tbuckley/cabot-search huggingface dataset:
Self-management intervention to reduce pulmonary exacerbations by supporting treatment adherence in adults with cystic fibrosis: a randomised controlled trial
Authors: Martin J Wildman, Alicia O’Cathain, Chin Maguire, Madelynne A Arden, Marlene Hutchings, Judy Bradley, Stephen J Walters, Pauline Whelan, John Ainsworth, Iain Buchan, Laura Mandefield, Laura Sutton, Paul Tappenden, Rachel A Elliott, Zhe Hui Hoo, Sarah J Drabble, Daniel Beever
Journal: Thorax (2021)

Recurrent pulmonary exacerbations lead to progressive lung damage in cystic fibrosis (CF). Inhaled medications (mucoactive agents and antibiotics) help prevent exacerbations, but objectively measured adherence is low. We investigated whether a multi-component (complex) self-management intervention to support adherence would reduce exacerbation rates over 12 months.Between October 2017 and May 2018, adults with CF (aged ≥16 years; 19 UK centres) were randomised to the intervention (data-logging nebulisers, a digital platform and behavioural change sessions with trained clinical interventionists) or usual care (data-logging nebulisers). Outcomes included pulmonary exacerbations (primary outcome), objectively measured adherence, body mass index (BMI), lung function (FEV1) and Cystic Fibrosis Questionnaire-Revised (CFQ-R). Analyses were by intent to treat over 12 months.Among intervention (n=304) and usual care (n=303) participants (51% female, median age 31 years), 88% completed 12-month follow-up. Mean exacerbation rate was 1.63/year with intervention and 1.77/year with usual care (adjusted ratio 0.96; 95% CI 0.83 to 1.12; p=0.64). Adjusted mean differences (95% CI) were in favour of the intervention versus usual care for objectively measured adherence (9.5% (8.6% to 10.4%)) and BMI (0.3 (0.1 to 0.6) kg/m2), with no difference for %FEV1 (1.4 (-0.2 to 3.0)). Seven CFQ-R subscales showed no between-group difference, but treatment burden reduced for the intervention (3.9 (1.2 to 6.7) points). No intervention-related serious adverse events occurred.While pulmonary exacerbations and FEV1 did not show statistically significant differences, the intervention achieved higher objectively measured adherence versus usual care. The adherence difference might be inadequate to influence exacerbations, though higher BMI and lower perceived CF treatment burden were observed.
Development of a New Fully Human Anti-CD20 Monoclonal Antibody for the Treatment of B-Cell Malignancies.
Authors: Gadi Gazit Bornstein, Christophe Queva, Mohammad Tabrizi, Anne VanAbbema, Carlos Chavez, Ping Wang, Naomi Laing, Sandhya Raja, Shenghua Wen, Xianhui Rong, Larry L. Green, Xiaodong Yang, David Blakey
Journal: Blood (2007)
Immunity elicited by natural infection or Ad26.COV2.S vaccination protects hamsters against SARS-CoV-2 variants of concern
Authors: Lisa H. Tostanoski, Jingyou Yu, Noe B. Mercado, Katherine McMahan, Catherine Jacob-Dolan, Amanda J. Martinot, Cesar Piedra-Mora, Tochi Anioke, Aiquan Chang, Victoria M. Giffin, David L. Hope, Huahua Wan, Esther A. Bondzie, Shant H. Mahrokhian, Linda M. Wrijil, Katherine Bauer, Laurent Pessaint, Maciel Porto, Joseph Piegols, Andrew Faudree, Brittany Spence, Swagata Kar, Fatima Amanat, Florian Krammer, Hanne Andersen, Mark G. Lewis, Frank Wegmann, Roland Zahn, Hanneke Schuitemaker, Dan H. Barouch
Journal: Science Translational Medicine (2021)

