tbuckley/cabot-search huggingface dataset:
A 4-year study of hamstring injury outcomes in elite track and field using the British Athletics rehabilitation approach
Authors: Noel Pollock, Shane Kelly, Justin Lee, Ben Stone, Michael Giakoumis, George Polglass, James Brown, Ben MacDonald
Journal: British Journal of Sports Medicine (2021)

The British Athletics Muscle Injury Classification (BAMIC) correlates with return to play in muscle injury. The aim of this study was to examine hamstring injury diagnoses and outcomes within elite track and field athletes following implementation of the British Athletics hamstring rehabilitation approach.All hamstring injuries sustained by elite track and field athletes on the British Athletics World Class Programme between December 2015 and November 2019 that underwent an MRI and had British Athletics medical team prescribed rehabilitation were included. Athlete demographics and specific injury details, including mechanism of injury, self-reported gait phase, MRI characteristics and time to return to full training (TRFT) were contemporaneously recorded.70 hamstring injuries in 46 athletes (24 women and 22 men, 24.6±3.7 years) were included. BAMIC grade and the intratendon c classification correlated with increased TRFT. Mean TRFT was 18.6 days for the entire cohort. Mean TRFT for intratendon classifications was 34±7 days (2c) and 48±17 days (3c). The overall reinjury rate was 2.9% and no reinjuries were sustained in the intratendon classifications. MRI variables of length and cross-sectional (CSA) area of muscle oedema, CSA of tendon injury and loss of tendon tension were associated with TRFT. Longitudinal length of tendon injury, in the intratendon classes, was not associated with TRFT.The application of BAMIC to inform hamstring rehabilitation in British Athletics results in low reinjury rates and favourable TRFT following hamstring injury. The key MRI variables associated with longer recovery are length and CSA of muscle oedema, CSA of tendon injury and loss of tendon tension.
Intrapulmonary bronchopulmonary anastomoses in COVID-19 respiratory failure
Authors: Csaba Galambos, Douglas Bush, Steven H. Abman
Journal: European Respiratory Journal (2021)

<b>Open intrapulmonary bronchopulmonary anastomoses (IBA) were identified in COVID-19 patients who died of respiratory failure. IBA may be the microanatomical basis of intrapulmonary right to left shunt leading to severe hypoxaemia in COVID-19.</b>https://bit.ly/3e2GajO
Structure-based phylogeny identifies avoralstat as a TMPRSS2 inhibitor that prevents SARS-CoV-2 infection in mice
Authors: Young Joo Sun, Gabriel Velez, Dylan E. Parsons, Kun Li, Miguel E. Ortiz, Shaunik Sharma, Paul B. McCray, Alexander G. Bassuk, Vinit B. Mahajan
Journal: Journal of Clinical Investigation (2021)

Drugs targeting host proteins can act prophylactically to reduce viral burden early in disease and limit morbidity, even with antivirals and vaccination. Transmembrane serine protease 2 (TMPRSS2) is a human protease required for SARS coronavirus 2 (SARS-CoV-2) viral entry and may represent such a target. We hypothesized that drugs selected from proteins related by their tertiary structure, rather than their primary structure, were likely to interact with TMPRSS2. We created a structure-based phylogenetic computational tool named 3DPhyloFold to systematically identify structurally similar serine proteases with known therapeutic inhibitors and demonstrated effective inhibition of SARS-CoV-2 infection in vitro and in vivo. Several candidate compounds, avoralstat, PCI-27483, antipain, and soybean trypsin inhibitor, inhibited TMPRSS2 in biochemical and cell infection assays. Avoralstat, a clinically tested kallikrein-related B1 inhibitor, inhibited SARS-CoV-2 entry and replication in human airway epithelial cells. In an in vivo proof of principle, avoralstat significantly reduced lung tissue titers and mitigated weight loss when administered prophylactically to mice susceptible to SARS-CoV-2, indicating its potential to be repositioned for coronavirus disease 2019 (COVID-19) prophylaxis in humans.
Abstract 16995: Inhibition of lncRNA MAAT Contributes to Multiple Types of Muscle Atrophy
Authors: Jin Li, Tingting Yang, Wen Pan, Junjie Xiao
Journal: Circulation (2018)

