tbuckley/cabot-search huggingface dataset:
Randomized Clinical Trial of Air Cleaners to Improve Indoor Air Quality and Chronic Obstructive Pulmonary Disease Health: Results of the CLEAN AIR Study
Authors: Nadia N. Hansel, Nirupama Putcha, Han Woo, Roger Peng, Gregory B. Diette, Ashraf Fawzy, Robert A. Wise, Karina Romero, Meghan F. Davis, Ana M. Rule, Michelle N. Eakin, Patrick N. Breysse, Meredith C. McCormack, Kirsten Koehler
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

Rationale: Indoor particulate matter is associated with worse chronic obstructive pulmonary disease (COPD) outcomes. It remains unknown whether reductions of indoor pollutants improve respiratory morbidity. Objectives: To determine whether placement of active portable high-efficiency particulate air cleaners can improve respiratory morbidity in former smokers. Methods: Eligible former smokers with moderate-to-severe COPD received active or sham portable high-efficiency particulate absolute air cleaners and were followed for 6 months in this blinded randomized controlled trial. The primary outcome was 6-month change in St. George's Respiratory Questionnaire (SGRQ). Secondary outcomes were exacerbation risk, respiratory symptoms, rescue medication use, and 6-minute-walk distance (6MWD). Intention-to-treat analysis included all subjects, and per-protocol analysis included adherent participants (greater than 80% use of air cleaner). Measurements and Main Results: A total of 116 participants were randomized, of which 84.5% completed the study. There was no statistically significant difference in total SGRQ score, but the active filter group had greater reduction in SGRQ symptom subscale (β, -7.7 [95% confidence interval (CI), -15.0 to -0.37]) and respiratory symptoms (Breathlessness, Cough, and Sputum Scale, β, -0.8 [95% CI, -1.5 to -0.1]); and lower rate of moderate exacerbations (incidence rate ratio, 0.32 [95% CI, 0.12-0.91]) and rescue medication use (incidence rate ratio, 0.54 [95% CI, 0.33-0.86]) compared with sham group (all P < 0.05). In per-protocol analysis, there was a statistically significant difference in primary outcome between the active filter versus sham group (SGRQ, β -4.76 [95% CI, -9.2 to -0.34]) and in moderate exacerbation risk, Breathlessness, Cough, and Sputum Scale, and 6MWD. Participants spending more time indoors were more likely to have treatment benefit. Conclusions: This is the first environmental intervention study conducted among former smokers with COPD showing potential health benefits of portable high-efficiency particulate absolute air cleaners, particularly among those with greater adherence and spending a greater time indoors.
Identification of a Functional <i>PDE5A</i> Variant at the Chromosome 4q27 Coronary Artery Disease Locus in an Extended Myocardial Infarction Family
Authors: Tan An Dang, Thorsten Kessler, Jana Wobst, Michael Wierer, Ingrid Braenne, Tim M. Strom, Stephanie Tennstedt, Hendrik B. Sager, Thomas Meitinger, Jeanette Erdmann, Heribert Schunkert
Journal: Circulation (2021)
GM-CSF drives myelopoiesis, recruitment and polarisation of tumour-associated macrophages in cholangiocarcinoma and systemic blockade facilitates antitumour immunity
Authors: Luis I Ruffolo, Katherine M Jackson, Peyton C Kuhlers, Benjamin S Dale, Nathania M Figueroa Guilliani, Nicholas A Ullman, Paul R Burchard, Shuyang S Qin, Peter G Juviler, Jessica Millian Keilson, Ashley B Morrison, Mary Georger, Rachel Jewell, Laura M Calvi, Timothy M Nywening, Michael R O'Dell, Aram F Hezel, Luis De Las Casas, Gregory B Lesinski, Jen Jen Yeh, Roberto Hernandez-Alejandro, Brian A Belt, David C Linehan
Journal: Gut (2021)

