tbuckley/cabot-search huggingface dataset:
Metformin Is Associated with Higher Incidence of Acidosis, but Not Mortality, in Individuals with COVID-19 and Pre-existing Type 2 Diabetes
Authors: Xu Cheng, Ye-Mao Liu, Haomiao Li, Xin Zhang, Fang Lei, Juan-Juan Qin, Ze Chen, Ke-Qiong Deng, Lijin Lin, Ming-Ming Chen, Xiaohui Song, Meng Xia, Xuewei Huang, Weifang Liu, Jingjing Cai, Xiao-Jing Zhang, Feng Zhou, Peng Zhang, Yibin Wang, Xinliang Ma, Qingbo Xu, Juan Yang, Ping Ye, Weiming Mao, Xiaodong Huang, Jiahong Xia, Bing-Hong Zhang, Jiao Guo, Lihua Zhu, Zhibing Lu, Yufeng Yuan, Xiang Wei, Zhi-Gang She, Yan-Xiao Ji, Hongliang Li
Journal: Cell Metabolism (2020)
Survival and Right Ventricular Function After Surgical Management of Acute Pulmonary Embolism
Authors: Joshua B. Goldberg, Daniel M. Spevack, Syed Ahsan, Yogita Rochlani, Tanya Dutta, Suguru Ohira, Masashi Kai, David Spielvogel, Steven Lansman, Ramin Malekan
Journal: Journal of the American College of Cardiology (2020)
Abstract 6484: Cross-linked multimeric pro-peptides of type III collagen (PC3X) in hepatocellular carcinoma - A biomarker that provides additional prognostic value in AFP positive patients
Authors: Christina Jensen, Signe H. Nielsen, Mohammed Eslam, Federica Genovese, Mette J. Nielsen, Roslyn Vongsuvanh, Raj Uchila, David van der Poorten, Jacob George, Morten A. Karsdal, Diana J. Leeming, Nicholas Willumsen
Journal: Cancer Research (2020)

Abstract Background: Non-invasive biomarkers for diagnosing and prognosing hepatocellular carcinoma (HCC) are urgently needed. Cirrhosis, a consequence of deposition and cross-linking of collagens, underlies HCC in 80-90% of cases, and associates with HCC initiation and progression. We evaluated circulating cross-linked pro-peptides of type III collagen (PC3X) as a diagnostic and prognostic biomarker for HCC. Methods: PC3X was measured by ELISA in plasma from patients with HCC (n=79), cirrhosis (n=86), non-cirrhotic hepatitis-B infection (n=74) and from healthy controls (n=44). PC3X was compared to the liver fibrosis marker PRO-C3 and the HCC tumor-cell derived marker alpha-fetoprotein (AFP). Diagnostic and prognostic potential was evaluated by AUROC and by calculating hazard ratios (HR) for progression free survival (PFS) and overall survival (OS). Results: PC3X, PRO-C3 and AFP were significantly elevated in patients with HCC compared to other liver diseases and healthy controls (p=0.0002, p&amp;lt;0.0001). In patients with normal AFP (&amp;lt;20 IU/ml), PC3X and PRO-C3 separated HCC from cirrhosis with an AUROC of 0.69 and 0.67, respectively. High PC3X and AFP predicted for poor PFS (HRPC3X=1.80, p=0.032; HRAFP=1.70, p=0.031) and OS (HRPC3X=2.12, p=0.024; HRAFP=2.55; p=0.003), whereas PRO-C3 did not (PFS: HR=1.19, p=0.059 and OS: HR=1.12, p=0.324). PC3X was independent of AFP (PFS: HR=1.74, p=0.045 and OS: HR=2.21, p=0.018) and combining the two improved prognostic value (PFS: HR=2.66, p=0.004 and OS: HR=5.86, p&amp;lt;0.0001). Conclusions: PC3X is associated with HCC independent of AFP and provides diagnostic and prognostic value for HCC patients. If validated, this suggests that PC3X has biomarker potential for HCC. Citation Format: Christina Jensen, Signe H. Nielsen, Mohammed Eslam, Federica Genovese, Mette J. Nielsen, Roslyn Vongsuvanh, Raj Uchila, David van der Poorten, Jacob George, Morten A. Karsdal, Diana J. Leeming, Nicholas Willumsen. Cross-linked multimeric pro-peptides of type III collagen (PC3X) in hepatocellular carcinoma - A biomarker that provides additional prognostic value in AFP positive patients [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6484.
Targeting acid ceramidase inhibits YAP/TAZ signaling to reduce fibrosis in mice
Authors: Sarah Alsamman, Stephanie A. Christenson, Amy Yu, Nadia M. E. Ayad, Meghan S. Mooring, Joe M. Segal, Jimmy Kuang-Hsien Hu, Johanna R. Schaub, Steve S. Ho, Vikram Rao, Megan M. Marlow, Scott M. Turner, Mai Sedki, Lorena Pantano, Sarani Ghoshal, Diego Dos Santos Ferreira, Hsiao-Yen Ma, Caroline C. Duwaerts, Regina Espanol-Suner, Lan Wei, Benjamin Newcomb, Izolda Mileva, Daniel Canals, Yusuf A. Hannun, Raymond T. Chung, Aras N. Mattis, Bryan C. Fuchs, Andrew M. Tager, Dean Yimlamai, Valerie M. Weaver, Alan C. Mullen, Dean Sheppard, Jennifer Y. Chen
Journal: Science Translational Medicine (2020)

