tbuckley/cabot-search huggingface dataset:
Living with multiple chronic conditions: how exercise helps me self-manage my conditions
Authors: Gregers Aagaard
Journal: British Journal of Sports Medicine (2021)

My name is Gregers, I am 72 years old and I live with several chronic conditions: osteoarthritis in the knees and hips, hypertension, gout, atrial tachycardia, low back pain, asthma, rapid eye movement sleep behaviour disorder, obstructive sleep apnoea, central sleep apnoea and periodic limb movement disorder.

My conditions have a great impact on my daily life, both physically and mentally. In particular, the osteoarthritis in my knees and hips and my low back pain are the two most painful and disabling conditions for me. My sleep disturbance conditions are the ones that affect my psychosocial health most though, as the thought of possibly developing diseases like Parkinson’s or dementia as sequelae to these conditions,1 is depressing to me.

With this article, I would like to share my story and the strategies I have to self-manage my chronic conditions.

Living with multiple chronic conditions means many visits to my general practitioner and specialists, at least one for each single disorder. In my experience, the doctors I have met were very informative and provided …
Long working hours and risk of 50 health conditions and mortality outcomes: a multicohort study in four European countries
Authors: Jenni Ervasti, Jaana Pentti, Solja T. Nyberg, Martin J. Shipley, Constanze Leineweber, Jeppe K. Sørensen, Lars Alfredsson, Jakob B. Bjorner, Marianne Borritz, Hermann Burr, Anders Knutsson, Ida E.H. Madsen, Linda L. Magnusson Hanson, Tuula Oksanen, Jan H. Pejtersen, Reiner Rugulies, Sakari Suominen, Töres Theorell, Hugo Westerlund, Jussi Vahtera, Marianna Virtanen, G. David Batty, Mika Kivimäki
Journal: The Lancet Regional Health - Europe (2021)

Studies on the association between long working hours and health have captured only a narrow range of outcomes (mainly cardiometabolic diseases and depression) and no outcome-wide studies on this topic are available. To achieve wider scope of potential harm, we examined long working hours as a risk factor for a wide range of disease and mortality endpoints. The data of this multicohort study were from two population cohorts from Finland (primary analysis, n=59 599) and nine cohorts (replication analysis, n=44 262) from Sweden, Denmark, and the UK, all part of the Individual-participant Meta-analysis in Working Populations (IPD-Work) consortium. Baseline-assessed long working hours (≥55 hours per week) were compared to standard working hours (35-40 h). Outcome measures with follow-up until age 65 years were 46 diseases that required hospital treatment or continuous pharmacotherapy, all-cause, and three cause-specific mortality endpoints, ascertained via linkage to national health and mortality registers. 2747 (4·6%) participants in the primary cohorts and 3027 (6·8%) in the replication cohorts worked long hours. After adjustment for age, sex, and socioeconomic status, working long hours was associated with increased risk of cardiovascular death (hazard ratio 1·68; 95% confidence interval 1·08-2·61 in primary analysis and 1·52; 0·90-2·58 in replication analysis), infections (1·37; 1·13-1·67 and 1·45; 1·13-1·87), diabetes (1·18; 1·01-1·38 and 1·41; 0·98-2·02), injuries (1·22; 1·00-1·50 and 1·18; 0·98-1·18) and musculoskeletal disorders (1·15; 1·06-1·26 and 1·13; 1·00-1·27). Working long hours was not associated with all-cause mortality. Follow-up of 50 health outcomes in four European countries suggests that working long hours is associated with an elevated risk of early cardiovascular death and hospital-treated infections before age 65. Associations, albeit weak, were also observed with diabetes, musculoskeletal disorders and injuries. In these data working long hours was not related to elevated overall mortality. NordForsk, the Medical Research Council, the National Institute on Aging, the Wellcome Trust, Academy of Finland, and Finnish Work Environment Fund.
Trends in Breast Cancer Screening Costs Among Privately Insured Women Aged 40 to 64 Years
Authors: Ilana B. Richman, Jessica B. Long, Natalia Kunst, Kelly Kyanko, Xiao Xu, Susan Busch, Cary P. Gross
Journal: JAMA Internal Medicine (2021)