Objective Intrahepatic cholangiocarcinoma (iCCA) is rising in incidence, and at present, there are limited effective systemic therapies. iCCA tumours are infiltrated by stromal cells, with high prevalence of suppressive myeloid populations including tumour-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs). Here, we show that tumour-derived granulocyte–macrophage colony-stimulating factor (GM-CSF) and the host bone marrow is central for monopoiesis and potentiation of TAMs, and abrogation of this signalling axis facilitates antitumour immunity in a novel model of iCCA. Methods Blood and tumours were analysed from iCCA patients and controls. Treatment and correlative studies were performed in mice with autochthonous and established orthotopic iCCA tumours treated with anti-GM-CSF monoclonal antibody. Results Systemic elevation in circulating myeloid cells correlates with poor prognosis in patients with iCCA, and patients who undergo resection have a worse overall survival if tumours are more infiltrated with CD68 + TAMs. Mice with spontaneous iCCA demonstrate significant elevation of monocytic myeloid cells in the tumour microenvironment and immune compartments, and tumours overexpress GM-CSF. Blockade of GM-CSF with a monoclonal antibody decreased tumour growth and spread. Mice bearing orthotopic tumours treated with anti-GM-CSF demonstrate repolarisation of immunosuppressive TAMs and MDSCs, facilitating T cell response and tumour regression. GM-CSF blockade dampened inflammatory gene networks in tumours and TAMs. Human tumours with decreased GM-CSF expression exhibit improved overall survival after resection. Conclusions iCCA uses the GM-CSF-bone marrow axis to establish an immunosuppressive tumour microenvironment. Blockade of the GM-CSF axis promotes antitumour T cell immunity.
Julian André Bradley
Authors: Jim Brockbank
Journal: BMJ (2021)

Julian Andre Bradley gave so much to the local medical community, and so many of us are deeply indebted to him for the support and guidance he gave to us throughout a 40 year career as a GP and 30 years as a programme director for GP training.

Julian’s early years were spent in Blyth, Northumberland, and later in Morpeth, where he attended King Edward VI Grammar School. He completed junior hospital posts at Westminster Hospital, London, and Croydon General Hospital. He moved on to the West Middlesex Hospital, Isleworth, in 1976, where he was medical registrar.

Julian decided to be a GP and joined the Park Road Surgery, Teddington, in 1979. He …
Screening for Lung Cancer in Individuals Who Never Smoked: An International Association for the Study of Lung Cancer Early Detection and Screening Committee Report
Authors: Anna Kerpel-Fronius, Martin Tammemägi, Milena Cavic, Claudia Henschke, Long Jiang, Ella Kazerooni, Choon-Taek Lee, Luigi Ventura, Dawei Yang, Stephen Lam, Rudolf M. Huber, Dawei Yang, Javier Zulueta, Lucia Viola, Anant Mohan, Choon-Taek Lee, Milena Cavic, Heidi Schmidt, Ella Kazerooni, Ricardo Sales dos Santos, Anna Kerpel-Fronius, Claudia Henschke, Luigi Ventura, Long Jiang, Gabriella Sozzi, Martin Tammemägi, Stephen Lam, Rudolf Huber
Journal: Journal of Thoracic Oncology (2021)
MultiK: an automated tool to determine optimal cluster numbers in single-cell RNA sequencing data
Authors: Siyao Liu, Aatish Thennavan, Joseph P. Garay, J. S. Marron, Charles M. Perou
Journal: Genome biology (2021)

Abstract Single-cell RNA sequencing (scRNA-seq) provides new opportunities to characterize cell populations, typically accomplished through some type of clustering analysis. Estimation of the optimal cluster number ( K ) is a crucial step but often ignored. Our approach improves most current scRNA-seq cluster methods by providing an objective estimation of the number of groups using a multi-resolution perspective. MultiK is a tool for objective selection of insightful Ks and achieves high robustness through a consensus clustering approach. We demonstrate that MultiK identifies reproducible groups in scRNA-seq data, thus providing an objective means to estimating the number of possible groups or cell-type populations present.
27518 Retrospective analysis of 578 inpatient dermatology consultations in hematology and bone marrow transplant patients: A 5-year study
Authors: Alexander S. Hines, Antonious Hazim, David A. Wetter, Alina G. Bridges, Michael J. Camilleri, Marian T. McEvoy, Rokea A. el-Azhary, Mark D.P. Davis, Julio C. Sartori-Valinotti
Journal: Journal of the American Academy of Dermatology (2021)
Abstract 15179: Ablation of AT2 Receptor Prevents eNOS Uncoupling in Ischemic Abductor Muscle of Diabetic Mice
Authors: Clément Mercier, Stéphanie Robillard, Valérie Breton, Pedro M Geraldes, Farah Lizotte
Journal: Circulation (2019)

