Citations

Abstract The lung, one the largest branching organs in our body and vital for survival at first breath, is commonly known as the gas-exchange organ. Recent novel findings on lung sensing cells, molecules, and lung-brain crosstalk in the emerging discipline of interoception have highlighted the consideration of the lung as a sensory organ. Acknowledging the central importance of lung sensing to human health and disease, NHLBI convened a workshop to synthesize the past, current, and future of lung sensing research, with in-person presentations by ∼20 interdisciplinary experts and a large virtual audience. Here, we highlight the key topics discussed and summarize a blueprint for the future in this important field.

ABSTRACT Inpatient, acute care clinical pharmacists have contributed to many notable improvements in patient outcomes. Several studies have shown a reduction in mortality and other clinical markers when pharmacists are integrated within the care team. Economic analyses of inpatient clinical pharmacy services (CPS) generally demonstrate cost savings related to specific medication classes, prevention of adverse drug events, decreased length of stay, and decreased rehospitalization. Studies also show high satisfaction from other health care professionals, noting improvements in medication‐related patient safety. Finally, studies conducted in tertiary care hospital settings report high levels of patient satisfaction with CPS. As such, the ECHO framework, based on economic, clinical, and humanistic outcomes, is used herein to organize the summary of literature associated with CPS. Given the growing body of evidence, numerous health professional and government organizations recognize the role of pharmacists as an integral part of the inpatient team. Yet implementation of CPS has not been fully realized by hospitals and health systems. This paper briefly describes inpatient CPS, highlights many benefits of and endorsements for clinical pharmacist participation on interdisciplinary teams, and provides high‐level recommendations for health system administrators and the profession of pharmacy to further encourage broader integration of CPS into patient care teams. Effectively positioning inpatient clinical pharmacists as indispensable team members will require intentional work and strategic planning with a focus on high‐impact value, visibility, and leadership.

Abstract Background Mono-allelic Dehydrodolichyl Diphosphate Synthase ( DHDDS) variants are associated with juvenile Parkinsonism, developmental delay and seizures. Symptoms are progressive, and various mechanisms, such as defective glycosylation, lysosomal dysfunction and cholesterol accumulation have been hypothesized to underlie disease symptoms. There is no treatment for DHDDS-related disease. Methods Patient-derived cortical forebrain organoids were created to elucidate disease mechanisms and evaluate potential treatments. In these neuronal models, glycosylation, lipidomics, proteomics, cholesterol/ganglioside accumulation, mitochondrial function and electrophysiological activity were assessed. Finally, we investigated the effects of nicotinamide mononucleotide (NMN), identified through a yeast-based drug screen, in neuronal cell models and in six patients in an off-label, N-of-1, observational series. Results DHDDS-patient derived organoids showed visual signs of degeneration after four months of culturing. This was accompanied by significant cholesterol accumulation in astrocytes, decreased mitochondrial respiration and loss of deep-layer neurons. In addition, we identified glycosylation abnormalities, showing for the first time that glycosylation in human tissue is affected by monoallelic DHDDS variants. Proteomic analysis revealed altered protein expression of proteins involved in lipid metabolism, cytoskeletal organization and neuronal development. We found that oral Nicotinamide Mononucleotide supplementation led to significant improvement in mitochondrial respiration and electrophysiological parameters in organoids, concurring with clinical improvements in all of the treated patients, particularly regarding their ataxia and tremor. Conclusion Our findings reveal a progressive phenotype in DHDDS-patient-derived brain organoids, with mitochondrial dysfunction and astrocyte-specific metabolic alterations contributing to disease pathology. Notably, NMN treatment led to clinical improvements in patients with heterozygous DHDDS variants, highlighting its potential as a therapeutic strategy.

Abstract Oncogenic BRAF alterations occur in a subset of diffuse gliomas across WHO grades and are increasingly identified through modern molecular diagnostics. In addition to standard glioma therapies, targeted treatments are available for patients with BRAF-altered glioma supported by variable evidence spanning randomized trials, single-arm studies, and real-world evidence. This joint consensus review from the Society for Neuro-Oncology (SNO) and the European Association of Neuro-Oncology (EANO) synthesizes current knowledge on the diagnosis and management of BRAF-altered gliomas across age groups, tumor grades, and lines of therapy. Particular emphasis is placed on expert consensus in clinical scenarios where high-quality trial evidence remains limited. The review addresses rationale testing for BRAF alterations, selection, and monitoring of targeted therapies, management of treatment-related toxicities, approaches to resistance, and priorities for future research. It aims to provide practical, evidence-based guidance for clinicians while highlighting gaps to inform prospective studies.

