tbuckley/cabot-search huggingface dataset:
Synthesis, in vitro and in vivo biological evaluation of novel lappaconitine derivatives as potential anti-inflammatory agents
Authors: Lei Pang, Chun-Yan Liu, Guo-Hua Gong, Zhe-Shan Quan
Journal: Acta Pharmaceutica Sinica B (2019)

Lappaconitine (LA), a natural compound with a novel C18-diterpenoid alkaloid skeleton, displayed extensive biological profile. Recent research on LA is focused mainly on its anti-tumor and analgesic effects, and therefore we aimed to investigate its anti-inflammatory potential. A series of novel LA derivatives with various substituents on the 20-N position was designed and synthesized. In the initial screening of LA derivatives against NO production, all the target compounds, except compound E2, exhibited excellent inhibitory ability relative to that of LA. Particularly, compound A4 exhibited the most potent inhibition with IC50 of 12.91 μmol/L. The elementary structure-activity relationships (SARs) of NO inhibitory activity indicated that replacement of the benzene ring with an electron donating group could improve the anti-inflammatory efficacy. Furthermore, compound A4 shows an anti-inflammatory mechanism by inhibiting NO, PGE2, and TNF-α generation via the suppression of NF-κB and MAPK signaling pathways. Notably, compound A4 could exert a significant therapeutic effect on LPS-induced acute lung injury (ALI) in vivo. Based on the above research, we further investigated the preliminary pharmacokinetic property of A4 in rats. Therefore, compound A4 could be a promising candidate for the development of anti-inflammatory agents in the future.
ERS guidelines on the diagnosis and treatment of chronic cough in adults and children
Authors: Alyn H. Morice, Eva Millqvist, Kristina Bieksiene, Surinder S. Birring, Peter Dicpinigaitis, Christian Domingo Ribas, Michele Hilton Boon, Ahmad Kantar, Kefang Lai, Lorcan McGarvey, David Rigau, Imran Satia, Jacky Smith, Woo-Jung Song, Thomy Tonia, Jan W.K. van den Berg, Mirjam J.G. van Manen, Angela Zacharasiewicz
Journal: European Respiratory Journal (2019)

These guidelines incorporate the recent advances in chronic cough pathophysiology, diagnosis and treatment. The concept of cough hypersensitivity has allowed an umbrella term that explains the exquisite sensitivity of patients to external stimuli such a cold air, perfumes, smoke and bleach. Thus, adults with chronic cough now have a firm physical explanation for their symptoms based on vagal afferent hypersensitivity. Different treatable traits exist with cough variant asthma (CVA)/eosinophilic bronchitis responding to anti-inflammatory treatment and non-acid reflux being treated with promotility agents rather the anti-acid drugs. An alternative antitussive strategy is to reduce hypersensitivity by neuromodulation. Low-dose morphine is highly effective in a subset of patients with cough resistant to other treatments. Gabapentin and pregabalin are also advocated, but in clinical experience they are limited by adverse events. Perhaps the most promising future developments in pharmacotherapy are drugs which tackle neuronal hypersensitivity by blocking excitability of afferent nerves by inhibiting targets such as the ATP receptor (P2X3). Finally, cough suppression therapy when performed by competent practitioners can be highly effective. Children are not small adults and a pursuit of an underlying cause for cough is advocated. Thus, in toddlers, inhalation of a foreign body is common. Persistent bacterial bronchitis is a common and previously unrecognised cause of wet cough in children. Antibiotics (drug, dose and duration need to be determined) can be curative. A paediatric-specific algorithm should be used.
Lumbar transcutaneous electrical nerve stimulation to improve exercise performance in COPD patients
Authors: Tristan Bonnevie, Francis-Edouard Gravier, Guillaume Prieur, Yann Combret, David Debeaumont, Maxime Patout, Bouchra Lamia, Jean-François Muir, Clement Médrinal, Antoine Cuvelier
Journal: European Respiratory Journal (2019)

<b>Lumbar transcutaneous electrical nerve stimulation aimed to block muscle group III–IV sensory afferents does not improve endurance exercise capacity in patients with COPD</b>http://bit.ly/2lZr6Mt
Dual-platform affinity proteomics identifies links between the recurrence of ovarian carcinoma and proteins released into the tumor microenvironment
Authors: Florian Finkernagel, Silke Reinartz, Maximiliane Schuldner, Alexandra Malz, Julia M. Jansen, Uwe Wagner, Thomas Worzfeld, Johannes Graumann, Elke Pogge von Strandmann, Rolf Müller
Journal: Theranostics (2019)

