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    Diversity in Osteopathic Medical School Admissions and the COMPASS Program: An Update

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    In the United States, the 40 colleges of osteopathic medicine and 157 schools of allopathic medicine face challenges in recruiting candidates who are underrepresented in medicine (URiM), and gaps in racial disparity appear to be widening. In this commentary, the authors provide an analysis of the data collected from 8 years of conducting a URiM recruitment and welcoming social events. The event is sponsored by a student special interest group called Creating Osteopathic Minority Physicians Who Achieve Scholastic Success (COMPASS) at the Touro College of Osteopathic Medicine - New York (TouroCOM-NY). The results of the 8-year data analysis supports the conclusion that the COMPASS program has benefited the school environment through increased diversity

    Comparing Cognitive Tests and Smartphone-Based Assessment in 2 US Community-Based Cohorts.

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    BACKGROUND: Smartphone-based cognitive assessments have emerged as promising tools, bridging gaps in accessibility and reducing bias in Alzheimer disease and related dementia research. However, their congruence with traditional neuropsychological tests and usefulness in diverse cohorts remain underexplored. METHODS AND RESULTS: A total of 406 FHS (Framingham Heart Study) and 59 BHS (Bogalusa Heart Study) participants with traditional neuropsychological tests and digital assessments using the Defense Automated Neurocognitive Assessment (DANA) smartphone protocol were included. Regression models investigated associations between DANA task digital measures and a neuropsychological global cognitive CONCLUSIONS: Our findings demonstrate that smartphone-based cognitive assessments exhibit concurrent validity with a composite measure of traditional neuropsychological tests. This supports the potential of using smartphone-based assessments in cognitive screening across diverse populations and the scalability of digital assessments to community-dwelling individuals

    Unveiling the Unique RAS Isoform and Domain Specific Regulation of BRAF Kinase

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    BRAF kinase is a key member of the MAPK pathway, important for cell growth and division. Upstream signals promote BRAF activation by interaction with the membrane bound GTPase, RAS, which leads to relief of autoinhibition and dimerization. The N-terminal regulatory domains of BRAF, including the BRAF specific region (BSR), the RAS binding domain (RBD), and the cysteine rich domain (CRD), govern the conformational state of the cytosolic, autoinhibited monomer and drive the RAS-RAF interaction. Active BRAF phosphorylates and activates its substrate MEK, which in turn phosphorylates and activates ERK. Mutations in RAS and BRAF are the cause of many cancers and RASopathy developmental disorders; however, therapeutic approaches are limited due to challenges in BRAF and RAS inhibition and an incomplete understanding of BRAF and RAS biochemistry. Here, we shed light on the details of BRAF activation and interaction with RAS in three parts: 1) we investigated the roles of the BSR, RBD, and CRD in regulating the RAS-RAF interaction and membrane recruitment; 2) we developed chemical probes to disrupt the RAS-RAF interaction and eliminate MAPK signaling in cancer; and 3) we elucidated the intramolecular interactions involved in RAF autoinhibition. Our findings point to unique contributions of each BRAF N-terminal domain in the regulation of autoinhibition and in determining isoform-specific RAS interactions

    Academic Instruction Librarians’ Conceptions of Teacher Agency and Affective Orientations toward the Concept

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    This article reports on findings of an online survey on academic instruction librarians’ conceptions and experiences of teacher agency in the context of their instruction work and, more specifically, on their affective orientations (positive, ambivalent, or negative emotions and feelings) toward teacher agency. Two key dimensions of participants’ conceptions of teacher agency are evident throughout this analysis: 1) views of teacher agency as an individual experience of autonomy (individual agency) and/or views of it as more relational and interactive (and thus potentially collective), and 2) beliefs about the feasibility of librarians’ teacher agency, given librarians’ roles and positions as educators. Participants generally expressed positive affect when they felt they were independently in control of their teaching (individual agency), or when they described reciprocal and collaborative relationships with faculty (potentially collective agency). Participants expressed negative affect about experiences of lacking teacher agency. Almost all participants expressed 1) a desire to experience meaning and purpose in teaching and 2) a sensitivity to the highly relational nature of librarians’ instructional work. Finally, the author discusses potential implications for academic instruction librarians’ teaching practices, professional development, and work environments

    Digital Clock Drawing as an Alzheimer\u27s Disease Susceptibility Biomarker: Associations with Genetic Risk Score and APOE in Older Adults

