tbuckley/cabot-search huggingface dataset:
Performance of existing definitions and tests for the diagnosis of invasive aspergillosis in critically ill, adult patients: A systematic review with qualitative evidence synthesis
Authors: M. Bassetti, D.R. Giacobbe, C. Grecchi, C. Rebuffi, V. Zuccaro, L. Scudeller, M. Akova, A. Alastruey-Izquierdo, S. Arikan-Akdagli, E. Azoulay, S. Blot, O.A. Cornely, C. Lass-Flörl, P. Koehler, M. Cuenca-Estrella, D.W. de Lange, F.G. De Rosa, J.J. De Waele, G. Dimopoulos, J. Garnacho-Montero, M. Hoenigl, S.S. Kanj, F. Lamoth, J. Maertens, I. Martin-Loeches, P. Muñoz, B.J. Kullberg, C. Agvald-Ohman, G. Poulakou, J. Rello, E. Righi, M. Sanguinetti, F.S. Taccone, J-F. Timsit, A. Torres, J.A. Vazquez, J. Wauters, T. Calandra, E. Asperges, S. Tejada, C. Lebihan, I. Karaiskos, M. Peghin, K.L. Mortensen, A. Vena, A. Cortegiani, T. Mercier
Journal: Journal of Infection (2020)
COVID-19: a need for real-time monitoring of weekly excess deaths
Authors: David A Leon, Vladimir M Shkolnikov, Liam Smeeth, Per Magnus, Markéta Pechholdová, Christopher I Jarvis
Journal: The Lancet (2020)

The first-line epidemiological response to coronavirus disease 2019 (COVID-19) requires estimation of key parameters, including case fatality risk, and reproduction number, to monitor and predict the probable course of the pandemic. The challenge for public health scientists is that these data are partly a function of testing coverage. The number of deaths attributed to COVID-19 is problematic because the criteria for defining a death almost certainly depends on whether the death occurs in somebody who tested positive for severe acute respiratory syndrome coronavirus 2. Furthermore, an unknown fraction of the cases classified as COVID-19 deaths had underlying health conditions and were probably already at an increased risk of death. Although some countries tend to attribute to COVID-19 most deaths of people who had the virus, others might tend to register other causes of death in the presence of major chronic diseases, even if the deceased person had COVID-19. As the pandemic progresses, consistent measurement of its scale, across time and space, should be a priority. Objective and comparable data are crucial to determine the effectiveness of different national strategies used to mitigate and suppress, and thus to better prepare for the probable continuation of, the epidemic over the next year or more. For the reasons outlined above, the metrics on incidence and fatality have shortcomings that make such comparisons problematic. Weekly excess deaths could provide the most objective and comparable way of assessing the scale of the pandemic and formulating lessons to be learned. This measure can be constructed by comparing the observed weekly deaths throughout 2020 to values expected from the experience of previous non-pandemic years. This approach allows for the assessment of the total mortality effects of the pandemic in different places. Crucially, the counts would be of deaths by all causes combined, thus side-stepping issues of what is or is not a death attributable to COVID-19. Unfortunately, most countries do not publish such statistics, and those countries that do typically do, do so with considerable delay. We therefore urge all national authorities who can collate counts of weekly deaths to expedite the publication of these data and place them in the public domain. The dissemination of this information should be done within 3–4 weeks of the period of observation. At a minimum, tabulations by sex and 5-year age groups are essential. Where not already in the public domain, countries should also release the equivalent weekly data for every calendar year from 2010, for calculation of excess deaths in 2020. LS reports grants from Wellcome, the Medical Research Council, the National Institute for Health Research, GlaxoSmithKline, the British Heart Foundation, and Diabetes UK. LS is also a trustee of the British Heart Foundation. All other authors declare no competing interests.
Artificial intelligence for teleophthalmology-based diabetic retinopathy screening in a national programme: an economic analysis modelling study
Authors: Yuchen Xie, Quang D Nguyen, Haslina Hamzah, Gilbert Lim, Valentina Bellemo, Dinesh V Gunasekeran, Michelle Y T Yip, Xin Qi Lee, Wynne Hsu, Mong Li Lee, Colin S Tan, Hon Tym Wong, Ecosse L Lamoureux, Gavin S W Tan, Tien Y Wong, Eric A Finkelstein, Daniel S W Ting
Journal: The Lancet Digital Health (2020)