The peritoneal fluid (ascites), replete with abundant tumor-promoting factors and extracellular vesicles (EVs) reflecting the tumor secretome, plays an essential role in ovarian high-grade serous carcinoma (HGSC) metastasis and immune suppression.A comprehensive picture of mediators impacting HGSC progression is, however, not available.Methods: Proteins in ascites from HGSC patients were quantified by the aptamer-based SOMAscan affinity proteomic platform.SOMAscan data were analyzed by bioinformatic methods to reveal clinically relevant links and functional connections, and were validated using the antibody-based proximity extension assay (PEA) Olink platform.Mass spectrometry was used to identify proteins in extracellular microvesicles released by HGSC cells.Results: Consistent with the clinical features of HGSC, 779 proteins in ascites identified by SOMAscan clustered into groups associated either with metastasis and a short relapse-free survival (RFS), or with immune regulation and a favorable RFS.In total, 346 proteins were linked to OC recurrence in either direction.Reanalysis of 214 of these proteins by PEA revealed an excellent median Spearman inter-platform correlation of ρ=0.82 for the 46 positively RFS-associated proteins in both datasets.Intriguingly, many proteins strongly associated with clinical outcome were constituents of extracellular vesicles.These include proteins either linked to a poor RFS, such as HSPA1A, BCAM and DKK1, or associated with a favorable outcome, such as the protein kinase LCK.Finally, based on these data we defined two protein signatures that clearly classify short-term and long-term relapse-free survivors. Conclusion:The ascites secretome points to metastasis-promoting events and an anti-tumor response as the major determinants of the clinical outcome of HGSC.Relevant proteins include both bone fide secreted and vesicle-encapsulated polypeptides, many of which have previously not been linked to HGSC recurrence.Besides a deeper understanding of the HGSC microenvironment our data provide novel potential tools for HGSC patient stratification.Furthermore, the first large-scale inter-platform validation of SOMAscan and PEA will be invaluable for other studies using these affinity proteomics platforms.
Predictors of severe asthma attack re-attendance in Ecuadorian children: a cohort study
Authors: Cristina Ardura-Garcia, Erick Arias, Paola Hurtado, Laura J. Bonnett, Carlos Sandoval, Augusto Maldonado, Lisa J. Workman, Thomas A.E. Platts-Mills, Philip J. Cooper, John D. Blakey
Journal: European Respiratory Journal (2019)

Asthma is a common cause of emergency care attendance in low- and middle-income countries (LMICs). While few prospective studies of predictors for emergency care attendance have been undertaken in high-income countries, none have been performed in a LMIC. We followed a cohort of 5–15-year-old children treated for asthma attacks in emergency rooms of public health facilities in Esmeraldas City, Ecuador. We collected blood and nasal wash samples, and performed spirometry and exhaled nitric oxide fraction measurements. We explored potential predictors for recurrence of severe asthma attacks requiring emergency care over 6 months’ follow-up. We recruited 283 children of whom 264 (93%) were followed-up for ≥6 months or until their next asthma attack. Almost half (46%) had a subsequent severe asthma attack requiring emergency care. Predictors of recurrence in adjusted analyses were (adjusted OR, 95% CI) younger age (0.87, 0.79–0.96 per year), previous asthma diagnosis (2.2, 1.2–3.9), number of parenteral corticosteroid courses in previous year (1.3, 1.1–1.5), food triggers (2.0, 1.1–3.6) and eczema diagnosis (4.2, 1.02–17.6). A parsimonious Cox regression model included the first three predictors plus urban residence as a protective factor (adjusted hazard ratio 0.69, 95% CI 0.50–0.95). Laboratory and lung function tests did not predict recurrence. Factors independently associated with recurrent emergency attendance for asthma attacks were identified in a low-resource LMIC setting. This study suggests that a simple risk-assessment tool could potentially be created for emergency rooms in similar settings to identify higher-risk children on whom limited resources might be better focused.
Utilizing the patient-reported outcomes measurement information system (PROMIS) to assess quality of life among breast cancer patients at an academic center.
Authors: Madeline B. Matthys, Andre Dempsey, Michelle E. Melisko, Amrita Basu, Nickolas Dreher, Laura van 't Veer, Laura Esserman
Journal: Journal of Clinical Oncology (2019)

