. Halbower, Jeffrey L. Segar, John K. McGuire, Michael V. Vitiello, Horacio O. de la Iglesia, Sue E. Poynter, Pearl L. Yu, Phyllis C. Zee, Steven W. Lockley, Katie L. Stone, Charles A. Czeisler
Journal: New England Journal of Medicine (2020)

The effects on patient safety of eliminating extended-duration work shifts for resident physicians remain controversial. We conducted a multicenter, cluster-randomized, crossover trial comparing two schedules for pediatric resident physicians during their intensive care unit (ICU) rotations: extended-duration work schedules that included shifts of 24 hours or more (control schedules) and schedules that eliminated extended shifts and cycled resident physicians through day and night shifts of 16 hours or less (intervention schedules). The primary outcome was serious medical errors made by resident physicians, assessed by intensive surveillance, including direct observation and chart review. The characteristics of ICU patients during the two work schedules were similar, but resident physician workload, described as the mean (±SD) number of ICU patients per resident physician, was higher during the intervention schedules than during the control schedules (8.8±2.8 vs. 6.7±2.2). Resident physicians made more serious errors during the intervention schedules than during the control schedules (97.1 vs. 79.0 per 1000 patient-days; relative risk, 1.53; 95% confidence interval [CI], 1.37 to 1.72; P<0.001). The number of serious errors unitwide were likewise higher during the intervention schedules (181.3 vs. 131.5 per 1000 patient-days; relative risk, 1.56; 95% CI, 1.43 to 1.71). There was wide variability among sites, however; errors were lower during intervention schedules than during control schedules at one site, rates were similar during the two schedules at two sites, and rates were higher during intervention schedules than during control schedules at three sites. In a secondary analysis that was adjusted for the number of patients per resident physician as a potential confounder, intervention schedules were no longer associated with an increase in errors. Contrary to our hypothesis, resident physicians who were randomly assigned to schedules that eliminated extended shifts made more serious errors than resident physicians assigned to schedules with extended shifts, although the effect varied by site. The number of ICU patients cared for by each resident physician was higher during schedules that eliminated extended shifts. (Funded by the National Heart, Lung, and Blood Institute; ROSTERS ClinicalTrials.gov number, NCT02134847.).
Human iPSC-Derived Cardiomyocytes Are Susceptible to SARS-CoV-2 Infection
Authors: Arun Sharma, Gustavo Garcia, Yizhou Wang, Jasmine T. Plummer, Kouki Morizono, Vaithilingaraja Arumugaswami, Clive N. Svendsen
Journal: Cell Reports Medicine (2020)

Coronavirus disease 2019 (COVID-19) is a pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 is defined by respiratory symptoms, but cardiac complications including viral myocarditis are also prevalent. Although ischemic and inflammatory responses caused by COVID-19 can detrimentally affect cardiac function, the direct impact of SARS-CoV-2 infection on human cardiomyocytes is not well understood. Here, we utilize human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) as a model to examine the mechanisms of cardiomyocyte-specific infection by SARS-CoV-2. Microscopy and RNA sequencing demonstrate that SARS-CoV-2 can enter hiPSC-CMs via ACE2. Viral replication and cytopathic effect induce hiPSC-CM apoptosis and cessation of beating after 72 h of infection. SARS-CoV-2 infection activates innate immune response and antiviral clearance gene pathways, while inhibiting metabolic pathways and suppressing ACE2 expression. These studies show that SARS-CoV-2 can infect hiPSC-CMs in vitro, establishing a model for elucidating infection mechanisms and potentially a cardiac-specific antiviral drug screening platform.
Long-Term Greenspace Exposure and Progression of Arterial Stiffness: The Whitehall II Cohort Study
Authors: Carmen de Keijzer, Maria Foraster, Xavier Basagaña, Cathryn Tonne, Lucia Alonso Garcia, Antònia Valentín, Mika Kivimäki, Mark J. Nieuwenhuijsen, Jordi Alonso, Josep M. Antó, Archana Singh-Manoux, Jordi Sunyer, Payam Dadvand
Journal: Environmental Health Perspectives (2020)

