tbuckley/cabot-search huggingface dataset:
Abstract
Journal: Allergy (2020)

Background : MP- AzeFlu (azelastine/fluticasone propionate in one spray) is the most effective allergic rhinitis (AR) treatment available. Its effect on asthma control in co- morbid patients is unknown. We examined whether MP- AzeFlu altered asthma control in patients with AR and asthma. Method : This pre- post historical cohort study, carried out using the Optimum Patient Care Database, included patients aged ≥12 years from UK general practice with active asthma in the year before MP- AzeFlu initiation. Active asthma was defined as a recorded diagnosis, with ≥ 1 prescription for reliever or controller inhaler in the year prior to and including the initiation date. The primary endpoint was change in number of acute respiratory events (i.e. an exacerbation or an antibiotic course for a respiratory event) between baseline and outcome years. Study outcomes were assessed by Wilcoxon signed rank test or McNemar ' s test.
Results : 1,188 patients were included (average age: 47 yrs; 58.4% female). Most were prescribed intranasal corticosteroids (60.4%) and Inhaled corticosteroid (ICS)/long- acting β2 - agonist (59.3%) at baseline. MP- AzeFlu initiation was associated with significantly fewer acute respiratory events ( P = .013). Significantly more patients had well- controlled asthma in the year after MP- AzeFlu initiation ( P = .004). These asthma control benefits were noted despite significant reduction in short- acting β2 - agonist (SABA) dose ( P   2 SABA puffs/week ( P < .001) and the average ICS dose remaining stable (64.0% of patients) or reduced (20.4% of patients). Conclusion : MP- AzeFlu initiation is associated with reduced acute respiratory events, improved asthma control and reduced SABA and maintenance ICS dose in patients with AR and asthma.
This study was funded by BGP Products Operations GmbH (A Mylan Company).
The role of omics in the pathophysiology, diagnosis and treatment of non-alcoholic fatty liver disease
Authors: Nikolaos Perakakis, Konstantinos Stefanakis, Christos S. Mantzoros
Journal: Metabolism (2020)

Non-alcoholic fatty liver disease (NAFLD) is a multifaceted metabolic disorder, whose spectrum covers clinical, histological and pathophysiological developments ranging from simple steatosis to non-alcoholic steatohepatitis (NASH) and liver fibrosis, potentially evolving into cirrhosis, hepatocellular carcinoma and liver failure. Liver biopsy remains the gold standard for diagnosing NAFLD, while there are no specific treatments. An ever-increasing number of high-throughput Omics investigations on the molecular pathobiology of NAFLD at the cellular, tissue and system levels produce comprehensive biochemical patient snapshots. In the clinical setting, these applications are considerably enhancing our efforts towards obtaining a holistic insight on NAFLD pathophysiology. Omics are also generating non-invasive diagnostic modalities for the distinct stages of NAFLD, that remain though to be validated in multiple, large, heterogenous and independent cohorts, both cross-sectionally as well as prospectively. Finally, they aid in developing novel therapies. By tracing the flow of information from genomics to epigenomics, transcriptomics, proteomics, metabolomics, lipidomics and glycomics, the chief contributions of these techniques in understanding, diagnosing and treating NAFLD are summarized herein.
Diagnostic accuracy of 3 urine lipoarabinomannan tuberculosis assays in HIV-negative outpatients
Authors: Tobias Broger, Mark P. Nicol, George B. Sigal, Eduardo Gotuzzo, Alexandra J. Zimmer, Shireen Surtie, Tatiana Caceres-Nakiche, Anna Mantsoki, Elena Ivanova Reipold, Rita Székely, Michael Tsionsky, Judith van Heerden, Tatiana Plisova, Kinuyo Chikamatsu, Todd L. Lowary, Abraham Pinter, Satoshi Mitarai, Emmanuel Moreau, Samuel G. Schumacher, Claudia M. Denkinger
Journal: Journal of Clinical Investigation (2020)

