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Advancing the Science in Gastric Pre-Neoplasia: Study Design Considerations.
Davitkov P, Altayar O, Shah SC, Gawron AJ, Mustafa RA, Sultan S, Morgan DR
(2020) Gastroenterology 158: 751-759
MeSH Terms: Biomedical Research, Biopsy, Endoscopy, Gastrointestinal, Gastric Mucosa, Humans, Incidence, Metaplasia, Population Surveillance, Precancerous Conditions, Prevalence, Research Design, Risk Factors, Stomach Neoplasms
Added March 3, 2020
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1 Members
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13 MeSH Terms
National Institutes of Health StrokeNet Training Core.
Vahidy FS, Sozener CB, Meeks JR, Chhatbar PY, Ramos-Estebanez C, Ayodele M, Richards RJ, Sharma R, Wilbrand SM, Prabhakaran S, Bregman BS, Adams HP, Jordan LC, Liebeskind DS, Tirschwell D, Janis LS, Marshall RS, Kleindorfer D
(2020) Stroke 51: 347-352
MeSH Terms: Biomedical Research, Fellowships and Scholarships, Financing, Organized, Humans, Mentors, National Institutes of Health (U.S.), Stroke, United States
Show Abstract · Added March 24, 2020
Background and Purpose- The National Institutes of Health (NIH) StrokeNet provides a nationwide infrastructure to advance stroke research. Capitalizing on this unique opportunity, the NIH StrokeNet Training Core (NSTC) was established with the overarching goal of enhancing the professional development of a diverse spectrum of professionals who are embedded in the stroke clinical trials network of the NIH StrokeNet. Methods- This special report provides a descriptive account of the rationale, organization, and activities of the NSTC since its inception in 2013. Current processes and their evolution over time for facilitating training of NIH StrokeNet trainees have been highlighted. Data collected for monitoring training are summarized. Outcomes data (publications and grants) collected by NSTC was supplemented by publicly available resources. Results- The NSTC comprises of cross-network faculty, trainees, and education coordinators. It helps in the development and monitoring of training programs and organizes educational and career development activities. Trainees are provided directed guidance towards their mandated research projects, including opportunities to present at the International Stroke Conference. The committee has focused on developing sustainable models of peer-to-peer interaction and cross-institutional mentorships. A total of 124 professionals (43.7% female, 10.5% underrepresented minorities) have completed training between 2013 and 2018, of whom 55% were clinical vascular neurologists. Of the total, 85% transitioned to a formal academic position and 95% were involved in stroke research post-training. Altogether, 1659 indexed publications have been authored or co-authored by NIH StrokeNet Trainees, of which 58% were published during or after their training years. Based on data from 109 trainees, 33% had submitted 72 grant proposals as principal or co-principal investigators of which 22.2% proposals have been funded. Conclusions- NSTC has provided a foundation to foster nationwide training in stroke research. Our data demonstrate strong contribution of trainees towards academic scholarship. Continued innovation in educational methodologies is required to adapt to unique training opportunities such as the NIH StrokeNet.
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8 MeSH Terms
Mindfulness-Based Blood Pressure Reduction (MB-BP): Stage 1 single-arm clinical trial.
Loucks EB, Nardi WR, Gutman R, Kronish IM, Saadeh FB, Li Y, Wentz AE, Webb J, Vago DR, Harrison A, Britton WB
(2019) PLoS One 14: e0223095
MeSH Terms: Blood Pressure, Blood Pressure Determination, Feasibility Studies, Female, Focus Groups, Follow-Up Studies, Humans, Hypertension, Interviews as Topic, Male, Middle Aged, Mindfulness, Patient Acceptance of Health Care, Qualitative Research, Treatment Outcome
Show Abstract · Added January 4, 2020
BACKGROUND AND OBJECTIVES - Impacts of mindfulness-based programs on blood pressure remain equivocal, possibly because the programs are not adapted to engage with determinants of hypertension, or due to floor effects. Primary objectives were to create a customized Mindfulness-Based Blood Pressure Reduction (MB-BP) program, and to evaluate acceptability, feasibility, and effects on hypothesized proximal self-regulation mechanisms. Secondary outcomes included modifiable determinants of blood pressure (BP), and clinic-assessed systolic blood pressure (SBP).