BackgroundDeep learning is a novel machine learning technique that has been shown to be as effective as human graders in detecting diabetic retinopathy from fundus photographs. We used a cost-minimisation analysis to evaluate the potential savings of two deep learning approaches as compared with the current human assessment: a semi-automated deep learning model as a triage filter before secondary human assessment; and a fully automated deep learning model without human assessment.MethodsIn this economic analysis modelling study, using 39 006 consecutive patients with diabetes in a national diabetic retinopathy screening programme in Singapore in 2015, we used a decision tree model and TreeAge Pro to compare the actual cost of screening this cohort with human graders against the simulated cost for semi-automated and fully automated screening models. Model parameters included diabetic retinopathy prevalence rates, diabetic retinopathy screening costs under each screening model, cost of medical consultation, and diagnostic performance (ie, sensitivity and specificity). The primary outcome was total cost for each screening model. Deterministic sensitivity analyses were done to gauge the sensitivity of the results to key model assumptions.FindingsFrom the health system perspective, the semi-automated screening model was the least expensive of the three models, at US$62 per patient per year. The fully automated model was $66 per patient per year, and the human assessment model was $77 per patient per year. The savings to the Singapore health system associated with switching to the semi-automated model are estimated to be $489 000, which is roughly 20% of the current annual screening cost. By 2050, Singapore is projected to have 1 million people with diabetes; at this time, the estimated annual savings would be $15 million.InterpretationThis study provides a strong economic rationale for using deep learning systems as an assistive tool to screen for diabetic retinopathy.FundingMinistry of Health, Singapore.
Covid-19 and Kidney Transplantation
Authors: Enver Akalin, Yorg Azzi, Rachel Bartash, Harish Seethamraju, Michael Parides, Vagish Hemmige, Michael Ross, Stefanie Forest, Yitz D Goldstein, Maria Ajaimy, Luz Liriano-Ward, Cindy Pynadath, Pablo Loarte-Campos, Purna B Nandigam, Jay Graham, Marie Le, Juan Rocca, Milan Kinkhabwala
Journal: New England Journal of Medicine (2020)

Kidney-Transplant Recipients with Covid-19 A cohort of 36 consecutive kidney-transplant recipients had less fever, lower CD3, CD4, and CD8 cell counts, more rapid clinical deterioration, and a high...
Covid-19: concerns grow over inflammatory syndrome emerging in children
Authors: Elisabeth Mahase
Journal: BMJ (2020)

Doctors in the UK have been warned over a rising number of children presenting with a multisystem inflammatory state and needing intensive care.

In an urgent alert shared by North Central London Clinical Commissioning Group and the Paediatric Intensive Care Society,1 doctors were told that while the unspecified number of cases may be connected to the current pandemic, the symptoms have been observed in both children who have tested positive and negative for covid-19.

“There is a growing concern that a SARS-CoV-2 related inflammatory syndrome is emerging in children in the UK or that there may be another as yet unidentified infectious pathogen associated with these cases,” the letter said.

