tbuckley/cabot-search huggingface dataset:
Disturbed gut microbiota and bile homeostasis in <i>Giardia</i> -infected mice contributes to metabolic dysregulation and growth impairment
Authors: Ambre Riba, Kasra Hassani, Alesia Walker, Niels van Best, Dunja von Zeschwitz, Teresa Anslinger, Nina Sillner, Stefanie Rosenhain, Daniel Eibach, Oumou Maiga-Ascofaré, Ulrike Rolle-Kampczyk, Marijana Basic, Anne Binz, Sabine Mocek, Beate Sodeik, Rudolf Bauerfeind, Antje Mohs, Christian Trautwein, Fabian Kiessling, Jürgen May, Martin Klingenspor, Felix Gremse, Philippe Schmitt-Kopplin, André Bleich, Natalia Torow, Martin von Bergen, Mathias W. Hornef
Journal: Science Translational Medicine (2020)

The protozoan parasite Giardia lamblia enhances bile secretion and microbiota–mediated bile acid deconjugation in mice, leading to growth impairment.
Development of A2G80 peptide-gene complex for targeted delivery to muscle cells
Authors: Kei Nirasawa, Keisuke Hamada, Yukiko Naraki, Yamato Kikkawa, Eri Sasaki, Yoko Endo-Takahashi, Nobuhito Hamano, Fumihiko Katagiri, Motoyoshi Nomizu, Yoichi Negishi
Journal: Journal of Controlled Release (2020)
Microglial autophagy–associated phagocytosis is essential for recovery from neuroinflammation
Authors: Rasmus Berglund, Andre Ortlieb Guerreiro-Cacais, Milena Z. Adzemovic, Manuel Zeitelhofer, Harald Lund, Ewoud Ewing, Sabrina Ruhrmann, Erik Nutma, Roham Parsa, Melanie Thessen-Hedreul, Sandra Amor, Robert A. Harris, Tomas Olsson, Maja Jagodic
Journal: Science Immunology (2020)

Multiple sclerosis (MS) is a leading cause of incurable progressive disability in young adults caused by inflammation and neurodegeneration in the central nervous system (CNS). The capacity of microglia to clear tissue debris is essential for maintaining and restoring CNS homeostasis. This capacity diminishes with age, and age strongly associates with MS disease progression, although the underlying mechanisms are still largely elusive. Here, we demonstrate that the recovery from CNS inflammation in a murine model of MS is dependent on the ability of microglia to clear tissue debris. Microglia-specific deletion of the autophagy regulator Atg7, but not the canonical macroautophagy protein Ulk1, led to increased intracellular accumulation of phagocytosed myelin and progressive MS-like disease. This impairment correlated with a microglial phenotype previously associated with neurodegenerative pathologies. Moreover, Atg7-deficient microglia showed notable transcriptional and functional similarities to microglia from aged wild-type mice that were also unable to clear myelin and recover from disease. In contrast, induction of autophagy in aged mice using the disaccharide trehalose found in plants and fungi led to functional myelin clearance and disease remission. Our results demonstrate that a noncanonical form of autophagy in microglia is responsible for myelin degradation and clearance leading to recovery from MS-like disease and that boosting this process has a therapeutic potential for age-related neuroinflammatory conditions.
Identification of psychiatric disorder subtypes from functional connectivity patterns in resting-state electroencephalography
Authors: Yu Zhang, Wei Wu, Russell T. Toll, Sharon Naparstek, Adi Maron-Katz, Mallissa Watts, Joseph Gordon, Jisoo Jeong, Laura Astolfi, Emmanuel Shpigel, Parker Longwell, Kamron Sarhadi, Dawlat El-Said, Yuanqing Li, Crystal Cooper, Cherise Chin-Fatt, Martijn Arns, Madeleine S. Goodkind, Madhukar H. Trivedi, Charles R. Marmar, Amit Etkin
Journal: Nature Biomedical Engineering (2020)
Covid-19 pandemic is magnifying healthcare inequalities, says England’s regulator
Authors: Adrian O’Dowd
Journal: BMJ (2020)

19 pandemic is magnifying healthcare inequalities, says England's regulator Adrian O'DowdExisting "fault lines" in health and social care services could be made much worse by the covid-19 pandemic, but the overall quality of care has been maintained so far despite the impact of the coronavirus, says England's healthcare regulator.In its annual State of Care report 1 for England, published on 16 October, the Care Quality Commission (CQC) said that covid-19 was magnifying inequalities despite the impressive performance of the NHS to date.
