To increase the number of independent National Institutes of Health (NIH)-funded neurosurgeons and to enhance neurosurgery research, the National Institute of Neurological Disorders and Stroke ...(NINDS) developed two national comprehensive programs (R25 established 2009 for residents/fellows and K12 2013 for early-career neurosurgical faculty) in consultation with neurosurgical leaders and academic departments to support in-training and early-career neurosurgeons. The authors assessed the effectiveness of these NINDS-initiated programs to increase the number of independent NIH-funded neurosurgeon-scientists and grow NIH neurosurgery research funding.
NIH funding data for faculty and clinical department funding were derived from the NIH, academic departments, and Blue Ridge Institute of Medical Research databases from 2006 to 2019.
Between 2009 and 2019, the NINDS R25 funded 87 neurosurgical residents. Fifty-three (61%) have completed the award and training, and 39 (74%) are in academic practice. Compared to neurosurgeons who did not receive R25 funding, R25 awardees were twice as successful (64% vs 31%) in obtaining K-series awards and received the K-series award in a significantly shorter period of time after training (25.2 ± 10.1 months vs 53.9 ± 23.0 months; p < 0.004). Between 2013 and 2019, the NINDS K12 has supported 19 neurosurgeons. Thirteen (68%) have finished their K12 support and all (100%) have applied for federal funding. Eleven (85%) have obtained major individual NIH grant support. Since the establishment of these two programs, the number of unique neurosurgeons supported by either individual (R01 or DP-series) or collaborative (U- or P-series) NIH grants increased from 36 to 82 (a 2.3-fold increase). Overall, NIH funding to clinical neurological surgery departments between 2006 and 2019 increased from $66.9 million to $157.3 million (a 2.2-fold increase).
Targeted research education and career development programs initiated by the NINDS led to a rapid and dramatic increase in the number of NIH-funded neurosurgeon-scientists and total NIH neurosurgery department funding.
Biomedical research training has undergone considerable change over the past several years. At its core, the goal of graduate and postdoctoral training is to provide individuals with the skills and ...knowledge to become outstanding scientists and expand knowledge through the scientific method. Historically, graduate school training has focused on preparation for academic positions. Increasingly, however, a shift toward preparation for a wider range of career options has emerged. This is largely because most biomedical PhD graduates do not become Principal Investigators in academic laboratories. Here we describe an National Institutes of Health Common Fund program with the major goal of culture change for biomedical research training and training that prepares individuals for a broader expanse of careers in the biomedical research enterprise. These “Broadening Experiences in Scientific Training” (BEST) awards, issued in 2012 and 2013, provided support to institutions to develop innovative approaches to achieving these goals, as a complement to traditional training. Awardees were tasked with catalyzing change at their institutions and sharing best practices across the training community. Awardees were required to participate in a cross‐site evaluation that assessed the impact of BEST activities on three main areas: (a) trainee confidence and knowledge to make career decisions, (b) influence of this added activity on time in training, and (c) ability of the institutions to sustain activities deemed to be beneficial. Here we present the fundamental approach to the BEST program and early evaluative data.
Multiple approaches to quantitative structure–activity relationship (QSAR) modeling using various statistical or machine learning techniques and different types of chemical descriptors have been ...developed over the years. Oftentimes models are used in consensus to make more accurate predictions at the expense of model interpretation. We propose a simple, fast, and reliable method termed Multi-Descriptor Read Across (MuDRA) for developing both accurate and interpretable models. The method is conceptually related to the well-known kNN approach but uses different types of chemical descriptors simultaneously for similarity assessment. To benchmark the new method, we have built MuDRA models for six different end points (Ames mutagenicity, aquatic toxicity, hepatotoxicity, hERG liability, skin sensitization, and endocrine disruption) and compared the results with those generated with conventional consensus QSAR modeling. We find that models built with MuDRA show consistently high external accuracy similar to that of conventional QSAR models. However, MuDRA models excel in terms of transparency, interpretability, and computational efficiency. We posit that due to its methodological simplicity and reliable predictive accuracy, MuDRA provides a powerful alternative to a much more complex consensus QSAR modeling. MuDRA is implemented and freely available at the Chembench web portal (https://chembench.mml.unc.edu/mudra ).
