tbuckley/cabot-search huggingface dataset:
Suicidality and gambling among young adults in Great Britain: results from a cross-sectional online survey
Authors: Heather Wardle, Sally McManus
Journal: The Lancet Public Health (2021)

BackgroundSuicide rates in young people have increased in England and Wales since 2010. There are a range of possible explanations for this increase, and problem gambling has been suggested as a potential risk factor. We aimed to examine the association between suicidality (suicidal thoughts and suicide attempts) and problem gambling specifically for young adults in Great Britain, where gambling has become more widely available and normalised in the past two decades.MethodsWe analysed data from the Emerging Adults Gambling Survey: a cross-sectional, online, non-probability sample survey of young adults aged 16–24 years living in Great Britain, who were selected from a YouGov online panel. Participants were eligible if they had not taken part in any other YouGov survey on gambling in the past year. We examined associations between problem gambling (defined as a score of 8 or higher on the Problem Gambling Severity Index [PGSI]) and suicidal thoughts and suicide attempts in the year before survey completion in a series of regression models, with and without adjustment for sociodemographic factors, alcohol use, video gaming, anxiety, loneliness, and impulsivity.Findings3549 eligible participants completed the survey between June 25 and Aug 16, 2019. 24 (37·0% [95% CI 25·6–50·2]) of 62 men who had attempted suicide in the past year had survey scores that were indicative of problem gambling, compared with 38 (3·6% [2·6–5·0]) of 1077 men who had not attempted suicide or had suicidal thoughts in the past year. 13 (14·5% [8·5–23·6]) of 85 women who had attempted suicide in the past year had survey scores that were indicative of problem gambling, compared with 25 (2·0% [1·4–3·0]) of 1184 women who had not attempted suicide or had suicidal thoughts in the past year. The adjusted odds ratio for attempted suicide was 9·0 (4·1–19·7) in men with scores that indicated problem gambling and 4·9 (2·0–12·0) in women with scores that indicated problem gambling, compared with participants of the same gender with PGSI scores of 0.InterpretationProblem gambling appears to be associated with suicide attempts in both young men and young women. This association persisted after adjusting for anxiety, impulsivity, life satisfaction, and other factors, which suggests that other mechanisms, such as the severity and multiplicity of harms experienced, or gambling to cope with life stressors, might underpin this relationship. Young people with problem-gambling behaviours should be considered at risk for suicidality.FundingWellcome Trust.
<i>BMJ</i> columnist among doctors receiving New Year honour
Authors: Abi Rimmer
Journal: BMJ (2021)

The BMJ columnist Partha Kar has been awarded an Order of the British Empire for services to people with diabetes.

Kar was among over 30 doctors who received an award in the 2021 New Year honours list (see Related content).1 The consultant in diabetes and endocrinology at Portsmouth Hospitals NHS Trust said that the OBE was unexpected. “It’s a very pleasant surprise and an end of year present for what has been a very difficult year for everyone,” he said.

“I genuinely believe there are many people in the …
Coronavirus 2019 Infectious Disease Epidemic: Where We Are, What Can Be Done and Hope For
Authors: Michele Carbone, John Lednicky, Shu-Yuan Xiao, Mario Venditti, Enrico Bucci
Journal: Journal of Thoracic Oncology (2021)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spreads mainly by means of aerosols (microdroplets) in enclosed environments, especially those in which temperature and humidity are regulated by means of air-conditioning. About 30% of individuals infected with SARS-CoV-2 develop coronavirus disease 2019 (COVID-19) disease. Among them, approximately 25% require hospitalization. In medicine, cases are identified as those who become ill. During this pandemic, cases have been identified as those with a positive SARS-CoV-2 polymerase chain reaction test, including approximately 70% who were asymptomatic—this has caused unnecessary anxiety. Individuals more than 65 years old, those affected by obesity, diabetes, asthma, or are immune-depressed owing to cancer and other conditions, are at a higher risk of hospitalization and of dying of COVID-19. Healthy individuals younger than 40 years very rarely die of COVID-19. Estimates of the COVID-19 mortality rate vary because the definition of COVID-19–related deaths varies. Belgium has the highest death rate at 154.9 per 100,000 persons, because it includes anyone who died with symptoms compatible with COVID-19, even those never tested for SARS-CoV-2. The United States includes all patients who died with a positive test, whether they died because of, or with, SARS-CoV-2. Countries that include only patients in which COVID-19 was the main cause of death, rather than a cofactor, have lower death rates. Numerous therapies are being developed, and rapid improvements are anticipated. Because of disinformation, only approximately 50% of the U.S. population plans to receive a COVID-19 vaccine. By sharing accurate information, physicians, health professionals, and scientists play a key role in addressing myths and anxiety, help public health officials enact measures to decrease infections, and provide the best care for those who become sick. In this article, we discuss these issues.
Filgotinib in combination with methotrexate or as monotherapy versus methotrexate monotherapy in patients with active rheumatoid arthritis and limited or no prior exposure to methotrexate: the phase 3, randomised controlled FINCH 3 trial
Authors: René Westhovens, William F C Rigby, Désirée van der Heijde, Daniel W T Ching, William Stohl, Jonathan Kay, Arvind Chopra, Beatrix Bartok, Franziska Matzkies, Zhaoyu Yin, Ying Guo, Chantal Tasset, John S Sundy, Angelika Jahreis, Neelufar Mozaffarian, Osvaldo Daniel Messina, Robert BM Landewé, Tatsuya Atsumi, Gerd R Burmester
Journal: Annals of the Rheumatic Diseases (2021)