Immunity from prior infection or Ad26.COV2.S vaccination protected hamsters from challenge with a heterologous strain of SARS-CoV-2 5 weeks later.
Rapid Assessment and Containment of <i>Candida auris</i> Transmission in Postacute Care Settings—Orange County, California, 2019
Authors: Ellora N. Karmarkar, Kathleen O’Donnell, Christopher Prestel, Kaitlin Forsberg, Lalitha Gade, Seema Jain, Douglas Schan, Nancy Chow, Darby McDermott, John Rossow, Mitsuru Toda, Ryan Ruiz, Sopheay Hun, Jennifer L. Dale, Annastasia Gross, Tyler Maruca, Janet Glowicz, Richard Brooks, Hosniyeh Bagheri, Teresa Nelson, Nicole Gualandi, Zenith Khwaja, Sam Horwich-Scholefield, Josh Jacobs, Michele Cheung, Maroya Walters, Kara Jacobs-Slifka, Nimalie D. Stone, Lydia Mikhail, Sudha Chaturvedi, Liore Klein, Paula Snippes Vagnone, Emily Schneider, Elizabeth L. Berkow, Brendan R. Jackson, Snigdha Vallabhaneni, Matthew Zahn, Erin Epson
Journal: Annals of Internal Medicine (2021)

, a multidrug-resistant yeast, can spread rapidly in ventilator-capable skilled-nursing facilities (vSNFs) and long-term acute care hospitals (LTACHs). In 2018, a laboratory serving LTACHs in southern California began identifying species of
IL‐37 regulates allergic inflammation by counterbalancing pro‐inflammatory IL‐1 and IL‐33
Authors: Alexandra Schröder, Lars P. Lunding, Ulrich M. Zissler, Christina Vock, Sina Webering, Johanna C. Ehlers, Zane Orinska, Adam Chaker, Carsten B. Schmidt‐Weber, Niklas J. Lang, Herbert B. Schiller, Marcus A. Mall, Heinz Fehrenbach, Charles A. Dinarello, Michael Wegmann
Journal: Allergy (2021)

Children with asthma have impaired production of interleukin (IL) 37; in mice, IL-37 reduces hallmarks of experimental allergic asthma (EAA). However, it remains unclear how IL-37 exerts its inhibitory properties in asthma. This study aimed to identify the mechanism(s) by which IL-37 controls allergic inflammation.IL-37 target cells were identified by single-cell RNA-seq of IL-1R5 and IL-1R8. Airway tissues were isolated by laser-capture microdissection and examined by microarray-based gene expression analysis. Mononuclear cells (MNC) and airway epithelial cells (AECs) were isolated and stimulated with allergen, IL-1β, or IL-33 together with recombinant human (rh) IL-37. Wild-type, IL-1R1- and IL-33-deficient mice with EAA were treated with rhIL-37. IL-1β, IL-33, and IL-37 levels were determined in sputum and nasal secretions from adult asthma patients without glucocorticoid therapy.IL-37 target cells included AECs, T cells, and dendritic cells. In mice with EAA, rhIL-37 led to differential expression of >90 genes induced by IL-1β and IL-33. rhIL-37 reduced production of Th2 cytokines in allergen-activated MNCs from wild-type but not from IL-1R1-deficient mice and inhibited IL-33-induced Th2 cytokine release. Furthermore, rhIL-37 attenuated IL-1β- and IL-33-induced pro-inflammatory mediator expression in murine AEC cultures. In contrast to wild-type mice, hIL-37 had no effect on EAA in IL-1R1- or IL-33-deficient mice. We also observed that expression/production ratios of both IL-1β and IL-33 to IL-37 were dramatically increased in asthma patients compared to healthy controls.IL-37 downregulates allergic airway inflammation by counterbalancing the disease-amplifying effects of IL-1β and IL-33.
Medicinal chemistry strategies towards the development of effective SARS-CoV-2 inhibitors
Authors: Shenghua Gao, Tianguang Huang, Letian Song, Shujing Xu, Yusen Cheng, Srinivasulu Cherukupalli, Dongwei Kang, Tong Zhao, Lin Sun, Jian Zhang, Peng Zhan, Xinyong Liu
Journal: Acta Pharmaceutica Sinica B (2021)

