tbuckley/cabot-search huggingface dataset:
Abstract P351: Longitudinal Association Between Low-to-moderate Alcohol Drinking and Cognition Trajectory in US Adults
Authors: Ruiyuan Zhang, Luqi Shen, Toni Miles, Ye Shen, Jose Cordero, Yanling Qi, lirong Liang, Changwei Li
Journal: Circulation (2020)

Background: Findings on the effect of alcohol drinking on cognitive function are mixed. The present study aimed to investigate the longitudinal associations of low-to-moderate alcohol drinking with cognition trajectories and changing rates among a nationally representative sample of middle-aged and older Americans. Method: A total of 19,887 participants in the Health and Retirement Study were included in the analyses. Performance of cognitive function was assessed every two years in 3 domains: mental status (MS), word recall (WR), and vocabulary (VOC). Trajectories of the total cognitive function (TCF) and individual domains were constructed using the SAS proc traj procedure. Age at cognition measurement was used as a time scale. Age related annual changing rates of cognition measures were estimated by regressing cognition scores over age for all individuals. Due to very few people, heavy drinkers were excluded. Multivariate logistic regression and linear regression were used to estimate the effect of low to moderate drinking on the cognition trajectories and annual changing rates after adjusting for baseline age, gender, race, years of education, marital status, smoking and body mass index. Result: Participants were clustered into a consistently low trajectory and a consistently high trajectory for each cognition measure. Low-to-moderate drinking was associated with a better trajectory and lower declining rate. Compared to never drinkers, current low-to-moderate drinkers were 0.67 (95% confidence interval [CI]: 0.59-0.75, P &lt;0.0001), 0.69 (95% CI: 0.61-0.79, P &lt;0.0001), 0.75 (95% CI: 0.69-0.81, P &lt;0.0001), and 0.63 (95% CI: 0.54-0.72, P &lt;0.0001) less likely to have a consistently low trajectory for TCF, MS, WR, and VOC, respectively. Meanwhile, current low-to-moderate drinking was associated with 0.05 (95% CI: 0.03-0.08, P &lt;0.0001), 0.02 (95% CI: 0.01-0.03, P =0.0001), 0.005 (95% CI: -0.003-0.01, P =0.23), 0.01 (95% CI: 0-0.02, P =0.04) units lower annual changing rates for those cognition measures. Racial differences were observed for trajectories of MS ( P =0.01), in which, low-to-moderate drinking was associated with the consistently low trajectory among whites (odds ratio=0.67, 95% CI: 0.58-0.76) but not among blacks (odds ratio =1.07, 95% CI: 0.79-1.45). There was no gender difference was observed. Conclusion: Current low-to-moderate alcohol drinkers associated with total cognitive function, word recall, mental status, and vocabulary in both men and women.
Extrapulmonary tuberculosis among migrants in Europe, 1995 to 2017
Authors: Sally E. Hayward, Kieran Rustage, Laura B. Nellums, Marieke J. van der Werf, Teymur Noori, Delia Boccia, Jon S. Friedland, Sally Hargreaves
Journal: Clinical Microbiology and Infection (2020)

The proportion of tuberculosis (TB) cases occurring in migrants in Europe is increasing. Extrapulmonary TB poses challenges in diagnosis and treatment and causes serious morbidity and mortality, yet its extent in migrant populations is unclear. We assessed patterns of extrapulmonary TB in migrants across the European Union (EU)/European Free Trade Association (EFTA). We investigated the proportion of extrapulmonary TB cases among migrants versus non-migrants, and variations by specific site of disease, reporting European region, and migrant region of origin.We carried out a cross-sectional secondary database analysis, utilizing 23 years of data collected between 1995 and 2017 from the European Surveillance System of the European Centre for Disease Prevention and Control for 32 EU/EFTA countries.In total, 1 270 896 TB cases were included, comprising 326 987 migrants (25.7%) and 943 909 non-migrants (74.3%). Of TB cases among migrants, 45.2% (n = 147 814) were extrapulmonary compared to 21.7% (n = 204 613) among non-migrants (p < 0.001). Lymphatic, bone/joint and peritoneal/digestive TB were more common among migrant than non-migrant extrapulmonary cases. A lower proportion of extrapulmonary TB was seen in Eastern Europe (17.4%, n = 98 656 of 566 170) and Southern Europe (29.6%, n = 62 481 of 210 828) compared with Western (35.7%, n = 89 498 of 250 517) and Northern Europe (41.8%, n = 101 792 of 243 381). Migrants from South-East Asia and Sub-Saharan Africa were at highest risk of extrapulmonary disease, with 62.0% (n = 55 401 of 89 353) and 54.5% (n = 38 327 of 70 378) of cases, respectively, being extrapulmonary.Among TB cases in the EU/EFTA, extrapulmonary disease is significantly more common in migrants than in non-migrants. There is a need to improve clinical awareness of extrapulmonary TB and to integrate its detection into screening programmes.
Estimated Resource Costs for Implementation of CDC’s Recommended COVID-19 Mitigation Strategies in Pre-Kindergarten through Grade 12 Public Schools — United States, 2020–21 School Year
Authors: Ketra L. Rice, Gabrielle F. Miller, Fátima Coronado, Martin I. Meltzer
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

