tbuckley/cabot-search huggingface dataset:
The mononuclear phagocyte system contributes to fibrosis in post-transplant obliterans bronchiolitis
Authors: Maria-Pia Di Campli, Abdulkader Azouz, Assiya Assabban, Jessika Scaillet, Marion Splittgerber, Alexandra Van Keymeulen, Frederick Libert, Myriam Remmelink, Alain Le Moine, Philippe Lemaitre, Stanislas Goriely
Journal: European Respiratory Journal (2020)

Bronchiolitis obliterans syndrome (BOS) is a fibrotic disease that is heavily responsible for the high mortality rates after lung transplantation. Myofibroblasts are primary effectors of this fibrotic process, but their origin is still debated. The purpose of this work was to identify the precursors of mesenchymal cells responsible for post-transplant airway fibro-obliteration. Lineage-tracing tools were used to track or deplete potential sources of myofibroblasts in the heterotopic tracheal transplantation model. Allografts were analysed by histology, confocal microscopy, flow cytometry or single-cell transcriptomic analysis. BOS explants were evaluated by histology and confocal microscopy. Myofibroblasts in the allografts were recipient-derived. When recipient mice were treated with tacrolimus, we observed rare epithelial-to-mesenchymal transition phenomena and an overall increase in donor-derived myofibroblasts (p=0.0467), but the proportion of these cells remained low (7%). Haematopoietic cells, and specifically the mononuclear phagocyte system, gave rise to the majority of myofibroblasts found in occluded airways. Ablation of Cx3cR1 + cells decreased fibro-obliteration (p=0.0151) and myofibroblast accumulation (p=0.0020). Single-cell RNA sequencing revealed similarities between myeloid-derived cells from allografts and both murine and human samples of lung fibrosis. Finally, myofibroblasts expressing the macrophage marker CD68 were increased in BOS explants when compared to controls (14.4% versus 8.5%, p=0.0249). Recipient-derived myeloid progenitors represent a clinically relevant source of mesenchymal cells infiltrating the airways after allogeneic transplantation. Therapies targeting the mononuclear phagocyte system could improve long-term outcomes after lung transplantation.
Urine Titin N-Fragment as a Biomarker of Muscle Injury for Critical Illness Myopathy
Authors: Hidehiko Nakano, Hideki Hashimoto, Masaki Mochizuki, Hiromu Naraba, Yuji Takahashi, Tomohiro Sonoo, Tsunehiro Matsubara, Kazuma Yamakawa, Kensuke Nakamura
Journal: American Journal of Respiratory and Critical Care Medicine (2020)
KCa channel activation normalizes endothelial function in Type 2 Diabetic resistance arteries by improving intracellular Ca2+ mobilization
Authors: Ramesh C. Mishra, Barry D. Kyle, Dylan J. Kendrick, Daniyil Svystonyuk, Teresa M. Kieser, Paul W.M. Fedak, Heike Wulff, Andrew P. Braun
Journal: Metabolism (2020)
Update οn the diagnosis and management of systemic lupus erythematosus
Authors: Antonis Fanouriakis, Nikolaos Tziolos, George Bertsias, Dimitrios T Boumpas
Journal: Annals of the Rheumatic Diseases (2020)

Clinical heterogeneity, unpredictable course and flares are characteristics of systemic lupus erythematosus (SLE). Although SLE is—by and large—a systemic disease, occasionally it can be organ-dominant, posing diagnostic challenges. To date, diagnosis of SLE remains clinical with a few cases being negative for serologic tests. Diagnostic criteria are not available and classification criteria are often used for diagnosis, yet with significant caveats. Newer sets of criteria (European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) 2019) enable earlier and more accurate classification of SLE. Several disease endotypes have been recognised over the years. There is increased recognition of milder cases at presentation, but almost half of them progress overtime to more severe disease. Approximately 70% of patients follow a relapsing-remitting course, the remaining divided equally between a prolonged remission and a persistently active disease. Treatment goals include long-term patient survival, prevention of flares and organ damage, and optimisation of health-related quality of life. For organ-threatening or life-threatening SLE, treatment usually includes an initial period of high-intensity immunosuppressive therapy to control disease activity, followed by a longer period of less intensive therapy to consolidate response and prevent relapses. Management of disease-related and treatment-related comorbidities, especially infections and atherosclerosis, is of paramount importance. New disease-modifying conventional and biologic agents—used alone, in combination or sequentially—have improved rates of achieving both short-term and long-term treatment goals, including minimisation of glucocorticoid use.
Evaluation of Work Satisfaction, Stress, and Burnout Among US Internal Medicine Physicians and Trainees
Authors: Mark Linzer, Cynthia D. Smith, Susan Hingle, Sara Poplau, Richard Miranda, Rebecca Freese, Kerri Palamara
Journal: JAMA Network Open (2020)