Background: Skeletal muscle atrophy is the consequence of many diseases, such as denervation, long-term inactivity, excessive fasting, ageing, and heart failure. Recently, increasing studies have shown that long noncoding RNAs (lncRNAs) play an important role in myogenesis and adult skeletal muscle regeneration. However, if lncRNAs are responsible for muscle atrophy remains largely unclear. Hypothesis: We aimed to select and investigate the role of lncRNAs in muscle atrophy. Methods and Results: LncRNA arrays indicated that several lncRNA transcripts were changed during denervation-induced muscle atrophy in mice. After detecting the expression of lncRNAs in multiple types of muscle atrophy in vivo (denervation, Angiotensin II and fasting induced muscle atrophy) and in vitro (Angiotensin II, H 2 O 2 and TNFα induced muscle atrophy) by qRT-PCRs, we identified that MAAT (Muscle Atrophy-Associated Transcript) was down-regulated in multiple types of muscle atrophy. Then lentivirus of shRNA and overexpression of MAAT were further used to study the role of MAAT in muscle atrophy in vitro and in vivo . We found that knockdown of MAAT promoted muscle atrophy, whereas upregulating MAAT prevented multiple types of muscle atrophy. Mechanistically, we found that MAAT negatively regulated the transcription of microRNA-29b through SOX6, and that MAAT influenced the expression of neighbor gene-MBNL by a cis-regulatory module. Conclusions: Inhibition of LncRNA MAAT contributes to muscle atrophy by increasing miR-29b and repressing MBNL. Overexpressing MAAT might be a novel approach to counteract muscle atrophy.
Association of bezafibrate with transplant-free survival in patients with primary biliary cholangitis
Authors: Atsushi Tanaka, Junko Hirohara, Toshiaki Nakano, Kosuke Matsumoto, Olivier Chazouillères, Hajime Takikawa, Bettina E. Hansen, Fabrice Carrat, Christophe Corpechot
Journal: Journal of Hepatology (2021)
Three-year survival, correlates and salvage therapies in patients receiving first-line pembrolizumab for advanced Merkel cell carcinoma
Authors: Paul Nghiem, Shailender Bhatia, Evan J Lipson, William H Sharfman, Ragini R Kudchadkar, Andrew S Brohl, Philip A Friedlander, Adil Daud, Harriet M Kluger, Sunil A Reddy, Brian C Boulmay, Adam Riker, Melissa A Burgess, Brent A Hanks, Thomas Olencki, Kari Kendra, Candice Church, Tomoko Akaike, Nirasha Ramchurren, Michi M Shinohara, Bob Salim, Janis M Taube, Erin Jensen, Mizuho Kalabis, Steven P Fling, Blanca Homet Moreno, Elad Sharon, Martin A Cheever, Suzanne L Topalian
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Merkel cell carcinoma (MCC) is an aggressive skin cancer associated with poor survival. Programmed cell death-1 (PD-1) pathway inhibitors have shown high rates of durable tumor regression compared with chemotherapy for MCC. The current study was undertaken to assess baseline and on-treatment factors associated with MCC regression and 3-year survival, and to explore the effects of salvage therapies in patients experiencing initial non-response or tumor progression after response or stable disease following first-line pembrolizumab therapy on Cancer Immunotherapy Trials Network-09/KEYNOTE-017. Methods In this multicenter phase II trial, 50 patients with advanced unresectable MCC received pembrolizumab 2 mg/kg every 3 weeks for ≤2 years. Patients were followed for a median of 31.8 months. Results Overall response rate to pembrolizumab was 58% (complete response 30%+partial response 28%; 95% CI 43.2 to 71.8). Among 29 responders, the median response duration was not reached (NR) at 3 years (range 1.0+ to 51.8+ months). Median progression-free survival (PFS) was 16.8 months (95% CI 4.6 to 43.4) and the 3-year PFS was 39.1%. Median OS was NR; the 3-year OS was 59.4% for all patients and 89.5% for responders. Baseline Eastern Cooperative Oncology Group performance status of 0, greater per cent tumor reduction, completion of 2 years of treatment and low neutrophil-to-lymphocyte ratio were associated with response and longer survival. Among patients with initial disease progression or those who developed progression after response or stable disease, some had extended survival with subsequent treatments including chemotherapies and immunotherapies. Conclusions This study represents the longest available follow-up from any first-line anti-programmed death-(ligand) 1 (anti-PD-(L)1) therapy in MCC, confirming durable PFS and OS in a proportion of patients. After initial tumor progression or relapse following response, some patients receiving salvage therapies survived. Improving the management of anti-PD-(L)1-refractory MCC remains a challenge and a high priority. Trial registration number NCT02267603 .
Towards a new era with safer µ-opiate receptor analgesia
Authors: Michael Camilleri
Journal: Gut (2021)