METHODS - This was a Stage 1 single-arm trial with one year follow-up. Focus groups and in-depth interviews were performed to evaluate acceptability and feasibility. Self-regulation outcomes, and determinants of BP, were assessed using validated questionnaires or objective assessments. The MB-BP curriculum was adapted from Mindfulness-Based Stress Reduction to direct participants' mindfulness skills towards modifiable determinants of blood pressure.
RESULTS - Acceptability and feasibility findings showed that of 53 eligible participants, 48 enrolled (91%). Of these, 43 (90%) attended at least 7 of the 10 MB-BP classes; 43 were followed to one year (90%). Focus groups (n = 19) and semi-structured interviews (n = 10) showed all participants viewed the delivery modality favorably, and identified logistic considerations concerning program access as barriers. A priori selected primary self-regulation outcomes showed improvements at one-year follow-up vs. baseline, including attention control (Sustained Attention to Response Task correct no-go score, p<0.001), emotion regulation (Difficulties in Emotion Regulation Score, p = 0.02), and self-awareness (Multidimensional Assessment of Interoceptive Awareness, p<0.001). Several determinants of hypertension were improved in participants not adhering to American Heart Association guidelines at baseline, including physical activity (p = 0.02), Dietary Approaches to Stop Hypertension-consistent diet (p<0.001), and alcohol consumption (p<0.001). Findings demonstrated mean 6.1 mmHg reduction in SBP (p = 0.008) at one year follow-up; effects were most pronounced in Stage 2 uncontrolled hypertensives (SBP≥140 mmHg), showing 15.1 mmHg reduction (p<0.001).
CONCLUSION - MB-BP has good acceptability and feasibility, and may engage with self-regulation and behavioral determinants of hypertension.
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15 MeSH Terms
Need for Multidisciplinary Research and Data-Driven Guidelines for the Cardiovascular Care of Patients With Cancer.
Meijers WC, Moslehi JJ
(2019) JAMA 322: 1775-1776
MeSH Terms: Antineoplastic Agents, Cardiac Resynchronization Therapy, Cardiomyopathies, Humans, Interdisciplinary Research, Neoplasms, Patient Care Team, Stroke Volume
Added January 15, 2020
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MeSH Terms
Unmet need in rheumatology: reports from the Targeted Therapies meeting 2019.
Winthrop KL, Weinblatt ME, Bathon J, Burmester GR, Mease PJ, Crofford L, Bykerk V, Dougados M, Rosenbaum JT, Mariette X, Sieper J, Melchers F, Cronstein BN, Breedveld FC, Kalden J, Smolen JS, Furst D
(2020) Ann Rheum Dis 79: 88-93
MeSH Terms: Arthritis, Psoriatic, Arthritis, Rheumatoid, Biomedical Research, Central Nervous System Sensitization, Clinical Trials as Topic, Congresses as Topic, Humans, Lupus Erythematosus, Systemic, Molecular Targeted Therapy, Needs Assessment, Research, Research Design, Rheumatic Diseases, Rheumatology, Spondylitis, Ankylosing
Show Abstract · Added March 25, 2020
OBJECTIVES - To detail the greatest areas of unmet scientific and clinical needs in rheumatology.
METHODS - The 21st annual international Advances in Targeted Therapies meeting brought together more than 100 leading basic scientists and clinical researchers in rheumatology, immunology, epidemiology, molecular biology and other specialties. During the meeting, breakout sessions were convened, consisting of 5 disease-specific groups with 20-30 experts assigned to each group based on expertise. Specific groups included: rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, systemic lupus erythematosus and other systemic autoimmune rheumatic diseases. In each group, experts were asked to identify unmet clinical and translational research needs in general and then to prioritise and detail the most important specific needs within each disease area.
RESULTS - Overarching themes across all disease states included the need to innovate clinical trial design with emphasis on studying patients with refractory disease, the development of trials that take into account disease endotypes and patients with overlapping inflammatory diseases, the need to better understand the prevalence and incidence of inflammatory diseases in developing regions of the world and ultimately to develop therapies that can cure inflammatory autoimmune diseases.
