tbuckley/cabot-search huggingface dataset:
Turbocharged Juul device challenges European tobacco regulators
Authors: Sairam V. Jabba, Sven-Eric Jordt
Journal: European Respiratory Journal (2020)

<b>Juul, the e-cigarette company, re-engineered their device for the European market, increasing nicotine delivery to US levels and adding a synthetic cooling agent to replace menthol. This approach takes advantage of insufficient EU tobacco regulation.</b>https://bit.ly/3iixAhU
Chest Pain in a Middle-aged Woman With Asthma
Authors: Karl Gordon Patti, Ari J. Bennett, David A. McNamara
Journal: JAMA Cardiology (2020)

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 Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Cardiology journal
Abstract 13: Clinical trial outcomes for cancer drug combinations can be predicted using cancer cell line monotherapy screens and a model of independent drug action
Authors: Alexander Ling, R. Stephanie Huang
Journal: Clinical Cancer Research (2020)

Abstract Drug combinations are a cornerstone of cancer therapy; however, the vast number of possible drug combinations makes it infeasible to experimentally evaluate all of these possibilities when identifying new therapies. For example, testing all possible 4-drug combinations for 200 compounds in 100 cell lines would require more than 6 billion experiments. To solve this problem, efforts have been made to develop computational models capable of accurately predicting drug combination efficacy without the need to experimentally test all of them. While these models have traditionally aimed to predict drug synergy, recent evidence has emerged suggesting that many cancer drug combinations may derive their efficacy from independent drug action (IDA), where patients only receive benefit from the single most effective drug in a drug combination. In light of these findings, we developed IDACombo, a computational method that uses IDA to predict the efficacy of drug combinations based on monotherapy data from high-throughput cancer cell line drug screens. We have demonstrated that IDACombo predictions closely agree with measured drug combination efficacies both in vitro (Pearson’s correlation = 0.94 when comparing predicted efficacies to measured efficacies for &amp;gt;5,000 combinations) and in a systematically selected set of clinical trials (accuracy &amp;gt;88% for predicting progression-free survival/time to progression or overall survival benefit in 26 first-line therapy trials). This work provides a framework for translating monotherapy cell line screening data into clinically meaningful efficacy predictions for hundreds of thousands of 2-drug combinations and millions of combinations of 3 or more drugs. Citation Format: Alexander Ling, R. Stephanie Huang. Clinical trial outcomes for cancer drug combinations can be predicted using cancer cell line monotherapy screens and a model of independent drug action [abstract]. In: Proceedings of the AACR Special Conference on Advancing Precision Medicine Drug Development: Incorporation of Real-World Data and Other Novel Strategies; Jan 9-12, 2020; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_1):Abstract nr 13.
Oxazaphosphorines combined with immune checkpoint blockers: dose-dependent tuning between immune and cytotoxic effects
Authors: Julia Delahousse, Charles Skarbek, Mélanie Desbois, Jean-Luc Perfettini, Nathalie Chaput, Angelo Paci
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Oxazaphosphorines (cyclophosphamide (CPA), ifosfamide (IFO)) are major alkylating agents of polychemotherapy protocols but limiting their toxicity and increasing their efficacy could be of major interest. Oxazaphosphorines are prodrugs that require an activation by cytochrome P450 (CYP). CPA is mainly metabolized (&gt;80%) to phosphoramide mustard while only 10%–50% of IFO is transformed in the alkylating entity, isophosphoramide mustard and 50%–90% of IFO release chloroacetaldehyde, a nephrotoxic and neurotoxic metabolite. Geranyloxy-IFO (G-IFO) was reported as a preactivated IFO to circumvent the toxic pathway giving directly the isophosphoramide mustard without CYP metabolization. The similarity in structure of CPA and IFO and the similarity in metabolic balance of CPA and G-IFO have led us to explore immunomodulatory effect of these components in mice and to investigate the combination of these oxazaphosphorines with immune checkpoint blockers (ICB). Methods The investigation of the immunomodulatory properties of IFO and G-IFO compared with CPA has been conducted through immune cell phenotyping by flow cytometry and analysis of the cytokine profile of T cells after ex-vivo restimulation. T cell-mediated antitumor efficacy was confirmed in CD4 + and CD8 + T cell-depleted mice. A combination of oxazaphosphorines with an anti-programmed cell death 1 (PD-1) antibody has been studied in MCA205 tumor-bearing mice. Results Studies on a MCA205 mouse model have demonstrated a dose-dependent effect of IFO and G-IFO on T cell immunity. These components in particular favored Th1 polarization when used at low dose (150 and eq. 100 mg/kg, respectively). Antitumor activity at low dose was abolished in mice depleted in CD4 + and CD8 + T cells. G-IFO at low dose (eq. 100 mg/kg) in combination with anti-PD-1 antidody showed high synergistic antitumor efficacy compared with IFO. Conclusion Oxazaphosphorines are characterized by a dual mechanism of antitumor action; low-dose schedules should be preferred in combination with ICB, and dose escalation was found to have better utility in polychemotherapy protocols where a conventional direct cytotoxic anticancer effect is needed. G-IFO, the novel oxazaphosphorine drug, has shown a better metabolic index compared with IFO as its metabolization gives mainly the alkylating mustard as CPA (and not IFO) and a best potential in combination with ICB.
Infographic. Effects of exercise in patients with fibromyalgia: an umbrella review
Authors: Alexandro Andrade, Fábio Hech Dominski
Journal: British Journal of Sports Medicine (2020)