disclosed with the article.Discussion | In this cross-sectional study, we found that 15% of authors of editorial commentaries accompanying RCTs on invasive cardiovascular interventions published from 2013 to 2019 reported financial associations with trial sponsors.Many of the authors with general payments or research funding reported on Open Payments did not disclose all of these financial associations in the commentary nor the accompanying disclosure forms.A limitation of this study is that the Open Payments database does not capture financial associations with industry for non-US-based authors.For this reason, 83 (58%) of the commentary authors did not have Open Payments records.The present analysis was also limited because it may not have captured all recent financial associations of authors with industry or trial sponsors, could not account for inaccuracies in the Open Payments data, and did not study nonfinancial associations.The disclosed and undisclosed financial associations with trial sponsors for a substantial number of editorial commentaries on RCTs of invasive cardiovascular interventions are concerning, all the more so because of the attention focused on the issue since the 1990s. 2As the financial associations of authors diminish the value of the commentaries, journal editors should strengthen their disclosure requirements, improve compliance, and consider once again whether they should allow authors to have such financial associations at all.
<i>Ex vivo</i>delivery of regulatory T-cells for control of alloimmune priming in the donor lung
Authors: Ei Miyamoto, Akihiro Takahagi, Akihiro Ohsumi, Tereza Martinu, David Hwang, Kristen M. Boonstra, Betty Joe, Juan Mauricio Umana, Ke F. Bei, Daniel Vosoughi, Mingyao Liu, Marcelo Cypel, Shaf Keshavjee, Stephen C. Juvet
Journal: European Respiratory Journal (2021)

Survival after lung transplantation (LTx) is hampered by uncontrolled inflammation and alloimmunity. Regulatory T-cells (Tregs) are being studied as a cellular therapy in solid organ transplantation. Whether these systemically administered Tregs can function at the appropriate location and time is an important concern. We hypothesised that in vitro-expanded recipient-derived Tregs can be delivered to donor lungs prior to LTx via ex vivo lung perfusion (EVLP), maintaining their immunomodulatory ability.In a rat model, Wistar Kyoto (WKy) CD4+CD25high Tregs were expanded in vitro prior to EVLP. Expanded Tregs were administered to Fisher 344 (F344) donor lungs during EVLP; left lungs were transplanted into WKy recipients. Treg localisation and function post-transplant were assessed. In a proof-of-concept experiment, cryopreserved expanded human CD4+CD25+CD127low Tregs were thawed and injected into discarded human lungs during EVLP.Rat Tregs entered the lung parenchyma and retained suppressive function. Expanded Tregs had no adverse effect on donor lung physiology during EVLP; lung water as measured by wet-to-dry weight ratio was reduced by Treg therapy. The administered cells remained in the graft at 3 days post-transplant where they reduced activation of intra-graft effector CD4+ T-cells; these effects were diminished by day 7. Human Tregs entered the lung parenchyma during EVLP where they expressed key immunoregulatory molecules (CTLA4+, 4-1BB+, CD39+ and CD15s+).Pre-transplant Treg administration can inhibit alloimmunity within the lung allograft at early time points post-transplant. Our organ-directed approach has potential for clinical translation.
CDNF: An innovative actor in disease-modifying approaches for Parkinson’s disease
Authors: Liliane Tenenbaum
Journal: Molecular Therapy (2021)

Although cerebral dopamine neurotrophic factor (CDNF) is considered a "neurotrophic factor (NF)," its mechanism of action differs from classic NFs that increase cell survival through intracellular signaling. CDNF is located in the endoplasmic reticulum (ER), is secreted in response to ER stress, and reduces ER stress after internalization.1 In this issue of Molecular Therapy, Albert et al.2 demonstrate that CDNF directly binds to α-synuclein in vitro and in vivo. They further show that CDNF reduced α-synuclein aggregation as well as internalization of α-synuclein preformed fibrils (PFFs) in neuronal cultures.
Functional significance of gain-of-function H19 lncRNA in skeletal muscle differentiation and anti-obesity effects
Authors: Yajuan Li, Yaohua Zhang, Qingsong Hu, Sergey D. Egranov, Zhen Xing, Zhao Zhang, Ke Liang, Youqiong Ye, Yinghong Pan, Sujash S. Chatterjee, Brandon Mistretta, Tina K. Nguyen, David H. Hawke, Preethi H. Gunaratne, Mien-Chie Hung, Leng Han, Liuqing Yang, Chunru Lin
Journal: Genome Medicine (2021)