CONCLUSIONS - Unmet needs for new therapies and trial designs, particularly for those with treatment refractory disease, remain a top priority in rheumatology.
© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
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15 MeSH Terms
Vaccine innovations for emerging infectious diseases-a symposium report.
Cable J, Srikantiah P, Crowe JE, Pulendran B, Hill A, Ginsberg A, Koff W, Mathew A, Ng T, Jansen K, Glenn G, Permar S, Wilson I, Weiner DB, Weissman D, Rappuoli R
(2020) Ann N Y Acad Sci 1462: 14-26
MeSH Terms: Animals, Clinical Trials as Topic, Communicable Disease Control, Communicable Diseases, Communicable Diseases, Emerging, Congresses as Topic, Humans, New York City, Research Report, Therapies, Investigational, Vaccines
Show Abstract · Added March 31, 2020
Vaccines have been incredibly successful at stemming the morbidity and mortality of infectious diseases worldwide. However, there are still no effective vaccines for many serious and potentially preventable infectious diseases. Advances in vaccine technology, including new delivery methods and adjuvants, as well as progress in systems biology and an increased understanding of the human immune system, hold the potential to address these issues. In addition, maternal immunization has opened an avenue to address infectious diseases in neonates and very young infants. This report summarizes the presentations from a 1-day symposium at the New York Academy of Sciences entitled "Innovative Vaccines against Resistant Infectious Diseases and Emerging Threats," held on May 20, 2019.
© 2019 New York Academy of Sciences.
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11 MeSH Terms
The human body at cellular resolution: the NIH Human Biomolecular Atlas Program.
HuBMAP Consortium
(2019) Nature 574: 187-192
MeSH Terms: Aging, Atlases as Topic, Biomedical Research, Female, Health, Humans, International Cooperation, Male, Models, Anatomic, Molecular Biology, National Institutes of Health (U.S.), Organ Specificity, Single-Cell Analysis, United States
Show Abstract · Added January 22, 2020
Transformative technologies are enabling the construction of three-dimensional maps of tissues with unprecedented spatial and molecular resolution. Over the next seven years, the NIH Common Fund Human Biomolecular Atlas Program (HuBMAP) intends to develop a widely accessible framework for comprehensively mapping the human body at single-cell resolution by supporting technology development, data acquisition, and detailed spatial mapping. HuBMAP will integrate its efforts with other funding agencies, programs, consortia, and the biomedical research community at large towards the shared vision of a comprehensive, accessible three-dimensional molecular and cellular atlas of the human body, in health and under various disease conditions.
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Targeting Gut Microbiome Interactions in Service-Related Gastrointestinal and Liver Diseases of Veterans.
Bajaj JS, Sharma A, Dudeja PK, Collaborators
(2019) Gastroenterology 157: 1180-1183.e1
MeSH Terms: Biomedical Research, Gastroenterology, Gastrointestinal Diseases, Gastrointestinal Microbiome, Humans, Liver Diseases, United States, United States Department of Veterans Affairs, Veterans Health, Veterans Health Services
Added October 29, 2019
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10 MeSH Terms
Androgenic Effects on Ventricular Repolarization: A Translational Study From the International Pharmacovigilance Database to iPSC-Cardiomyocytes.
Salem JE, Yang T, Moslehi JJ, Waintraub X, Gandjbakhch E, Bachelot A, Hidden-Lucet F, Hulot JS, Knollmann BC, Lebrun-Vignes B, Funck-Brentano C, Glazer AM, Roden DM
(2019) Circulation 140: 1070-1080
MeSH Terms: Androgens, Antineoplastic Agents, Cell Differentiation, Cells, Cultured, Databases, Factual, Humans, Hypogonadism, Induced Pluripotent Stem Cells, International Cooperation, Long QT Syndrome, Male, Myocytes, Cardiac, Pharmacovigilance, Phenylthiohydantoin, Risk, Torsades de Pointes, Translational Medical Research
Show Abstract · Added November 12, 2019
BACKGROUND - Male hypogonadism, arising from a range of etiologies including androgen-deprivation therapies (ADTs), has been reported as a risk factor for acquired long-QT syndrome (aLQTS) and torsades de pointes (TdP). A full description of the clinical features of aLQTS associated with ADT and of underlying mechanisms is lacking.