Acid ceramidase inhibition promotes YAP/TAZ degradation to inactivate fibroblasts, decrease matrix stiffness, and reduce fibrosis in mice.
Air pollution and family related determinants of asthma onset and persistent wheezing in children: nationwide case-control study
Authors: Gitte J Holst, Carsten B Pedersen, Malene Thygesen, Jørgen Brandt, Camilla Geels, Jakob H Bønløkke, Torben Sigsgaard
Journal: BMJ (2020)

Abstract Objective To identify risk factors (air pollution and family related) for the onset of asthma and persistent wheezing in children. Design Nationwide case-control study. Setting Denmark. Participants All Danish children born from 1997 to 2014 and followed for asthma onset and persistent wheezing from age 1 year to 15 years. Main outcome measure Onset of asthma and persistent wheezing. Results A higher incidence of asthma was found in children of parents with asthma (adjusted hazard ratio 2.29 (95% confidence interval 2.22 to 2.35) and mothers who smoked during pregnancy (1.20, 1.18 to 1.22), whereas a lower incidence was found in children of parents with high educational attainment (0.72, 0.69 to 0.75) and high incomes (0.85, 0.81 to 0.89). Exposure to particulate matter ≤2.5 µm (PM 2.5 ) and ≤10 µm (PM 10 ) and nitrate was associated with an increased risk of asthma and persistent wheezing, with hazard ratios per 5 µg/m 3 increase in pollutant concentrations 1.05 (1.03 to 1.07) for PM 2.5 , 1.04 (1.02 to 1.06) for PM 10 , and 1.04 (1.03 to 1.04) for nitrogen dioxide. Only the positive association of PM 2.5 with asthma and persistent wheezing remained robust across the different models and in sensitivity analyses. Conclusions The findings of this study suggest that children exposed to higher levels of PM 2.5 are more likely to develop asthma and persistent wheezing than children who are not exposed. Other risk factors associated with these outcomes were parental asthma, parental education, and maternal smoking during pregnancy.
Polarimetric Signatures of Vascular Tissue Response to Drug-Eluting Stent Implantation in Patients
Authors: Kenichiro Otsuka, Martin Villiger, Laurens J.C. van Zandvoort, Tara Neleman, Antonios Karanasos, Jouke Dijkstra, Gijs van Soest, Evelyn Regar, Seemantini K. Nadkarni, Joost Daemen, Brett E. Bouma
Journal: JACC. Cardiovascular imaging (2020)
Abstract 281: Two Thumbs versus Two Fingers Compression in Infant Resuscitation
Authors: George Love
Journal: Circulation (2013)