As school districts across the United States consider how to safely operate during the 2020-21 academic year, CDC recommends mitigation strategies that schools can adopt to reduce the risk for transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19) (1). To identify the resources and costs needed to implement school-based mitigation strategies and provide schools and jurisdictions with information to aid resource allocation, a microcosting methodology was employed to estimate costs in three categories: materials and consumables, additional custodial staff members, and potential additional transportation. National average estimates, using the national pre-kindergarten through grade 12 (preK-12) public enrollment of 50,685,567 students, range between a mean of $55 (materials and consumables only) to $442 (all three categories) per student. State-by-state estimates of additional funds needed as a percentage of fiscal year 2018 student expenditures (2) range from an additional 0.3% (materials and consumables only) to 7.1% (all three categories); however, only seven states had a maximum estimate above 4.2%. These estimates, although not exhaustive, highlight the level of resources needed to ensure that schools reopen and remain open in the safest possible manner and offer administrators at schools and school districts and other decision-makers the cost information necessary to budget and prioritize school resources during the COVID-19 pandemic.
The case for an adverse interaction between aspirin and non-steroidal anti-inflammatory drugs: Is it time to believe the hype?**editorials published in the journal of the american college of cardiologyreflect the views of the authors and do not necessarily represent the views of jaccor the american college of cardiology.
Authors: Jeptha P. Curtis, Harlan M. Krumholz
Journal: Journal of the American College of Cardiology (2004)
Liver Disease and Coronavirus Disease 2019: From Pathogenesis to Clinical Care
Authors: Antonio Saviano, Florian Wrensch, Marc G. Ghany, Thomas F. Baumert
Journal: Hepatology (2020)

Infection with the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), a novel coronavirus that emerged in late 2019, is posing an unprecedented challenge to global health. Coronavirus disease 2019 (COVID‐19), the clinical disease caused by SARS‐CoV‐2, has a variable presentation ranging from asymptomatic infection to life‐threatening acute respiratory distress syndrome and multiorgan failure. Liver involvement is common during COVID‐19 and exhibits a spectrum of clinical manifestations from asymptomatic elevations of liver function tests to hepatic decompensation. The presence of abnormal liver tests has been associated with a more severe presentation of COVID‐19 disease and overall mortality. Although SARS‐CoV‐2 RNA has been detected in the liver of patients with COVID‐19, it remains unclear whether SARS‐CoV‐2 productively infects and replicates in liver cells and has a direct liver‐pathogenic effect. The cause of liver injury in COVID‐19 can be attributed to multiple factors, including virus‐induced systemic inflammation, hypoxia, hepatic congestion, and drug‐induced liver disease. Among patients with cirrhosis, COVID‐19 has been associated with hepatic decompensation and liver‐related mortality. Additionally, COVID‐19’s impact on health care resources can adversely affect delivery of care and outcomes of patients with chronic liver disease. Understanding the underlying mechanisms of liver injury during COVID‐19 will be important in the management of patients with COVID‐19, especially those with advanced liver disease. This review summarizes our current knowledge of SARS‐CoV‐2 virus‐host interactions in the liver as well the clinical impact of liver disease in COVID‐19.
Convergent network effects along the axis of gene expression during prostate cancer progression
Authors: Konstantina Charmpi, Tiannan Guo, Qing Zhong, Ulrich Wagner, Rui Sun, Nora C. Toussaint, Christine E. Fritz, Chunhui Yuan, Hao Chen, Niels J. Rupp, Ailsa Christiansen, Dorothea Rutishauser, Jan H. Rüschoff, Christian Fankhauser, Karim Saba, Cedric Poyet, Thomas Hermanns, Kathrin Oehl, Ariane L. Moore, Christian Beisel, Laurence Calzone, Loredana Martignetti, Qiushi Zhang, Yi Zhu, María Rodríguez Martínez, Matteo Manica, Michael C. Haffner, Ruedi Aebersold, Peter J. Wild, Andreas Beyer
Journal: Genome biology (2020)