Introduction: Peripheral artery disease is a severe complication of diabetes. We have reported that the deletion of angiotensin type 2 receptor (AT2R) in diabetic mice promoted vascular angiogenesi...
Bleeding avoidance strategies in percutaneous coronary intervention
Authors: Davide Capodanno, Deepak L. Bhatt, C. Michael Gibson, Stefan James, Takeshi Kimura, Roxana Mehran, Sunil V. Rao, Philippe Gabriel Steg, Philip Urban, Marco Valgimigli, Stephan Windecker, Dominick J. Angiolillo
Journal: Nature Reviews Cardiology (2021)
27596 Improvement in absolute psoriasis area and severity index through 5 years of continuous treatment with guselkumab in the VOYAGE 1 trial
Authors: Luis Puig, Bruce Strober, Tsen-Fang Tsai, Diamant Thaçi, Melinda Gooderham, Megan Miller, Ya-Wen Yang, Yin You, Yaung-Kaung Shen, Andrew Blauvelt
Journal: Journal of the American Academy of Dermatology (2021)
Capabilities of Imaging Methods in Preoperative Planning for the Elimination of Acquired Maxillofacial Defects
Authors: A. A. Trefilov, E. V. Kryukov, V. N. Troyan, S. V. Tereshhuk, V. A. Suharev, I. A. Aseeva, E. V. Gaydukova
Journal: Radiology - Practice (2021)

In this work a comparative analysis of the possibilities and efficiency of lower extremities perforator vessels visualization using the methods of Doppler ultrasound (DUS) and computed tomographic angiography (CTA) is carried out. As a result, it is shown that DUS has a number of advantages over CTA, allowing to obtain a clearer image of perforator vessels, to determine the exact location of their anatomical localization.
Functional genomics atlas of synovial fibroblasts defining rheumatoid arthritis heritability
Authors: Xiangyu Ge, Mojca Frank-Bertoncelj, Kerstin Klein, Amanda McGovern, Tadeja Kuret, Miranda Houtman, Blaž Burja, Raphael Micheroli, Chenfu Shi, Miriam Marks, Andrew Filer, Christopher D. Buckley, Gisela Orozco, Oliver Distler, Andrew P. Morris, Paul Martin, Stephen Eyre, Caroline Ospelt
Journal: Genome biology (2021)

Abstract Background Genome-wide association studies have reported more than 100 risk loci for rheumatoid arthritis (RA). These loci are shown to be enriched in immune cell-specific enhancers, but the analysis so far has excluded stromal cells, such as synovial fibroblasts (FLS), despite their crucial involvement in the pathogenesis of RA. Here we integrate DNA architecture, 3D chromatin interactions, DNA accessibility, and gene expression in FLS, B cells, and T cells with genetic fine mapping of RA loci. Results We identify putative causal variants, enhancers, genes, and cell types for 30–60% of RA loci and demonstrate that FLS account for up to 24% of RA heritability. TNF stimulation of FLS alters the organization of topologically associating domains, chromatin state, and the expression of putative causal genes such as TNFAIP3 and IFNAR1. Several putative causal genes constitute RA-relevant functional networks in FLS with roles in cellular proliferation and activation. Finally, we demonstrate that risk variants can have joint-specific effects on target gene expression in RA FLS, which may contribute to the development of the characteristic pattern of joint involvement in RA. Conclusion Overall, our research provides the first direct evidence for a causal role of FLS in the genetic susceptibility for RA accounting for up to a quarter of RA heritability.
BI07: The effect of the COVID‐19 pandemic on immunosuppressed patients undergoing skin surveillance
Journal: British Journal of Dermatology (2021)