Compression Technique Comparison 2010 Standards. We’ve noticed a marked lack of ability in all levels of students performing infant CPR to adequately achieve an adequaterate &amp; depth using two fingers. The groups were tested in three ways: 1. 2010 standard with no variation2. 2010 Standard allowing students to “stack” two fingers onto the two fingers doing compressions.3.Two thumb encircling hands technique allowed for single rescuer. All groups were tested blindly without allowing them to know they were in the study. Group 1: These students were not allowed to vary their finger position from the course video examples and followed the demonstrations completely. Results from this group: All students in this group complained of finger pain and requested to do the two thumbs encircling hands techniques for skills check off. In keeping with AHA standards, all groups used the two finger technique for skills check off. Group 2: Test Results from this group using an additional two fingers stacked atop the two fingers allowed for compressions were: Students in this group improved compression efficiency in depth by over 40% when compared to the first group. Compressions were slightly faster and the hands off time was improved by .2 seconds. Group 3: Test Results from this group using the two thumbs encircling hands technique were: This group showed a 48.9% improvement of depth of compression, 10.5% improvement in complete releases, an almost .4 second decrease in compression time and a .26 second improvement in hands off time. An additional 8 students were tested in this technique to validate the data. All these students were female and all were renewal students. After their initial testing was completed, we allowed them to use the two thumbs encircling hands technique with the following Results: An additional group of 9 Heartsaver students were tested at random. Their test results back up the results from the BLS groups in that all had trouble performing sets of 30 compressions with two fingers for a prolonged period of time, in this case 2 minutes. 33% ( 1 of 3) could keep up a passing depth of compressions for two minutes.
Alcohol misuse among doctors
Authors: G M Cunningham, N. I Jowett
Journal: BMJ (1997)

Nicotine replacement therapy should be prescribable on NHSEditor-I welcome the publication of the open letter to the prime minister about tobacco-the most important preventable cause of death in Europe. 1 As Jo E Asvall points out in the letter, tobacco control demands the support of, and action by, the total government, not just the Department of Health.Among the actions Asvall calls for is that "support for smoking cessation is made widely available, particularly through primary health care professionals, including doctors, nurses, pharmacists, and dentists."Nicotine replacement therapy (nicotine gum, patches, nasal spray, and oral inhaler) is now fully established as an effective adjunct to such professional advice and support.Systematic review of many trials has shown a doubling of sustained smoking cessation when nicotine replacement therapy is compared with placebo. 2 The offer of nicotine patches to motivated subjects for a week in the first instance could be a useful policy. 3 But the recommendation of such therapy by health professionals and the use of such therapy by smokers are severely limited by NHS "blacklisting."I can prescribe on the NHS for alcohol problems and even obesity.I can also prescribe for tobacco addiction-but only products of unproved efficacy for this problem, such as tranquillisers and antidepressants, not one of proved effectiveness.Why not nicotine replacement therapy?So much for evidence based medicine.
Effect of early and late prenatal vitamin D and maternal asthma status on offspring asthma or recurrent wheeze
Authors: Mengdi Lu, Augusto A. Litonjua, George T. O’Connor, Robert S. Zeiger, Leonard Bacharier, Michael Schatz, Vincent J. Carey, Scott T. Weiss, Hooman Mirzakhani
Journal: Journal of Allergy and Clinical Immunology (2020)
Face coverings for covid-19: from medical intervention to social practice
Authors: Helene-Mari van der Westhuizen, Koot Kotze, Sarah Tonkin-Crine, Nina Gobat, Trisha Greenhalgh
Journal: BMJ (2020)

Helene-Mari van der Westhuizen and colleagues argue that face coverings should be considered not as medical equipment but as a social practice informed by norms and expectations
Woman whose endometriosis went undiagnosed for 15 years wins £0.5m pay-out
Authors: Clare Dyer
Journal: BMJ (2020)

A woman whose endometriosis was undiagnosed for nearly 15 years has won £500 000 (€553 000; $659 000) compensation from the NHS in an out-of-court settlement.