BACKGROUND: Arterial stiffness, and its progression with age, is an important indicator of cardiovascular aging.Greenspace exposure may protect against arterial stiffness by promoting physical activity, fostering social cohesion, and reducing stress and exposure to air pollution and noise.OBJECTIVES: The aim of this study was to investigate the association of long-term exposure to outdoor greenspace with arterial stiffness and its progression over time.METHODS: This prospective cohort study was based on 4,349 participants (55-83 years of age) of the Whitehall II Study, United Kingdom.Arterial stiffness was assessed in two medical examinations (2007-2009 and 2012-2013) by measuring the carotid-femoral pulse wave velocity (cf-PWV).Residential surrounding greenspace was characterized using satellite-based indices of greenspace including normalized difference vegetation index (NDVI), enhanced vegetation index (EVI), and vegetation continuous fields (VCF) across buffers of 500 and 1,000 m surrounding the participants' residential locations at each follow-up.The association between the greenspace indicators and baseline cf-PWV and 4-year progression of cf-PWV was assessed using linear mixed-effects models with the participant as a random effect, controlling for demographic, lifestyle, and (individual and area) socioeconomic factors.RESULTS: No statistically significant associations were observed between residential surrounding greenspace and baseline or 4-y progression of cf-PWV; interquartile range (IQR) increases in NDVI, EVI, and VCF in the 500-m buffer were associated with -0:04 m=s [95% confidence interval (CI): -0:12, 0.04], -0:03 m=s (95% CI: -0:10, 0.05), and -0:02 m=s (95% CI: -0:08, 0.04) in baseline cf-PWV and 0:06 m=s (95% CI: -0:02, 0.14), 0:05 m=s (95% CI: -0:03, 0.14), and 0:00 m=s (95% CI: -0:09, 0.09) in 4-y progression in cf-PWV, respectively.The associations were similar when using 1,000-m buffers.
Efficacy and safety of risankizumab vs. secukinumab in patients with moderate‐to‐severe plaque psoriasis (IMMerge): results from a phase III, randomized, open‐label, efficacy–assessor‐blinded clinical trial*
Authors: R.B. Warren, A. Blauvelt, Y. Poulin, S. Beeck, M. Kelly, T. Wu, Z. Geng, C. Paul
Journal: British Journal of Dermatology (2020)

Patients with plaque psoriasis treated with biologic therapies need more efficacious, safe and convenient treatments to improve quality of life. Risankizumab and secukinumab inhibit interleukin-23 and interleukin-17A, respectively, and are effective in adult patients with moderate-to-severe plaque psoriasis but have different dosing regimens.To compare directly the efficacy and safety of risankizumab vs. secukinumab over 52 weeks.IMMerge was an international, phase III, multicentre, open-label, efficacy-assessor-blinded, active-comparator study, in which adult patients with chronic, moderate-to-severe plaque psoriasis were randomized in a 1 : 1 ratio to treatment with risankizumab 150 mg or secukinumab 300 mg. Primary efficacy endpoints were the proportions of patients achieving ≥ 90% improvement from baseline in Psoriasis Area and Severity Index (PASI 90) at week 16 (noninferiority comparison with margin of 12%) and week 52 (superiority comparison).In total 327 patients from nine countries were treated with risankizumab (n = 164) or secukinumab (n = 163). Risankizumab was noninferior to secukinumab in the proportion of patients achieving PASI 90 at week 16 [73·8% vs. 65·6%; difference of 8·2%, 96·25% confidence interval (CI)-2·2 to 18·6; within the 12% noninferiority margin] and superior to secukinumab at week 52 (86·6% vs. 57·1%; difference of 29·8%, 95% CI 20·8-38·8; P < 0·001), thus meeting both primary endpoints. All secondary endpoints (PASI 100, static Physician's Global Assessment 0 or 1, and PASI 75) at week 52 demonstrated superiority for risankizumab vs. secukinumab (P < 0·001). No new safety concerns were identified.At week 52, risankizumab demonstrated superior efficacy and similar safety with less frequent dosing compared with secukinumab.
Gene and Stem Cell Therapies for Fetal Care
Authors: Amy E. O’Connell, Stephanie Guseh, Larissa Lapteva, Christy L. Cummings, Louise Wilkins-Haug, Jerry Chan, William H. Peranteau, Graça Almeida-Porada, Stella Kourembanas
Journal: JAMA Pediatrics (2020)