BACKGROUND. Inadequate tuberculosis (TB) diagnostics are a major hurdle in the reduction of disease burden, and accurate point-of-care tests (POCTs) are urgently needed. We assessed the diagnostic accuracy of Fujifilm SILVAMP TB lipoarabinomannan (FujiLAM) POCT for TB diagnosis in HIV-negative outpatients and compared it with Alere Determine TB LAM Ag (AlereLAM) POCT and a laboratory-based ultrasensitive electrochemiluminescence LAM research assay (EclLAM).
AB1330-HPR ASSOCIATION OF INTERSTITIAL LUNG DISEASE AND QUALITY OF LIFE IN CHINESE RHEUMATOID ARTHRITIS
Authors: Y. Wang, R. Zhao, C. Dong, Z. Gu
Journal: Annals of the Rheumatic Diseases (2020)

Background: The health-related quality of life (HRQL) of patients with rheumatoid arthritis associated interstitial lung disease (RA-ILD) is less concerned(1). This study hypothesized that HRQL of such patients decreased. Objectives: The aim of this study was to assess the difference in HRQL between RA with and without ILD, and to predict risk factors of HRQL in Chinese RA-ILD. Methods: A cross-sectional survey of RA-ILD patients included socio-demographic characteristics, clinical variables, psychological factors and HRQL. Data were analyzed by Student’s t or chi-square test. Linear regression analysis was used to investigate the predictors of HRQL in RA-ILD. Results: The data showed that 35.17% (51/145) of RA patients had ILD. There are significant differences in age, sex, smoking history, disease duration and activity between RA with and without ILD. HRQL of RA-ILD was impaired. Physical component score (PCS) of patients with RA-ILD was also worse than that of RA without ILD (48.91±2.48 vs. 50.80±2.55). Linear regression analysis showed that DAS28 and fatigue were risk factors for PCS in patients with RA-ILD, while depression and rural residence were risk factors for mental components summary in Table 1. Table 1. Stepwise multiple linear regression analysis of PCS and MCS in RA-ILD Predictors B SE t P 95%CI PCS DAS28 -0.777 0.227 -3.425 0.001 -1.236,-0.319 Fatigue -0.655 0.206 -3.177 0.003 -1.071, -0.238 MCS Depression 2.188 0.669 3.272 0.002 0.836, 3.539 Rural residents -1.609 0.756 -2.128 0.040 -3.137,-0.081 Footnotes : CI=Confidence interval. PCS=Physical component score; MCS=Mental component score; DAS28=28-joint disease activity score. Conclusion: Compared with RA without ILD, HRQL of patients with RA-ILD was significantly impaired. Disease activity, fatigue, depression and rural residence were independent predictors of HRQL in Chinese RA-ILD. References: [1]Zamora-Legoff JA, Krause ML, Crowson CS, Ryu JH, Matteson EL. Patterns ofinterstitial lung disease and mortality in rheumatoid arthritis. Rheumatology (Oxford, England). 2017;56(3):344-50. Disclosure of Interests: None declared
Use of Administrative Claims Data to Estimate Treatment Effects for 30 Versus 12 Months of Dual Antiplatelet Therapy After Percutaneous Coronary Intervention
Authors: Kamil F. Faridi, Hector Tamez, Jordan B. Strom, Yang Song, Neel M. Butala, Changyu Shen, Eric A. Secemsky, Laura Mauri, Jeptha P. Curtis, C. Michael Gibson, Robert W. Yeh
Journal: Circulation (2020)
FRI0159 Longstanding active giant cell arteritis (gca) treated with infliximab: report of four casesinfliximab
Authors: F Cantini, L Niccoli, C Salvarani, L Boiardi, I Olivieri, A Padula
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> TNF-alpha was demonstrated in up to 60% of the cells in all areas of inflamed arteries of patients with GCA, suggesting a primary role in the inflammatory process. Infliximab, a chimeric monoclonal anti-TNF-alpha, demonstrated remarkable efficacy and safety in the treatment of several rheumatic conditions associated with a chronic inflammatory response. <h3>Objectives</h3> To date, no data are available on the therapeutic employment of infliximab in patients with GCA. The aim of this study was to evaluate the efficacy of infliximab infusions in longstanding, still requiring corticosteroids (CS) GCA. <h3>Methods</h3> Four patients (3F,1M; median age:75 ys.) with longstanding (median disease duration: 4 ys.), biopsy proven, active GCA, still requiring CS and whose disease course hab been complicated by serious CS-related adverse events, were scheduled to receive 3 infusions of infliximab (3 mg/Kg) at weeks 0, 2 and 6. If a clinical and humoral remission was obtained, CS were withdrawn after the 2nd infusion. <h3>Results</h3> Three patients had a complete remission of clinical signs/symptoms and normalisation of ESR and CRP after the 2nd infusion. The remission persisted after the 3rd infusion and over the follow-up (7, 6 and 6 months, respectively). The fourth patient did not respond to therapy and withdrew from the study after the 2nd infusion. Infliximab was well tolerated without any side-effects. <h3>Conclusion</h3> Our encouraging results suggest that TNF-alpha blockade may represent a valid alternative therapeutic approach to longstanding GCA, still requiring CS and complicated by severe adverse events. The small number of patients and the open study design do not allow conclusive considerations.
Enterotoxigenic <i>Bacteroides fragilis</i> induces the stemness in colorectal cancer via upregulating histone demethylase JMJD2B
Authors: Qian-Qian Liu, Chun-Min Li, Lin-Na Fu, Hao-Lian Wang, Juan Tan, Yun-Qian Wang, Dan-Feng Sun, Qin-Yan Gao, Ying-Xuan Chen, Jing-Yuan Fang
Journal: Gut Microbes (2020)

