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International audience; Purpose: Neurodevelopmental disorders (NDDs), such as intellectual disability (ID) and autism spectrum disorder (ASD), exhibit genetic and phenotypic heterogeneity, making them difficult to differentiate without a molecular diagnosis. The Clinical Genome Resource Intellectual Disability/Autism Gene Curation Expert Panel (GCEP) uses systematic curation to distinguish ID/ASD genes that are appropriate for clinical testing (ie, with substantial evidence supporting their relationship to disease) from those that are not.Methods: Using the Clinical Genome Resource gene-disease validity curation framework, the ID/Autism GCEP classified genes frequently included on clinical ID/ASD testing panels as Definitive, Strong, Moderate, Limited, Disputed, Refuted, or No Known Disease Relationship.Results: As of September 2021, 156 gene-disease pairs have been evaluated. Although most (75%) were determined to have definitive roles in NDDs, 22 (14%) genes evaluated had either Limited or Disputed evidence. Such genes are currently not recommended for use in clinical testing owing to the limited ability to assess the effect of identified variants.Conclusion: Our understanding of gene-disease relationships evolves over time; new relationships are discovered and previously-held conclusions may be questioned. Without periodic re-examination, inaccurate gene-disease claims may be perpetuated. The ID/Autism GCEP will continue to evaluate these claims to improve diagnosis and clinical care for NDDs.

Mental illness is extremely prevalent, yet many pharmacy students get little exposure to mental health training. The majority of studies assessing mental health training and Mental Health First Aid (MHFA) are focused on undergraduate programs. This study critically evaluated the impact of MHFA on pharmacy students' knowledge, confidence, and perceptions as they pertain to mental health, as well as the appropriateness of MHFA as a training course for pharmacy students.There were two parts to this study: (1) a pre-/post-survey that assessed the impact of MHFA on pharmacy students as well as the appropriateness of MHFA for students at this level of education and training and (2) a college-wide survey that assessed the impact of mental health training of any type on confidence in mental health-related skills and the perceived usefulness of mental health training for pharmacy students.Participants of the MHFA portion of the study demonstrated a statistically significant improvement in knowledge of mental health-related topics and confidence to interact with someone experiencing mental illness (P .05) after completing the MHFA course. Perceptions of mental illness did not improve significantly following a single training. The college-wide survey (N = 275) revealed a significantly higher confidence level among students who had previously completed any mental health training program compared to those who had not (P .05).MHFA training significantly increased students' knowledge and confidence in approaching and interacting with persons experiencing mental illness.

Introduction Survey results from 2016 and 2018 at the University of Michigan College of Pharmacy highlighted mental health concerns for the student population, including struggles with depression, anxiety, and academic distress. This led to creation of a pilot well-being elective course for first year doctor of pharmacy students. This article describes how this course was assessed and adapted for the future. Methods The well-being elective course used a course-specific survey and the Brief Inventory of Thriving to assess student outcomes. The course-specific survey was based upon the course objectives and the University of Michigan Common Agenda for Well-Being. Both surveys were given pre- and post-course to identify change. Results Course survey results illustrated an improvement in student well-being over a single semester. Compared with pre-course responses, students who completed the course were significantly more likely to agree with statements indicating they had strong time management skills, resilience to manage the fluctuations of life, were able to make thoughtful choices to reduce harm and promote well-being, and overall rated their well-being as excellent. Additionally, nearly all students felt a sense of strengthened community with peers and faculty within the course, better able to recognize or refer a peer for help, and felt the course contributed to their overall well-being. Conclusions Implementation of this well-being elective pilot course provided students the tools and resources to improve upon their overall well-being in an effort to address anxiety, depression, and academic distress.

Vanadium disulfide (VS_{2}) attracts elevated interests for its charge-density wave (CDW) phase transition, ferromagnetism, and catalytic reactivity, but the electronic structure of monolayer has not been well understood yet. Here we report synthesis of epitaxial 1T VS_{2} monolayer on bilayer graphene grown by molecular-beam epitaxy (MBE). Angle-resolved photoemission spectroscopy (ARPES) measurements reveal that Fermi surface with six elliptical pockets centered at the M points shows gap opening at low temperature. Temperature-dependence of the gap size suggests existence of CDW phase transition above room temperature. Our observations provide important evidence to understand the strongly correlated electron physics and the related surface catalytic properties in two-dimensional transition-metal dichalcogenides (TMDCs)., Comment: 25 pages, 4 figures, accepted in Current Applied Physics