Gene and stem cell therapies have become viable therapeutic options for many postnatal disorders. For select conditions, prenatal application would provide improved outcomes. The fetal state allows for several theoretical advantages over postnatal therapy, including immune immaturity and cellular niche accessibility.Advances in prenatal diagnostic accuracy and surgical precision, as well as improvements in stem cell and gene therapy methods, have made prenatal gene and stem cell therapy realistic. Studies in mouse models and early human trials demonstrate the feasibility of these approaches. Additional efforts are under way to streamline fetal applications of stem cell and gene therapy while carefully considering best ethical practice and following established regulatory pathways.Fetal stem cell and gene therapy bring important therapeutic opportunities for select disorders that present in the fetal and neonatal periods. While this field is in its infancy, these therapies are starting to be available clinically, and clinicians should be aware of their benefits and challenges.
Sputum neutrophil elastase in bronchiectasis: a Southern European cohort study
Authors: Andrea Gramegna, Stefano Aliberti, Oriol Sibila, Carlotta Di Francesco, Giovanni Sotgiu, Lidia Perea, Leonardo Terranova, Martina Oriano, Tommaso Pilocane, Laura Saderi, James D. Chalmers, Paola Marchisio, Francesco Blasi
Journal: European Respiratory Journal (2020)

<b>Activity of neutrophil elastase is a generalisable biomarker related to disease severity and clinical characteristics across different populations of patients with bronchiectasis</b>https://bit.ly/2XKDUqn
ModelTeller: Model Selection for Optimal Phylogenetic Reconstruction Using Machine Learning
Authors: Shiran Abadi, Oren Avram, Saharon Rosset, Tal Pupko, Itay Mayrose
Journal: Molecular Biology and Evolution (2020)

Statistical criteria have long been the standard for selecting the best model for phylogenetic reconstruction and downstream statistical inference. Although model selection is regarded as a fundamental step in phylogenetics, existing methods for this task consume computational resources for long processing time, they are not always feasible, and sometimes depend on preliminary assumptions which do not hold for sequence data. Moreover, although these methods are dedicated to revealing the processes that underlie the sequence data, they do not always produce the most accurate trees. Notably, phylogeny reconstruction consists of two related tasks, topology reconstruction and branch-length estimation. It was previously shown that in many cases the most complex model, GTR+I+G, leads to topologies that are as accurate as using existing model selection criteria, but overestimates branch lengths. Here, we present ModelTeller, a computational methodology for phylogenetic model selection, devised within the machine-learning framework, optimized to predict the most accurate nucleotide substitution model for branch-length estimation. We demonstrate that ModelTeller leads to more accurate branch-length inference than current model selection criteria on data sets simulated under realistic processes. ModelTeller relies on a readily implemented machine-learning model and thus the prediction according to features extracted from the sequence data results in a substantial decrease in running time compared with existing strategies. By harnessing the machine-learning framework, we distinguish between features that mostly contribute to branch-length optimization, concerning the extent of sequence divergence, and features that are related to estimates of the model parameters that are important for the selection made by current criteria.
Effectiveness and safety of tumor site marking with near-infrared fluorescent clips in colorectal laparoscopic surgery: A case series study
Authors: Satoshi Narihiro, Masashi Yoshida, Hironori Ohdaira, Takayuki Sato, Daisuke Suto, Sojun Hoshimoto, Norihiko Suzuki, Rui Marukuchi, Teppei Kamada, Hideyuki Takeuchi, Yutaka Suzuki
Journal: International Journal of Surgery (2020)

In colorectal laparoscopic surgery, accuracy of tumor marking has been an important but not fully resolved issue. The tattoo marking technique or intraoperative endoscopy have been used but they either carry the risk of accidental intestinal puncture or require either longer operation times, a skilled endoscopist and/or intraoperative colon insufflation. We supposed that tumor site marking with the near-infrared fluorescent clips, ZEOCLIP FS clips (Zeon Medical Co., Ltd., Tokyo, Japan) might overcome disadvantages of both tattoo marking and intraoperative endoscopy-based tumor localization methods. This is the first report on the case series using near-infrared fluorescent marking clip. We summarize the early results in 30 patients, who underwent colorectal laparoscopic surgery; we focus particularly on effectiveness and safety of the method.Thirty consecutive patients, who underwent laparoscopic surgery for colorectal cancer after previous endoscopic ZEOCLIP FS placement were enrolled from May 2019 till October 2019. The primary endpoint was the rate of intraoperative clip detection and the secondary endpoints were: the rate of adverse effects, percentage of slipped clips and usefulness of plain abdominal radiography to preoperatively confirm the clip retention. Locations of fluorescent clips were identified with a full-color fluorescence laparoscope. All operations and clip placements were performed by the same senior surgeon with sufficient experience in both procedures.Fluorescent clips could be detected in 94.1% of tumor lesions. Three (2.1%) clips dropped before surgery. Plain abdominal radiography was sufficient to assess clip retention in all cases. No adverse effects related to either clip placement or clip detection were observed.The ZEOCLIP FS could be easily detected from the serosal side of the intestinal tract when placed 1-2 days before surgery. Fluorescent clip-guided laparoscopy may be considered a safe and effective method for localization of colorectal tumor sites. The Research Registry UIN: researchregistry5400.
Abstract 17152: Identification of Cardiac Glycosides as Agonists of RXFP1 via Ultra High Throughput Screening
Authors: Abdallah Bitar, Sang Jun Lee, Mitch Hull, Luke Lairson, Weijun Shen, Peter G Schultz
Journal: Circulation (2016)