Coronavirus and Cardiovascular Disease, Myocardial Injury, and Arrhythmia
Authors: Gennaro Giustino, Sean P. Pinney, Anuradha Lala, Vivek Y. Reddy, Hillary A. Johnston-Cox, Jeffrey I. Mechanick, Jonathan L. Halperin, Valentin Fuster
Journal: Journal of the American College of Cardiology (2020)
Nuclear Non-Coding RNAs Regulate VEGF-A Expression and Are Secreted from Transduced Cells to Surrounding Tissue and Blood Circulation in Mouse Myocardial Infarction Model
Authors: T Turunen, P Laitinen, Vaananen M-A., T C Roberts, K V Morris, S Yla-Herttuala, M P Turunen
Journal: Molecular Therapy (2017)
Effect of Positive End-Expiratory Pressure and Proning on Ventilation and Perfusion in COVID-19 Acute Respiratory Distress Syndrome
Authors: François Perier, Samuel Tuffet, Tommaso Maraffi, Glasiele Alcala, Marcus Victor, Anne-Fleur Haudebourg, Nicolas De Prost, Marcelo Amato, Guillaume Carteaux, Armand Mekontso Dessap
Journal: American Journal of Respiratory and Critical Care Medicine (2020)
COVID-19-associated acute kidney injury: consensus report of the 25th Acute Disease Quality Initiative (ADQI) Workgroup
Authors: Mitra K. Nadim, Lui G. Forni, Ravindra L. Mehta, Michael J. Connor, Kathleen D. Liu, Marlies Ostermann, Thomas Rimmelé, Alexander Zarbock, Samira Bell, Azra Bihorac, Vincenzo Cantaluppi, Eric Hoste, Faeq Husain-Syed, Michael J. Germain, Stuart L. Goldstein, Shruti Gupta, Michael Joannidis, Kianoush Kashani, Jay L. Koyner, Matthieu Legrand, Nuttha Lumlertgul, Sumit Mohan, Neesh Pannu, Zhiyong Peng, Xose L. Perez-Fernandez, Peter Pickkers, John Prowle, Thiago Reis, Nattachai Srisawat, Ashita Tolwani, Anitha Vijayan, Gianluca Villa, Li Yang, Claudio Ronco, John A. Kellum
Journal: Nature Reviews Nephrology (2020)

Abstract Kidney involvement in patients with coronavirus disease 2019 (COVID-19) is common, and can range from the presence of proteinuria and haematuria to acute kidney injury (AKI) requiring renal replacement therapy (RRT; also known as kidney replacement therapy). COVID-19-associated AKI (COVID-19 AKI) is associated with high mortality and serves as an independent risk factor for all-cause in-hospital death in patients with COVID-19. The pathophysiology and mechanisms of AKI in patients with COVID-19 have not been fully elucidated and seem to be multifactorial, in keeping with the pathophysiology of AKI in other patients who are critically ill. Little is known about the prevention and management of COVID-19 AKI. The emergence of regional ‘surges’ in COVID-19 cases can limit hospital resources, including dialysis availability and supplies; thus, careful daily assessment of available resources is needed. In this Consensus Statement, the Acute Disease Quality Initiative provides recommendations for the diagnosis, prevention and management of COVID-19 AKI based on current literature. We also make recommendations for areas of future research, which are aimed at improving understanding of the underlying processes and improving outcomes for patients with COVID-19 AKI.