Nottingham University Hospitals NHS Trust agreed to settle the claim by Frances Bell, 37, after admitting that a laparoscopy should have been performed in 2001, when she was 18.

She had first attended a gynaecology appointment with symptoms of endometriosis in 1997 …
Molecular epidemiology and clinical impact of rhinovirus infections in adults during three epidemic seasons in 11 European countries (2007–2010)
Authors: Kalina T Zlateva, Anneloes L van Rijn, Peter Simmonds, Frank E J Coenjaerts, Anton M van Loon, Theo J M Verheij, Jutte J C de Vries, Paul Little, Christopher C Butler, Erik W van Zwet, Herman Goossens, Margareta Ieven, Eric C J Claas
Journal: Thorax (2020)

Background Differences in clinical impact between rhinovirus (RVs) species and types in adults are not well established. The objective of this study was to determine the epidemiology and clinical impact of the different RV species. Methods We conducted a prospective study of RVs infections in adults with acute cough/lower respiratory tract infection (LRTI) and asymptomatic controls. Subjects were recruited from 16 primary care networks located in 11 European countries between 2007 and 2010. RV detection and genotyping was performed by means of real time and conventional reverse-transcriptase polymerase chain reaction assays, followed by sequence analysis. Clinical data were obtained from medical records and patient symptom diaries. Results RVs were detected in 566 (19%) of 3016 symptomatic adults, 102 (4%) of their 2539 follow-up samples and 67 (4%) of 1677 asymptomatic controls. Genotyping was successful for 538 (95%) symptomatic subjects, 86 (84%) follow-up infections and 62 (93%) controls. RV-A was the prevailing species, associated with an increased risk of LRTI as compared with RV-B (relative risk (RR), 4.5; 95% CI 2.5 to 7.9; p&lt;0.001) and RV-C (RR 2.2; 95% CI 1.2 to 3.9; p=0.010). In symptomatic subjects, RV-A loads were higher than those of RV-B (p=0.015). Symptom scores and duration were similar across species. More RV-A infected patients felt generally unwell in comparison to RV-C (p=0·023). Of the 140 RV types identified, five were new types; asymptomatic infections were associated with multiple types. Interpretation In adults, RV-A is significantly more often detected in cases with acute cough/LRTI than RV-C, while RV-B infection is often found in asymptomatic patients.
Infectious Diseases Outbreak Management Tool for endurance mass participation sporting events: an international effort to counteract the COVID-19 spread in the endurance sport setting
Authors: Paolo Emilio Adami, John Cianca, Brian McCloskey, Wayne Derman, Juergen Michael Steinacker, Francis O'Connor, Sergio Migliorini, Richard Budgett, Fumihiro Yamasawa, Inggard Lereim, Xavier Bigard, Chris Troyanos, Frederic Garrandes, Stephane Bermon
Journal: British Journal of Sports Medicine (2020)

The COVID-19 pandemic has caused considerable economic damage throughout the world in addition to a severe health crisis. Social distancing is the main preventative measure for person to person transmission of SARS CoV-2.1 This has essentially put a halt to all mass participation endurance sporting events, with road races, triathlons, cycling, Nordic skiing and rowing events being indefinitely postponed or cancelled. The benefits of endurance exercise have been widely demonstrated,2 therefore, the current halt has had significant health and social consequences worldwide. From a financial perspective, the economic impact on the endurance sport mass participation industry has also been catastrophic. Endurance events are estimated to generate over US$3 billion/year in the USA alone.3 Taking the example of road running, 17.6 million people registered for road running events in the USA in 2019.4 Endurance sports, thanks to the competition format, allow elite and amateur athletes to compete together, attracting large crowds of participants (e.g. Henley Royal Regatta, Vasaloppet, Gran Fondos, International Triathlon Union World Championship Grand Final). Therefore, the cessation of endurance events represents a huge societal loss.