Introduction: Relaxin, a peptide hormone, has garnered much attention in the treatment of congestive heart failure based on its favorable hemodynamic profile. In the RELAX-AHF trial, serelaxin (a r...
Department of Error
Journal: The Lancet (2020)

sample collection and data generation, processing and formatting for maximal information gain.Open datasets will enable ready access to this valuable information by the computational community to help understand antigen response mechanisms, inform vaccine devel opment, and enable antiviral drug design.As countries across the world increase widespread testing to confirm SARSCoV2 exposure and assess immunity, mass spectrometry has a significant role in fighting the disease.Through collaborative actions, and the collective efforts of the COVID19 MS Coalition, a molecular level quantita tive understanding of SARSCoV2 and its effect will benefit all.
Apixaban vs Enoxaparin for Postoperative Prophylaxis: Safety of an Oral Alternative for the Prevention of Venous Thromboembolism
Authors: Elisabeth Diver
Journal: JAMA Network Open (2020)

Saketh R. Guntupalli, MD; Alyse Brennecke, MS; Kian Behbakht, MD; Anna Tayebnejad, BS; Christopher A. Breed, MD; Lisa Marie Babayan, PAC; Georgina Cheng, MD, PhD; Amin A. Ramzan, MD; Lindsay J. Wheeler, MD; Bradley R. Corr, MD; Carolyn Lefkowits, MD; Jeanelle Sheeder, PhD; Koji Matsuo, MD, PhD; Dina Flink, PhD
Performance Characteristics of Pulmonary Function Tests for the Detection of Interstitial Lung Disease in Adults With Early Diffuse Cutaneous Systemic Sclerosis
Authors: Elana J. Bernstein, Sara Jaafar, Shervin Assassi, Robyn T. Domsic, Tracy M. Frech, Jessica K. Gordon, Rachel J. Broderick, Faye N. Hant, Monique E. Hinchcliff, Ami A. Shah, Victoria K. Shanmugam, Virginia D. Steen, Dinesh Khanna
Journal: Arthritis & Rheumatology (2020)

Interstitial lung disease (ILD) is the leading cause of death in patients with systemic sclerosis (SSc). Although pulmonary function tests (PFTs) are commonly used to screen for ILD in patients with SSc, studies have shown that they lack sensitivity for the detection of ILD in general SSc cohorts. This study was undertaken to assess the performance characteristics of PFTs for the detection of ILD in patients with early diffuse cutaneous SSc (dcSSc), a population at high risk for the development of ILD.We performed a retrospective cohort study of patients enrolled in the Prospective Registry of Early Systemic Sclerosis at 11 sites in the US between April 2012 and January 2019. Patients were included if they underwent spirometry and high-resolution computed tomography (HRCT) of the chest. We calculated the performance characteristics of PFTs for the detection of ILD on HRCT.The study included 212 patients, 54% of whom had radiographic ILD. For the detection of ILD on HRCT imaging, a forced vital capacity (FVC) <80% predicted had a sensitivity of 63%. The combination of FVC <80% predicted or diffusing capacity for carbon monoxide (DLco) <80% predicted improved the sensitivity to 85%. An FVC <80% predicted had a negative predictive value (NPV) of 61%, while the combination of FVC <80% predicted or DLco <80% predicted had an NPV of 70%.PFTs alone are an inadequate screening tool for the diagnosis of ILD in patients with early dcSSc. HRCT should be part of the ILD screening algorithm in patients with dcSSc.