Chronic abdominal pain may result from diverse conditions that include inflammatory diseases such as chronic pancreatitis and inflammatory bowel diseases (IBD), particularly Crohn’s disease, disorders that are associated with visceral hypersensitivity such as chronic functional abdominal pain, also referred to as centrally mediated disorders of gastrointestinal pain,1 as well as the pain component of irritable bowel syndrome which is emphasised as a significant feature of symptom-based criteria with pain at least 1 day per week.2 Treatment of chronic abdominal pain remains a challenge in clinical practice, with more and more clinicians resorting to prescribing opioid medications for pain relief. Indeed, in a systematic review and meta-analysis of patients with IBD, 21% of outpatients and 62% of hospitalised patients were opioid users.3 Among 346 patients with gastroparesis included in the National Institutes of Health Gastroparesis Consortium, upper abdominal pain was severe or very severe in 34% of patients, particularly females, with similar prevalence in idiopathic and diabetic gastroparesis and with significant association with opiate use.4

A recent review outlined novel peripheral approaches in development for visceral pain.5 Two of these approaches are worthy of additional commentary: biased µ-opioid receptor (µ-OR) ligands and targeting µ-ORs under acidic conditions.

When conventional opioids bind to µ-ORs, they induce analgesia through activation of G protein-mediated pathways. However, they also activate β-arrestin, which induces respiratory depression …
Utility of 18F–Prostate-Specific Membrane Antigen 1007 in Imaging of Tumor Thrombus of Renal Cell Carcinoma
Authors: Yuping Zeng, Jiandong Luo, Hengbin Liao, Ping Chen
Journal: Clinical Nuclear Medicine (2021)

A 64-year-old man was referred for 18F-prostate-specific membrane antigen 1007 PET/CT with a suspicion of recurrence and metastases of renal cell carcinoma after the resection of right renal cell carcinoma. The scan showed intense tracer concentration in the inferior vena cava and the right atrium, which was later proven on histopathologic examination as tumor thrombus of renal cell carcinoma. Adding on to previous studies with 18F-prostate-specific membrane antigen 1007 in the primary renal tumor, the case proved that the tumor thrombus of renal cell carcinoma could also show intense tracer concentration and further highlights its utility in renal cell carcinoma.
First line treatment of aplastic anemia with thymoglobuline in Europe and Asia: Outcome of 955 patients treated 2001‐2012
Authors: Andrea Bacigalupo, Rosi Oneto, Hubert Schrezenmeier, Britta Hochsmann, Carlo Dufour, Seiji Kojima, Xiaofan Zhu, Xiaojuan Chen, Surapol Issaragrisil, Suporn Chuncharunee, Dae Chul Jeong, Sabrina Giammarco, Maria Teresa Van Lint, Yizhou Zheng, Carlos Vallejo
Journal: American Journal of Hematology (2018)