IL-2 Plus IL-15 Leads to Enhanced Ex Vivo Expansion of Human Invariant Natural Killer T Cells
Authors: Melissa Mavers, Federico Simonetta, Alexander W. Lee, Toshihito Hirai, Kristina Maas-Bauer, Jeanette Baker, Maite Alvarez, Mustafa Turkoz, Everett H. Meyer, Robert S. Negrin
Journal: Blood (2017)
Percutaneous Coronary Intervention for Vulnerable Coronary Atherosclerotic Plaque
Authors: Gregg W. Stone, Akiko Maehara, Ziad A. Ali, Claes Held, Mitsuaki Matsumura, Lars Kjøller-Hansen, Hans Erik Bøtker, Michael Maeng, Thomas Engstrøm, Rune Wiseth, Jonas Persson, Thor Trovik, Ulf Jensen, Stefan K. James, Gary S. Mintz, Ovidiu Dressler, Aaron Crowley, Ori Ben-Yehuda, David Erlinge
Journal: Journal of the American College of Cardiology (2020)
Accurate brain age prediction with lightweight deep neural networks
Authors: Han Peng, Weikang Gong, Christian F. Beckmann, Andrea Vedaldi, Stephen M. Smith
Journal: Medical Image Analysis (2020)

Deep learning has huge potential for accurate disease prediction with neuroimaging data, but the prediction performance is often limited by training-dataset size and computing memory requirements. To address this, we propose a deep convolutional neural network model, Simple Fully Convolutional Network (SFCN), for accurate prediction of brain age using T1-weighted structural MRI data. Compared with other popular deep network architectures, SFCN has fewer parameters, so is more compatible with small dataset size and 3D volume data. The network architecture was combined with several techniques for boosting performance, including data augmentation, pre-training, model regularization, model ensemble and prediction bias correction. We compared our overall SFCN approach with several widely-used machine learning models. It achieved state-of-the-art performance in UK Biobank data (N = 14,503), with mean absolute error (MAE) = 2.14y in brain age prediction and 99.5% in sex classification. SFCN also won (both parts of) the 2019 Predictive Analysis Challenge for brain age prediction, involving 79 competing teams (N = 2,638, MAE = 2.90y). We describe here the details of our approach, and its optimisation and validation. Our approach can easily be generalised to other tasks using different image modalities, and is released on GitHub.
Axitinib plus avelumab in the treatment of recurrent glioblastoma: a stratified, open-label, single-center phase 2 clinical trial (GliAvAx)
Authors: Gil Awada, Laila Ben Salama, Jennifer De Cremer, Julia Katharina Schwarze, Lydia Fischbuch, Laura Seynaeve, Stephanie Du Four, Anne-Marie Vanbinst, Alex Michotte, Hendrik Everaert, Anne Rogiers, Peter Theuns, Johnny Duerinck, Bart Neyns
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background No treatment demonstrated to improve survival in patients with recurrent glioblastoma (rGB) in a randomized trial. Combining axitinib with the programmed cell death ligand 1 blocking monoclonal antibody avelumab may result in synergistic activity against rGB. Methods Adult patients with rGB following prior surgery, radiation therapy and temozolomide chemotherapy were stratified according to their baseline use of corticosteroids. Patients with a daily dose of ≤8 mg of methylprednisolone (or equivalent) initiated treatment with axitinib (5 mg oral two times per day) plus avelumab (10 mg/kg intravenous every 2 weeks) (Cohort-1). Patients with a higher baseline corticosteroid dose initiated axitinib monotherapy; avelumab was added after 6 weeks of therapy if the corticosteroid dose could be tapered to ≤8 mg of methylprednisolone (Cohort-2). Progression-free survival at 6 months (6-m-PFS%), per immunotherapy response assessment for neuro-oncology criteria, served as the primary endpoint. Results Between June 2017 and August 2018, 54 patients (27 per cohort) were enrolled and initiated study treatment (median age: 55 years; 63% male; 91% Eastern Cooperative Oncology Group Performance Status 0–1). Seventeen (63%) patients treated in Cohort-2 received at least one dose of avelumab. The 6-m-PFS% was 22.2% (95% CI 6.5% to 37.9%) and 18.5% (95% CI 3.8% to 33.2%) in Cohort-1 and Cohort-2, respectively; median overall survival was 26.6 weeks (95% CI 20.8 to 32.4) in Cohort-1 and 18.0 weeks (95% CI 12.5 to 23.5) in Cohort-2. The best objective response rate was 33.3% and 22.2% in Cohort-1 and Cohort-2, respectively, with a median duration of response of 17.9 and 19.0 weeks. The most frequent treatment-related adverse events were dysphonia (67%), lymphopenia (50%), arterial hypertension and diarrhea (both 48%). There were no grade 5 adverse events. Conclusion The combination of avelumab plus axitinib has an acceptable toxicity profile but did not meet the prespecified threshold for activity justifying further investigation of this treatment in an unselected population of patients with rGB.