Objectives To investigate efficacy and safety of the Janus kinase-1 inhibitor filgotinib in patients with active rheumatoid arthritis (RA) with limited or no prior methotrexate (MTX) exposure. Methods This 52-week, phase 3, multicentre, double-blind clinical trial ( NCT02886728 ) evaluated once-daily oral filgotinib in 1252 patients with RA randomised 2:1:1:2 to filgotinib 200 mg with MTX (FIL200 +MTX), filgotinib 100 mg with MTX (FIL100 +MTX), filgotinib 200 mg monotherapy (FIL200), or MTX. The primary endpoint was proportion achieving 20% improvement in American College of Rheumatology criteria (ACR20) at week 24. Results The primary endpoint was achieved by 81% of patients receiving FIL200+ MTX versus 71% receiving MTX (p&lt;0.001). A significantly greater proportion treated with FIL100+ MTX compared with MTX achieved an ACR20 response (80%, p=0.017) at week 24. Significant improvement in Health Assessment Questionnaire-Disability Index was seen at week 24; least-squares mean change from baseline was −1.0 and −0.94 with FIL200+MTX and FIL100+MTX, respectively, versus −0.81 with MTX (p&lt;0.001, p=0.008, respectively). Significantly higher proportions receiving FIL200+MTX (54%) and FIL100+MTX (43%) achieved DAS28(CRP) &lt;2.6 versus MTX (29%) (p&lt;0.001 for both) at week 24. Hierarchical testing stopped for comparison of ACR20 for FIL200 monotherapy (78%) versus MTX (71%) at week 24 (p=0.058). Adverse event rates through week 52 were comparable between all treatments. Conclusions FIL200+MTX and FIL100+MTX both significantly improved signs and symptoms and physical function in patients with active RA and limited or no prior MTX exposure; FIL200 monotherapy did not have a superior ACR20 response rate versus MTX. Filgotinib was well tolerated, with acceptable safety compared with MTX.
Human skin is colonized by T cells that recognize CD1a independently of lipid
Authors: Rachel N. Cotton, Tan-Yun Cheng, Marcin Wegrecki, Jérôme Le Nours, Dennis P. Orgill, Bohdan Pomahac, Simon G. Talbot, Richard A. Willis, John D. Altman, Annemieke de Jong, Graham Ogg, Ildiko Van Rhijn, Jamie Rossjohn, Rachael A. Clark, D. Branch Moody
Journal: Journal of Clinical Investigation (2021)

CD1a-autoreactive T cells contribute to skin disease, but the identity of immunodominant self-lipid antigens and their mode of recognition are not yet solved. In most models, MHC and CD1 proteins serve as display platforms for smaller antigens. Here, we showed that CD1a tetramers without added antigen stained large T cell pools in every subject tested, accounting for approximately 1% of skin T cells. The mechanism of tetramer binding to T cells did not require any defined antigen. Binding occurred with approximately 100 lipid ligands carried by CD1a proteins, but could be tuned upward or downward with certain natural self-lipids. TCR recognition mapped to the outer A′ roof of CD1a at sites remote from the antigen exit portal, explaining how TCRs can bind CD1a rather than carried lipids. Thus, a major antigenic target of CD1a T cell autoreactivity in vivo is CD1a itself. Based on their high frequency and prevalence among donors, we conclude that CD1a-specific, lipid-independent T cells are a normal component of the human skin T cell repertoire. Bypassing the need to select antigens and effector molecules, CD1a tetramers represent a simple method to track such CD1a-specific T cells from tissues and in any clinical disease.
A comparability study of natural and deglycosylated PD-L1 levels in lung cancer: evidence from immunohistochemical analysis
Authors: Jie Mei, Junying Xu, Xuejing Yang, Dingyi Gu, Weijian Zhou, Huiyu Wang, Chaoying Liu
Journal: Molecular Cancer (2021)