Abstract Background Tumor-specific genomic aberrations are routinely determined by high-throughput genomic measurements. It remains unclear how complex genome alterations affect molecular networks through changing protein levels and consequently biochemical states of tumor tissues. Results Here, we investigate the propagation of genomic effects along the axis of gene expression during prostate cancer progression. We quantify genomic, transcriptomic, and proteomic alterations based on 105 prostate samples, consisting of benign prostatic hyperplasia regions and malignant tumors, from 39 prostate cancer patients. Our analysis reveals the convergent effects of distinct copy number alterations impacting on common downstream proteins, which are important for establishing the tumor phenotype. We devise a network-based approach that integrates perturbations across different molecular layers, which identifies a sub-network consisting of nine genes whose joint activity positively correlates with increasingly aggressive tumor phenotypes and is predictive of recurrence-free survival. Further, our data reveal a wide spectrum of intra-patient network effects, ranging from similar to very distinct alterations on different molecular layers. Conclusions This study uncovers molecular networks with considerable convergent alterations across tumor sites and patients. It also exposes a diversity of network effects: we could not identify a single sub-network that is perturbed in all high-grade tumor regions.
Associations of Various Subspecialties in Surgery With Career Satisfaction and Personal Life Among Surgeons by Gender
Authors: Lei Liang, Dong-Sheng Huang, Tian Yang
Journal: JAMA Surgery (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 Surgery 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 Surgery journal
RBIO-02. COMBINING RADIOTHERAPY WITH PI3K ISOFORM-SPECIFIC INHIBITOR DECREASES RADIORESISTANCE AND SUPPRESSES TUMOR GROWTH IN GLIOBLASTOMA CELLS
Authors: Mi Youn Seol, Hong In Yoon
Journal: Neuro-Oncology (2020)