Fibromyalgia (FM) syndrome is a complex disease thus making it difficult to diagnose. FM is characterised as a musculoskeletal disease, with generalised pain in four of the five regions (quadrants and axial skeleton) for a period of >3 months, associated to psychological disorders such as depression, anxiety, fatigue and deteriorating mental health which directly affect the quality of life, work performance, and social and occupational functions.1 2

FM has been treating with exercise. It is important to evaluate the exercise modality that presents the best results in reducing symptoms in terms of several variables. In our recent umbrella review3 of systematic reviews and meta-analyses published in the Seminars in Arthritis and …
Targeted Intraoperative Radiotherapy for Early Breast Cancer
Authors: Gerd Fastner, Maria Cristina Leonardi, Philip M. Poortmans
Journal: JAMA Oncology (2020)

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 Oncology HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Oncology journal
Hypofractionated Versus Conventional Fractionated Radiotherapy After Breast-Conserving Surgery in the Modern Treatment Era: A Multicenter, Randomized Controlled Trial From China
Authors: Shu-Lian Wang, Hui Fang, Chen Hu, Yong-Wen Song, Wei-Hu Wang, Jing Jin, Yue-Ping Liu, Hua Ren, Juan Liu, Gao-Feng Li, Xiang-Hui Du, Yu Tang, Hao Jing, Yu-Chao Ma, Zhou Huang, Bo Chen, Yuan Tang, Ning Li, Ning-Ning Lu, Shu-Nan Qi, Yong Yang, Guang-Yi Sun, Xin-Fan Liu, Ye-Xiong Li
Journal: Journal of Clinical Oncology (2020)