Abstract Antidepressants are widely prescribed for major depressive disorder, yet only one-third of patients achieve remission after initial treatment. Previous genome-wide association studies (GWAS) of clinically assessed antidepressant response combined multiple antidepressant classes, potentially obscuring class-specific effects. This study focused on selective serotonin reuptake inhibitors (SSRIs), often first-line due to better tolerability. Data from 15 cohorts across four ancestries were integrated: European (N = 3887; 11 studies), East Asian (N = 1068; 4), African (N = 277; 1), and Admixed American (N = 250; 1). GWAS of non-remission and percentage improvement were conducted within cohorts, followed by ancestry-specific meta-analyses and trans-ancestry meta-regression. Single nucleotide polymorphism (SNP)-based heritability was estimated in European samples. Polygenic scores were used for leave-one-out prediction and to assess shared genetic architecture with psychiatric traits. Gene-level and gene-set enrichment analyses were also performed. No genome-wide significant variants were identified for either outcome in any ancestry-specific or trans-ancestry analyses. However, trans-ancestry meta-regression yielded eight independent loci with suggestive associations (p < 1 × 10 −5 ) for non-remission and 17 for percentage improvement. Gene-set analyses revealed nominal enrichment of the serotonergic synapse pathway for non-remission. SNP-based heritability estimates were not significantly different from zero for either outcome. Better SSRI response was nominally associated with lower genetic predisposition to major depressive disorder, post-traumatic stress disorder, and schizophrenia. This study represents the largest trans-ancestry GWAS of SSRI response, highlighting emerging biological signals. Limited power emphasises the need for larger and ancestrally diverse cohorts to better characterise the genetic architecture of antidepressant response.

BACKGROUND/OBJECTIVES Pediatric hospital medicine (PHM) is a growing field with a unique scholarly perspective and evolving role in academic leadership. Since the last systematic assessment of PHM research in 2009, predating subspecialty certification in 2016 and fellowship accreditation in 2020, the research infrastructure within PHM has not been reevaluated. We sought to assess the current state of PHM research by assessing the number, scope, and scholarly domains of research faculty, as well as research funding and support. METHODS Using the Pediatrics Research in Inpatient Settings Network, we distributed a cross-sectional survey to PHM group leaders across the United States and Canada. The 16-item instrument, adapted from prior PHM and adult hospital medicine surveys, assessed program demographics, faculty effort allocation, research support, funding, and scholarly domains. Surveys were distributed via REDCap with follow-up reminders. Descriptive statistics were used. RESULTS 49 programs responded (51% response rate), representing 1702 faculty (∼40% of US pediatric hospitalists). Fewer than half of programs (n = 21, 43%) reported faculty with more than 50% research effort. One-hundred and ninety faculty members (11%) had dedicated research time, and 72% of those conducting quality improvement research did so without any protected effort. Most PHM programs (n = 27, 55%) received less than $100 000 in total annual research funding. CONCLUSIONS Despite recent PHM subspecialty designation and pediatric hospitalist desire to conduct research, dedicated time and associated supports are uncommon in PHM groups. Improvements in the PHM research pipeline will require understanding institutional financial constraints and diversifying and strengthening research funding.

Abstract Clinical medical physics is a profession that intersects with various groups as part of a broader healthcare team, including dosimetrists, radiation therapists, radiologic and MRI technologists, IT specialists, and physicians. Success in this field requires academic and technical excellence as well as comprehensive skills for working effectively within an interdisciplinary healthcare team. When hiring medical physics residents, the selection of well‐rounded and highly qualified candidates can be facilitated through a holistic review process that ensures consideration of traditional metrics such as academic performance while also accounting for the importance of various experiences, personal attributes, and intrinsic motivations that impact clinical performance and patient care. The Association of American Medical Colleges (AAMC) emphasizes an overall consideration of Experiences, Attributes, Competencies, and Metrics (EACM) as important for the search process. As part of the healthcare community, medical physics shares the same commitment to high‐quality patient care. By adopting the AAMC's EACM framework, medical physics residency programs can strengthen the fairness, rigor, and overall effectiveness of their application review processes—ultimately benefiting applicants, the medical physics community, and the patients we serve. This Society of Directors of Academic Medical Physics Programs (SDAMPP) task report aims to provide information and resources for applying holistic review to the applicant selection process for medical physics residency programs. Our objective is to enable program directors to reevaluate their selection methods in the context of institutional and program missions and goals and to improve the quality and specificity of recruitment by integrating holistic review concepts into their residency recruitment processes. This initiative can inspire change in recruitment practices, aid programs in hiring well‐rounded and well‐qualified residents, and support the professional growth of our trainees in healthcare. This report provides an overview of holistic reviews and its core principles. We review the current literature and provide evidence from successful implementations of holistic review in other medical fields to illustrate how it can benefit our field. Furthermore, we outline actionable recommendations to facilitate transitioning to a holistic review framework and address potential barriers with practical solutions. A supplemental workbook is provided to guide residency programs in developing their own holistic application review and interview processes. With this report, we aim to provide practical implementation guidelines that will allow residency program directors to implement a selection methodology that comprehensively assesses the full qualifications of individual candidates and ultimately fosters the development of versatile and competent clinical medical physicists who are best equipped to advance the field, meet patient needs, and improve patient care.