This study uses the Mini Z 2.0 survey to assess burnout among male and female members of the American College of Physicians who are internists and internal medicine trainees.
European Respiratory Society statement on thoracic ultrasound
Authors: Christian B. Laursen, Amelia Clive, Rob Hallifax, Pia Iben Pietersen, Rachelle Asciak, Jesper Rømhild Davidsen, Rahul Bhatnagar, Eihab O. Bedawi, Niels Jacobsen, Courtney Coleman, Anthony Edey, Gabriele Via, Giovanni Volpicelli, Gilbert Massard, Francesco Raimondi, Matthew Evison, Lars Konge, Jouke Annema, Najib M. Rahman, Nick Maskell
Journal: European Respiratory Journal (2020)

Thoracic ultrasound is increasingly considered to be an essential tool for the pulmonologist. It is used in diverse clinical scenarios, including as an adjunct to clinical decision making for diagnosis, a real-time guide to procedures and a predictor or measurement of treatment response. The aim of this European Respiratory Society task force was to produce a statement on thoracic ultrasound for pulmonologists using thoracic ultrasound within the field of respiratory medicine. The multidisciplinary panel performed a review of the literature, addressing major areas of thoracic ultrasound practice and application. The selected major areas include equipment and technique, assessment of the chest wall, parietal pleura, pleural effusion, pneumothorax, interstitial syndrome, lung consolidation, diaphragm assessment, intervention guidance, training and the patient perspective. Despite the growing evidence supporting the use of thoracic ultrasound, the published literature still contains a paucity of data in some important fields. Key research questions for each of the major areas were identified, which serve to facilitate future multicentre collaborations and research to further consolidate an evidence-based use of thoracic ultrasound, for the benefit of the many patients being exposed to clinicians using thoracic ultrasound.
Role of myeloid-derived suppressor cells in the promotion and immunotherapy of colitis-associated cancer
Authors: Yungang Wang, Yanxia Ding, Yijun Deng, Yu Zheng, Shengjun Wang
Journal: Journal for ImmunoTherapy of Cancer (2020)

Colitis-associated cancer (CAC) is a specific type of colorectal cancer that develops from inflammatory bowel disease (IBD). Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells that are essential for the pathological processes of inflammation and cancer. Accumulating evidence indicates that MDSCs play different but vital roles during IBD and CAC development and impede CAC immunotherapy. New insights into the regulatory network of MDSCs in the CAC pathogenesis are opening new avenues for developing strategies to enhance the effectiveness of CAC treatment. In this review, we explore the role of MDSCs in chronic inflammation, dysplasia and CAC and summarize the potential CAC therapeutic strategies based on MDSC blockade.
<i>ZNF582</i> hypermethylation promotes metastasis of nasopharyngeal carcinoma by regulating the transcription of adhesion molecules <i>Nectin‐3</i> and <i>NRXN3</i>
Authors: Yin Zhao, Xiao‐Hong Hong, Kang Li, Ying‐Qing Li, Ying‐Qin Li, Shi‐Wei He, Pan‐Pan Zhang, Jun‐Yan Li, Qian Li, Ye‐Lin Liang, Yang Chen, Jun Ma, Na Liu, Yu‐Pei Chen
Journal: Cancer Communications (2020)

Abstract Background Epigenetic regulation plays an important role in the development and progression of nasopharyngeal carcinoma (NPC). However, the epigenetic mechanisms underlying NPC metastasis remains poorly understood. We aimed to find functional genes which regulate the metastasis of NPC and identify therapeutic targets for NPC treatment. Methods Bisulfite pyrosequencing was used to analyze zinc finger protein 582 ( ZNF582 ) methylation in NPC tissues and cell lines. Quantitative reverse transcription‐polymerase chain reaction (qRT‐PCR) and Western blotting were used to determine the expression of ZNF582. In vitro and in vivo experiments were performed to evaluate the biological function of ZNF582 in NPC. ZNF582‐targeting genes were identified by chromatin immunoprecipitation sequencing (ChIP‐seq) and were confirmed by ChIP‐qPCR and luciferase assay. Results ZNF582 promoter was hypermethylated in NPC, and both the mRNA and protein levels of ZNF582 were down‐regulated in NPC tissues and cell lines. The restoration of ZNF582 inhibited NPC migration, invasion, and metastasis, while the knockdown of ZNF582 promoted NPC migration, invasion, and metastasis in vitro and in vivo . ZNF582 directly regulated the transcription and expression of adhesion molecules Nectin‐3 and NRXN3 . Both Nectin‐3 and NRXN3 were identified as functional targets of ZNF582, and the restoration or abrogation of these genes reversed the tumor suppressor effect of ZNF582 in NPC metastasis. Conclusions ZNF582 acts as a tumor suppressor gene in NPC by regulating the transcription and expression of adhesion molecules Nectin‐3 and NRXN3 , which may provide novel therapeutic targets for NPC treatment.
The mortality of lung cancer attributable to smoking among adults in China and the United States during 1990–2017
Authors: Xiaoxue Liu, Yong Yu, Minsheng Wang, Sumaira Mubarik, Fang Wang, Yafeng Wang, Runtang Meng, Chuanhua Yu
Journal: Cancer Communications (2020)