Cytisine for smoking cessation in patients with tuberculosis: a multicentre, randomised, double-blind, placebo-controlled phase 3 trial
Authors: Omara Dogar, Ada Keding, Rhian Gabe, Anna-Marie Marshall, Rumana Huque, Deepa Barua, Razia Fatima, Amina Khan, Raana Zahid, Sonia Mansoor, Daniel Kotz, Melanie Boeckmann, Helen Elsey, Eva Kralikova, Steve Parrott, Jinshuo Li, Anne Readshaw, Aziz Sheikh, Kamran Siddiqi
Journal: The Lancet Global Health (2020)

Smoking cessation is important in patients with tuberculosis because it can reduce the high rates of treatment failure and mortality. We aimed to assess the effectiveness and safety of cystine as a smoking cessation aid in patients with tuberculosis in Bangladesh and Pakistan.We did a randomised, double-blind, placebo-controlled, trial at 32 health centres in Bangladesh and Pakistan. Eligible patients were adults (aged >18 years in Bangladesh; aged >15 years in Pakistan) with pulmonary tuberculosis diagnosed in the previous 4 weeks, who smoked tobacco on a daily basis and were willing to stop smoking. Patients were randomly assigned (1:1) to receive behavioural support plus either oral cytisine (9 mg on day 0, which was gradually reduced to 1·5 mg by day 25) or placebo for 25 days. Randomisation was done using pregenerated block randomisation lists, stratified by trial sites. Investigators, clinicians, and patients were masked to treatment allocation. The primary outcome was continuous abstinence at 6 months, defined as self-report (of not having used more than five cigarettes, bidis, a water pipe, or smokeless tobacco products since the quit date), confirmed biochemically by a breath carbon monoxide reading of less than 10 parts per million. Primary and safety analysis were done in the intention-to-treat population. This trial is registered with the International Standard Randomised Clinical Trial Registry, ISRCTN43811467, and enrolment is complete.Between June 6, 2017, and April 30, 2018, 2472 patients (1527 patients from Bangladesh; 945 patients from Pakistan) were enrolled and randomly assigned to receive cytisine (n=1239) or placebo (n=1233). At 6 months, 401 (32·4%) participants in the cytisine group and 366 (29·7%) participants in the placebo group had achieved continuous abstinence (risk difference 2·68%, 95% CI -0·96 to 6·33; relative risk 1·09, 95% CI 0·97 to 1·23, p=0·114). 53 (4·3%) of 1239 participants in the cytisine group and 46 (3·7%) of 1233 participants in the placebo group reported serious adverse events (94 events in the cytisine group and 90 events in the placebo group), which included 91 deaths (49 in the cytisine group and 42 in the placebo group). None of the adverse events were attributed to the study medication.Our findings do not support the addition of cytisine to brief behavioural support for the treatment of tobacco dependence in patients with tuberculosis.European Union Horizon 2020 and Health Data Research UK.For the Bengali and Urdu translations of the abstract see Supplementary Materials section.