No randomized trials have compared hypofractionated radiotherapy (HFRT) with conventional fractionated radiotherapy (CFRT) after breast-conserving surgery in the Asian population. This study aimed to determine whether a 3.5-week schedule of HFRT is noninferior to a standard 6-week schedule of CFRT in China.Patients from 4 Chinese institutions who had undergone breast-conserving surgery and had T1-2N0-3 invasive breast cancers participated this study. Patients were randomly assigned (1:1) using a computer-generated central randomization schedule, without stratification, to receive whole-breast irradiation with or without nodal irradiation, followed by tumor-bed boost, either at a dose of 50 Gy in 25 fractions over 5 weeks with a boost of 10 Gy in five fractions over 1 week (CFRT) or 43.5 Gy in 15 fractions over 3 weeks with a boost of 8.7 Gy in three daily fractions (HFRT). The primary endpoint was 5-year local recurrence (LR), and a 5% margin of 5-year LR was used to establish noninferiority.Between August 2010 and November 2015, 734 patients were assigned to the HFRT (n = 368) or CFRT (n = 366) group. At a median follow-up of 73.5 months (interquartile range, 60.5-91.4 months), the 5-year cumulative incidence of LR was 1.2% in the HFRT group and 2.0% in the CFRT group (hazard ratio, 0.62; 95% CI, 0.20 to 1.88; P = .017 for noninferiority). There were no significant differences in acute and late toxicities, except that the HFRT group had less grade 2-3 acute skin toxicity than the CFRT group (P = .019).CFRT and HFRT with a tumor-bed boost may have similar low LR and toxicity.
Intestinal microbiota-derived tryptophan metabolites are predictive of Ah receptor activity
Authors: Fangcong Dong, Fuhua Hao, Iain A. Murray, Philip B. Smith, Imhoi Koo, Alyssa M. Tindall, Penny M. Kris-Etherton, Krishne Gowda, Shantu G. Amin, Andrew D. Patterson, Gary H. Perdew
Journal: Gut Microbes (2020)

Commensal microbiota-dependent tryptophan catabolism within the gastrointestinal tract is known to exert profound effects upon host physiology, including the maintenance of epithelial barrier and immune function. A number of abundant microbiota-derived tryptophan metabolites exhibit activation potential for the aryl hydrocarbon receptor (AHR). Gene expression facilitated by AHR activation through the presence of dietary or microbiota-generated metabolites can influence gastrointestinal homeostasis and confer protection from intestinal challenges. Utilizing untargeted mass spectrometry-based metabolomics profiling, combined with AHR activity screening assays, we identify four previously unrecognized tryptophan metabolites, present in mouse cecal contents and human stool, with the capacity to activate AHR. Using GC/MS and LC/MS platforms, quantification of these novel AHR activators, along with previously established AHR-activating tryptophan metabolites, was achieved, providing a relative order of abundance. Using physiologically relevant concentrations and quantitative gene expression analyses, the relative efficacy of these tryptophan metabolites with regard to mouse or human AHR activation potential is examined. These data reveal indole, 2-oxindole, indole-3-acetic acid and kynurenic acid as the dominant AHR activators in mouse cecal contents and human stool from participants on a controlled diet. Here we provide the first documentation of the relative abundance and AHR activation potential of a panel of microbiota-derived tryptophan metabolites. Furthermore, these data reveal the human AHR to be more sensitive, at physiologically relevant concentrations, to tryptophan metabolite activation than mouse AHR. Additionally, correlation analyses indicate a relationship linking major tryptophan metabolite abundance with AHR activity, suggesting these cecal/fecal metabolites represent biomarkers of intestinal AHR activity.
Exposure to Road Traffic Noise and Incidence of Acute Myocardial Infarction and Congestive Heart Failure: A Population-Based Cohort Study in Toronto, Canada
Authors: Li Bai, Saeha Shin, Tor H. Oiamo, Richard T. Burnett, Scott Weichenthal, Michael Jerrett, Jeffrey C. Kwong, Ray Copes, Alexander Kopp, Hong Chen
Journal: Environmental Health Perspectives (2020)