e23171 Background: NCI PROMIS assesses physical, mental and social health across multiple health conditions. Despite interest in using PROMIS in oncology trials and clinical care, reference values in cancer are not well established. Methods: Electronic intake questionnaires assessing self-reported history and 8 PROMIS domains (depression, anxiety, fatigue, sleep-related impairment (SRI), sleep disturbance, cognitive function, applied cognition and physical function) are sent to all new patients (pts). 2886 pts with self-reported breast cancer completed the questionnaire/consented to research. PROMIS T-Scores were calculated using the Health Measures system. Results: For all domains except depression, cognitive function and applied cognition, pts had clinically meaningful ( &gt; 3 point diff.) worse mean PROMIS scores than US means (50). Compared to stage 0-III, stage IV pts had worse scores for all assessed domains (p &lt; 0.05). Among Stage IV pts &lt; 49, QoL was significantly worse in 7/8 domains (see table). Across all age groups, there were significant differences in mean PROMIS scores for Stage IV pts in anxiety, depression, cognitive function and applied cognition (p &lt; 0.05). Conclusions: PROMIS scores among pts indicate impaired QoL in multiple domains. These scores provide insight into the physical, mental and social health of our pts and can serve as robust estimates for breast cancer trials and clinical care. [Table: see text]
Effects of Family History on Relative and Absolute Risks for Colorectal Cancer: A Systematic Review and Meta-Analysis
Authors: Victorine H. Roos, Carolina Mangas-Sanjuan, Mar Rodriguez-Girondo, Lucia Medina-Prado, Ewout W. Steyerberg, Patrick M.M. Bossuyt, Evelien Dekker, Rodrigo Jover, Monique E. van Leerdam
Journal: Clinical Gastroenterology and Hepatology (2019)
Inducible nitric oxide synthase inhibitors: A comprehensive update
Authors: Richa Minhas, Yogita Bansal, Gulshan Bansal
Journal: Medicinal Research Reviews (2019)

Abstract Inducible nitric oxide synthase (iNOS), which is expressed in response to bacterial/proinflammatory stimuli, generates nitric oxide (NO) that provides cytoprotection. Overexpression of iNOS increases the levels of NO, and this increased NO level is implicated in pathophysiology of complex multifactorial diseases like Parkinson's disease, Alzheimer's disease, multiple sclerosis, rheumatoid arthritis, and inflammatory bowel disease. Selective inhibition of iNOS is an effective approach in treatment of such complex diseases. l ‐Arginine, being a substrate for iNOS, is the natural lead to develop iNOS inhibitors. More than 200 research reports on development of nitric oxide synthase inhibitors by different research groups across the globe have appeared in literature so far. The first review on iNOS, in 2002, discussed the iNOS inhibitors under two classes that is, amino acid and non‐amino acid derivatives. Other review articles discussing specific chemical classes of iNOS inhibitors also appeared during last decade. In the present review, all reports on both natural and synthetic iNOS inhibitors, published 2002 onwards, are studied, classified, and discussed to provide comprehensive information on iNOS inhibitors. The synthetic inhibitors are broadly classified into two categories that is, arginine and non‐arginine analogs. The latter are further classified into amidines, five‐ or six‐membered heterocyclics, fused cyclics, steroidal type, and chalcones analogs. Structures of the most/significantly potent compounds from each report are provided to know the functional groups important for incurring iNOS inhibitory activity and selectivity. This review is aimed to provide a comprehensive view to the medicinal chemists for rational designing of novel and potent iNOS inhibitors.
Advances in Fluid Assessment and Kidney Injury Prediction
Authors: Jennifer Abbasi
Journal: JAMA (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Oncogenic KRAS Sensitizes Lung Adenocarcinoma to GSK-J4–Induced Metabolic and Oxidative Stress
Authors: Beom-Jin Hong, Woo-Yong Park, Hwa-Ryeon Kim, Jin Woo Moon, Ho Yeon Lee, Jun Hyung Park, Seon-Kyu Kim, Youngbin Oh, Jae-Seok Roe, Mi-Young Kim
Journal: Cancer Research (2019)