Am J Hematol. 2018;93:643–648 - DOI 10.1002/ajh.25081 First published: 02 March 2018 We have a correction in the affiliations for Carlos Vallejo10. Correction: 10Hospital Universitario de Donostia, San Sebastian, Spain and PETHEMA- Spain
An exosomal-carried short periostin isoform induces cardiomyocyte proliferation
Authors: Carolina Balbi, Giuseppina Milano, Tudor E. Fertig, Edoardo Lazzarini, Sara Bolis, Yoshiaki Taniyama, Fumihiro Sanada, Dario Di Silvestre, Pierluigi Mauri, Mihaela Gherghiceanu, Thomas F. Lüscher, Lucio Barile, Giuseppe Vassalli
Journal: Theranostics (2021)

Although a small number of cardiomyocytes may reenter the cell cycle after injury, the adult mammalian heart is incapable of a robust cardiomyocyte proliferation. Periostin, a secreted extracellular matrix protein, has been implicated as a regulator of cardiomyocyte proliferation; however, this role remains controversial. Alternative splicing of the human periostin gene results in 6 isoforms lacking sequences between exons 17 and 21, in addition to full-length periostin. We previously showed that exosomes (Exo) secreted by human cardiac explant-derived progenitor cells (CPC) carried periostin. Here, we aimed to investigate their cell cycle activity. Methods: CPC were derived as the cellular outgrowth of ex vivo cultured cardiac atrial explants. Exo were purified from CPC conditioned medium using size exclusion chromatography. Exosomal periostin was analyzed by Western blotting using a pair of antibodies (one raised against aa 537-836, and one raised against amino acids mapping at exon 17 of human periostin), by ELISA, and by cryo-EM with immune-gold labeling. Cell cycle activity was assessed in neonatal rat cardiomyocytes, in human induced pluripotent stem cell (iPS)-derived cardiomyocytes, and in adult rat cardiomyocytes after myocardial infarction. The role of periostin in cell cycle activity was investigated by transfecting donor CPC with a siRNA against this protein. Results: Periostin expression in CPC-secreted exosomes was detected using the antibody raised against aa 537-836 of the human protein, but not with the exon 17-specific antibody, consistent with an isoform lacking exon 17. Periostin was visualized on vesicle surfaces by cryo-EM and immune-gold labeling. CPC-derived exosomes induced cell proliferation in neonatal rat cardiomyocytes both in vitro and in vivo, in human iPS-derived cardiomyocytes, and in adult rat cardiomyocytes after myocardial infarction. Exo promoted phosphorylation of focal adhesion kinase (FAK), actin polymerization, and nuclear translocation of Yes-associated protein (YAP) in cardiomyocytes. Knocking down of periostin or YAP, or blocking FAK phosphorylation with PF-573228 nullified Exo-induced proliferation. A truncated human periostin peptide (aa 22-669), but not recombinant human full-length periostin, mimicked the pro-proliferative activity of exosomes. Conclusions: Our results show, for the first time, that CPC-secreted exosomes promote cardiomyocyte cell cycle-reentry via a short periostin isoform expressed on their surfaces, whereas recombinant full-length periostin does not. These findings highlight isoform-specific roles of periostin in cardiomyocyte proliferation.
Effects of Fluoroquinolones on Outcomes of Patients With Aortic Dissection or Aneurysm
Authors: Shao-Wei Chen, Yi-Hsin Chan, Victor Chien-Chia Wu, Yu-Ting Cheng, Dong-Yi Chen, Chia-Pin Lin, Kuo-Chun Hung, Shang-Hung Chang, Pao-Hsien Chu, An-Hsun Chou
Journal: Journal of the American College of Cardiology (2021)
Real-world SARS CoV-2 testing in Northern England during the first wave of the COVID-19 pandemic
Authors: Hamzah Z. Farooq, Emma Davies, Benjamin Brown, Thomas Whitfield, Peter Tilston, Ashley McEwan, Andrew Birtles, Robert O'Hara, Hannah Spencer, Louise Hesketh, Shazaad Ahmad, Malcolm Guiver, Nicholas Machin
Journal: Journal of Infection (2021)
Long-Term Exposure to Fine Particle Elemental Components and Natural and Cause-Specific Mortality—a Pooled Analysis of Eight European Cohorts within the ELAPSE Project
Authors: Jie Chen, Sophia Rodopoulou, Kees de Hoogh, Maciej Strak, Zorana J. Andersen, Richard Atkinson, Mariska Bauwelinck, Tom Bellander, Jørgen Brandt, Giulia Cesaroni, Hans Concin, Daniela Fecht, Francesco Forastiere, John Gulliver, Ole Hertel, Barbara Hoffmann, Ulla Arthur Hvidtfeldt, Nicole A. H. Janssen, Karl-Heinz Jöckel, Jeanette Jørgensen, Klea Katsouyanni, Matthias Ketzel, Jochem O. Klompmaker, Anton Lager, Karin Leander, Shuo Liu, Petter Ljungman, Conor J. MacDonald, Patrik K.E. Magnusson, Amar Mehta, Gabriele Nagel, Bente Oftedal, Göran Pershagen, Annette Peters, Ole Raaschou-Nielsen, Matteo Renzi, Debora Rizzuto, Evangelia Samoli, Yvonne T. van der Schouw, Sara Schramm, Per Schwarze, Torben Sigsgaard, Mette Sørensen, Massimo Stafoggia, Anne Tjønneland, Danielle Vienneau, Gudrun Weinmayr, Kathrin Wolf, Bert Brunekreef, Gerard Hoek
Journal: Environmental Health Perspectives (2021)