Novel therapies are urgently needed to improve global treatment of SARS-CoV-2 infection. Herein, we briefly provide a concise report on the medicinal chemistry strategies towards the development of effective SARS-CoV-2 inhibitors with representative examples in different strategies from the medicinal chemistry perspective.
Preterm birth reduces the risk of IgE sensitization up to early adulthood: A population‐based birth cohort study
Authors: Niki Mitselou, Niklas Andersson, Anna Bergström, Inger Kull, Antonios Georgelis, Marianne van Hage, Anna M. Hedman, Catarina Almqvist, Jonas F. Ludvigsson, Erik Melén
Journal: Allergy (2021)

Immunoglobulin E (IgE) sensitization is associated with asthma and allergic diseases. Gestational age influences early immune system development, thereby potentially affecting the process of tolerance induction to allergens.To study IgE sensitization to common allergens by gestational age from childhood up to early adulthood.Population-based birth cohort, data from the Swedish BAMSE study were used. Allergen-specific IgE antibodies to a mix of common food (fx5) and inhalant (Phadiatop) allergens were analysed at 4, 8, 16 and 24 years. Sensitization was defined as allergen-specific IgE ≥0.35 kUA /L to fx5 and/or Phadiatop at each time point. Using logistic regression and generalized estimated equations, adjusted odds ratios (aORs) for sensitization in relation to gestational age were calculated. Replication was sought within the Swedish twin study STOPPA.In BAMSE, 3522 participants were screened for IgE antibodies during follow-up; of these, 197 (5.6%) were born preterm (<37 gestational weeks) and 330 (9.4%) post-term (≥42 weeks). Preterm birth reduced the risk of sensitization to common food and/or inhalant allergens up to early adulthood by 29% (overall aOR = 0.71; 95% CI: 0.52-0.98), and to food allergens specifically by 40% (overall aOR = 0.60; 95% CI: 0.38-0.93). No relation was found between post-term birth and IgE sensitization at any time point. Replication analyses in STOPPA (N = 675) showed similar risk estimates for sensitization to food and/or inhalant allergens (aOR = 0.72; 95% CI: 0.42-1.21), which resulted in a combined meta-analysis aOR = 0.71 (95% CI: 0.54-0.94).Our study suggests an inverse association between preterm birth and long-term IgE sensitization.
Over 50,000 Metagenomically Assembled Draft Genomes for the Human Oral Microbiome Reveal New Taxa
Authors: Jie Zhu, Liu Tian, Peishan Chen, Mo Han, Liju Song, Xin Tong, Xiaohuan Sun, Fangming Yang, Zhipeng Lin, Xing Liu, Chuan Liu, Xiaohan Wang, Yuxiang Lin, Kaiye Cai, Yong Hou, Xun Xu, Huanming Yang, Jian Wang, Karsten Kristiansen, Liang Xiao, Tao Zhang, Huijue Jia, Zhuye Jie
Journal: Genomics Proteomics & Bioinformatics (2021)

The oral cavity of each person is home to hundreds of bacterial species. While taxa for oral diseases have been studied using culture-based characterization as well as amplicon sequencing, metagenomic and genomic information remains scarce compared to the fecal microbiome. Here, using metagenomic shotgun data for 3346 oral metagenomic samples together with 808 published samples, we obtain 56,213 metagenome-assembled genomes (MAGs), and more than 64% of the 3589 species-level genome bins (SGBs) contain no publicly available genomes. The resulting genome collection is representative of samples around the world and contains many genomes from candidate phyla radiation (CPR) that lack monoculture. Also, it enables the discovery of new taxa such as a genus Candidatus Bgiplasma within the family Acholeplasmataceae. Large-scale metagenomic data from massive samples also allow the assembly of strains from important oral taxa such as Porphyromonas and Neisseria. The oral microbes encode genes that could potentially metabolize drugs. Apart from these findings, a strongly male-enriched Campylobacter species was identified. Oral samples would be more user-friendly collected than fecal samples and have the potential for disease diagnosis. Thus, these data lay down a genomic framework for future inquiries of the human oral microbiome.
Climate crisis: Over 200 health journals urge world leaders to tackle “catastrophic harm”
Authors: Jacqui Wise
Journal: BMJ (2021)