Estimates of the rate of infection and asymptomatic COVID-19 disease in a population sample from SE England
Authors: Philippa M. Wells, Katie J. Doores, Simon Couvreur, Rocio Martinez Nunez, Jeffrey Seow, Carl Graham, Sam Acors, Neophytos Kouphou, Stuart J.D. Neil, Richard S. Tedder, Pedro M. Matos, Kate Poulton, Maria Jose Lista, Ruth E. Dickenson, Helin Sertkaya, Thomas J.A. Maguire, Edward J. Scourfield, Ruth C.E. Bowyer, Deborah Hart, Aoife O'Byrne, Kathryn J.A. Steel, Oliver Hemmings, Carolina Rosadas, Myra O. McClure, Joan Capedevilla-pujol, Jonathan Wolf, Sebastien Ourselin, Matthew A. Brown, Michael H. Malim, Tim Spector, Claire J. Steves
Journal: Journal of Infection (2020)

Understanding of the true asymptomatic rate of infection of SARS-CoV-2 is currently limited, as is understanding of the population-based seroprevalence after the first wave of COVID-19 within the UK. The majority of data thus far come from hospitalised patients, with little focus on general population cases, or their symptoms.We undertook enzyme linked immunosorbent assay characterisation of IgM and IgG responses against SARS-CoV-2 spike glycoprotein and nucleocapsid protein of 431 unselected general-population participants of the TwinsUK cohort from South-East England, aged 19-86 (median age 48; 85% female). 382 participants completed prospective logging of 14 COVID-19 related symptoms via the COVID Symptom Study App, allowing consideration of serology alongside individual symptoms, and a predictive algorithm for estimated COVID-19 previously modelled on PCR positive individuals from a dataset of over 2 million.We demonstrated a seroprevalence of 12% (51 participants of 431). Of 48 seropositive individuals with full symptom data, nine (19%) were fully asymptomatic, and 16 (27%) were asymptomatic for core COVID-19 symptoms: fever, cough or anosmia. Specificity of anosmia for seropositivity was 95%, compared to 88% for fever cough and anosmia combined. 34 individuals in the cohort were predicted to be Covid-19 positive using the App algorithm, and of those, 18 (52%) were seropositive.Seroprevalence amongst adults from London and South-East England was 12%, and 19% of seropositive individuals with prospective symptom logging were fully asymptomatic throughout the study. Anosmia demonstrated the highest symptom specificity for SARS-CoV-2 antibody response.NIHR BRC, CDRF, ZOE global LTD, RST-UKRI/MRC.
Adjuvant Sorafenib for Renal Cell Carcinoma at Intermediate or High Risk of Relapse: Results From the SORCE Randomized Phase III Intergroup Trial
Authors: Tim Eisen, Eleni Frangou, Bhavna Oza, Alastair W.S. Ritchie, Benjamin Smith, Rick Kaplan, Ian D. Davis, Martin R. Stockler, Laurence Albiges, Bernard Escudier, James Larkin, Axel Bex, Steven Joniau, Barry Hancock, Gregers G. Hermann, Joaquim Bellmunt, Elizabeth Hodgkinson, Grant D. Stewart, Jim Barber, Janet Brown, Rhona McMenemin, Paul Nathan, Lisa M. Pickering, Mahesh K.B. Parmar, Angela Meade
Journal: Journal of Clinical Oncology (2020)

SORCE is an international, randomized, double-blind, three-arm trial of sorafenib after surgical excision of primary renal cell carcinoma (RCC) found to be at intermediate or high risk of recurrence.We randomly assigned participants (2:3:3) to 3 years of placebo (arm A), 1 year of sorafenib followed by 2 years of placebo (arm B), or 3 years of sorafenib (arm C). The initial sorafenib dose was 400 mg twice per day orally, amended to 400 mg daily. The primary outcome analysis, which was revised as a result of external results, was investigator-reported disease-free survival (DFS) comparing 3 years of sorafenib versus placebo.Between July 2007 and April 2013, we randomly assigned 1,711 participants (430, 642, and 639 participants in arms A, B, and C, respectively). Median age was 58 years, 71% of patients were men, 84% had clear cell histology, 53% were at intermediate risk of recurrence, and 47% were at high risk of recurrence. We observed no differences in DFS or overall survival in all randomly assigned patients, patients with high risk of recurrence, or patients with clear cell RCC only. Median DFS was not reached for 3 years of sorafenib or for placebo (hazard ratio, 1.01; 95% CI, 0.83 to 1.23; P = .95). We observed nonproportional hazards; the restricted mean survival time (RMST) was 6.81 years for 3 years of sorafenib and 6.82 years for placebo (RMST difference, 0.01 year; 95% CI, -0.49 to 0.48 year; P = .99). Despite offering treatment adaptations, more than half of participants stopped treatment by 12 months. Grade 3 hand-foot skin reaction was reported in 24% of participants on sorafenib.Sorafenib should not be used as adjuvant therapy for RCC. Active surveillance remains the standard of care for patients at intermediate or high risk of recurrence after nephrectomy and is the appropriate control of our current international adjuvant RCC trial, RAMPART.