Ultrasonic-assisted soldering (UAS) creates an enhanced metal-to-glass bond that is linked to the increased wettability of the solder line. Precision experiments are performed using an automated UAS system, with precise control over a large number of experimental parameters, to investigate the wetting properties of solder to glass. Results show that wettability is increased with (i) increasing ultrasonic power and (ii) decreasing solder tip height above substrate, both of which are linked to the acoustic radiation pressure delivered by the vibrating solder tip to the liquid solder melt. Surface tension forces dominate the mechanics and a capillary shape equation is derived that includes the effect of acoustic radiation pressure. Numerical solutions to the capillary shape equation compare well with experimental observations, suggesting the solder bead geometry can be predicted a priori from the model.

Mitochondria are specialized compartments that produce requisite ATP to fuel cellular functions and serve as centers of metabolite processing, cellular signaling, and apoptosis. To accomplish these roles, mitochondria rely on the genetic information in their small genome (mitochondrial DNA) and the nucleus. A growing appreciation for mitochondria's role in a myriad of human diseases, including inherited genetic disorders, degenerative diseases, inflammation, and cancer, has fueled the study of biochemical mechanisms that control mitochondrial function. The mitochondrial transcriptional machinery is different from nuclear machinery. The in vitro re-constituted transcriptional complexes of Saccharomyces cerevisiae (yeast) and humans, aided with high-resolution structures and biochemical characterizations, have provided a deeper understanding of the mechanism and regulation of mitochondrial DNA transcription. In this review, we will discuss recent advances in the structure and mechanism of mitochondrial transcription initiation. We will follow up with recent discoveries and formative findings regarding the regulatory events that control mitochondrial DNA transcription, focusing on those involved in cross-talk between the mitochondria and nucleus. ispartof: JOURNAL OF BIOLOGICAL CHEMISTRY vol:295 issue:52 pages:18406-18425 ispartof: location:United States status: published

This paper assesses use of ExamSoft strength and opportunity (SO) reports amongst doctor of pharmacy students, student perceptions of the reports, and the effect of instructing students on how best to use the reports.Second-year pharmacy students enrolled in the medicinal chemistry and pharmacology course sequence completed a baseline survey regarding use of SO reports in the fall semester. Educational interventions describing best practices on how to use the SO report were provided to students. A follow-up survey was conducted in the winter semester.Eighty-four percent (69/82) of students returned a valid baseline survey, and 89% (71/80) returned a valid follow-up survey. At baseline, 55% (38/69) always/sometimes downloaded the report; this increased to 68% (48/71) after educational interventions (P = .06). Students who downloaded the report were asked to provide their perceived usefulness of the SO report. At baseline, 76% (29/38) of students downloading the report rated it as either somewhat/very useful; this increased to 94% (45/48) following educational interventions (P = .002). Fewer students reported not being able to interpret the report post-intervention vs. baseline, although the decrease was not significant (9% vs. 21%, respectively; P = .07).Our findings indicate that providing students with a downloadable SO report after exams is beneficial. There was a trend towards increased student use and a significant increase in perceived usefulness of the report following brief educational interventions. Our pilot data suggest that educational interventions on use of SO reports should be included in student ExamSoft training.

SWI/SNF-related intellectual disability disorders (SSRIDDs) are rare neurodevelopmental disorders characterized by developmental disability, coarse facial features, and fifth digit/nail hypoplasia that are caused by pathogenic variants in genes that encode for members of the SWI/SNF (or BAF) family of chromatin remodeling complexes. We have identified 12 individuals with rare variants (10 loss-of-function, 2 missense) in the BICRA (BRD4 interacting chromatin remodeling complex-associated protein) gene, also known as GLTSCR1, which encodes a subunit of the non-canonical BAF (ncBAF) complex. These individuals exhibited neurodevelopmental phenotypes that include developmental delay, intellectual disability, autism spectrum disorder, and behavioral abnormalities as well as dysmorphic features. Notably, the majority of individuals lack the fifth digit/nail hypoplasia phenotype, a hallmark of most SSRIDDs. To confirm the role of BICRA in the development of these phenotypes, we performed functional characterization of the zebrafish and Drosophila orthologs of BICRA. In zebrafish, a mutation of bicra that mimics one of the loss-of-function variants leads to craniofacial defects possibly akin to the dysmorphic facial features seen in individuals harboring putatively pathogenic BICRA variants. We further show that Bicra physically binds to other non-canonical ncBAF complex members, including the BRD9/7 ortholog, CG7154, and is the defining member of the ncBAF complex in flies. Like other SWI/SNF complex members, loss of Bicra function in flies acts as a dominant enhancer of position effect variegation but in a more context-specific manner. We conclude that haploinsufficiency of BICRA leads to a unique SSRIDD in humans whose phenotypes overlap with those previously reported.