Background: Epidemiological evidence for the association between traffic-related noise and the incidence of major cardiovascular events such as acute myocardial infarction (AMI) and congestive heart failure (CHF) is inconclusive, especially in North America. Objectives: We evaluated the associations between long-term exposure to road traffic noise and the incidence of AMI and CHF. Methods: Our study population comprised ∼1 million people 30–100 years of age who lived in Toronto, Canada, from 2001 to 2015 and were free of AMI (referred to as the AMI cohort) or CHF (the CHF cohort) at baseline. Outcomes were ascertained from health administrative databases using validated algorithms. Annual average noise levels were estimated as the A-weighted equivalent sound pressure level over the 24-h period (LAeq24) and during nighttime (LAeqNight), respectively, using propagation modeling, and assigned to participants’ annual six-digit postal code addresses during follow-up. We calculated hazard ratios (HRs) and 95% confidence intervals (CIs) for incident AMI and CHF in relation to LAeq24 and LAeqNight using random-effects Cox proportional hazards models adjusting for individual- and census tract–level covariates, including traffic-related air pollutants [e.g., ultrafine particles (UFPs) and nitrogen dioxide]. Results: During follow-up, there were 37,441 AMI incident cases and 95,138 CHF incident cases. Each interquartile range change in LAeq24 was associated with an increased risk of incident AMI (HR=1.07; 95% CI: 1.06, 1.08) and CHF (HR=1.07; 95% CI: 1.06, 1.09). Similarly, LAeqNight was associated with incident AMI (HR=1.07; 95% CI: 1.05, 1.08) and CHF (HR=1.06; 95% CI: 1.05, 1.07). These results were robust to various sensitivity analyses and remained elevated after controlling for long-term exposure to UFPs and nitrogen dioxide. We found near-linear relationships between noise and the incidence of AMI and CHF with no evidence of threshold values. Conclusion: In this large cohort study in Toronto, Canada, chronic exposure to road traffic noise was associated with elevated risks for AMI and CHF incidence. https://doi.org/10.1289/EHP5809
High Amount of Transcription Factor IRF8 Engages AP1-IRF Composite Elements in Enhancers to Direct Type 1 Conventional Dendritic Cell Identity
Authors: Sunkyung Kim, Prachi Bagadia, David A. Anderson, Tian-Tian Liu, Xiao Huang, Derek J. Theisen, Kevin W. O’Connor, Ray A. Ohara, Arifumi Iwata, Theresa L. Murphy, Kenneth M. Murphy
Journal: Immunity (2020)
Use of oscillatory positive expiratory pressure (OPEP) devices to augment sputum clearance in COPD: a systematic review and meta-analysis
Authors: Saeed M Alghamdi, Ruth Emily Barker, Abdullah S S Alsulayyim, Ali M Alasmari, Winston A S Banya, Michael I Polkey, Surinder S Birring, Nicholas S Hopkinson
Journal: Thorax (2020)

Introduction Oscillating positive expiratory pressure (OPEP) devices are intended to facilitate sputum clearance in chronic obstructive pulmonary disease (COPD), but there is uncertainty as to their place in treatment pathways. We aimed to review the existing literature to establish the evidence base for their use. Methods A systematic search of records up to March 2020 was performed on PubMed, CINAHL, Medline (Ovid), Cochrane and Embase to retrieve clinical trials that evaluated the efficacy of OPEP devices in patients with COPD. Two independent reviewers retrieved the titles, abstracts and full texts, and completed the data extraction. Results Following full-text review of 77 articles, eight (six randomised control trials and 2 cross-over studies) were eligible for inclusion. Pooled analysis showed low-grade evidence that the use of OPEP devices was associated with decreased COPD symptoms and exacerbations (OR 0.37, 95% CI 0.19 to 0.72), and enhanced exercise capacity; 6 min walk distance (mean difference (95% CI), 49.8 m (14.2 m to 85.5 m); p=0.009]). However, studies were mostly short term with the majority having a high risk of bias. The average acceptance, completion and drop-out rates were 82%, 91% and 8%, respectively. Conclusion The use of OPEP devices can have a positive impact in COPD, but confidence in effect sizes is low and there is a need for further, higher quality studies to examine their long-term efficacy in COPD as well as to identify specific patient phenotypes that are more likely to respond. PROSPERO registration number CRD 42016041835.
Mortality rates are lower with higher continuity of care, review finds
Authors: Elisabeth Mahase
Journal: BMJ (2020)

Higher continuity of care is associated with lower mortality rates, while discontinuity can cause patients to feel as though they are not being taken seriously, two studies have found in the British Journal of General Practice .12

However, despite mounting evidence that relationship continuity in primary care benefits patients, it is in decline, and “decisive action is required from policy makers and practitioners to counter this,” researchers warned.