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    BACKGROUND: Alzheimer\u27s disease (AD) is the leading cause of dementia in older adults, but most people are not diagnosed until significant neuronal loss has likely occurred along with a decline in cognition. Non-invasive and cost-effective digital biomarkers for AD have the potential to improve early detection. OBJECTIVE: We examined the validity of DCTclockTM (a digitized clock drawing task) as an AD susceptibility biomarker. DESIGN: We used two primary independent variables, Apolipoprotein E (APOE) ε4 allele carrier status and polygenic risk score (PRS). We examined APOE and PRS associations with DCTclockTM composite scores as dependent measures. SETTING: We used existing data from the Framingham Heart Study (FHS), a community-based study with the largest dataset of digital clock drawing data to date. PARTICIPANTS: The sample consisted of 2,398 older adults ages 60-94 with DCTclockTM data (mean age of 72.3, 55% female and 92% White). MEASUREMENTS: PRS was calculated using 38 variants identified in a recent large genome-wide association study (GWAS) and meta-analysis of late-onset AD (LOAD). RESULTS: Results showed that DCTclockTM performance decreased with advancing age, lower education, and the presence of one or more copies of APOE ε4. Lower DCTclockTM Total Score as well as lower composite scores for Information Processing Speed (both command and copy conditions) and Drawing Efficiency (command condition) were significantly associated with higher PRS levels and more copies of APOE ε4. APOE and PRS associations displayed similar effect sizes in both men and women. CONCLUSIONS: Our results indicate that higher AD genetic risk is associated with poorer DCTclockTM performance in older adults without dementia. This is the first study to demonstrate significant differences in clock drawing performance on the basis of APOE status or PRS

    Elastin-like polypeptide as a model to study Intrinsically Disordered Proteins

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    The elastin-like polypeptide (ELP) is a well-studied structural protein that is easily amenable to amino acid (AA) sequence modifications and has the potential to yield a wide variety of uses in bioengineering and biomedical applications. One unique property of ELP is the inclusion of intrinsically disordered domains (IDP) within the structure that allow for its diversity of physical properties. While it is generally understood that amino acid sequence dictates protein folding arrangements, the contributions of specific amino acid sequences to the intrinsic disorder of ELP has yet to be fully resolved. Therefore, identifying the contributions of specific amino acid sequences to the final physical properties of ELP at the sequence level is an important step in understanding the basis of ELP’s unique biophysical properties. The results of this study resolve the role of amino acid sequence and repeat composition on the disordered structure of ELP. Experimentally, an enhanced synthetic ELP[AV-60] was developed, produced, and purified, with novel photocrosslinking and a transition temperature of 37°C. Computationally, the conserved AA sequence of valine-proline (VP) in the endogenous ELN sequence and its major function in the structure of ELP was identified. Finally, we identified a specific AA monomeric unit, VPGXAG with potential for application in IDPs research

    How to Respond to Racist Patients: Recommendations from a Literature Review

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    Introduction: Dealing with racist patients is not uncommon, and these interactions can sever the therapeutic alliance, as well as leave providers feeling isolated, dehumanized, and ashamed. Investigation of published recommendations for handling these situations can give victims, peers, and institutions the tools necessary to prepare, protect, and support providers through these challenging encounters. Methods: This paper is a literature review. For inclusion in this review, studies must have met the criteria of providing recommendations for healthcare providers or institutions on how to deal with racist patients. Excluded articles did not include recommendations on how to handle such situations or did not otherwise meet inclusion criteria. PubMed Medline was searched in January 2022 using a combination of the following keywords and associated MeSH terms: “Racism” AND “Physician-Patient relations”. The resulted articles then underwent forward and backward citation searching. A total of 44 articles were included after evaluation of 272 articles via this process. Results: For the affected individual, recommended responses include addressing the comment firmly and directly in real time, setting boundaries and behavior expectation, reporting the incident to supervisors and to the hospital, and seeking support from peers and/or professionals. At the peer level, core practices are supporting the victim, addressing the patient if necessary, debriefing with the victim and team, and checking-in with the victim in the following days. At the institution level, core practices are enacting reporting system and tracking incidents, developing specific policies and procedures about biased patients, and training staff with focused antibias and antidiscrimination sessions. Discussion: There are steps to be taken at every level to create a supportive and inclusive practice that protects providers against racist patients. One limitation of this study was that it was not a systematic review so there may be other recommendations published that are not reflected here

    Ksp1 Is an Autophagic Receptor Protein for the Snx4-Assisted Autophagy of Ssn2/Med13