Two-dimensional electron gases (2DEGs) on the SrTiO3 (STO) surface or in STO-based heterostructures have exhibited many intriguing phenomena, which are strongly dependent on the 2DEG-carrier density. We report that the tunability of the 2DEG-carrier density is significantly enhanced by adding a monolayer LaTiO3 (LTO) onto the STO. Ultraviolet (UV) irradiation induced maximum carrier density of the 2DEG in LTO/STO is increased by a factor of ~4 times, compared to that of the bare STO. By oxygen gas exposure, it becomes 10 times smaller than that of the bare STO. This enhanced tunability is attributed to the drastic surface property change of a polar LTO layer by UV irradiation and O2 exposure. This indicates that the 2DEG controllability in LTO/STO is more reliable than that on the bare STO driven by defects, such an oxygen vacancy., Comment: 19 pages, 4 figures

Primary care physicians (PCPs) are often asked to perform disability evaluations for patients with psychiatric disorders, which are now a leading cause of disability worldwide. After acknowledging the limitations of disability assessments for all conditions, this review aims to provide PCPs with practical knowledge to inform their assessments and interventions with a focus on patients with depression. After the disability definitions and programs in the United States are reviewed, a pragmatic approach to assessing function and discussing return to work is offered. Individualized assessment is key, and functional recovery rather than symptom relief should be prioritized. Finally, evidence-based interventions for enhancing the likelihood of return to work are considered. We believe the principles of functional assessment and recovery lend themselves to ready adaptation for use in other psychiatric conditions and chronic somatic syndromes, including chronic pain. The key principles of this approach are as follows: 1) a patient is not categorically disabled, but has specific limitations in specific contexts; 2) graded, work-oriented rehabilitation with tailored problem-solving strategies are essential; 3) involving a multidisciplinary team in coordinated care optimizes functional recovery; 4) return to work is an iterative process aimed at restoring meaningful function in a stepwise fashion; and 5) the relationship between symptoms and function is bidirectional. PCPs can use these principles to plan optimal recovery paths for psychiatrically ill patients presenting with a wide array of biopsychosocial realities.

As the electronics, automobile and other industries seek to eliminate the use of flux when joining dissimilar materials, ultrasonic-assisted soldering (UAS) has emerged as a prime candidate to replace conventional soldering to improve wetting at bonded joint surfaces. A challenge for UAS is to effectively scale up techniques for industrial use. This paper presents a modular, open-sourced automated system that was designed to allow for flexible and repeatable experimentation of the UAS process. Key process parameters include solder tip speed, tip distance from the substrate, ultrasonic power supplied to the molten solder, and the extrusion rate of the solder onto the substrate. Each of these parameters are user-controlled in our automated system, which is capable of soldering a general curved path while maintaining leading-edge orientation of the soldering tip. A compatible, low-cost profilometer attachment is retrofitted to our system in order to non-destructively characterize the wetting behavior of the solder-substrate system.

Mutations in the torsinA-interacting protein 1 (TOR1AIP1) gene result in a severe muscular dystrophy with minimal literature in the pediatric population. We review a case of TOR1AIP1 gene mutation in a 16-year-old Caucasian female with a long history of muscle weakness. Extensive clinical workup was performed and MRI at time of initial presentation demonstrated no significant muscular atrophy with heterogenous STIR hyperintensity of the lower extremity muscles. MRI findings seven years later included extensive atrophy of the lower extremities, with severe progression, including the gluteal muscles, iliopsoas, rectus femoris, and obturator internus. There was also significant atrophy of the rectus abdominis and internal and external oblique muscles, and iliacus muscles. The MRI findings showed more proximal involvement of lower extremities and no atrophy of the tibialis anterior, making TOR1AIP1 the more likely genetic cause. Muscle biopsy findings supported TOR1AIP1 limb-girdle muscular dystrophy. Though rare, TOR1AIP1 gene mutation occurs in pediatric patients and MRI can aid in diagnosis and help differentiate from other types of muscular dystrophy. Genetic and pathology workup is also crucial to accurate diagnosis and possible treatment of these patients.