Child health leaders have stressed that there is currently a small number of cases and that advice to …
Motorised spiral enteroscopy: first prospective clinical feasibility study
Authors: Torsten Beyna, Marianna Arvanitakis, Markus Schneider, Christian Gerges, Daniel Böing, Jacques Devière, Horst Neuhaus
Journal: Gut (2020)

Objective Currently available methods for small bowel endoscopy are often time consuming; motorised PowerSpiral Enteroscopy (PSE) is a further development of spiral enteroscopy to facilitate the approach to the small bowel. The aim of this bicentric prospective trial was to study feasibility and yield of peroral PSE. Design Consecutive patients with suspected small bowel disease and indication for antegrade enteroscopy were included in two tertiary referral centres. Primary objective was diagnostic yield of antegrade PSE. Secondary objectives included technical success (defined as successful endoscope insertion at least to ligament of Treitz), depth of maximum insertion (DMI), median insertion time to DMI, rate of therapeutic procedures and adverse events. Results During a 30-month period, 140 procedures were performed on 132 patients (58 female, 74 male; median age: 68 (20–100) years) under general anaesthesia. Overall diagnostic yield of PSE was 74.2%; with 68.2% of procedures including some form of endotherapy. Technical success rate of PSE was 97%; median DMI was 450 cm (0–600) with a median insertion time to DMI of 25 min (3–122). Antegrade panenteroscopy to the cecum was achieved in 14 cases (10.6%). Overall adverse event (AE) rate was 14.4%; two major serious AEs occurred (1.5%), one delayed perforation, one bleeding from Mallory-Weiss lesion. Conclusion This pilot clinical trial demonstrates that PSE is effective for diagnostic and therapeutic antegrade enteroscopy and may compare favourably with traditional methods of deep enteroscopy in ease of use and procedural duration. More comparative data are required to assess clinical application and safety of PSE. Trial registration number NCT02965209
Lipid-based biomarkers for CVD, COPD, and aging – A translational perspective
Authors: Kim Ekroos, Oksana Lavrynenko, Bjoern Titz, Calin Pater, Julia Hoeng, Nikolai V. Ivanov
Journal: Progress in Lipid Research (2020)

For many diseases, there is an unmet need for new or better biomarkers for improved disease risk assessment and monitoring, as available markers lack sufficient specificity. Lipids are drawing major interest as potential candidates for filling these gaps. This has recently been demonstrated by the identification of selective ceramides for prediction of cardiovascular mortality, enabling improved risk assessment of cardiovascular disease compared with conventional clinical markers. In this review, we discuss current lipid biomarker findings and the possible connection between cardiovascular disease, chronic obstructive pulmonary disease, and aging. Moreover, we discuss how to overcome the current roadblocks facing lipid biomarker research. We stress the need for improved quantification, standardization of methodologies, and establishment of initial reference values to allow for an efficient transfer path of research findings into the clinical landscape, and, ultimately, to put newly identified biomarkers into practical use.
Information Technology–Based Tracing Strategy in Response to COVID-19 in South Korea—Privacy Controversies
Authors: Sangchul Park, Gina Jeehyun Choi, Haksoo Ko
Journal: JAMA (2020)

Yan Bai, MD; Lingsheng Yao, MD; Tao Wei, MD; Fei Tian, MD; Dong-Yan Jin, PhD; Lijuan Chen, PhD; Meiyun Wang, MD, PhD
Tuberous sclerosis 1 (Tsc1) mediated mTORC1 activation promotes glycolysis in tubular epithelial cells in kidney fibrosis
Authors: Hongdi Cao, Jing Luo, Yu Zhang, Xiaoming Mao, Ping Wen, Hao Ding, Jing Xu, Qi Sun, Weichun He, Chunsun Dai, Ke Zen, Yang Zhou, Junwei Yang, Lei Jiang
Journal: Kidney International (2020)
Abstract 13987: Underutilization of Oral Anticoagulant Therapy in At-Risk Patients With Atrial Fibrillation—Insights From a Multistate Healthcare System
Authors: Tyler J Gluckman, Amir Ali, Mansen Wang, Howard Mun, Sally Alfred, John L Petersen
Journal: Circulation (2019)