The enrichment of Enterotoxigenic Bacteroides fragilis (ETBF) has been identified in CRC patients and associated with worse prognosis. Cancer stem cells (CSCs) play essential roles in CRC development. However, whether ETBF is involved in CSCs regulation is unknown. To clarify the role of ETBF in CSCs properties, we performed extreme limited dilution assays (ELDA) in nude mice injected with ETBF-treated or untreated CRC cells subcutaneously, tumor organoids culture in azoxymethane (AOM) mouse model after gavaging with or without ETBF, and cell sphere formation assay after incubating CRC cell lines with or without ETBF. The results indicated that ETBF increased the stemness of CRC cells in vivo and in vitro. Furthermore, ETBF enhanced the expression of core stemness transcription factors Nanog homeobox (NANOG) and sex determining region Y-box 2 (SOX2). Histone H3 Lysine 9 trimethylation (H3K9me3) is critical in regulating CSCs properties. As an epigenetic and transcriptional regulator, JmjC-domain containing histone demethylase 2B (JMJD2B) is essential for embryonic stem cell (ESC) transformation and H3K9me3 demethylation. Mechanistically, ETBF infection significantly upregulated JMJD2B levels in CRC cell lines and nude mice xenograft model. JMJD2B epigenetically upregulated NANOG expression via demethylating its promoter H3K9me3, to mediate ETBF-induced stemness of CRC cells. Subsequently, we found that the Toll-like receptor 4 (TLR4) pathway, activated by ETBF, contributed to the enhanced expression of JMJD2B via nuclear transcription factor nuclear factor of activated T cells 5 (NFAT5). Finally, in human CRC samples, the amount of ETBF positively correlated with nuclear NFAT5, JMJD2B, and NANOG expression levels. In summary, ETBF upregulated JMJD2B levels in a TLR4-NFAT5-dependent pathway, and played an important role in stemness regulation, which promoted colorectal carcinogenesis.
Efficacy of early prone position for COVID-19 patients with severe hypoxia: a single-center prospective cohort study
Authors: Xuefeng Zang, Qian Wang, Hua Zhou, Sanhong Liu, Xinying Xue, Weidong Zhang, Quansheng Gao, Jiang Xie, Chunguo Jiang, Xinmin Ding, Jie Zhang, Feiping Lu, Wei Chen, Jie Zhen, Ping He, Meng’en Zhu, Xiaomeng Zhang, Xiaodong Yuan, Rong Tian, Xiaohui Wang, Nan Zhang, Jun Guo, Xuelei Zang, Xidong Ma, Zhiqiang Xue
Journal: Intensive Care Medicine (2020)
Phase Ib Study of Lenvatinib Plus Pembrolizumab in Patients With Unresectable Hepatocellular Carcinoma
Authors: Richard S. Finn, Masafumi Ikeda, Andrew X. Zhu, Max W. Sung, Ari D. Baron, Masatoshi Kudo, Takuji Okusaka, Masahiro Kobayashi, Hiromitsu Kumada, Shuichi Kaneko, Marc Pracht, Konstantin Mamontov, Tim Meyer, Tomoki Kubota, Corina E. Dutcus, Kenichi Saito, Abby B. Siegel, Leonid Dubrovsky, Kalgi Mody, Josep M. Llovet
Journal: Journal of Clinical Oncology (2020)