At some point, the pandemic will give way to isolated clusters of cases with no widespread community transmission and people will be able to return to mass participation sporting …
Germline genetic factors influence the outcome of interferon-α therapy in polycythemia vera
Authors: Roland Jäger, Heinz Gisslinger, Elisabeth Fuchs, Edith Bogner, Jelena D. Milosevic Feenstra, Jakob Weinzierl, Fiorella Schischlik, Bettina Gisslinger, Martin Schalling, Michael Zörer, Kurt Krejcy, Christoph Klade, Robert Kralovics
Journal: Blood (2020)
TIGIT Blockade and IL15 in Tumor Immunotherapy: Together is Better
Authors: Gabriella Pietra, Maria Cristina Mingari, Lorenzo Moretta
Journal: Clinical Cancer Research (2020)

IL15 and TIGIT blockade enhances the natural killer (NK) cell-mediated activity against MHC-I-deficient melanoma both in vitro and in preclinical models. IL15-induced harnessing of NK cells, associated with their unleashing by TIGIT blockade, may represent a therapeutic approach for tumors, which lack HLA-I molecules thus escaping the CD8+ T cell-mediated control.See related article by Chauvin et al., p. 5520.
National, regional, and state-level pneumonia and severe pneumonia morbidity in children in India: modelled estimates for 2000 and 2015
Authors: Brian Wahl, Maria Deloria Knoll, Anita Shet, Madhu Gupta, Rajesh Kumar, Li Liu, Yue Chu, Molly Sauer, Katherine L O'Brien, Mathuram Santosham, Robert E Black, Harry Campbell, Harish Nair, David A McAllister
Journal: The Lancet Child & Adolescent Health (2020)

The absolute number of pneumonia deaths in India has declined substantially since 2000. However, pneumonia remains a major cause of morbidity in children in the country. We used a risk factor-based model to estimate pneumonia and severe pneumonia morbidity in Indian states in 2000 and 2015.
Histopathological findings and viral tropism in UK patients with severe fatal COVID-19: a post-mortem study
Authors: Brian Hanley, Kikkeri N Naresh, Candice Roufosse, Andrew G Nicholson, Justin Weir, Graham S Cooke, Mark Thursz, Pinelopi Manousou, Richard Corbett, Robert Goldin, Safa Al-Sarraj, Alireza Abdolrasouli, Olivia C Swann, Laury Baillon, Rebecca Penn, Wendy S Barclay, Patrizia Viola, Michael Osborn
Journal: The Lancet Microbe (2020)

SummaryBackgroundSevere COVID-19 has a high mortality rate. Comprehensive pathological descriptions of COVID-19 are scarce and limited in scope. We aimed to describe the histopathological findings and viral tropism in patients who died of severe COVID-19.MethodsIn this case series, patients were considered eligible if they were older than 18 years, with premortem diagnosis of severe acute respiratory syndrome coronavirus 2 infection and COVID-19 listed clinically as the direct cause of death. Between March 1 and April 30, 2020, full post-mortem examinations were done on nine patients with confirmed COVID-19, including sampling of all major organs. A limited autopsy was done on one additional patient. Histochemical and immunohistochemical analyses were done, and histopathological findings were reported by subspecialist pathologists. Viral quantitative RT-PCR analysis was done on tissue samples from a subset of patients.FindingsThe median age at death of our cohort of ten patients was 73 years (IQR 52–79). Thrombotic features were observed in at least one major organ in all full autopsies, predominantly in the lung (eight [89%] of nine patients), heart (five [56%]), and kidney (four [44%]). Diffuse alveolar damage was the most consistent lung finding (all ten patients); however, organisation was noted in patients with a longer clinical course. We documented lymphocyte depletion (particularly CD8-positive T cells) in haematological organs and haemophagocytosis. Evidence of acute tubular injury was noted in all nine patients examined. Major unexpected findings were acute pancreatitis (two [22%] of nine patients), adrenal micro-infarction (three [33%]), pericarditis (two [22%]), disseminated mucormycosis (one [10%] of ten patients), aortic dissection (one [11%] of nine patients), and marantic endocarditis (one [11%]). Viral genomes were detected outside of the respiratory tract in four of five patients. The presence of subgenomic viral RNA transcripts provided evidence of active viral replication outside the respiratory tract in three of five patients.InterpretationOur series supports clinical data showing that the four dominant interrelated pathological processes in severe COVID-19 are diffuse alveolar damage, thrombosis, haemophagocytosis, and immune cell depletion. Additionally, we report here several novel autopsy findings including pancreatitis, pericarditis, adrenal micro-infarction, secondary disseminated mucormycosis, and brain microglial activation, which require additional investigation to understand their role in COVID-19.FundingImperial Biomedical Research Centre, Wellcome Trust, Biotechnology and Biological Sciences Research Council.
Meniscal ramp lesions: anatomy, biomechanics and clinical outcomes (PhD Academy Award)
Authors: Nicholas N. DePhillipo
Journal: British Journal of Sports Medicine (2020)