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    Ksp1 is a casein II-like kinase whose activity prevents aberrant macroautophagy/autophagy induction in nutrient-rich conditions in yeast. Here, we describe a kinase-independent role of Ksp1 as a novel autophagic receptor protein for Ssn2/Med13, a known cargo of Snx4-assisted autophagy of transcription factors. In this pathway, a subset of conserved transcriptional regulators, Ssn2/Med13, Rim15, and Msn2, are selectively targeted for vacuolar proteolysis following nitrogen starvation, assisted by the sorting nexin heterodimer Snx4-Atg20. Here we show that phagophores also engulf Ksp1 alongside its cargo for vacuolar proteolysis. Ksp1 directly associates with Atg8 following nitrogen starvation at the interface of an Atg8-family interacting motif (AIM)/LC3-interacting region (LIR) in Ksp1 and the LIR/AIM docking site (LDS) in Atg8. Mutating the LDS site prevents the autophagic degradation of Ksp1. However, deletion of the C terminal canonical AIM still permitted Ssn2/Med13 proteolysis, suggesting that additional non-canonical AIMs may mediate the Ksp1-Atg8 interaction. Ksp1 is recruited to the perivacuolar phagophore assembly site by Atg29, a member of the trimeric scaffold complex. This interaction is independent of Atg8 and Snx4, suggesting that Ksp1 is recruited early to phagophores, with Snx4 delivering Ssn2/Med13 thereafter. Finally, normal cell survival following prolonged nitrogen starvation requires Ksp1. Together, these studies define a kinase-independent role for Ksp1 as an autophagic receptor protein mediating Ssn2/Med13 degradation. They also suggest that phagophores built by the trimeric scaffold complex are capable of receptor-mediated autophagy. These results demonstrate the dual functionality of Ksp1, whose kinase activity prevents autophagy while it plays a scaffolding role supporting autophagic degradation

    Laboratory Evaluation of Warm Mix Additives at Lower than Traditional Compaction Temperatures

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    The study aims to evaluate the impact of warm mix additives (WMA) on the rheological and performance properties of asphalt binders and mixtures. For this purpose, PG 76-28 and PG 58-28 were obtained with one organic (Sasobit Redux) and three chemical WMA (Rediset, Evotherm, and Zycotherm). All WMA-modified asphalt binders were aged at three different aging levels. Laboratory tests such as performance grade (PG), critical temperature differential (ΔTc), asphalt binder cracking device (ABCD), linear amplitude sweep test (LAS), and Fourier transform infrared spectroscopy (FTIR) were performed. In addition to the binder testing plan, this study also evaluated the impact of WMA type, binder grade, and compaction temperature on the volumetrics and performance of the mixtures when compacted at lower than traditional temperatures (260℉, 220℉, and 180℉). The cracking, rutting, and moisture damage resistance of all mixtures were evaluated using the Indirect Tensile Cracking Test (IDEAL-CT), Asphalt Pavement Analyzer (APA), and tensile strength ratio (TSR), respectively. Laboratory testing showed WMA\u27s feasibility to improve the binder and mixture properties performance compared to the control mixture and binder. Finally, All mixtures were evaluated using the multi-factor analysis of variance (ANOVA), and ranking was developed based on the mean difference of each mixture

    RESISTING INTERNALIZED STIGMA (RIS): ACCEPTABILITY AND FEASIBILITY OF A COGNITIVE BEHAVIORAL STIGMA INTERVENTION FOR EARLY PSYCHOSIS

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    The clinical high-risk state for psychosis (CHR-P) was created to help identify individuals experiencing early signs of psychosis to help forestall worsening symptoms. CHR-P individuals may experience stigma that may stem from internal or external processes, including from receiving specialized care. Research has demonstrated associations between internalized stigma and psychosocial and functional outcomes, which underscores the need for interventions to help mitigate the impact of stigma while balancing the need for treatment. To date, there is only one stigma intervention specifically designed for individuals designated as CHR-P, which is psychoeducational in nature. Based on the recent call to action that highlights the need for specialized stigma interventions for CHR-P groups, this study piloted the first manualized, cognitive-behaviorally based stigma intervention designed for early psychosis, including those at risk. The study took place at the University of Pennsylvania’s Psychosis Evaluation and Recovery Center and recruited 9 CHR-P and first episode psychosis subjects to participate in two simultaneously run groups. Psychosocial and functional outcomes were assessed at baseline and follow-up and demonstrated reductions in stigma and depression and elevations in sense of purpose, self-esteem, and social cognitive performance. Qualitative interviews showed acceptability, feasibility, and ideas for manual refinement

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