Introduction: Oral anticoagulant (OAC) therapy significantly reduces the risk of thromboembolism among at-risk patients with atrial fibrillation (AF). Current guidelines provide strong support for ...
Diagnostic and Prognostic Utilities of Insulin-Like Growth Factor Binding Protein-7 in Patients With Dyspnea
Authors: Nasrien E. Ibrahim, Marc Afilalo, Annabel Chen-Tournoux, Robert H. Christenson, Hanna K. Gaggin, Judd E. Hollander, Peter Kastner, Phillip D. Levy, Anika Mang, Serge Masson, John T. Nagurney, Richard M. Nowak, Peter S. Pang, W. Frank Peacock, Vinzent Rolny Dipl-Stat, E. Lea Walters, James L. Januzzi
Journal: JACC Heart Failure (2020)
Deamidation Shunts RelA from Mediating Inflammation to Aerobic Glycolysis
Authors: Jun Zhao, Mao Tian, Shu Zhang, Alireza Delfarah, Ruoyun Gao, Youliang Rao, Ali Can Savas, Anjie Lu, Larissa Bubb, Xiao Lei, Rosa Moshirian, Wenjie Zhu, Cheng Peng, Taijiao Jiang, Lin Chen, Nicholas A. Graham, Pinghui Feng
Journal: Cell Metabolism (2020)
Risk factors of critical &amp; mortal COVID-19 cases: A systematic literature review and meta-analysis
Authors: Zhaohai Zheng, Fang Peng, Buyun Xu, Jingjing Zhao, Huahua Liu, Jiahao Peng, Qingsong Li, Chongfu Jiang, Yan Zhou, Shuqing Liu, Chunji Ye, Peng Zhang, Yangbo Xing, Hangyuan Guo, Weiliang Tang
Journal: Journal of Infection (2020)
Clinical Usefulness of Plasma Activities of Gelatinase (Matrix Metalloproteinase-2 and 9) in Chronic Liver Disease
Authors: 권오상, 임도윤, 권광안, 정문기, 박동균, 김선숙, 김연석, 권소영, 구양서, 김유경, 최덕주, 김주현, 황유진, 변관수, 이창홍
Journal: Clinical and Molecular Hepatology (2003)
Impact of Stopping Trastuzumab in Early Breast Cancer: A Population-Based Study in Ontario, Canada
Authors: Moira Rushton, Isac Lima, Meltem Tuna, Chris Johnson, Josee Ivars, Kathy Pritchard, Steven Hawken, Susan Dent
Journal: JNCI Journal of the National Cancer Institute (2020)

Adjuvant trastuzumab for early-stage (I-III) HER2-positive breast cancer (BC) has led to statistically significant improvement in cancer outcomes but carries a risk of cardiotoxicity. Trastuzumab is discontinued early in many patients for asymptomatic changes in left ventricular ejection fraction. We evaluated the impact of early discontinuation of trastuzumab on cancer outcomes.
Heightened Innate Immune Responses in the Respiratory Tract of COVID-19 Patients
Authors: Zhuo Zhou, Lili Ren, Li Zhang, Jiaxin Zhong, Yan Xiao, Zhilong Jia, Li Guo, Jing Yang, Chun Wang, Shuai Jiang, Donghong Yang, Guoliang Zhang, Hongru Li, Fuhui Chen, Yu Xu, Mingwei Chen, Zhancheng Gao, Jian Yang, Jie Dong, Bo Liu, Xiannian Zhang, Weidong Wang, Kunlun He, Qi Jin, Mingkun Li, Jianwei Wang
Journal: Cell Host & Microbe (2020)
Respiratory Pathophysiology of Mechanically Ventilated Patients with COVID-19: A Cohort Study
Authors: David R. Ziehr, Jehan Alladina, Camille R. Petri, Jason H. Maley, Ari Moskowitz, Benjamin D. Medoff, Kathryn A. Hibbert, B. Taylor Thompson, C. Corey Hardin
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