Sj€ ogren syndrome (OR 0Á39, 95% CI 0Á22-0Á71) and AIDS was associated with lower odds of mixed connective tissue disorder (OR 0Á12, 95% CI 0Á05-0Á28).While the association between other systemic diseases and HIV/AIDS is well established, there is a lack of large studies investigating RSSs in HIV/AIDS.Our study provides data regarding the prevalence of RSSs in HIV/AIDS and identifies lower odds for multiple RSSs in PLWHA.Future studies are needed to investigate the mechanisms underlying these findings, as well as to establish the role of factors such as CD4 count and HAART in favouring or preventing the development of RSS in HIV/AIDS.
Validation of Pre-Transplant Biomarker Measurement and Risk Score for Non-Relapse Mortality after Allogeneic Hematopoietic Cell Transplant (HCT)
Authors: Michael J. Leukam, Lucy Godley, Justin Kline, Richard A. Larson, Hongtao Liu, Olatoyosi Odenike, Wendy Stock, Michael R. Bishop, Andrew Artz
Journal: Blood (2017)
Effectiveness of Adding Everolimus to the First-line Treatment of Advanced Breast Cancer in Premenopausal Women Who Experienced Disease Progression While Receiving Selective Estrogen Receptor Modulators
Authors: Ying Fan, Tao Sun, Zhimin Shao, Qingyuan Zhang, Quchang Ouyang, Zhongsheng Tong, Shusen Wang, Yang Luo, Yuee Teng, Xiaojia Wang, Shu Wang, Qiang Liu, Jifeng Feng, Kunwei Shen, Yanqiu Song, Jiayu Wang, Fei Ma, Qing Li, Pin Zhang, Binghe Xu
Journal: JAMA Oncology (2021)

The effectiveness of the mammalian target of rapamycin (mTOR) inhibitor everolimus in premenopausal women with hormone receptor (HR)-positive/ERBB2-negative advanced breast cancer who experienced disease progression while receiving selective estrogen receptor modulators (SERMs) is unknown.To compare the effectiveness of everolimus plus letrozole vs letrozole alone in premenopausal women with HR-positive/ERBB2-negative advanced breast cancer who experienced disease progression while receiving SERMs.The Everolimus Trial for Advanced Premenopausal Breast Cancer (MIRACLE) was a multicenter, open-label phase 2 randomized clinical trial of everolimus plus letrozole vs letrozole alone as first-line treatment conducted from December 8, 2014, to September 26, 2018. Participants included premenopausal women with HR-positive, ERBB2-negative advanced breast cancer who experienced disease progression while receiving SERMs. Analysis was performed on an intent-to-treat basis from January 5, 2015, to December 30, 2019.Patients were randomly assigned in a 1:1 ratio to receive everolimus (10 mg orally once daily) plus letrozole (2.5 mg orally once daily) (n = 101) or letrozole alone (2.5 mg orally once daily) (n = 98). Both groups received goserelin, 3.6 mg, subcutaneously on day 1 of each 28-day cycle. Patients in the letrozole group were permitted to cross over to receive everolimus with letrozole if disease progression occurred.The primary end point was progression-free survival (PFS), defined as the time from randomization to confirmed disease progression or death due to any cause.A total of 199 women (mean [SD] age, 44.3 [6.3] years) were randomized. Patients receiving everolimus plus letrozole achieved a significantly longer median PFS compared with those receiving letrozole alone (19.4 months [95% CI, 16.3-22.0 months] vs 12.9 months [95% CI, 7.6-15.7 months]; hazard ratio, 0.64 [95% CI, 0.46-0.89]; P = .008). A total of 56 of the 98 patients in the letrozole group (57.1%) were crossed over to also receive everolimus. The median PFS after crossover was 5.5 months (95% CI, 3.8-8.2 months).In this randomized clinical trial, PFS was significantly longer among premenopausal patients with HR-positive/ERBB2-negative advanced breast cancer who received everolimus plus letrozole than among those who received letrozole alone. The results revealed that everolimus was effective even among patients receiving treatment with the same endocrine agent after disease progression.ClinicalTrials.gov Identifier: NCT02313051.
Author Correction: Community-wide hackathons to identify central themes in single-cell multi-omics
Authors: Kim-Anh Lê Cao, Al J. Abadi, Emily F. Davis-Marcisak, Lauren Hsu, Arshi Arora, Alexis Coullomb, Atul Deshpande, Yuzhou Feng, Pratheepa Jeganathan, Melanie Loth, Chen Meng, Wancen Mu, Vera Pancaldi, Kris Sankaran, Dario Righelli, Amrit Singh, Joshua S. Sodicoff, Genevieve L. Stein-O’Brien, Ayshwarya Subramanian, Joshua D. Welch, Yue You, Ricard Argelaguet, Vincent J. Carey, Ruben Dries, Casey S. Greene, Susan Holmes, Michael I. Love, Matthew E. Ritchie, Guo-Cheng Yuan, Aedin C. Culhane, Elana Fertig
Journal: Genome biology (2021)
Real-world effectiveness of eribulin in heavily pretreated patients with metastatic breast cancer in China: A multicenter retrospective study.
Authors: Yannan Zhao, Ning Xie, Wei Li, Wenyan Chen, Zheng Lv, Yabing Zheng, Tao Sun, Jieqiong Liu, Jian Zhang, Shihui Hu, Yajun Wang, Cc Gong, Yi Li, Yizhao Xie, Rui Ge, Fei Xu, Biyun Wang
Journal: Journal of Clinical Oncology (2021)