Abstract Emerging evidence has revealed that the removal of N-linked glycosylation could enhance PD-L1 detection. However, whether PD-L1 antibodies against different epitopes of PD-L1 antigens responding to deglycosylation has not been characterized. In this study, we compared natural and deglycosylated PD-L1 expression in lung cancer (LuCa) using a panel of PD-L1 antibodies (28–8, CAL10, 73–10 and SP142). We found that removal of N-linked glycosylation markedly enhanced PD-L1 detection when the 28–8, CAL10 and SP142 monoclonal antibodies (mAbs) were used but slightly inhibited PD-L1 detection when the 73–10 mAb was used. Moreover, for the CAL10 and SP142 mAbs, deglycosylated PD-L1 levels showed stronger correlations with the response to anti-PD-1 therapy. Overall, our research provides a comprehensive insight into the application of deglycosylated PD-L1 detection, which expands the clinical significance of this established strategy in LuCa.
Mitigating oxygen stress enhances aged mouse hematopoietic stem cell numbers and function
Authors: Maegan L. Capitano, Safa F. Mohamad, Scott Cooper, Bin Guo, Xinxin Huang, Andrea M. Gunawan, Carol Sampson, James Ropa, Edward F. Srour, Christie M. Orschell, Hal E. Broxmeyer
Journal: Journal of Clinical Investigation (2021)

Bone marrow (BM) hematopoietic stem cells (HSCs) become dysfunctional during aging (i.e., they are increased in number but have an overall reduction in long-term repopulation potential and increased myeloid differentiation) compared with young HSCs, suggesting limited use of old donor BM cells for hematopoietic cell transplantation (HCT). BM cells reside in an in vivo hypoxic environment yet are evaluated after collection and processing in ambient air. We detected an increase in the number of both young and aged mouse BM HSCs collected and processed in 3% O2 compared with the number of young BM HSCs collected and processed in ambient air (~21% O2). Aged BM collected and processed under hypoxic conditions demonstrated enhanced engraftment capability during competitive transplantation analysis and contained more functional HSCs as determined by limiting dilution analysis. Importantly, the myeloid-to-lymphoid differentiation ratio of aged BM collected in 3% O2 was similar to that detected in young BM collected in ambient air or hypoxic conditions, consistent with the increased number of common lymphoid progenitors following collection under hypoxia. Enhanced functional activity and differentiation of old BM collected and processed in hypoxia correlated with reduced "stress" associated with ambient air BM collection and suggests that aged BM may be better and more efficiently used for HCT if collected and processed under hypoxia so that it is never exposed to ambient air O2.
What level of immobilisation is necessary for treatment of torus (buckle) fractures of the distal radius in children?
Authors: Daniel C Perry, Phoebe Gibson, Damian Roland, Shrouk Messahel
Journal: BMJ (2021)

### What you need to know

Torus (buckle) fractures are the most common fractures of the wrist in children, involving the distal radius and/or ulna bone (fig 1).1 They typically occur in children up to age 14, usually after a low energy fall.2 The flexibility of immature bone in children enables force to be absorbed as with the “crumple zone” of a car: crushing—or buckling—as it is injured. Such fractures differ from greenstick fractures, in which the bone bends (rather than crushes), resulting in a complete break in one cortex and a bend on the opposite side (akin to snapping a fresh twig from a tree). Torus fractures result in a mild deformity without a break in the bone surface, and pain is the main clinical feature. The child may need assistance with schoolwork, time off physical activities, and help with self-care during the recovery period.



Fig 1 
Anteroposterior (a) and lateral (b) radiographs of the wrist showing a torus fracture of the distal radius and ulna with compression of the bones dorsally, though no break in the bone surface 



Parents typically expect that any fracture needs plaster cast immobilisation to ensure adequate healing. However, torus fractures heal quickly, with pain almost completely resolved three weeks after …
2021 Update to the 2017 ACC Expert Consensus Decision Pathway for Optimization of Heart Failure Treatment: Answers to 10 Pivotal Issues About Heart Failure With Reduced Ejection Fraction
Authors: Thomas M. Maddox, James L. Januzzi, Larry A. Allen, Khadijah Breathett, Javed Butler, Leslie L. Davis, Gregg C. Fonarow, Nasrien E. Ibrahim, JoAnn Lindenfeld, Frederick A. Masoudi, Shweta R. Motiwala, Estefania Oliveros, J. Herbert Patterson, Mary Norine Walsh, Alan Wasserman, Clyde W. Yancy, Quentin R. Youmans
Journal: Journal of the American College of Cardiology (2021)
Lava Narsingh Joshi
Authors: Satyan M Rajbhandari
Journal: BMJ (2021)