PURPOSE The immunomodulatory effect of lenvatinib (a multikinase inhibitor) on tumor microenvironments may contribute to antitumor activity when combined with programmed death receptor-1 (PD-1) signaling inhibitors in hepatocellular carcinoma (HCC). We report results from a phase Ib study of lenvatinib plus pembrolizumab (an anti–PD-1 antibody) in unresectable HCC (uHCC). PATIENTS AND METHODS In this open-label multicenter study, patients with uHCC received lenvatinib (bodyweight ≥ 60 kg, 12 mg; &lt; 60 kg, 8 mg) orally daily and pembrolizumab 200 mg intravenously on day 1 of a 21-day cycle. The study included a dose-limiting toxicity (DLT) phase and an expansion phase (first-line patients). Primary objectives were safety/tolerability (DLT phase), and objective response rate (ORR) and duration of response (DOR) by modified RECIST (mRECIST) and RECIST version 1.1 (v1.1) per independent imaging review (IIR; expansion phase). RESULTS A total of 104 patients were enrolled. No DLTs were reported (n = 6) in the DLT phase; 100 patients (expansion phase; included n = 2 from DLT phase) had received no prior systemic therapy and had Barcelona Clinic Liver Cancer stage B (n = 29) or C disease (n = 71). At data cutoff, 37% of patients remained on treatment. Median duration of follow-up was 10.6 months (95% CI, 9.2 to 11.5 months). Confirmed ORRs by IIR were 46.0% (95% CI, 36.0% to 56.3%) per mRECIST and 36.0% (95% CI, 26.6% to 46.2%) per RECIST v1.1. Median DORs by IIR were 8.6 months (95% CI, 6.9 months to not estimable [NE]) per mRECIST and 12.6 months (95% CI, 6.9 months to NE) per RECIST v1.1. Median progression-free survival by IIR was 9.3 months per mRECIST and 8.6 months per RECIST v1.1. Median overall survival was 22 months. Grade ≥ 3 treatment-related adverse events occurred in 67% (grade 5, 3%) of patients. No new safety signals were identified. CONCLUSION Lenvatinib plus pembrolizumab has promising antitumor activity in uHCC. Toxicities were manageable, with no unexpected safety signals.
COVID-19 and the digital divide in the UK
Authors: Geoff Watts
Journal: The Lancet Digital Health (2020)

Any health-care development that doesn't rapidly become available to all individuals has the unintended but inevitable consequence of fuelling health inequality. The response to COVID-19 is no exception. Although we have neither effective drugs or vaccines to deploy, we do have other resources that bear on our capacity to respond to the disease: resources that include digital health-care technologies. Regrettably their benefits are still far from being equitably distributed.
AB0965 EVALUATION OF THE IMPACT OF THE JOB STRESS ON THE ONSET OF MUSCULOSKELETAL DISORDERS IN THE HEALTHCARE WORKERS OF THE GENERAL HOSPITAL OF DOUALA, CAMEROON
Authors: F. Kemta Lekpa, M. N. Hugo Bertrand
Journal: Annals of the Rheumatic Diseases (2020)