THU0473 IS PAIN INTENSITY ASSOCIATED WITH EARLY MORTALITY IN PATIENTS WITH PSORIATIC ARTHRITIS?
Authors: J. Vela, R. Cordtz, S. Kristensen, K. Kjær Petersen, L. Arent-Nielsen, C. T. Torp-Pedersen, L. Dreyer
Journal: Annals of the Rheumatic Diseases (2020)

Background: Studies regarding excess mortality among patients with psoriatic arthritis (PsA) are conflicting due to the heterogenous nature of the disease. Thus, identifying risk factors for mortality is crucial, but few studies have examined these in PsA. Presence of chronic pain can cause excess mortality and since pain is prevalent among patients with PsA this association should be explored. Objectives: To investigate whether higher cumulative pain intensity is associated with an excess mortality ratio in patients with PsA. Methods: A nested case-control study was performed using data from the national Danish healthcare registers and the DANBIO rheumatology register. Cases were patients who died while followed in routine care. Cases were matched on sex, year of birth and calendar period of DANBIO entry with up to five controls. The main exposure of interest was the mean pain intensity (all causes) reported during the time followed in routine rheumatology practice. The pain intensity was measured on a visual analogue scale (VAS) ranging from 0 (no pain) to 100 (worst imaginable pain). Conditional logistic regression was used to calculate the odds of mortality per 5 unit increase in VAS pain while adjusting for inflammatory markers. Results: The Danbio PsA cohort consisted of 8019 patients. In total, 266 cases, i.e. PsA patients who died during the observational period, were identified and matched with 1198 controls (4.5 controls per case). Increasing pain intensity was associated with increased odds of mortality (OR 1.05, 95%CI 1.01 to 1.09) in the crude model, but the association disappeared when adjusting for age, sex, calendar time, socioeconomic status, average c-reactive protein and swollen joint count during the observation period (OR 0.98, 95%CI 0.93-1.03). Age, average CRP, biological DMARD use, glucocorticoid use, and comorbidities (see table) increased the odds of mortality. Table regression estimates from fully adjusted model Odds Ratio 95% CI Age 2,73 1,60-4,68 C-reactive protein 1,05 1,03-1,07 Swollen joint count 1,08 0,97-1,22 Health assessment questionnaire 1,25 0,84-1,86 bDMARD use 2,62 1,51-4,57 cDMARD use 0,69 0,46-1,03 Glucocorticoid use 3,90 2,51-6,05 Chronic obstructive pulmonary disease 2,19 1,20-4,02 Diabetes mellitus 2,65 1,62-4,31 Cancer 6,15 3,88-9,76 Cardiovascular disease 2,61 1,71-3,97 Conclusion: These results indicate that experienced pain in itself is not associated with excess mortality. Age, recent glucocorticoid use, biological DMARD use, chronic pulmonary disease, diabetes, cancer and cardiovascular disease were all associated with an increased mortality. Disclosure of Interests: : None declared
Vancomycin-Induced Linear IgA Bullous Dermatosis
Authors: J Raymond Go, Omar M Abu Saleh
Journal: New England Journal of Medicine (2020)

A 67-year-old man presented with a diffuse bullous eruption while receiving treatment with vancomycin. Direct immunofluorescence revealed linear deposition of IgA along the basement membrane zone, a finding consistent with linear IgA bullous dermatosis.