Climate crisis: Over 200 health journals urge world leaders to tackle "catastrophic harm" Jacqui WiseMore than 200 health journals have called on governments to take emergency action to tackle the "catastrophic harm to health" from climate change.A joint editorial says that while recent targets to reduce emissions and conserve biodiversity are welcome, they are not enough and need to be matched with credible short and longer term plans.
Sleep in times of crises: A scoping review in the early days of the COVID-19 crisis
Authors: Guido Simonelli, Dominique Petit, Julia Pizzamiglio Delage, Xavier Michaud, Marie Denise Lavoie, Charles M. Morin, Roger Godbout, Rebecca Robillard, Annie Vallières, Julie Carrier, Célyne Bastien
Journal: Sleep Medicine Reviews (2021)
National Food Strategy: urgent and robust government support is needed
Authors: Michael Craig Watson, John Lloyd
Journal: BMJ (2021)

We welcome the publication of the National Food Strategy report as it quite rightly includes sections on food production, education, marketing, and supporting those on low incomes.12 This government has indicated that it will consider the report and respond with a white paper within six months. With high and rising rates of obesity, we believe that this action should be sooner.

Over recent …
Integrated analysis of the faecal metagenome and serum metabolome reveals the role of gut microbiome-associated metabolites in the detection of colorectal cancer and adenoma
Authors: Feng Chen, Xudong Dai, Chang-Chun Zhou, Ke-xin Li, Yu-juan Zhang, Xiao-Ying Lou, Yuan-Min Zhu, Yan-Lai Sun, Bao-Xiang Peng, Wei Cui
Journal: Gut (2021)

Objective To profile gut microbiome-associated metabolites in serum and investigate whether these metabolites could distinguish individuals with colorectal cancer (CRC) or adenoma from normal healthy individuals. Design Integrated analysis of untargeted serum metabolomics by liquid chromatography-mass spectrometry and metagenome sequencing of paired faecal samples was applied to identify gut microbiome-associated metabolites with significantly altered abundance in patients with CRC and adenoma. The ability of these metabolites to discriminate between CRC and colorectal adenoma was tested by targeted metabolomic analysis. A model based on gut microbiome-associated metabolites was established and evaluated in an independent validation cohort. Results In total, 885 serum metabolites were significantly altered in both CRC and adenoma, including eight gut microbiome-associated serum metabolites (GMSM panel) that were reproducibly detected by both targeted and untargeted metabolomics analysis and accurately discriminated CRC and adenoma from normal samples. A GMSM panel-based model to predict CRC and colorectal adenoma yielded an area under the curve (AUC) of 0.98 (95% CI 0.94 to 1.00) in the modelling cohort and an AUC of 0.92 (83.5% sensitivity, 84.9% specificity) in the validation cohort. The GMSM model was significantly superior to the clinical marker carcinoembryonic antigen among samples within the validation cohort (AUC 0.92 vs 0.72) and also showed promising diagnostic accuracy for adenomas (AUC=0.84) and early-stage CRC (AUC=0.93). Conclusion Gut microbiome reprogramming in patients with CRC is associated with alterations of the serum metabolome, and GMSMs have potential applications for CRC and adenoma detection.
British Society of Gastroenterology guidelines for the management of iron deficiency anaemia in adults
Authors: Jonathon Snook, Neeraj Bhala, Ian L P Beales, David Cannings, Chris Kightley, Robert PH Logan, D Mark Pritchard, Reena Sidhu, Sue Surgenor, Wayne Thomas, Ajay M Verma, Andrew F Goddard
Journal: Gut (2021)