To the Editor:Five to twenty percent of hospitalized patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are admitted to the ICU, with mortality reported between 26% and 61.5% (1-3).Nearly all ICU patients present with respiratory failure, and up to 88% are managed with invasive mechanical ventilation (1-3).Descriptions of the pathophysiological characteristics of coronavirus disease (COVID-19) respiratory failure are limited.Reports of preserved respiratory system mechanics despite severe hypoxemia in early small series have led some investigators to hypothesize that a significant proportion of COVID-19 respiratory failure is not the typical acute respiratory distress syndrome (ARDS) and warrants alternative management (4, 5).A detailed characterization of COVID-19 respiratory failure and its response to established ARDS therapies is needed before rigorous comparisons of established and new strategies can be contemplated.We describe the respiratory pathophysiology of patients with COVID-19 respiratory failure treated with invasive mechanical ventilation at two tertiary care hospitals in Boston, Massachusetts. MethodsPopulation and setting.We studied all adult inpatients with SARS-CoV-2 infection and respiratory failure managed with invasive mechanical ventilation at Massachusetts General Hospital and Beth Israel Deaconess Medical Center between March 11 and March 30, 2020.The studies were granted exemption by the hospital institutional review boards.Informed consent was waived.Clinical management occurred at the discretion of the treating physician.Hospital treatment guidelines recommended ventilation with VTs of ,6 ml/kg predicted body weight, early consideration of prone ventilation for Pa O 2 : FI O 2 , 200, and conservative fluid management.Positive end-expiratory pressure (PEEP) was titrated per institutional protocols and included use of the lower-PEEP/higher-FI O 2 ARDS network table, titration by best tidal compliance, and esophageal manometry (6).Both institutions recommended
Epidemiological characteristics of the first 53 laboratory-confirmed cases of COVID-19 epidemic in Hong Kong, 13 February 2020
Authors: Kin On Kwok, Valerie Wing Yu Wong, Wan In Wei, Samuel Yeung Shan Wong, Julian Wei-Tze Tang
Journal: Eurosurveillance (2020)

Background COVID-19, caused by SARS-CoV-2, first appeared in China and subsequently developed into an ongoing epidemic. Understanding epidemiological factors characterising the transmission dynamics of this disease is of fundamental importance. Aims This study aimed to describe key epidemiological parameters of COVID-19 in Hong Kong. Methods We extracted data of confirmed COVID-19 cases and their close contacts from the publicly available information released by the Hong Kong Centre for Health Protection. We used doubly interval censored likelihood to estimate containment delay and serial interval, by fitting gamma, lognormal and Weibull distributions to respective empirical values using Bayesian framework with right truncation. A generalised linear regression model was employed to identify factors associated with containment delay. Secondary attack rate was also estimated. Results The empirical containment delay was 6.39 days; whereas after adjusting for right truncation with the best-fit Weibull distribution, it was 10.4 days (95% CrI: 7.15 to 19.81). Containment delay increased significantly over time. Local source of infection and number of doctor consultations before isolation were associated with longer containment delay. The empirical serial interval was 4.58–6.06 days; whereas the best-fit lognormal distribution to 26 certain-and-probable infector–infectee paired data gave an estimate of 4.77 days (95% CrI: 3.47 to 6.90) with right-truncation. The secondary attack rate among close contacts was 11.7%. Conclusion With a considerable containment delay and short serial interval, contact-tracing effectiveness may not be optimised to halt the transmission with rapid generations replacement. Our study highlights the transmission risk of social interaction and pivotal role of physical distancing in suppressing the epidemic.
ZO-1 Regulates Intercalated Disc Composition and Atrioventricular Node Conduction
Authors: Wenli Dai, Rangarajan D. Nadadur, Jaclyn A. Brennan, Heather L. Smith, Kaitlyn M. Shen, Margaret Gadek, Brigitte Laforest, Mingyi Wang, Joanna Gemel, Ye Li, Jing Zhang, Bruce D. Ziman, Jiajie Yan, Xun Ai, Eric C. Beyer, Edward G. Lakata, Narayanan Kasthuri, Igor R. Efimov, Michael T. Broman, Ivan P. Moskowitz, Le Shen, Christopher R. Weber
Journal: Circulation Research (2020)