Genetic and epigenetic changes (e.g., histone methylation) contribute to cancer development and progression, but our understanding of whether and how specific mutations affect a cancer's sensitivity to histone demethylase (KDM) inhibitors is limited. Here, we evaluated the effects of a panel of KDM inhibitors on lung adenocarcinomas (LuAC) with various mutations. Notably, LuAC lines harboring KRAS mutations showed hypersensitivity to the histone H3K27 demethylase inhibitor GSK-J4. Specifically, GSK-J4 treatment of KRAS mutant-containing LuAC downregulated cell-cycle progression genes with increased H3K27me3. In addition, GSK-J4 upregulated expression of genes involved in glutamine/glutamate transport and metabolism. In line with this, GSK-J4 reduced cellular levels of glutamate, a key source of the TCA cycle intermediate α-ketoglutarate (αKG) and of the antioxidant glutathione, leading to reduced cell viability. Supplementation with an αKG analogue or glutathione protected KRAS-mutant LuAC cells from GSK-J4-mediated reductions in viability, suggesting GSK-J4 exerts its anticancer effects by inducing metabolic and oxidative stress. Importantly, KRAS knockdown in mutant LuAC lines prevented GSK-J4-induced decrease in glutamate levels and reduced their susceptibility to GSK-J4, whereas overexpression of oncogenic KRAS in wild-type LuAC lines sensitized them to GSK-J4. Collectively, our study uncovers a novel association between a genetic mutation and KDM inhibitor sensitivity and identifies the underlying mechanisms. This suggests GSK-J4 as a potential treatment option for cancer patients with KRAS mutations. SIGNIFICANCE: This study not only provides a novel association between KRAS mutation and GSK-J4 sensitivity but also demonstrates the underlying mechanisms, suggesting a potential use of GSK-J4 in cancer patients with KRAS mutations.
Does maintenance azithromycin reduce asthma exacerbations? An individual participant data meta-analysis
Authors: Sarah A. Hiles, Vanessa M. McDonald, Michelle Guilhermino, Guy G. Brusselle, Peter G. Gibson
Journal: European Respiratory Journal (2019)

Background Preventing exacerbations is an important goal of asthma treatment. Long-term treatment with azithromycin may help achieve this. Our aim was to conduct a systematic review and individual participant data (IPD) meta-analysis to examine the efficacy of azithromycin in reducing exacerbations in asthma, and in the subphenotypes of noneosinophilic asthma, eosinophilic asthma and severe asthma. Method We completed a systematic search of Embase, MEDLINE, PubMed, Cochrane Library, ClinicalTrials.gov and reference lists of previous systematic reviews in February 2019. We included parallel-group, double-blind, randomised controlled trials in adults comparing at least 8 weeks of azithromycin treatment with placebo, where the outcome of exacerbations was assessed over at least 6 months. Data were extracted from published sources, Cochrane Risk of Bias Tool was applied and IPD were sought from authors. Reviews were undertaken in duplicate. We conducted an IPD meta-analysis on the primary outcome of exacerbations and a random effects meta-analysis for secondary outcomes. Results Three studies were identified (n=604). In the IPD meta-analysis, treatment with azithromycin was associated with a reduced rate of exacerbations (oral corticosteroid course due to worsening asthma, antibiotic use for lower respiratory tract infection, hospitalisation and/or emergency department visits) in asthma as well as in the noneosinophilic, eosinophilic and severe asthma subgroups. Examining each exacerbation type separately, patients with eosinophilic asthma reported fewer oral corticosteroid courses, and patients with noneosinophilic and severe asthma reported fewer antibiotic courses. Azithromycin was well tolerated. Discussion Maintenance use of azithromycin reduces exacerbations in patients with eosinophilic, noneosinophilic and severe asthma.
A real-time PCR for specific detection of the Legionella pneumophila serogroup 1 ST1 complex
Authors: C. Ginevra, J. Chastang, S. David, M. Mentasti, E. Yakunin, V.J. Chalker, V. Chalifa-Caspi, L. Valinsky, S. Jarraud, J. Moran-Gilad
Journal: Clinical Microbiology and Infection (2019)
Effect of a Prize-Linked Savings Intervention on Savings and Healthy Behaviors Among Men in Kenya
Authors: Ellen Moscoe, Kawango Agot, Harsha Thirumurthy
Journal: JAMA Network Open (2019)