Iron deficiency anaemia (IDA) is a major cause of morbidity and burden of disease worldwide. It can generally be diagnosed by blood testing and remedied by iron replacement therapy (IRT) using the oral or intravenous route. The many causes of iron deficiency include poor dietary intake and malabsorption of dietary iron, as well as a number of significant gastrointestinal (GI) pathologies. Because blood is iron-rich it can result from chronic blood loss, and this is a common mechanism underlying the development of IDA-for example, as a consequence of menstrual or GI blood loss.Approximately a third of men and postmenopausal women presenting with IDA have an underlying pathological abnormality, most commonly in the GI tract. Therefore optimal management of IDA requires IRT in combination with appropriate investigation to establish the underlying cause. Unexplained IDA in all at-risk individuals is an accepted indication for fast-track secondary care referral in the UK because GI malignancies can present in this way, often in the absence of specific symptoms. Bidirectional GI endoscopy is the standard diagnostic approach to examination of the upper and lower GI tract, though radiological scanning is an alternative in some situations for assessing the large bowel. In recurrent or refractory IDA, wireless capsule endoscopy plays an important role in assessment of the small bowel.IDA may present in primary care or across a range of specialties in secondary care, and because of this and the insidious nature of the condition it has not always been optimally managed despite the considerable burden of disease- with investigation sometimes being inappropriate, incorrectly timed or incomplete, and the role of IRT for symptom relief neglected. It is therefore important that contemporary guidelines for the management of IDA are available to all clinicians. This document is a revision of previous British Society of Gastroenterology guidelines, updated in the light of subsequent evidence and developments.
Quantification of polyreactive immunoglobulin G facilitates the diagnosis of autoimmune hepatitis
Authors: Richard Taubert, Bastian Engel, Jana Diestelhorst, Katharina L. Hupa‐Breier, Patrick Behrendt, Niklas T. Baerlecken, Kurt‐Wolfram Sühs, Maciej K. Janik, Kalliopi Zachou, Marcial Sebode, Christoph Schramm, María‐Carlota Londoño, Sarah Habes, Ye H. Oo, Claudine Lalanne, Simon Pape, Maren Schubert, Michael Hust, Stefan Dübel, Mario Thevis, Danny Jonigk, Julia Beimdiek, Falk F. R. Buettner, Joost P. H. Drenth, Luigi Muratori, David H. Adams, Jessica K. Dyson, Amédée Renand, Isabel Graupera, Ansgar W. Lohse, George N. Dalekos, Piotr Milkiewicz, Martin Stangel, Benjamin Maasoumy, Torsten Witte, Heiner Wedemeyer, Michael P. Manns, Elmar Jaeckel
Journal: Hepatology (2021)

Abstract Background and Aims Detection of autoantibodies is a mainstay of diagnosing autoimmune hepatitis (AIH). However, conventional autoantibodies for the workup of AIH lack either sensitivity or specificity, leading to substantial diagnostic uncertainty. We aimed to identify more accurate serological markers of AIH with a protein macroarray. Approach and Results During the search for more‐precise autoantibodies to distinguish AIH from non‐AIH liver diseases (non‐AIH‐LD), IgG antibodies with binding capacities to many human and foreign proteins were identified with a protein macroarray and confirmed with solid‐phase ELISAs in AIH patients. Subsequently, polyreactive IgG (pIgG) was exemplarily quantified by reactivity against human huntingtin‐interacting protein 1‐related protein in bovine serum albumin blocked ELISA (HIP1R/BSA). The diagnostic fidelity of HIP1R/BSA binding pIgG to diagnose AIH was assessed in a retrospective training, a retrospective multicenter validation, and a prospective validation cohort in cryoconserved samples from 1,568 adults from 10 centers from eight countries. Reactivity against HIP1R/BSA had a 25% and 14% higher specificity to diagnose AIH than conventional antinuclear and antismooth muscle antibodies, a significantly higher sensitivity than liver kidney microsomal antibodies and antisoluble liver antigen/liver pancreas antigen, and a 12%–20% higher accuracy than conventional autoantibodies. Importantly, HIP1R/BSA reactivity was present in up to 88% of patients with seronegative AIH and in up to 71% of AIH patients with normal IgG levels. Under therapy, pIgG returns to background levels of non‐AIH‐LD. Conclusions pIgG could be used as a promising marker to improve the diagnostic workup of liver diseases with a higher specificity for AIH compared to conventional autoantibodies and a utility in autoantibody‐negative AIH. Likewise, pIgG could be a major source of assay interference in untreated AIH.
Collusion of α-Synuclein and Aβ aggravating co-morbidities in a novel prion-type mouse model
Authors: Grace M. Lloyd, Jess-Karan S. Dhillon, Kimberly-Marie M. Gorion, Cara Riffe, Susan E. Fromholt, Yuxing Xia, Benoit I. Giasson, David R. Borchelt
Journal: Molecular Neurodegeneration (2021)