Abstract Glioblastoma (GBM) is the most malignant tumor that occurs within the brain and shows the dismal prognosis. The phosphoinositide 3-kinase (PI3K)-AKT signaling pathway plays a principal role in GBM. Also, Activated PI3K-AKT signaling by irradiation induces radioresistance. But, the pan-PI3K inhibitors cause side-effects in clinical trial. Different PI3K isoforms play non-redundant roles in brain tumor growth and regulating radioresistance. So it is expected that selective inhibition of PI3K isoforms decrease side effects. We demonstrated whether combining radiotherapy with the PI3K isoform inhibitor reduces radioresistance and tumor growth in GBM. Glioma261 expressed luciferase (GL261-luc) cell lines were used to investigate the synergistic effects of combining radiotherapy with the PI3K isoform inhibitors. GL261-luc were irradiated 1Gy with or without PI3K isoform inhibitors. GL261-luc irradiated by 1Gy was suppressed cell proliferation about 70% compared to control (p&amp;lt; 0.001). When irradiated with PI3K-isform inhibitor, each growth rate was about 18% (PI3K-pan, p&amp;lt; 0.00001), 25% (PI3K-alpha, p&amp;lt; 0.00001), 30% (PI3K-delta, p&amp;lt; 0.00001), 45% (PI3K-gamma/delta, p&amp;lt; 0.00001). Significant increase of DNA DSB and decrease of the migration ability were shown by combination radiotherapy with PI3K- isoform inhibitor. Especially, combining radiotherapy, PI3K-alpha inhibitor showed the effect similar to PI3K-pan inhibitor (In vitro). So, we analyzed combination therapy effects using PI3K-alphs inhibitor and radiotherapy in vivo. We demonstrated that combining radiotherapy with the PI3K-alpha isoform inhibitor markedly delayed tumor growth than radiotherapy only (p&amp;lt; 0.0001). Also, we confirmed that survival rate of intracranial GBM mouse was increased by combination therapy (p&amp;lt; 0.01). In addition, the expression of PD1, regulator of cancer immune system, in spleenocyte was increased by combination therapy (p&amp;lt; 0.001) (In vivo). Our results demonstrate that combining radiotherapy with the PI3K-alpha isoform improve radiosensitivity, which result in significant tumor growth delay and improved survival.
NIMG-65. STUDY OF LOCAL PERTURBATION IN COMPUTATIONAL MODELLING ON TUMOR TREATING FIELDS (TTFIELDS) THERAPY
Authors: Oshrit Zeevi, Zeev Bomzon, Tal Marciano
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION Tumor Treating Fields (TTFields) are an approved therapy for glioblastoma (GBM). A recent study combining post-hoc analysis of clinical trial data and extensive computational modelling demonstrated that TTFields dose at the tumor has a direct impact on patient survival (Ballo MT, et al. Int J Radiat Oncol Biol Phys, 2019). Hence, there is rationale for developing TTFields treatment planning tools that rely on numerical simulations and patient-specific computational models. To assist in the development of such tools is it important to understand how inaccuracies in the computational models influence the estimation of the TTFields dose delivered to the tumor bed. Here we analyze the effect of local perturbations in patient-specific head models on TTFields dose at the tumor bed. METHODS Finite element models of human heads with tumor were created. To create defects in the models, conductive spheres with varying conductivities and radii were placed into the model’s brains at different distances from the tumor. Virtual transducer arrays were placed on the models, and delivery of TTFields numerically simulated. The error in the electric field induced by the defects as a function of defect conductivity, radius, and distance to tumor was investigated. RESULTS Simulations showed that when a defect of radius R is placed at a distance, d &amp;gt;7R, the error is below 1% regardless of the defect conductivity. Further the defects induced errors in the electric field that were below 1% when σrR/d &amp;lt; 0.16, where σrR/d &amp;lt; 0.16, where σr = (σsphere – σsurrounding)/(σsphere + σsurrounding).σsurroundings is the average conductivity around the sphere and σsphere is the conductivity of the sphere. CONCLUSIONS This study demonstrates the limited impact of local perturbations in the model on the calculated field distribution. These results could be used as guidelines on required model accuracy for TTFields treatment planning.
Hydroxychloroquine as Postexposure Prophylaxis to Prevent Severe Acute Respiratory Syndrome Coronavirus 2 Infection
Authors: Ruanne V. Barnabas, Elizabeth R. Brown, Anna Bershteyn, Helen C. Stankiewicz Karita, Christine Johnston, Lorna E. Thorpe, Angelica Kottkamp, Kathleen M. Neuzil, Miriam K. Laufer, Meagan Deming, Michael K. Paasche-Orlow, Patricia J. Kissinger, Alfred Luk, Kristopher Paolino, Raphael J. Landovitz, Risa Hoffman, Torin T. Schaafsma, Meighan L. Krows, Katherine K. Thomas, Susan Morrison, Harald S. Haugen, Lara Kidoguchi, Mark Wener, Alexander L. Greninger, Meei-Li Huang, Keith R. Jerome, Anna Wald, Connie Celum, Helen Y. Chu, Jared M. Baeten
Journal: Annals of Internal Medicine (2020)

Effective prevention against coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is currently limited to nonpharmaceutical strategies. Laboratory and observational data suggested that hydroxychloroquine had biological activity against SARS-CoV-2, potentially permitting its use for prevention.
An Alternating Irradiation Strategy‐Driven Combination Therapy of PDT and RNAi for Highly Efficient Inhibition of Tumor Growth and Metastasis
Authors: Dong Yue, Xiaojun Cai, Mengni Fan, Jingwu Zhu, Jiang Tian, Lihuang Wu, Qian Jiang, Zhongwei Gu
Journal: Advanced Healthcare Materials (2020)