Abstract Background Statistical data on the burden and relevant risk factors of lung cancer are valuable for policy‐making. This study aimed to compare the mortality of lung cancer attributable to smoking stratified by sex and age among adults in China and the United States (US). Methods We extracted age‐standardized mortality rates of lung cancer during 1990‐2017 using the comparative risk assessment framework of the 2017 Global Burden of Disease study. We performed an age‐period‐cohort analysis to estimate time trend of lung cancer mortality attributable to smoking. Results During 1990‐2017, the age‐standardized mortality rate of lung cancer was increasing in China but decreasing in the US for both sexes. The mortality attributable to smoking in China showed a generally increasing trend, while a continuous decrease was observed in the US. The age‐period‐cohort analysis showed a similar trend of age effect among adults between China and the US: the mortality substantially increased from the 30‐34 to 80‐84 age group and subsequently decreased in the 90‐94 age group. However, the period effect rapidly increased in Chinese adults during 1990‐2017, while it tended to be stable in the US although it was still slightly increasing in women. The cohort effect generally peaked in the earlier cohort born in 1902‐1906 in the two countries. Conclusions During 1990‐2017, the lung cancer mortality attributable to smoking and the period effect are generally increasing in Chinese adults; the mortality attributable to smoking is decreasing in the US adults, but the period effect tends to be stable. The rapid aging and prevalence of smoking may intensify the increasing mortality of lung cancer in China.
Incidence, Characteristics, Predictors, and Outcomes of Surgical Explantation After Transcatheter Aortic Valve Replacement
Authors: Sameer A. Hirji, Edward D. Percy, Siobhan McGurk, Alexandra Malarczyk, Morgan T. Harloff, Farhang Yazdchi, Ashraf A. Sabe, Vinayak N. Bapat, Gilbert H.L. Tang, Deepak L. Bhatt, Vinod H. Thourani, Martin B. Leon, Patrick O’Gara, Pinak B. Shah, Tsuyoshi Kaneko
Journal: Journal of the American College of Cardiology (2020)
A hopefulness survey of SWOG members: Relationships among hope, job stress, and burnout.
Authors: David B. Feldman, Mark Allen O'Rourke, Robert S. Krouse, Marie Bakitas, Heidi Deininger, Matthew F. Hudson, Benjamin W. Corn
Journal: Journal of Clinical Oncology (2020)

185 Background: Hope is a cognitive, goal-directed phenomenon that is measurable. It is “a cognitive set that is based on a reciprocally-derived sense of successful agency (goal-directed determination) and pathways (planning to meet goals).” Although hope has been explored in patients, few studies have investigated hope in physicians and other healthcare providers. Low hope has been shown to predict work burnout in other professions. This survey in the SWOG Cancer Research Network tests the relationships among hope, work stress, burnout, and general satisfaction with life. Methods: SWOG members randomly selected and invited to participate by email linked to a 10-minute online survey consisting of the following: The Adult Hope Scale, Satisfaction with Life Scale, demographic questionnaire, and items assessing burnout, work stress, and general social support. Of 1000 invitees, 226 responded to the survey, including physicians ( n = 77) and RNs ( n = 46). Results: On average, respondents reported relatively high work stress ( M = 3.59 out of 5). Levels of work stress were positively associated with burnout ( r = .58, p &lt; .001), but not with general satisfaction with life ( r = .11, p = .08). Hope levels were negatively associated with burnout ( r = -.21, p = .003) and positively associated with satisfaction with life ( r = .58, p &lt; .001). Consistent with past research showing that people with greater availability of general social support suffer from lower rates of burnout and experience higher levels of psychological well-being, we found that social support was negatively associated with burnout ( r = -.18, p = .007) and positively associated with life satisfaction ( r = .38, p &lt; .001). In addition, we tested a meditational model using Hayes’ bootstrapping approach via the PROCESS macro in SPSS. In this model, hope partially mediated the relationships between social support and both burnout and life satisfaction. In the model, job stress also predicted burnout, but, as in the previous correlational analysis, had no relationship with general life satisfaction. Conclusions: Our cross-sectional results suggest that hope may mitigate the effects of burnout. Our data indicate that the particular combination of social support and hope may prove helpful for reducing job burnout and increasing general satisfaction with life. Single-session hope-enhancement workshops that incorporate both of these elements have been shown to increase hope and psychological well-being in non-medical populations. Such interventions for healthcare professionals warrant further study.
Association of Past <i>Chlamydia trachomatis</i> Infection With Miscarriage
Authors: Andrew W. Horne, Nick Wheelhouse, Patrick J. Horner, W. Colin Duncan
Journal: JAMA Network Open (2020)