Abstract Background The misfolding of host-encoded proteins into pathological prion conformations is a defining characteristic of many neurodegenerative disorders, including Alzheimer’s disease, Parkinson’s disease, and Lewy body dementia. A current area of intense study is the way in which the pathological deposition of these proteins might influence each other, as various combinations of co-pathology between prion-capable proteins are associated with exacerbation of disease. A spectrum of pathological, genetic and biochemical evidence provides credence to the notion that amyloid β (Aβ) accumulation can induce and promote α-synuclein pathology, driving neurodegeneration. Methods To assess the interplay between α-synuclein and Aβ on protein aggregation kinetics, we crossed mice expressing human α-synuclein (M20) with APPswe/PS1dE9 transgenic mice (L85) to generate M20/L85 mice. We then injected α-synuclein preformed fibrils (PFFs) unilaterally into the hippocampus of 6-month-old mice, harvesting 2 or 4 months later. Results Immunohistochemical analysis of M20/L85 mice revealed that pre-existing Aβ plaques exacerbate the spread and deposition of induced α-synuclein pathology. This process was associated with increased neuroinflammation. Unexpectedly, the injection of α-synuclein PFFs in L85 mice enhanced the deposition of Aβ; whereas the level of Aβ deposition in M20/L85 bigenic mice, injected with α-synuclein PFFs, did not differ from that of mice injected with PBS. Conclusions These studies reveal novel and unexpected interplays between α-synuclein pathology, Aβ and neuroinflammation in mice that recapitulate the pathology of Alzheimer’s disease and Lewy body dementia.
Cardiovascular Outcomes in Patients With Type 2 Diabetes and Obesity: Comparison of Gastric Bypass, Sleeve Gastrectomy, and Usual Care
Authors: Ali Aminian, Rickesha Wilson, Alexander Zajichek, Chao Tu, Kathy E. Wolski, Philip R. Schauer, Michael W. Kattan, Steven E. Nissen, Stacy A. Brethauer
Journal: Diabetes Care (2021)

OBJECTIVE To determine which one of the two most common metabolic surgical procedures is associated with greater reduction in risk of major adverse cardiovascular events (MACE) in patients with type 2 diabetes mellitus (T2DM) and obesity. RESEARCH DESIGN AND METHODS A total of 13,490 patients including 1,362 Roux-en-Y gastric bypass (RYGB), 693 sleeve gastrectomy (SG), and 11,435 matched nonsurgical patients with T2DM and obesity who received their care at the Cleveland Clinic (1998–2017) were analyzed, with follow-up through December 2018. With multivariable Cox regression analysis we estimated time to incident extended MACE, defined as first occurrence of coronary artery events, cerebrovascular events, heart failure, nephropathy, atrial fibrillation, and all-cause mortality. RESULTS The cumulative incidence of the primary end point at 5 years was 13.7% (95% CI 11.4–15.9) in the RYGB groups and 24.7% (95% CI 19.0–30.0) in the SG group, with an adjusted hazard ratio (HR) of 0.77 (95% CI 0.60–0.98, P = 0.04). Of the six individual end points, RYGB was associated with a significantly lower cumulative incidence of nephropathy at 5 years compared with SG (2.8% vs. 8.3%, respectively; HR 0.47 [95% CI 0.28–0.79], P = 0.005). Furthermore, RYGB was associated with a greater reduction in body weight, glycated hemoglobin, and use of medications to treat diabetes and cardiovascular diseases. Five years after RYGB, patients required more upper endoscopy (45.8% vs. 35.6%, P &amp;lt; 0.001) and abdominal surgical procedures (10.8% vs. 5.4%, P = 0.001) compared with SG. CONCLUSIONS In patients with obesity and T2DM, RYGB may be associated with greater weight loss, better diabetes control, and lower risk of MACE and nephropathy compared with SG.