ZO-1 (Zona occludens 1), encoded by the tight junction protein 1 (TJP1) gene, is a regulator of paracellular permeability in epithelia and endothelia. ZO-1 interacts with the actin cytoskeleton, gap, and adherens junction proteins and localizes to intercalated discs in cardiomyocytes. However, the contribution of ZO-1 to cardiac physiology remains poorly defined.We aim to determine the role of ZO-1 in cardiac function.Inducible cardiomyocyte-specific Tjp1 deletion mice (Tjp1fl/fl; Myh6Cre/Esr1*) were generated by crossing the Tjp1 floxed mice and Myh6Cre/Esr1* transgenic mice. Tamoxifen-induced loss of ZO-1 led to atrioventricular (AV) block without changes in heart rate, as measured by ECG and ex vivo optical mapping. Mice with tamoxifen-induced conduction system-specific deletion of Tjp1 (Tjp1fl/fl; Hcn4CreERt2) developed AV block while tamoxifen-induced conduction system deletion of Tjp1 distal to the AV node (Tjp1fl/fl; Kcne1CreERt2) did not demonstrate conduction defects. Western blot and immunostaining analyses of AV nodes showed that ZO-1 loss decreased Cx (connexin) 40 expression and intercalated disc localization. Consistent with the mouse model study, immunohistochemical staining showed that ZO-1 is abundantly expressed in the human AV node and colocalizes with Cx40. Ventricular conduction was not altered despite decreased localization of ZO-1 and Cx43 at the ventricular intercalated disc and modestly decreased left ventricular ejection fraction, suggesting ZO-1 is differentially required for AV node and ventricular conduction.ZO-1 is a key protein responsible for maintaining appropriate AV node conduction through maintaining gap junction protein localization.
Linking hypoxia and iron homeostasis: a 'plate' full of factors (Commentary)
Authors: V. Nathan Subramaniam, Daniel Wallace
Journal: Gut (2014)

Hepcidin, a 25-amino acid peptide expressed almost exclusively in the liver, is the central regulator of systemic body iron homeostasis. Since its initial identification and characterisation as an antimicrobial peptide, it has become clear that hepcidin plays a role in many metabolic processes. [...]it was shown to be increased in patients with oesophageal cancer 12 and patients with chronic pancreatitis. 13 In another study, it was shown to be decreased in patients with metabolic syndrome. 14 In cancer it could be postulated that in addition to enhancing angiogenesis, increased levels of PDGF-BB could benefit tumour growth via hepcidin suppression leading to both increased iron availability and increased red blood cell production and hence oxygen supply.
Abstract 15092: Prognostic Value of Acid Base Balance in Acute Heart Failure
Authors: Hiroki Nakano, Toshiyuki Nagai, Yasuyuki Honda, Satoshi Honda, Yasuhiro Hamatani, Naotsugu Iwakami, Chisa Matsumoto, Yasuhide Asaumi, Takeshi Aiba, Teruo Noguchi, Kengo Kusano, Hiroyuki Yokoyama, Hisao Ogawa, Satoshi Yasuda, Taishiro Chikamori, Toshihisa Anzai
Journal: Circulation (2018)

Backgrounds: The acid-base balance could be changed according to pulmonary edema and low tissue perfusion in acute heart failure (AHF) patients. However, its long-term prognostic significance remai...
Covid-19: balancing personal risk and professional duty
Authors: Denis W Harkin
Journal: BMJ (2020)

The covid-19 pandemic is a global health and societal emergency123; doctors and healthcare workers will stand together on the front line making life and death decisions at personal risk. Together we shall endure this challenge, relying on our medical professionalism.

The ancient oath of Hippocrates4 bound physicians to act for patients’ benefit and to do no harm. Today the principles …