Abstract Background Exercise training is well established as the most effective way to enhance muscle performance and muscle building. The composition of skeletal muscle fiber type affects systemic energy expenditures, and perturbations in metabolic homeostasis contribute to the onset of obesity and other metabolic dysfunctions. Long noncoding RNAs (lncRNAs) have been demonstrated to play critical roles in diverse cellular processes and diseases, including human cancers; however, the functional importance of lncRNAs in muscle performance, energy balance, and obesity remains elusive. We previously reported that the lncRNA H19 regulates the poly-ubiquitination and protein stability of dystrophin (DMD) in muscular dystrophy. Methods Here, we identified mouse/human H19- interacting proteins using mouse/human skeletal muscle tissues and liquid chromatography–mass spectrometry (LC-MS). Human induced pluripotent stem-derived skeletal muscle cells (iPSC-SkMC) from a healthy donor and Becker Muscular Dystrophy (BMD) patients were utilized to study DMD post-translational modifications and associated proteins. We identified a gain-of-function (GOF) mutant of H19 and characterized the effects on myoblast differentiation and fusion to myotubes using iPSCs. We then conjugated H19 RNA gain-of-function oligonucleotides (Rgof) with the skeletal muscle enrichment peptide agrin (referred to as AGR- H19 -Rgof) and evaluated AGR- H19 -Rgof’s effects on skeletal muscle performance using wild-type (WT) C57BL/6 J mice and its anti-obesity effects using high-fat diet (HFD)- and leptin deficiency-induced obese mouse models. Results We demonstrated that both human and mouse H19 associated with DMD and that the H19 GOF exhibited enhanced interaction with DMD compared to WT H19 . DMD was found to associate with serine/threonine-protein kinase MRCK alpha (MRCKα) and α-synuclein (SNCA) in iPSC-SkMC derived from BMD patients. Inhibition of MRCKα and SNCA-mediated phosphorylation of DMD antagonized the interaction between H19 and DMD. These signaling events led to improved skeletal muscle cell differentiation and myotube fusion. The administration of AGR- H19 -Rgof improved the muscle mass, muscle performance, and base metabolic rate of WT mice. Furthermore, mice treated with AGR- H19 -Rgof exhibited resistance to HFD- or leptin deficiency-induced obesity. Conclusions Our study suggested the functional importance of the H19 GOF mutant in enhancing muscle performance and anti-obesity effects.
Circulating heart failure biomarkers beyond natriuretic peptides: review from the Biomarker Study Group of the Heart Failure Association (<scp>HFA</scp>), European Society of Cardiology (<scp>ESC</scp>)
Authors: Wouter C. Meijers, Antoni Bayes‐Genis, Alexandre Mebazaa, Johann Bauersachs, John G.F. Cleland, Andrew J.S. Coats, James L. Januzzi, Alan S. Maisel, Kenneth McDonald, Thomas Mueller, A. Mark Richards, Petar Seferovic, Christian Mueller, Rudolf A. de Boer
Journal: European Journal of Heart Failure (2021)

New biomarkers are being evaluated for their ability to advance the management of patients with heart failure. Despite a large pool of interesting candidate biomarkers, besides natriuretic peptides virtually none have succeeded in being applied into the clinical setting. In this review, we examine the most promising emerging candidates for clinical assessment and management of patients with heart failure. We discuss high-sensitivity cardiac troponins (Tn), procalcitonin, novel kidney markers, soluble suppression of tumorigenicity 2 (sST2), galectin-3, growth differentiation factor-15 (GDF-15), cluster of differentiation 146 (CD146), neprilysin, adrenomedullin (ADM), and also discuss proteomics and genetic-based risk scores. We focused on guidance and assistance with daily clinical care decision-making. For each biomarker, analytical considerations are discussed, as well as performance regarding diagnosis and prognosis. Furthermore, we discuss potential implementation in clinical algorithms and in ongoing clinical trials.
ANALYSIS OF LUNG CANCER HISTOLOGY BY FAMILY ONCOLOGIC HISTORY IN A UNIVERSITY HOSPITAL IN LATVIA
Authors: Jelena Grusina Ujumaza, Genadijs Ambalovs, Andrejs Vanags, Ilze Strumfa, Jazeps Basko, Janis Gardovskis, Uldis Kopeika, Ainis Pirtnieks
Journal: Journal of Thoracic Oncology (2011)
Representation of Women Among Editors in Chief of Leading Medical Journals
Authors: Ana-Catarina Pinho-Gomes, Amy Vassallo, Kelly Thompson, Kate Womersley, Robyn Norton, Mark Woodward
Journal: JAMA Network Open (2021)