Abstract Hypoxia and hypoxia induced overexpression of vascular endothelial growth factor (VEGF) not only seriously affects the treatment effects of photodynamic therapy (PDT) but also promotes tumor metastasis. Herein, an alternating irradiation strategy (referred to as alternate use of low/high dose of light [ALH DL ] irradiation)‐driven combination therapy of PDT and RNA interference (RNAi) is developed to synergistically inhibit tumor growth and metastasis. A cationic amphipathic peptide (ALS) served as a carrier in the co‐delivery system of photochlor (HPPH) and siVEGF (ALSH/siVEGF). At the beginning of ALH DL ‐driven ALSH/siVEGF treatment, short‐term LDL irradiation can facilitate the tumor penetration, cellular uptake, and endosome escape of ALSH/siVEGF. Moreover, accompanied by HDL‐mediated rapid cell apoptosis and LDL‐mediated efficient VEGF silencing, the joint use of PDT and RNAi achieved remarkable antitumor effects both in vitro and in vivo. Importantly, benefited from the excellent performance of ALH DL in slowing the rapid deterioration of the anoxic environment of tumors, and ALSH/siVEGF treatment‐mediated highly improved VEGF silencing efficacy and inhibitory effect on angiogenesis, the liver and lung metastases of HeLa cells have been successfully suppressed. Together, this study clearly indicates that ALH DL ‐driven combination therapy of PDT and RNAi is a highly effective modality for inhibition of tumor growth and metastasis.
ATRT-04. INHERITED RHABDOID PREDISPOSITION SYNDROME: A CASE OF CHOROID PLEXUS CARCINOMA AND ATYPICAL TERATOID RHABDOID TUMOR IN SIBLINGS
Authors: Alexis Judd, Erin Wright, Sarah Rush
Journal: Neuro-Oncology (2020)

Abstract Choroid plexus carcinoma (CPC) and Atypical teratoid/rhabdoid tumor (ATRT) are aggressive, malignant brain cancers most commonly arising in children less than 3 years of age. These tumors often have genetic alterations in the tumor suppressor gene SMARCB1/INI1. Rhabdoid predisposition syndrome (RTPS) categorizes patients with germline mutations in SMARCB1 or SMARCA4, leading to a markedly increased risk of developing rhabdoid tumors. Both CPC and ATRT have been demonstrated in patients with these rhabdoid predisposition syndromes. In general, these tumors tend to have a poor prognosis. However, with the presence of a SMARCB1 mutation they may have improved overall survival. We present two interesting cases of siblings with maternally inherited SMARCB1 mutations: one a 21-month-old male who presented with an ATRT and another a 10 month old female who presented with a CPC. The ATRT was treated as per the Children’s Oncology Group study ACNS0333 with high dose chemotherapy and stem cell rescue as well as cranial radiation. The CPC was treated as per CPT-SIOP 2009 with etoposide, cyclophosphamide and vincristine. Unlike other patients with these aggressive tumors, both of these patients are alive without evidence of disease recurrence 8 and 7 years post therapy, respectively. Additional genomic testing on both tumors is currently pending in order to potentially identify other mutations that may impact survival. These cases further illustrate the similar profile of two very different tumors with improved overall survival that may be secondary to mutations in SMARCB1 in RTPS.
A real-life comparative effectiveness study into the addition of antibiotics to the management of asthma exacerbations in primary care
Authors: Clare S. Murray, Sarah J. Lucas, John Blakey, Alan Kaplan, Alberto Papi, James Paton, Wanda Phipatanakul, David Price, Oon Hoe Teoh, Mike Thomas, Steve Turner, Nikolaos G. Papadopoulos
Journal: European Respiratory Journal (2021)

Background Asthma exacerbations are major contributors to asthma morbidity and mortality. They are usually managed with bronchodilators and oral corticosteroids (OCS), but clinical trial evidence suggests that antibiotics could be beneficial. We aimed to assess whether treatment of asthma exacerbations with antibiotics in addition to OCS improved outcomes in larger, more representative routine-care populations. Method A retrospective comparative effectiveness study into managing asthma exacerbations with OCS alone versus OCS plus antibiotics was conducted using the Optimum Patient Care Research Database. The dataset included 28 637 patients; following propensity score matching 20 024 adults and 4184 children were analysed. Results Antibiotics in addition to OCS were prescribed for the treatment of asthma exacerbations in 45% of adults and 32% of children. Compared to OCS alone, OCS plus antibiotics was associated with reduced risk of having an asthma/wheeze consultation in the following 2 weeks (children hazard ratio (HR) 0.84 (95% CI 0.73–0.96), p=0.012; adults HR 0.86 (95% CI 0.81–0.91), p&lt;0.001), but an increase in risk of a further OCS prescription for a new/ongoing exacerbation within 6 weeks in adults (HR 1.11 (95% CI 1.01–1.21), p=0.030), but not children. Penicillins, but not macrolides, were associated with a reduction in the odds of a subsequent asthma/wheeze consultation compared to OCS alone, in both adults and children. Conclusion Antibiotics were frequently prescribed in relation to asthma exacerbations, contrary to guideline recommendations. Overall, the routine addition of antibiotics to OCS in the management of asthma exacerbations appeared to confer little clinical benefit, especially when considering the risks of antibiotic overuse.