Lava Narsingh Joshi qualified in Nepal, did his postgraduate training in cardiology in Bangladesh, and practised as a consultant cardiologist and intensivist in Nepal. He was dedicated to improve postgraduate medical training in Nepal. He was president of the Society of Internal Medicine of Nepal (SIMON) in 2015-17 and during his …
Empowering Physical Examination: The “Laying On” of Ultrasound⁎⁎Editorials published in JACC: Cardiovascular Imaging reflect the views of the authors and do not necessarily represent the views of JACC: Cardiovascular Imaging or the American College of Cardiology.
Authors: Bruce J. Kimura, Anthony N. DeMaria
Journal: JACC. Cardiovascular imaging (2008)
Abstract 14106: High Cardiovascular Risk and Frequent Cardiovascular Medication Use Among Oral Anticoagulant-Naive Initiators of Rivaroxaban and Vitamin K Antagonists
Authors: Luis A Garcia Rodriguez, Tania Schink, Irene D Bezemer, Ron M Herings, Leif Friberg, Yanina Balabanova, Gunnar Brobert, Kiliana Suzart-Woischnik, Pareen Vora, Ana Ruigomez
Journal: Circulation (2018)

Introduction: Vitamin K antagonists (VKA) are the standard of care for stroke prevention in non-valvular atrial fibrillation (SPAF), venous thromboembolism treatment (VTE-T) and VTE prevention afte...
Surgery for malignant pleural mesothelioma after radiotherapy (SMART): final results from a single-centre, phase 2 trial
Authors: B C John Cho, Laura Donahoe, Penelope A Bradbury, Natasha Leighl, Shaf Keshavjee, Andrew Hope, Prodipto Pal, Michael Cabanero, Kasia Czarnecka, Karen McRae, Ming-Sound Tsao, Marc de Perrot
Journal: The Lancet Oncology (2021)
Interpersonal psychotherapy delivered by nonspecialists for depression and posttraumatic stress disorder among Kenyan HIV–positive women affected by gender-based violence: Randomized controlled trial
Authors: Susan M. Meffert, Thomas C. Neylan, Charles E. McCulloch, Kelly Blum, Craig R. Cohen, Elizabeth A. Bukusi, Helen Verdeli, John C. Markowitz, James G. Kahn, David Bukusi, Harsha Thirumurthy, Grace Rota, Ray Rota, Grace Oketch, Elizabeth Opiyo, Linnet Ongeri
Journal: PLoS Medicine (2021)

HIV-positive women suffer a high burden of mental disorders due in part to gender-based violence (GBV). Comorbid depression and posttraumatic stress disorder (PTSD) are typical psychiatric consequences of GBV. Despite attention to the HIV-GBV syndemic, few HIV clinics offer formal mental healthcare. This problem is acute in sub-Saharan Africa, where the world's majority of HIV-positive women live and prevalence of GBV is high.
PUL01.03 Effect of Tumor Size Change and Duration of Response on OS With First-Line Pembrolizumab Plus Pemetrexed-platinum For Metastatic Nonsquamous Non‒Small-Cell Lung Cancer
Authors: S.F. Powell, S. Novello, M.C. Garassino, D. Rodríguez-Abreu, M. Wang, J. Yang, F. Souza, J.E. Gray
Journal: Journal of Thoracic Oncology (2021)
Gut microbiota: impacts on gastrointestinal cancer immunotherapy
Authors: Harry Cheuk Hay Lau, Joseph Jao-Yiu Sung, Jun Yu
Journal: Gut Microbes (2021)