Women remain underrepresented among editors of scientific journals, particularly in senior positions. However, to what extent this applies to medical journals of different specialties remains unclear.To investigate the gender distribution of the editors in chief at leading medical journals.Cross-sectional study of the editors in chief at the top 10 international medical journals of 41 categories related to the medical specialties of the Clarivate Analytics Web of Science Journal Citation Reports in 2019.Proportion of women as editors in chief.This study found that, overall, women represented 21% (94 of 44) of the editors in chief, with wide variation across medical specialties from 0% to 82%. There were 5 categories for which none of the editors in chief were women (dentistry, oral surgery and medicine; allergy; psychiatry; anesthesiology; and ophthalmology) and only 3 categories for which women outnumbered men as editors in chief (primary health care, microbiology, and genetics and heredity). In 27 of the 41 categories, women represented less than a third of the editors in chief (eg, 1 of 10 for critical care medicine, 2 of 10 for gastroenterology and hepatology, and 3 of 10 for endocrinology and metabolism).This study found that women are underrepresented among editors in chief of leading medical journals. For the benefit of medical research, a joint effort from editorial boards, publishers, authors, and academic institutions is required to address this gender gap.
Tumor-self-targeted “thermoferroptosis-sensitization” magnetic nanodroplets for multimodal imaging-guided tumor-specific therapy
Authors: Junrui Wang, Weixiang Song, Xingyue Wang, Zhuoyan Xie, Wenli Zhang, Weixi Jiang, Shuling Liu, Jingxin Hou, Yixin Zhong, Jie Xu, Haitao Ran, Dajing Guo
Journal: Biomaterials (2021)
Staphylococcus argenteus transmission among healthy Royal Marines: A molecular epidemiology case-study
Authors: Elita Jauneikaite, Bruno Pichon, Mia Mosavie, Joanne L. Fallowfield, Trish Davey, Neil Thorpe, Andrew Nelstrop, Shiranee Sriskandan, Lucy E Lamb
Journal: Journal of Infection (2021)

Objectives During a prospective study of S. aureus carriage in Royal Marines recruits, six S. argenteus strains were identified in four recruits. As S. argenteus sepsis leads to mortality similar to S. aureus, we determined the potential for within same troop transmission, to evaluate future outbreak risk.Methods We used whole-genome sequencing to characterise S. argenteus and investigate phylogenetic relationships between isolates.Results S. argenteus strains (t5078, ST2250) were detected in 4/40 recruits in the same troop (training cohort) in weeks 1, 6 or 15 of training. No mec, tsst or LukPV genes were detected. We identified differences of 1–17 core SNPs between S. argenteus from different recruits. In two recruits, two S. argenteus strains were isolated; these could be distinguished by 2 and 15 core SNPs.Conclusions The identification of S. argenteus within a single troop from the total recruit population suggests a common source for transmission, though high number of SNPs were identified, both within-host and within-cluster. The high number of SNPs between some isolates may indicate a common source of diverse isolates or a high level of S. argenteus mutation in carriage. S. argenteus is newly recognized species; and understanding of the frequency of genetic changes during transmission and transition from asymptomatic carriage to disease is required.
Updating changes in human gut microbial communities associated with <i>Clostridioides difficile</i> infection
Authors: Giovanny Herrera, Daniel Paredes-Sabja, Manuel Alfonso Patarroyo, Juan David Ramírez, Marina Muñoz
Journal: Gut Microbes (2021)

Clostridioides difficile is the causative agent of antibiotic-associated diarrhea, a worldwide public health problem. Different factors can promote the progression of C. difficile infection (CDI), mainly altered intestinal microbiota composition. Microbial species belonging to different domains (i.e., bacteria, archaea, eukaryotes, and even viruses) are synergistically and antagonistically associated with CDI. This review was aimed at updating changes regarding CDI-related human microbiota composition using recent data and an integral approach that included the different microorganism domains. The three domains of life contribute to intestinal microbiota homeostasis at different levels in which relationships among microorganisms could explain the wide range of clinical manifestations. A holistic understanding of intestinal ecosystem functioning will facilitate identifying new predictive factors for infection and developing better treatment and new diagnostic tools, thereby reducing this disease’s morbidity and mortality.
Author Correction: Avocado: a multi-scale deep tensor factorization method learns a latent representation of the human epigenome
Authors: Jacob Schreiber, Timothy Durham, Jeffrey Bilmes, William Stafford Noble
Journal: Genome biology (2021)