e13057 Background: Eribulin is a nontaxane microtubule inhibitor approved in China for patients with locally advanced or metastatic breast cancer previously treated with anthracyclines and taxane. The aim of this study was to evaluate the efficacy and safety profile of eribulin and explore potential predictive factors for the efficacy of eribulin among Chinese women with metastatic breast cancer (MBC) in real-world practice. Methods: A total of 272 consecutive MBC patients who were treated with eribulin from November 2019 to October 2020 in 9 institutions nationwide were included in this study. Eribulin was administered intravenously at a dose of 1.4 mg/m2 on days 1 and 8 of a 21-day cycle. Efficacy outcomes included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and clinical benefit rate (CBR). Adverse events (AEs) were graded according to The National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 5.0. Results: Eribulin showed a median PFS of 3.9 months (95% confidence interval [CI] 3.3–4.3); however, the OS data were immature. The ORR was 16.2%, and the CBR was 21.7%. A total of 51.8% of patients received eribulin monotherapy, and 48.2% of patients were treated with eribulin combine with targeted therapy or other chemotherapy. The number of metastatic sites, duration of previous taxane treatment for MBC, and combination regimen with bevacizumab were significant in Cox multivariate analysis (p=0.048, p=0.039, and p=0.045, respectively) and were significantly associated with PFS of eribulin. The most common AEs with eribulin treatment were hematological toxicities, including neutropenia, leukopenia, and anemia. Conclusions: This is the first cohort of eribulin real-world data base on retrieval currently after eribulin launched in China. Eribulin was effective with a manageable toxicity profile in clinical practice. Furthermore, when prescribed in combination with other agents, eribulin did not increase the toxic effects of each agents. Eribulin monotherapy or combine with other agents is alternative for the heavily pretreated patients with MBC. [Table: see text]
Fate mapping of single NK cells identifies a type 1 innate lymphoid-like lineage that bridges innate and adaptive recognition of viral infection
Authors: Sophie Flommersfeld, Jan P. Böttcher, Jonatan Ersching, Michael Flossdorf, Philippa Meiser, Ludwig O. Pachmayr, Justin Leube, Inge Hensel, Sebastian Jarosch, Qin Zhang, M. Zeeshan Chaudhry, Immanuel Andrae, Matthias Schiemann, Dirk.H. Busch, Luka Cicin-Sain, Joseph C. Sun, Georg Gasteiger, Gabriel D. Victora, Thomas Höfer, Veit R. Buchholz, Simon Grassmann
Journal: Immunity (2021)