Inconsistent associations between long-term exposure to particles with an aerodynamic diameter
Design and Evaluation of an In Vitro Mild Traumatic Brain Injury Modeling System Using 3D Printed Mini Impact Device on the 3D Cultured Human iPSC Derived Neural Progenitor Cells
Authors: Wen Shi, Pengfei Dong, Mitchell A. Kuss, Linxia Gu, Forrest Kievit, Hyung Joon Kim, Bin Duan
Journal: Advanced Healthcare Materials (2021)

Despite significant progress in understanding the disease mechanism of traumatic brain injury (TBI), promising preclinical therapeutics have seldom been translated into successful clinical outcomes, partially because the model animals have physiological and functional differences in the central nervous system (CNS) compared to humans. Human relevant models are thus urgently required. Here, an in vitro mild TBI (mTBI) modeling system is reported based on 3D cultured human induced pluripotent stem cells (iPSC) derived neural progenitor cells (iPSC-NPCs) to evaluate consequences of single and repetitive mTBI using a 3D printed mini weight-drop impact device. Computational simulation is performed to understand the single/cumulative effects of weight-drop impact on the NPC differentiated neurospheres. Experimental results reveal that neurospheres show reactive astrogliosis and glial scar formation after repetitive (10 hits) mild impacts, while no astrocyte activation is found after one or two mild impacts. A 3D co-culture model of human microglia cells with neurospheres is further developed. It is found that astrocyte response is promoted even after two mild impacts, possibly caused by the chronic neuroinflammation after microglia activation. The in vitro mTBI modeling system recapitulates several hallmarks of the brain impact injury and might serve as a good platform for future drug screening.
Nasal versus oronasal masks for home non-invasive ventilation in patients with chronic hypercapnia: a systematic review and individual participant data meta-analysis
Authors: Marius Lebret, Antoine Léotard, Jean Louis Pépin, Wolfram Windisch, Emelie Ekkernkamp, Mercedes Pallero, M-Ángeles Sánchez-Quiroga, Nicholas Hart, Julia L Kelly, Maxime Patout, Georg Chistian Funk, Marieke L Duiverman, Juan F Masa, Anita Simonds, Patrick Brian Murphy, Peter J Wijkstra, Michael Dreher, Jan Storre, Charles Khouri, Jean-Christian Borel
Journal: Thorax (2021)