Background: Job stress (workload) and its repercussions on health have already been described. However, very few publications has been performed in sub-Saharan Africa. Objectives: To assess the link between job stress and musculoskeletal disorders (MSD) among healthcare workers of the Douala General Hospital. Methods: In this cross-sectional study, the job stress, evaluated according to the Karasek model, made it possible to measure job-strain (high psychological demand and low decision-making latitude), iso-strain (job-strain and lack of social support), and low-strain (relaxed or low-load work). Results: Among the 261 participants in the study, 67.43% were women. The average age was 39.80 ± 9.4 years. The average length of professional service was 8.91 ± 7.30 years [1 - 35 years]. Regarding the job stress, 65.14% of the healthcare workers followed at least 11 patients per day. 78.54% had more than 40 hours of weekly work and 46.36% carried heavy loads during work. Job-strain was found in 58.62% of the participants, iso-strain in 7.66% and low-strain in 5.36%. MSDs were described by 225 participants (86.21%). They were mainly low back pain (68.44%), neck pain (52%) and shoulders’ pain (37.78%). In multivariate analysis, only weekly work&gt; 40 hours (OR = 2.59; 95% CI 1.11–6.02, p = 0.026) and job-strain (OR = 3.14; 95% CI 1.33–7.39, p = 0.009) remained associated with the presence of MSD. Conclusion: The healthcare workers in our study are exposed to a high psychological and physical job stress, causing MSDs. Ergonomic programs should be designed for these workers. Disclosure of Interests: None declared
Zero-order and prolonged release of atenolol from microporous FAU and BEA zeolites, and mesoporous MCM-41: Experimental and theoretical investigations
Authors: A.J. Wise, J. Sobhani Sefy, E. Barbu, A.J. O'Malley, S.M. van der Merwe, P.A. Cox
Journal: Journal of Controlled Release (2020)
Risks of reacting to risk: rights and wrongs of health checks at 25 for BAME groups
Authors: Temitope Fisayo
Journal: BMJ (2020)

MPs are considering reducing the age at which NHS health checks begin for black, Asian, and minority ethnic (BAME) people to 25.1 I am concerned that this operationalises risk as a stable entity23 inherent to BAME people living in the UK. In truth, risk fluctuates. Individuals enter and exit states of risk as their social circumstances change, such …
Mist1+ gastric isthmus stem cells are regulated by Wnt5a and expand in response to injury and inflammation in mice
Authors: Henrik Nienhüser, Woosook Kim, Ermanno Malagola, Tuo Ruan, Giovanni Valenti, Moritz Middelhoff, Adam Bass, Channing J Der, Yoku Hayakawa, Timothy C Wang
Journal: Gut (2020)

Background and aims The gastric epithelium undergoes continuous turnover. Corpus epithelial stem cells located in the gastric isthmus serve as a source of tissue self-renewal. We recently identified the transcription factor Mist1 as a marker for this corpus stem cell population that can give rise to cancer. The aim here was to investigate the regulation of the Mist1+ stem cells in the response to gastric injury and inflammation. Methods We used Mist1CreERT;R26-Tdtomato mice in two models of injury and inflammation: the acetic acid-induced ulcer and infection with Helicobacter felis . We analysed lineage tracing at both early (7 to 30 days) and late (30 to 90 days) time points. Mist1CreERT;R26-Tdtomato;Lgr5DTR-eGFP mice were used to ablate the corpus basal Lgr5+ cell population. Constitutional and conditional Wnt5a knockout mice were used to investigate the role of Wnt5a in wound repair and lineage tracing from the Mist1+ stem cells. Results In both models of gastric injury, Mist1+ isthmus stem cells more rapidly proliferate and trace entire gastric glands compared with the normal state. In regenerating tissue, the number of traced gastric chief cells was significantly reduced, and ablation of Lgr5+ chief cells did not affect Mist1-derived lineage tracing and tissue regeneration. Genetic deletion of Wnt5a impaired proliferation in the gastric isthmus and lineage tracing from Mist1+ stem cells. Similarly, depletion of innate lymphoid cells, the main source of Wnt5a, also resulted in reduced proliferation and Mist1+ isthmus cell tracing. Conclusion Gastric Mist1+ isthmus cells are the main supplier of regenerated glands and are activated in part through Wnt5a pathway.
Why Healthcare Workers Ought to Be Prioritized in ASMR During the SARS-CoV-2 Pandemic
Authors: Mark P. Aulisio, Thomas May
Journal: The American Journal of Bioethics (2020)