The overall aim of my thesis was to systematically evaluate medial meniscal ‘ramp’ lesions and how they affect anterior cruciate ligament reconstruction (ACLR).

There has been a recent surge in publications in the past decade regarding meniscal ramp lesions. Ramp lesions by definition are associated with ACL tears and have a high incidence (40%) in various ACL tear populations.1 A ramp lesion involves tearing of the posteromedial meniscus at the meniscocapsular junction and is of specific interest due to its reported ‘blind spot’ when viewing arthroscopically. Its name is derived from the arthroscopic appearance of a downwards slope or ramp and authors have associated an arbitrarily tear length of 2.5 cm to describe an unstable ramp lesion.2 Because of this slope or ramp area, the posteromedial capsule of the knee creates a fold which allows for a potential hidden space, thus resulting in misdiagnosis and failure …
Abstract 6600: Rapid generation of TCR-engineered T lymphocytes by linking the single cell transcriptome to its corresponding T cell receptor in antigen specific T cells
Authors: Linnan Zhu, Fei Wang, Qumiao Xu, Hai-Xi Sun, Ziyi Li, Yanling Liang, Zhenkun Zhuang, Ying Gu, Cheng-chi Chao
Journal: Cancer Research (2020)

Abstract Adoptive cell transfer of T-cell receptor (TCR)-engineered T cells has emerged as a powerful and potentially curative therapy for cancers and infectious diseases. However, how to rapidly identify and obtain therapeutic TCRs remains a major challenge in this field. Here, we simultaneously performed deep single-cell RNA and TCR V(D)J sequencing on 879 single T cells from in vitro stimulated CMV pp65NLV-specific CD8+ T cells. The correlation analysis of single-cell transcriptome and TCR V(D)J sequences revealed a differential distribution of T cell transcriptomic profiles among TCR clones. Two distinct cell types were identified in the T cell population. TYPE I T cell subtype, which represents the gene signatures of T cell activation and cytotoxicity, mainly includes TCR clone 1, 2 &amp; 4, while TYPE II subtype, which represents the gene signatures of naïve status, mainly includes TCR clone 3 and other low frequency clones. Based on their temporal phases of T cell activation, the selected TCR sequences from clone 1 (TCRZWX1) and clone 3 (TCRZWX3) were functionally validated by constructing TCR-engineered T cells in vitro. The two clones showed distinct cell stages corresponding to their transcriptome patterns. TCRZWX1 transgenic T cells displayed effector functions including secretion of pro-inflammatory cytokines, IFN-γ and TNF-α, and cytotoxicity in response to CMV pp65NLV peptide. However, TCRZWX3 transgenic T cells displayed non-detectable levels of IFN-γ, which might correlate with a low affinity TCR. Our results provide a novel approach using correlative analysis of the single-cell transcriptome and TCR V(D)J sequences for rapidly identifying potential therapeutic TCRs for T cell therapy. Citation Format: Linnan Zhu, Fei Wang, Qumiao Xu, Hai-Xi Sun, Ziyi Li, Yanling Liang, Zhenkun Zhuang, Ying Gu, Cheng-chi Chao. Rapid generation of TCR-engineered T lymphocytes by linking the single cell transcriptome to its corresponding T cell receptor in antigen specific T cells [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6600.