Upon viral infection, natural killer (NK) cells expressing certain germline-encoded receptors are selected, expanded, and maintained in an adaptive-like manner. Currently, these are thought to differentiate along a common pathway. However, by fate mapping of single NK cells upon murine cytomegalovirus (MCMV) infection, we identified two distinct NK cell lineages that contributed to adaptive-like responses. One was equivalent to conventional NK (cNK) cells while the other was transcriptionally similar to type 1 innate lymphoid cells (ILC1s). ILC1-like NK cells showed splenic residency and strong cytokine production but also recognized and killed MCMV-infected cells, guided by activating receptor Ly49H. Moreover, they induced clustering of conventional type 1 dendritic cells and facilitated antigen-specific T cell priming early during MCMV infection, which depended on Ly49H and the NK cell-intrinsic expression of transcription factor Batf3. Thereby, ILC1-like NK cells bridge innate and adaptive viral recognition and unite critical features of cNK cells and ILC1s.
Scotland is (over)ripe for corporate takeover of general practice
Authors: Andrew J Ashworth
Journal: BMJ (2021)

London’s doctors may fear privatisation by large corporations but in Scotland it could be happening already.1

In England, partners join together as a firm. In Scotland, however, they create a legal person distinct from the partners who comprise the firm.2 Health boards contract with partnerships which must include a GP but may be made up of other members (who may be limited companies with separate legal identities), so they don’t …
Oral Anticoagulants for Nonvalvular Atrial Fibrillation in Patients With High Risk of Gastrointestinal Bleeding
Authors: Gregory Y. H. Lip, Allison V. Keshishian, Yan Zhang, Amiee Kang, Amol D. Dhamane, Xuemei Luo, Christian Klem, Mauricio Ferri, Jenny Jiang, Huseyin Yuce, Steven Deitelzweig
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Many patients with nonvalvular atrial fibrillation (NVAF) are at a high risk of gastrointestinal (GI) bleeding due to conditions including older age; stage III to V chronic kidney disease (CKD); HAS-BLED (hypertension, kidney or liver disease, stroke history, prior bleeding, unstable international normalized ratio, age &gt;65, drug or alcohol use) score of 3 or greater; corticosteroid, antiplatelet or nonsteroidal anti-inflammatory drug (NSAID) use; or GI conditions. <h3>Objective</h3> To compare the risk of stroke and/or systemic embolism (SE) and major bleeding (MB) among patients with NVAF and high risk of GI bleeding who received non–vitamin K antagonist oral anticoagulants (NOACs) vs those who received warfarin. <h3>Design, Setting, and Participants</h3> This retrospective cohort study included patients with NVAF who were 75 years and older; had stage III to V CKD; had an HAS-BLED score of 3 or greater; used corticosteroids, antiplatelets, or NSAIDs; or had GI conditions. Data were collected from the Centers for Medicare &amp; Medicaid Services and 4 commercial insurance databases between January 1, 2012, and September 30, 2015. Data analysis was conducted from April to August 2020. <h3>Exposures</h3> New prescription for apixaban, dabigatran, rivaroxaban, or warfarin between January 1, 2013, and September 30, 2015 (identification period). <h3>Main Outcomes and Measures</h3> Six propensity score–matched cohorts were created to compare between study drugs. For the primary objective, Cox models were used to estimate stroke and/or SE and MB hazard ratios (HRs). <h3>Results</h3> A total of 381 054 patients (187 489 [49.2%] women) with NVAF and at least 1 high-risk GI bleeding factor were identified (HAS-BLED score ≥3: 284 527 [74.7%]; aged ≥75 years: 252 835 [66.4%]; corticosteroid, antiplatelet, or NSAID therapy: 107 675 [28.3%]; prior GI bleeding conditions: 74 818 [19.6%]; and stage III-V CKD: 56 892 [14.9%]). All NOACs were associated with a lower risk of stroke and/or SEvswarfarin (apixaban: HR, 0.60; 95% CI, 0.52-0.68; dabigatran: HR, 0.75; 95% CI, 0.64-0.88; rivaroxaban: HR, 0.79; 95% CI, 0.73-0.86). Compared with warfarin, apixaban and dabigatran were associated with a lower risk of MB (apixaban: HR, 0.59; 95% CI, 0.56-0.63; dabigatran: HR, 0.78; 95% CI, 0.70-0.86), while rivaroxaban was associated with a higher risk (HR, 1.11; 95% CI, 1.05-1.16). <h3>Conclusions and Relevance</h3> In this study of patients with NVAF and high risk of GI bleed, NOACs were associated with lower rates of stroke and/or SE, but NOACs had varying risks of MB compared with warfarin. These results may help inform treatment options in this patient population.