Objective Training clinician–scientists is a primary objective of many academic neurology departments, as these individuals are uniquely positioned to perform insightful clinical or laboratory‐based ...research informed both by clinical knowledge and their own experiences caring for patients. Despite its importance, training clinician–scientists has perhaps never been so challenging. The National Institute of Neurologic Disorders and Stroke (NINDS) R25 program was designed in an attempt to support these individuals, decrease the time needed to obtain National Institutes of Health K awards, and to help educate a cohort of trainees preparing for a career in academic neurology. We endeavored to describe the structure and features of the program while examining its outcomes. Methods R25 outcome data from 2009 to 2024 were reviewed. Statistical comparisons were made using 2‐sided Mann–Whitney U testing. Results A total of 67% of adult neurologists who received an R25 had a successful application for a National Institutes of Health K award compared with 45% of adult neurologists who had not received R25 support ( p < 0.0001). Among child neurologists, 73% who applied went on to receive K funding after R25 support, compared with 45% who had not been part of the R25 program ( p < 0.001). The average time between completion of residency and obtaining a K award for R25 participants was decreased by 26 months among those with an MD/PhD degree, and 32 months for those with an MD degree compared with non‐R25 individuals. Interpretation The R25 program has been successful in achieving its training goals, but stands as only one component of support for aspiring clinician–scientists. Investments and commitments made by academic neurology departments are key to supporting this success. ANN NEUROL 2024
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•About 450 million people are suffering from over 7000 rare diseases worldwide.•Current drug discovery pipeline is inefficient and unsustainable for rare diseases.•Knowledge mining ...can boost the development of therapeutics for rare diseases.
The conventional drug discovery pipeline has proven to be unsustainable for rare diseases. Herein, we discuss recent advances in biomedical knowledge mining applied to discovering therapeutics for rare diseases. We summarize current chemogenomics data of relevance to rare diseases and provide a perspective on the effectiveness of machine learning (ML) and biomedical knowledge graph mining in rare disease drug discovery. We illustrate the power of these methodologies using a chordoma case study. We expect that a broader application of knowledge graph mining and artificial intelligence (AI) approaches will expedite the discovery of viable drug candidates against both rare and common diseases.
Hospitalization presents an opportunity to begin people with opioid use disorder (OUD) on medications for opioid use disorder (MOUD) and link them to care after discharge; regrettably, people ...admitted to the hospital with an underlying OUD typically do not receive MOUD and are not connected with subsequent treatment for their condition. To address this gap, we launched a multi-site randomized controlled trial to test the effectiveness of a hospital-based addiction consultation team (the Substance Use Treatment and Recovery Team (START)) consisting of an addiction medicine specialist and care manager team that provide collaborative care and a specified intervention to people with OUD during the inpatient stay. Successful implementation of new practices can be impacted by organizational context, though no previous studies have examined context prior to implementation of addiction consultation services (ACS). This study assessed pre-implementation context for implementing a specialized ACS and tailoring it accordingly.
We conducted semi-structured interviews with hospital administrators, physicians, physician assistants, nurses, and social workers at the three study sites between April and August 2021 before the launch of the pragmatic trial. Using an analytical framework based on the Consolidated Framework for Implementation Research, we completed a thematic analysis of interview data to understand potential barriers or enablers and perceptions about acceptability and feasibility.
We interviewed 28 participants across three sites. The following themes emerged across sites: (1) START is an urgently needed model for people with OUD; (2) Intervention adaptations are recommended to meet local and cultural needs; (3) Linking people with OUD to community clinicians is a highly needed component of START; (4) It is important to engage stakeholders across departments and roles throughout implementation. Across sites, participants generally saw a need for change from usual care to support people with OUD, and thought the START was acceptable and feasible to implement. Differences among sites included tailoring the START to support the needs of varying patient populations and different perceptions of the prevalence of OUD.
Hospitals planning to implement an ACS in the inpatient setting may wish to engage in a systematic pre-implementation contextual assessment using a similar framework to understand and address potential barriers and contextual factors that may impact implementation. Pre-implementation work can help ensure the ACS and other new practices fit within each unique hospital context.
Defining clinical outcome pathways Korn, Daniel; Thieme, Andrew J.; Alves, Vinicius M. ...
Drug discovery today,
June 2022, 2022-Jun, 2022-06-00, 20220601, Letnik:
27, Številka:
6
Journal Article
Recenzirano
Odprti dostop
•We define the concept of Clinical Outcome Pathways (COP).•COPs is a chain of key events: Initiating-Intermediate-Clinical Outcome.•COPs will deepen our understanding of the biological pathways of ...drug action.•COP concept could accelerate drug discovery and repurposing.
Here, we propose a broad concept of ‘Clinical Outcome Pathways’ (COPs), which are defined as a series of key molecular and cellular events that underlie therapeutic effects of drug molecules. We formalize COPs as a chain of the following events: molecular initiating event (MIE) → intermediate event(s) → clinical outcome. We illustrate the concept with COP examples both for primary and alternative (i.e., drug repurposing) therapeutic applications. We also describe the elucidation of COPs for several drugs of interest using the publicly accessible Reasoning Over Biomedical Objects linked in Knowledge-Oriented Pathways (ROBOKOP) biomedical knowledge graph-mining tool. We propose that broader use of COP uncovered with the help of biomedical knowledge graph mining will likely accelerate drug discovery and repurposing efforts.
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