Interventions to reduce men's alcohol use and risky sexual behaviors are essential for reducing new HIV infections in high-prevalence settings in sub-Saharan Africa. Prize-linked savings accounts can motivate savings and may decrease expenditures on risky behaviors, but few studies have examined the HIV prevention potential of such savings interventions among men.To evaluate the effect of prize-linked savings accounts on savings behavior and expenditures on alcohol, gambling, and transactional sex among men in Kenya.Randomized clinical trial among communities in Siaya County, Kenya. Participants were men 21 years or older who owned a mobile phone, were engaged in fishing or transportation sector work, and were willing to open an account with a local bank; they were screened for eligibility between September 3 and October 5, 2018.Eligible participants were offered savings accounts endowed with 1000 Kenya shillings (US $10) and randomized (1:1) to receive weekly lottery-based rewards contingent on growth in savings balance or to a control group that received standard interest.The primary outcome was an indicator of whether a participant saved any money in the bank account (intent-to-treat analysis) during the study period. Secondary outcomes included total amount saved in the bank account, total amount saved in all sources, and expenditures on alcohol, gambling, and transactional sex.A total of 425 men were screened, 329 (77.4%) met eligibility criteria, 300 (70.6%) were enrolled (with 152 randomized to the intervention group and 148 to the control group), and 270 of 300 (90.0%) opened bank accounts. Participants' mean age was 33.7 years (interquartile range, 13.5 years), 84.3% (253 of 300) were married, and the mean weekly earnings were US $30 (interquartile range, US $23). During a mean (SD) follow-up of 9 (2) weeks, 37.3% (50 of 134) in the intervention group saved money in a bank account vs 27.2% (37 of 136) in the control group, although the difference was not statistically significant (odds ratio, 1.62; 95% CI, 0.96-2.74). The intervention group had higher growth in bank savings balances (US $10.26; 95% CI, US $5.00-US $58.20 vs US $4.87; 95% CI, US $0.67-US $9.00) and higher total savings from all sources (US $201; 95% CI, US $133-US $269 vs US $145; 95% CI, US $88-US $202), but neither difference was statistically significant. The intervention did not have a significant effect on alcohol, gambling, and transactional sex expenditures.Prize-linked savings accounts modestly increased savings among high-risk men in Kenya over a 9-week period, but the difference compared with standard-interest savings accounts was not significant. Testing of more powerful savings products is needed to assess whether such savings-led interventions can reduce men's expenditures on alcohol, gambling, and transactional sex.Social Science Registry identifier: AEARCTR-0003224, and ClinicalTrials.gov identifier: NCT04013295.
Primary Analysis of JUMP, a Phase 3b, Expanded-Access Study Evaluating the Safety and Efficacy of Ruxolitinib in Patients with Myelofibrosis (N = 2233)
Authors: Haifa Kathrin Al-Ali, Lynda Foltz, Giuseppe A. Palumbo, Bruno Martino, Francesca Palandri, Anna Marina Liberati, Philipp Le Coutre, Carmen Garcia-Hernandez, Andrey Zaritskey, Renato Tavares, Martin Griesshammer, Vikas Gupta, Pia Raanani, Pilar Giraldo, Catherine Bouard, Julian Perez Ronco, Ranjan Tiwari, Francesco Mannelli, Alessandro M. Vannucchi
Journal: Blood (2017)
Gene Ontology Causal Activity Modeling (GO-CAM) moves beyond GO annotations to structured descriptions of biological functions and systems
Authors: Paul D. Thomas, David P. Hill, Huaiyu Mi, David Osumi-Sutherland, Kimberly Van Auken, Seth Carbon, James P. Balhoff, Laurent-Philippe Albou, Benjamin Good, Pascale Gaudet, Suzanna E. Lewis, Christopher J. Mungall
Journal: Nature Genetics (2019)
Kenneth Michael Citron
Authors: Janet H Darbyshire
Journal: BMJ (2019)

Kenneth Michael Citron studied medicine at Guy’s Hospital, London, where he won the Golding Bird medal in bacteriology and the Leonard Lubbock prize in clinical pathology. After house appointments at Guy’s, he was found to have pulmonary tuberculosis, which was treated successfully with bed rest before effective antibiotic treatment was available.

He was a research fellow in bacteriology at Guy’s, and then held a variety of clinical posts in medicine before he finally trained in respiratory medicine at the Royal Brompton Hospital, London. In 1959, he was appointed consultant physician on the medical academic unit at the Royal Brompton Hospital and honorary senior lecturer at the cardiothoracic institute. As physician in charge of chest clinics in Wandsworth and Battersea, he developed a comprehensive respiratory medicine service for a large population in south-west London. At this time, the clinical application of newly discovered drugs for tuberculosis, then a common disease, was a challenging and stimulating task. The British Thoracic Society appointed Kenneth chairman of a series of …