The association of gut microbiota with gastrointestinal carcinogenesis has been heavily investigated since the recent advance in sequencing technology. Accumulating evidence has revealed the critical roles of commensal microbes in cancer progression. Given by its importance, emerging studies have focussed on targeting microbiota to ameliorate therapeutic effectiveness. It is now clear that the microbial community is closely related to the efficacy of chemotherapy, while the correlation of microbiota with immunotherapy is much less studied. Herein, we review the up-to-date findings on the influence of gut microbiota on three common immunotherapies including adoptive cell transfer, immune checkpoint blockade, and CpG-oligodeoxynucleotide therapy. We then explore three microbiota-targeted strategies that may improve treatment efficacy, involving dietary intervention, probiotics supplementation, and fecal microbiota transplantation.
MO01.42 Myelopreservation with Trilaciclib Regardless of Risk of Chemotherapy-Induced Febrile Neutropenia and/or Anemia or Red Blood Cell Transfusions
Authors: M. Hussein, T.A. Gersten, K. Lerro, I. Sinielnikov, A. Spira, R. Agajanian, A. Calles, S. Gurubhagavatula, G. Kuusk, E. Thara, O. Vynnychenko, Y. Pritchett, R.K. Malik, S.R. Morris, M. Maglakelidze
Journal: Journal of Thoracic Oncology (2021)
Diagnostic value of cutaneous manifestation of SARS‐CoV‐2 infection*
Authors: A. Visconti, V. Bataille, N. Rossi, J. Kluk, R. Murphy, S. Puig, R. Nambi, R. C. E. Bowyer, B. Murray, A. Bournot, J. Wolf, S. Ourselin, C. J. Steves, T. D. Spector, M. Falchi
Journal: British Journal of Dermatology (2021)

One of the challenging aspects of SARS-CoV-2 infection is its diverse multisystemic disease presentation.To evaluate the diagnostic value of cutaneous manifestations of SARS-CoV-2 infection and investigate their duration and timing in relation to other COVID-19 symptoms.We used data from 336 847 UK users of the COVID Symptom Study app to assess the diagnostic value of body rash or an acral rash in SARS-CoV-2 infection, and data from an independent online survey of 11 544 respondents to investigate skin-specific symptoms and collect their photographs.Using data from the app, we show significant association between skin rashes and a positive swab test result (odds ratio 1·67, 95% confidence interval 1·42-1·97). Strikingly, among the respondents of the independent online survey, we found that 17% of SARS-CoV-2-positive cases reported skin rashes as the first presentation, and 21% as the only clinical sign of COVID-19. Together with the British Association of Dermatologists, we have compiled a catalogue of images of the most common skin manifestations of COVID-19 from 400 individuals (https://covidskinsigns.com), which we have made publicly available to assist clinicians in recognition of this early clinical feature of COVID-19.Skin rashes cluster with other COVID-19 symptoms, are predictive of a positive swab test, and occur in a significant number of cases, either alone or before other classical symptoms. Recognizing rashes is important in identifying new and earlier cases of COVID-19.
FcεR1-expressing nociceptors trigger allergic airway inflammation
Authors: Theo Crosson, Jo-Chiao Wang, Benjamin Doyle, Hannah Merrison, Mohammad Balood, Alexandre Parrin, Maud Pascal, Barbara C. Mindt, Corey R. Seehus, Alp Ozcan, Xuan Huang, Elise Semenara, Nicole Y.Y. Lai, Abdelilah Majdoubi, Raja-Elie E. Abdulnour, Trevor Rajchgot, Moutih Rafei, Simmie L. Foster, Jacques Thibodeau, Jörg H. Fritz, Bruce D. Levy, Clifford J. Woolf, Sebastien Talbot
Journal: Journal of Allergy and Clinical Immunology (2021)
Massive haemoptysis: an unusual connection
Authors: Aimee Leadbetter, Quentin Jones, Paul Foley, Andy Beale
Journal: Thorax (2021)

A 60-year-old man presented with a 4-day history of small volume haemoptysis. His medical history revealed a pericardiectomy with pericardial window creation for severe constrictive pericarditis secondary to seropositive rheumatoid arthritis in 1997 and pulmonary tuberculosis aged 7, with a treated recurrence in 2005. He was a lifelong smoker of 20 cigarettes per day. He lived independently. His regular medication included prednisolone 10 mg and meloxicam.

On examination, he looked unwell. His heart rate was 140, respiratory rate 22 and oxygen saturations 96% on air. Auscultation revealed crepitations at the left lung base. He had 500 mL of brisk haemoptysis. His haemoglobin fell from 85 to 73 g/L. Inflammatory markers were raised (C reactive protein 169 mg/L, white cell count 14.7×109/L, neutrophil count 12.9×109/L), prothrombin time ratio was mildly raised (1.4), platelet count …
Effect of denosumab on osteolytic lesion activity after total hip arthroplasty: a single-centre, randomised, double-blind, placebo-controlled, proof of concept trial
Authors: Mohit M Mahatma, Raveen L Jayasuriya, David Hughes, Nigel Hoggard, Simon C Buckley, Andrew Gordon, Andrew J Hamer, Mohammed W Tomouk, Robert M Kerry, Richard Eastell, Jeremy M Wilkinson
Journal: The Lancet Rheumatology (2021)