This case-control study assesses the association between past Chlamydia trachomatis infection with first-trimester miscarriage by using an enzyme-linked immunosorbent assay to detect antibodies to the protein Pgp3.
Outcomes from a multidisciplinary thoracic oncology conference (MTOC) versus serial care (SC) in a community healthcare system.
Authors: Matthew Smeltzer, Meredith Ray, Nicholas Faris, Meghan Meadows, Carrie Fehnel, Olawale Akinbobola, Bianca M Jackson, Courtney Foust, Laura McHugh, Raymond S. Signore, Edward T. Robbins, Raymond U. Osarogiagbon
Journal: Journal of Clinical Oncology (2020)

55 Background: Lung cancer care delivery is complex, with disparate quality and outcomes. Prospective multidisciplinary case planning is a recommended but poorly validated solution. We conducted a prospective comparative effectiveness trial to evaluate the impact of multidisciplinary care on care processes and long-term survival in a large community-based healthcare system. Methods: We previously reported primary objective results comparing patients in the multidisciplinary clinic (MDC) with those not cared for in the MDC i.e. usual, SC. However, a subset of the SC subjects (and all MDC subjects) were discussed at a weekly MTOC. In this secondary analysis, we compare all subjects who were prospectively discussed at MTOC (with or without MDC) with ‘true’ SC (TSC). Subjects were frequency matched by age range, race, insurance, performance status, and initial clinical stage. We compared the thoroughness of staging, use of guideline-concordant treatment, and survival. Models were stratified by frequency matched variables and adjusted for age, sex, and histology as covariates. Statistical methods included chi-square, logistic regression with adjusted Odds Ratios (aOR), and Proportional Hazards models with adjusted Hazard Ratios (aHR); both with 95% confidence intervals. Results: Of 526 subjects enrolled, 246 (47%) were discussed at MTOC. MTOC patients were older (median age 68 v 66, p = 0.03), less intense smokers (p = 0.03), and more commercially insured (p = 0.02). Fewer MTOC subjects were clinical stage IV (33% v 45%, p = 0.01). The MTOC patients had significantly greater odds of bimodal staging (aOR: 2.2 [1.3, 3.8]), trimodal staging (2.6 [1.8, 3.8]), invasive stage confirmation (2.6 [1.7, 3.9]), and mediastinal stage confirmation (2.4 [1.6, 3.6]; all p &lt; 0.01). The additional stage confirmation resulted in more patients who were up- or down-staged in MTOC (44% v 33%, p = 0.03). MTOC patients were twice as likely to receive National Comprehensive Cancer Network guideline-concordant treatment (aOR: 2.0 [1.3, 3.2]). Despite more thorough care, time from initial lesion detection to treatment was similar (mean: 2.86 vs. 2.83 months, p = 0.71). Health-related quality of life measures did not differ between the two arms (P = 0.07 to 0.99). We found no difference in overall (aHR: 1.1 [0.9, 1.4]) or disease free survival (aHR: 1.1 [0.9, 1.3]) between MTOC and TSC. Conclusions: MTOC improved the thoroughness of care and delivery of appropriate treatment, without delays in treatment initiation or survival improvement.
Fine Particulate Matter Exposure and Cancer Incidence: Analysis of SEER Cancer Registry Data from 1992–2016
Authors: Nathan C. Coleman, Richard T. Burnett, Majid Ezzati, Julian D. Marshall, Allen L. Robinson, C. Arden Pope
Journal: Environmental Health Perspectives (2020)