Should healthcare workers be prioritized in the allocation of scarce medical resources (ASMR) during the SARS-CoV-2 pandemic? The ABPD Task Force rightly raises this question while indicating that ...
15-Deoxy-Δ12,14-prostaglandin J2 upregulates heme oxygenase-1 and vascular endothelial growth factor through activation of Nrf2 in human breast cancer cells
Authors: Eun-Hee Kim, Hye-Kyung Na, Young-Joon Surh
Journal: Cancer Research (2006)

1485  Elevated expression or activity of heme oxygenase-1 (HO-1), a ubiquitous stress-responsive enzyme, has been reported to stimulate proliferation and to accelerate angiogenesis in several types of tumor cells. 15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2), an endogenous ligand of peroxisome proliferator-activated receptor γ, has been known to induce HO-1 in certain cell lines. In the present work, we found that treatment of human breast cancer (MCF-7) cells with nontoxic doses of 15d-PGJ2 led to concentration- and time-dependent increases in the expression and activity of HO-1. The induction of HO-1 expression preceded the upregulation of vascular endothelial growth factor (VEGF) in MCF-7 cells stimulated with 15d-PGJ2. To determine whether the induction of HO-1 is responsible for VEGF production, a specific inhibitor of HO-1 was utilized. The upregulation of VEGF production by 15d-PGJ2 was abrogated by the HO-1 inhibitor, ZnPP. Moreover, ZnPP decreased the in vitro capillary formation induced by 15d-PGJ2 in human umbilical vein endothelial cells. Likewise, ZnPP treatment inhibited the migrative phenotype of 15d-PGJ2-treated MCF-7 cells as determined by the wound migration assay. Nrf2, a basic-leucine zipper transcription factor, plays a key role in regulating the antioxidant response element (ARE)-mediated expression of antioxidant enzymes including HO-1. 15d-PGJ2 induced increased nuclear translocation and subsequent ARE binding of Nrf2. MCF-7 cells transfected with dominant negative Nrf2 exhibited reduced expression of HO-1 and VEGF in response to 15d-PGJ2 treatment. Taken together, these results suggest that 15d-PGJ2-induced expression of HO-1 via the Nrf2 signaling is implicated in angiogenesis in human breast cancer. To the best of our knowledge, this is the first demonstration of involvement of Nrf2 in VEGF induction and angiogenesis.
Inferring Multiple Sclerosis Stages from the Blood Transcriptome via Machine Learning
Authors: Massimo Acquaviva, Ramesh Menon, Marco Di Dario, Gloria Dalla Costa, Marzia Romeo, Francesca Sangalli, Bruno Colombo, Lucia Moiola, Vittorio Martinelli, Giancarlo Comi, Cinthia Farina
Journal: Cell Reports Medicine (2020)

Peripheral blood mononuclear cells (PBMCs) bear specific dysregulations in genes and pathways at distinct stages of multiple sclerosis (MS) that may help with classifying MS and non-MS subjects, specifying the early stage of disease, or discriminating among MS courses. Here we describe an unbiased machine learning workflow to build MS stage-specific classifiers based on PBMC transcriptomics profiles from more than 300 individuals, including healthy subjects and patients with clinically isolated syndromes, relapsing-remitting MS, primary or secondary progressive MS, or other neurological disorders. The pipeline, designed to optimize and compare the performance of distinct machine learning algorithms in the training cohort, generates predictive models not influenced by demographic features, such as age and gender, and displays high accuracy in the independent validation cohort. Proper application of machine learning to transcriptional profiles of circulating blood cells may allow identification of disease state and stage in MS.
Neural Stem Cells Direct Axon Guidance via Their Radial Fiber Scaffold
Authors: Navjot Kaur, Wenqi Han, Zhuo Li, M. Pilar Madrigal, Sungbo Shim, Sirisha Pochareddy, Forrest O. Gulden, Mingfeng Li, Xuming Xu, Xiaojun Xing, Yutaka Takeo, Zhen Li, Kangrong Lu, Yuka Imamura Kawasawa, Begoña Ballester-Lurbe, Juan Antonio Moreno-Bravo, Alain Chédotal, José Terrado, Ignacio Pérez-Roger, Anthony J. Koleske, Nenad Sestan
Journal: Neuron (2020)