Background The optimal interface for the delivery of home non-invasive ventilation (NIV) to treat chronic respiratory failure has not yet been determined. The aim of this individual participant data (IPD) meta-analysis was to compare the effect of nasal and oronasal masks on treatment efficacy and adherence in patients with COPD and obesity hypoventilation syndrome (OHS). Methods We searched Medline and Cochrane Central Register of Controlled Trials for prospective randomised controlled trials (RCTs) of at least 1 month’s duration, published between January 1994 and April 2019, that assessed NIV efficacy in patients with OHS and COPD. The main outcomes were diurnal PaCO 2 , PaO 2 and NIV adherence (PROSPERO CRD42019132398). Findings Of 1576 articles identified, 34 RCTs met the inclusion criteria and IPD were obtained for 18. Ten RCTs were excluded because only one type of mask was used, or mask data were missing. Data from 8 RCTs, including 290 IPD, underwent meta-analysis. Oronasal masks were used in 86% of cases. There were no differences between oronasal and nasal masks for PaCO 2 (0.61 mm Hg (95% CI −2.15 to 3.38); p=0.68), PaO 2 (−0.00 mm Hg (95% CI −4.59 to 4.58); p=1) or NIV adherence (0·29 hour/day (95% CI −0.74 to 1.32); p=0.58). There was no interaction between the underlying pathology and the effect of mask type on any outcome. Interpretation Oronasal masks are the most used interface for the delivery of home NIV in patients with OHS and COPD; however, there is no difference in the efficacy or tolerance of oronasal or nasal masks.
Deep learning identified pathological abnormalities predictive of graft loss in kidney transplant biopsies
Authors: Zhengzi Yi, Fadi Salem, Madhav C. Menon, Karen Keung, Caixia Xi, Sebastian Hultin, M. Rizwan Haroon Al Rasheed, Li Li, Fei Su, Zeguo Sun, Chengguo Wei, Weiqing Huang, Samuel Fredericks, Qisheng Lin, Khadija Banu, Germaine Wong, Natasha M. Rogers, Samira Farouk, Paolo Cravedi, Meena Shingde, R. Neal Smith, Ivy A. Rosales, Philip J. O’Connell, Robert B. Colvin, Barbara Murphy, Weijia Zhang
Journal: Kidney International (2021)

Interstitial fibrosis, tubular atrophy, and inflammation are major contributors to kidney allograft failure. Here we sought an objective, quantitative pathological assessment of these lesions to improve predictive utility and constructed a deep-learning-based pipeline recognizing normal vs. abnormal kidney tissue compartments and mononuclear leukocyte infiltrates. Periodic acid- Schiff stained slides of transplant biopsies (60 training and 33 testing) were used to quantify pathological lesions specific for interstitium, tubules and mononuclear leukocyte infiltration. The pipeline was applied to the whole slide images from 789 transplant biopsies (478 baseline [pre-implantation] and 311 post-transplant 12-month protocol biopsies) in two independent cohorts (GoCAR: 404 patients, AUSCAD: 212 patients) of transplant recipients to correlate composite lesion features with graft loss. Our model accurately recognized kidney tissue compartments and mononuclear leukocytes. The digital features significantly correlated with revised Banff 2007 scores but were more sensitive to subtle pathological changes below the thresholds in the Banff scores. The Interstitial and Tubular Abnormality Score (ITAS) in baseline samples was highly predictive of one-year graft loss, while a Composite Damage Score in 12-month post-transplant protocol biopsies predicted later graft loss. ITASs and Composite Damage Scores outperformed Banff scores or clinical predictors with superior graft loss prediction accuracy. High/intermediate risk groups stratified by ITASs or Composite Damage Scores also demonstrated significantly higher incidence of estimated glomerular filtration rate decline and subsequent graft damage. Thus, our deep-learning approach accurately detected and quantified pathological lesions from baseline or post-transplant biopsies and demonstrated superior ability for prediction of post-transplant graft loss with potential application as a prevention, risk stratification or monitoring tool.