Previous research has identified an association between fine particulate matter (PM2.5) air pollution and lung cancer. Most of the evidence for this association, however, is based on research using lung cancer mortality, not incidence. Research that examines potential associations between PM2.5 and incidence of non-lung cancers is limited.The primary purpose of this study was to evaluate the association between the incidence of cancer and exposure to PM2.5 using >8.5 million cases of cancer incidences from U.S. registries. Secondary objectives include evaluating the sensitivity of the associations to model selection, spatial control, and latency period as well as estimating the exposure-response relationship for several cancer types.Surveillance, Epidemiology, and End Results (SEER) program data were used to calculate incidence rates for various cancer types in 607 U.S. counties. County-level PM2.5 concentrations were estimated using integrated empirical geographic regression models. Flexible semi-nonparametric regression models were used to estimate associations between PM2.5 and cancer incidence for selected cancers while controlling for important county-level covariates. Primary time-independent models using average incidence rates from 1992-2016 and average PM2.5 from 1988-2015 were estimated. In addition, time-varying models using annual incidence rates from 2002-2011 and lagged moving averages of annual estimates for PM2.5 were also estimated.The incidences of all cancer and lung cancer were consistently associated with PM2.5. The incident rate ratios (IRRs), per 10-μg/m3 increase in PM2.5, for all and lung cancer were 1.09 (95% CI: 1.03, 1.14) and 1.19 (95% CI: 1.09, 1.30), respectively. Less robust associations were observed with oral, rectal, liver, skin, breast, and kidney cancers.Exposure to PM2.5 air pollution contributes to lung cancer incidence and is potentially associated with non-lung cancer incidence. https://doi.org/10.1289/EHP7246.
Differences in Postmating Transcriptional Responses between Conspecific and Heterospecific Matings in<i>Drosophila</i>
Authors: Yasir H Ahmed-Braimah, Mariana F Wolfner, Andrew G Clark
Journal: Molecular Biology and Evolution (2020)

Abstract In many animal species, females undergo physiological and behavioral changes after mating. Some of these changes are driven by male-derived seminal fluid proteins and are critical for fertilization success. Unfortunately, our understanding of the molecular interplay between female and male reproductive proteins remains inadequate. Here, we analyze the postmating response in a Drosophila species that has evolved strong gametic incompatibility with its sister species; Drosophila novamexicana females produce only ∼1% fertilized eggs in crosses with Drosophila americana males, compared to ∼98% produced in within-species crosses. This incompatibility is likely caused by mismatched male and female reproductive molecules. In this study, we use short-read RNA sequencing to examine the evolutionary dynamics of female reproductive genes and the postmating transcriptome response in crosses within and between species. First, we found that most female reproductive tract genes are slow-evolving compared to the genome average. Second, postmating responses in con- and heterospecific matings are largely congruent, but heterospecific matings induce expression of additional stress-response genes. Some of those are immunity genes that are activated by the Imd pathway. We also identify several genes in the JAK/STAT signaling pathway that are induced in heterospecific, but not conspecific mating. While this immune response was most pronounced in the female reproductive tract, we also detect it in the female head and ovaries. These results show that the female’s postmating transcriptome-level response is determined in part by the genotype of the male, and that divergence in male reproductive genes and/or traits can have immunogenic effects on females.
Allele-Specific Role of ERBB2 in the Oncogenic Function of EGFR L861Q in EGFR-Mutant Lung Cancers
Authors: Hiroki Sato, Michael Offin, Daisuke Kubota, Helena A. Yu, Clare Wilhelm, Shinichi Toyooka, Romel Somwar, Mark G. Kris, Marc Ladanyi
Journal: Journal of Thoracic Oncology (2020)
Targeting Cyclic Guanosine Monophosphate to Treat Heart Failure
Authors: Michele Emdin, Alberto Aimo, Vincenzo Castiglione, Giuseppe Vergaro, Georgios Georgiopoulos, Luigi Francesco Saccaro, Carlo Mario Lombardi, Claudio Passino, Elisabetta Cerbai, Marco Metra, Michele Senni
Journal: Journal of the American College of Cardiology (2020)
Dysplastic progression of a choledochal cyst on video cholangioscopy
Authors: Benjamin Warren, Samuel Han, Raj J. Shah
Journal: Endoscopy (2020)

Choledochal cysts are rare congenital cystic dilatations of the biliary tree. Surgical resection is felt to reduce the risk of malignant degeneration, which can be seen in 40 % – 60 % by the fifth decade [1] [2]. Proposed mechanisms for malignancy include reflux of pancreatic juices in the setting of an anomalous pancreaticobiliary junction (APBJ) causing chronic inflammation or bile stasis, leading to “carcinogenic” bile acid generation [3]. We present a patient with choledochal cysts where serial cholangioscopy demonstrated visual and pathologic evidence of the metaplasia to dysplasia sequence.