Following publication of the original article [1], the following error was identified in the Results section, under the heading Avocado imputes epigenomic tracks more accurately than prior methods."Conversely, ChromImpute performs the best on MSE1obs (Avocado/ChromImpute p value = 2.37e -22, PREDICTD/ChromImpute p value = 2.85e -12) but the worst on MSE1imp, suggesting that it may over-call peaks.Additionally, Ernst and Kellis proposed six other evaluation performance measures, which show similar trends as the MSE1imp metric (Additional file 2: Fig. S2)."The second sentence above should read (with the changed text in bold) "Additionally, Ernst and Kellis proposed six other evaluation performance measures, which show similar trends as the MSE1obs metric (Additional file 2: Fig. S2)."Because this was a typo, the primary results and conclusions in the paper still hold.However, to improve the clarity of our claims in light of this correction, we would like to make two additional edits:In the Background section, we would like to change:"Using data from the Roadmap Epigenomics Consortium, we demonstrate that Avocado yields imputed values that are more accurate than those produced by
Helios represses megakaryocyte priming in hematopoietic stem and progenitor cells
Authors: Giovanni Cova, Chiara Taroni, Marie-Céline Deau, Qi Cai, Vincent Mittelheisser, Muriel Philipps, Matthieu Jung, Marie Cerciat, Stéphanie Le Gras, Christelle Thibault-Carpentier, Bernard Jost, Leif Carlsson, Angela M. Thornton, Ethan M. Shevach, Peggy Kirstetter, Philippe Kastner, Susan Chan
Journal: The Journal of Experimental Medicine (2021)

Our understanding of cell fate decisions in hematopoietic stem cells is incomplete. Here, we show that the transcription factor Helios is highly expressed in murine hematopoietic stem and progenitor cells (HSPCs), where it is required to suppress the separation of the platelet/megakaryocyte lineage from the HSPC pool. Helios acts mainly in quiescent cells, where it directly represses the megakaryocyte gene expression program in cells as early as the stem cell stage. Helios binding promotes chromatin compaction, notably at the regulatory regions of platelet-specific genes recognized by the Gata2 and Runx1 transcriptional activators, implicated in megakaryocyte priming. Helios null HSPCs are biased toward the megakaryocyte lineage at the expense of the lymphoid and partially resemble cells of aging animals. We propose that Helios acts as a guardian of HSPC pluripotency by continuously repressing the megakaryocyte fate, which in turn allows downstream lymphoid priming to take place. These results highlight the importance of negative and positive priming events in lineage commitment.
Autoimmunity affecting the biliary tract fuels the immunosurveillance of cholangiocarcinoma
Authors: Juliette Paillet, Céleste Plantureux, Sarah Lévesque, Julie Le Naour, Gautier Stoll, Allan Sauvat, Pamela Caudana, Jimena Tosello Boari, Norma Bloy, Sylvie Lachkar, Isabelle Martins, Paule Opolon, Andrea Checcoli, Agathe Delaune, Noémie Robil, Pierre de la Grange, Juliette Hamroune, Franck Letourneur, Gwennhael Autret, Patrick S.C. Leung, M. Eric Gershwin, Jie S. Zhu, Mark J. Kurth, Bouchra Lekbaby, Jérémy Augustin, Youra Kim, Shashi Gujar, Cédric Coulouarn, Laura Fouassier, Laurence Zitvogel, Eliane Piaggio, Chantal Housset, Patrick Soussan, Maria Chiara Maiuri, Guido Kroemer, Jonathan G. Pol
Journal: The Journal of Experimental Medicine (2021)

Cholangiocarcinoma (CCA) results from the malignant transformation of cholangiocytes. Primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC) are chronic diseases in which cholangiocytes are primarily damaged. Although PSC is an inflammatory condition predisposing to CCA, CCA is almost never found in the autoimmune context of PBC. Here, we hypothesized that PBC might favor CCA immunosurveillance. In preclinical murine models of cholangitis challenged with syngeneic CCA, PBC (but not PSC) reduced the frequency of CCA development and delayed tumor growth kinetics. This PBC-related effect appeared specific to CCA as it was not observed against other cancers, including hepatocellular carcinoma. The protective effect of PBC was relying on type 1 and type 2 T cell responses and, to a lesser extent, on B cells. Single-cell TCR/RNA sequencing revealed the existence of TCR clonotypes shared between the liver and CCA tumor of a PBC host. Altogether, these results evidence a mechanistic overlapping between autoimmunity and cancer immunosurveillance in the biliary tract.
In adults with obesity, metabolic–bariatric surgery vs. usual care is associated with lower all-cause mortality
Authors: Scott Kahan, Adriana Williams
Journal: Annals of Internal Medicine (2021)

Source Citation Syn NL, Cummings DE, Wang LZ, et al. Association of metabolic–bariatric surgery with long-term survival in adults with and without diabetes: a one-stage meta-analysis of matched cohort and prospective controlled studies with 174 772 participants. Lancet. 2021;397:1830-41. 33965067