The first study involved a systematic review of 13 quantitative studies (published from 2010 to 2018 in English …
Co-implantation of magnesium and zinc ions into titanium regulates the behaviors of human gingival fibroblasts
Authors: Lanyu Wang, Qiming Luo, Xianming Zhang, Jiajun Qiu, Shi Qian, Xuanyong Liu
Journal: Bioactive Materials (2020)

Soft tissue sealing around implants acts as a barrier between the alveolar bone and oral environment, protecting implants from the invasion of bacteria or external stimuli. In this work, magnesium (Mg) and zinc (Zn) are introduced into titanium by plasma immersed ion implantation technology, and their effects on the behaviors of human gingival fibroblasts (HGFs) as well as the underlying mechanisms are investigated. Surface characterization confirms Mg and Zn exist on the surface in metallic and oxidized states. Contact angle test suggests that surface wettability of titanium changes after ion implantation and thus influences protein adsorption of surfaces. In vitro studies disclose that HGFs on Mg ion-implanted samples exhibit better adhesion and migration while cells on Zn ion-implanted samples have higher proliferation rate and amounts. The results of immunofluorescence staining and real-time reverse-transcriptase polymerase chain reaction (RT-PCR) suggest that Mg mainly regulates the motility and adhesion of HGFs through activating the MAPK signal pathway whereas Zn influences HGFs proliferation by triggering the TGF-β signal pathway. The synergistic effect of Mg and Zn ions ensure that HGFs cultured on co-implanted samples possessed both high proliferation rate and motility, which are critical to soft tissue sealing of implants.
Highly Resistant Cholera Outbreak Strain in Zimbabwe
Authors: Tapfumanei Mashe, Daryl Domman, Andrew Tarupiwa, Portia Manangazira, Isaac Phiri, Kudzai Masunda, Prosper Chonzi, Elisabeth Njamkepo, Masindi Ramudzulu, Sekesai Mtapuri-Zinyowera, Anthony M Smith, François-Xavier Weill
Journal: New England Journal of Medicine (2020)

Highly Resistant Cholera Outbreak Strain in Zimbabwe Whole genomes of 11 Vibrio cholerae O1 isolates from the 2018–2019 outbreak in Zimbabwe were sequenced to investigate the determinants of antimi...
Lung and gut microbiota are altered by hyperoxia and contribute to oxygen-induced lung injury in mice
Authors: Shanna L. Ashley, Michael W. Sjoding, Antonia P. Popova, Tracy X. Cui, Matthew J. Hoostal, Thomas M. Schmidt, William R. Branton, Michael G. Dieterle, Nicole R. Falkowski, Jennifer M. Baker, Kevin J. Hinkle, Kristine E. Konopka, John R. Erb-Downward, Gary B. Huffnagle, Robert P. Dickson
Journal: Science Translational Medicine (2020)

Inhaled oxygen alters the microbiota of mice and humans, which may contribute to oxygen-induced lung injury.
Anaphylaxis following vaccination among children in Asia: A large‐linked database study
Authors: Young June Choe, Hyesung Lee, Ju Hwan Kim, Won Suk Choi, Ju‐Young Shin
Journal: Allergy (2020)

Dr Shin reported receiving grants from the Ministry of Food and Drug Safety, the Ministry of Health and welfare, the National Research Foundation of Korea, and Government-wide R&D Fund for infectious disease research; grants from pharmaceutical companies including Amgen, Pfizer, Hoffmann-La Roche, Dong-A ST, Yungjin outside the submitted work. No other disclosures were reported. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Need for Additional Trials of Vitamin C for Sepsis
Authors: D. Clark Files, Kathleen D. Liu, Michael Matthay
Journal: JAMA (2020)

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