METHODS - We searched the international pharmacovigilance database VigiBase for men (n=6 560 565 individual case safety reports) presenting with aLQTS, TdP, or sudden death associated with ADT. In cardiomyocytes derived from induced pluripotent stem cells from men, we studied electrophysiological effects of ADT and dihydrotestosterone.
RESULTS - Among subjects receiving ADT in VigiBase, we identified 184 cases of aLQTS (n=168) and/or TdP (n=68; 11% fatal), and 99 with sudden death. Of the 10 ADT drugs examined, 7 had a disproportional association (reporting odds ratio=1.4-4.7; <0.05) with aLQTS, TdP, or sudden death. The minimum and median times to sudden death were 0.25 and 92 days, respectively. The androgen receptor antagonist enzalutamide was associated with more deaths (5430/31 896 [17%]; <0.0001) than other ADT used for prostate cancer (4208/52 089 [8.1%]). In induced pluripotent stem cells, acute and chronic enzalutamide (25 µM) significantly prolonged action potential durations (action potential duration at 90% when paced at 0.5 Hz; 429.7±27.1 (control) versus 982.4±33.2 (acute, <0.001) and 1062.3±28.9 ms (chronic; <0.001), and generated afterdepolarizations and/or triggered activity in drug-treated cells (11/20 acutely and 8/15 chronically). Enzalutamide acutely and chronically inhibited delayed rectifier potassium current, and chronically enhanced late sodium current. Dihydrotestosterone (30 nM) reversed enzalutamide electrophysiological effects on induced pluripotent stem cells.
CONCLUSIONS - QT prolongation and TdP are a risk in men receiving enzalutamide and other ADTs.
CLINICAL TRIAL REGISTRATION - URL: https://www.clinicaltrials.gov. Unique identifier: NCT03193138.
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17 MeSH Terms
The Most Valuable Resource Is Time: Insights From a Novel National Program to Improve Retention of Physician-Scientists With Caregiving Responsibilities.
Jones RD, Miller J, Vitous CA, Krenz C, Brady KT, Brown AJ, Daumit GL, Drake AF, Fraser VJ, Hartmann KE, Hochman JS, Girdler S, Libby AM, Mangurian C, Regensteiner JG, Yonkers K, Jagsi R
(2019) Acad Med 94: 1746-1756
MeSH Terms: Adult, Biomedical Research, Career Choice, Education, Medical, Faculty, Medical, Female, Financing, Organized, Humans, Male, Middle Aged, Physicians, Program Development, Prospective Studies, Research Personnel
Show Abstract · Added August 5, 2020
PURPOSE - To enhance understanding of challenges related to work-life integration in academic medicine and to inform the ongoing implementation of an existing program and the development of other interventions to promote success of physician-scientists.
METHOD - This study is part of a prospective analysis of the effects of the Fund to Retain Clinical Scientists (FRCS), a national program launched by the Doris Duke Charitable Foundation at 10 U.S. institutions, which provides financial support to physician-scientists facing caregiving challenges. In early 2018, 28 of 33 program awardees participated in semistructured interviews. Questions were about challenges faced by physician-scientists as caregivers and their early perceptions of the FRCS. Multiple analysts reviewed deidentified transcripts, iteratively revised the coding scheme, and interpreted the data using qualitative thematic analysis.
RESULTS - Participants' rich descriptions illuminated 5 interconnected themes: (1) Time is a critical and limited resource, (2) timing is key, (3) limited time resources and timing conflicts may have a particularly adverse effect on women's careers, (4) flexible funds enable reclamation and repurposing of time resources, and (5) FRCS leaders should be cognizant of time and timing conflicts when developing program-related offerings.
CONCLUSIONS - Programs such as the FRCS are instrumental in supporting individuals to delegate time-consuming tasks and to control how they spend their valuable time. Qualitative analysis suggests that access to and command of valuable time resources are crucial to career advancement, research productivity, and work-life flexibility, especially during critical time points along the physician-scientist trajectory.
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MeSH Terms