Spatial proteomic differences in chronic traumatic encephalopathy, Alzheimer's disease, and primary age-related tauopathy hippocampi.

Introduction: Alzheimer's disease (AD), primary age-related tauopathy (PART), and chronic traumatic encephalopathy (CTE) all feature hyperphosphorylated tau (p-tau)-immunoreactive neurofibrillary degeneration, but differ in neuroanatomical distribution and progression of neurofibrillary degeneration and amyloid beta (Aβ) deposition.

Methods: We used Nanostring GeoMx Digital Spatial Profiling to compare the expression of 70 proteins in neurofibrillary tangle (NFT)-bearing and non-NFT-bearing neurons in hippocampal CA1, CA2, and CA4 subregions and entorhinal cortex of cases with autopsy-confirmed AD (n = 8), PART (n = 7), and CTE (n = 5).

Results: There were numerous subregion-specific differences related to Aβ processing, autophagy/proteostasis, inflammation, gliosis, oxidative stress, neuronal/synaptic integrity, and p-tau epitopes among these different disorders.

Antisemitism in Medicine: An International Perspective.

Throughout history, Jewish people have long been recognized for their achievements in the world of medical science. For example, prior to the Holocaust, many outstanding physicians in Germany were Jewish. However, even in the 1930s, refugee European Jewish doctors faced significant barriers when they tried to escape and practice elsewhere because of long-standing prejudices and anti-Jewish quotas in medical schools and hospitals around the world.

Diversity-Related, Student-Led National Medical Organizations: Leadership Opportunities for Learners.

Introduction: In light of the lack of diversity in academic medicine leadership, diversity-related, student-led national medical organizations (NMOs) provide a space for solace and reprieve among common peers while providing an opportunity to develop leadership competencies in a supportive environment. Despite the impact NMOs have had on cultivating generations of leaders in medicine, trainees may not identify opportunities for leadership development that are transferable to future careers in academic medicine.

Methods: We designed and implemented a dynamic 60-minute workshop with an interactive PowerPoint presentation, author-owned video testimonials (from past student leaders of NMOs), two case presentations, and reflection exercises.

Organization Theory for Implementation Science (OTIS): reflections and recommendations.

Organizations exert influence on the implementation of evidence-based practices and other innovations that are independent of the influence of organizations' individual constituents. Despite their influence, nuanced explanations of organizations' influence remain limited in implementation science. Organization theories are uniquely suited to offer insights and explain organizational influences on implementation.

Harvey Cushing: France Military Hospital Surgical Unit Head and World War I United States Army Medical Corps Commissioner.

Background: This historical account reviews the course and lasting impact of Dr. Harvey Cushing (1869-1939) in neurosurgery.

Methods: The writing of this project was sparked by the discovery of original scientific and bibliographical information about Cushing.

Utilization and Outcomes Associated With Intravascular Ultrasound during Abdominal and Thoracic Endovascular Aortic Interventions in the United States in the Contemporary Era (2016-2023).

Background: Intravascular ultrasound (IVUS) use in aortic endovascular interventions, including thoracic endovascular aneurysm repair (TEVAR) and endovascular aneurysm repair (EVAR), may have similar benefits to those seen in coronary and peripheral interventions, but limited utilization and outcome data exist.

Methods: Centers for Medicare and Medicaid Services claims data were used to identify patients undergoing TEVAR and EVAR from 2016 to 2023. Utilization trends were stratified by region, urbanicity, distressed communities index, community versus academic center, Medicare versus dual enrollment status, indication, urgency, and presence of dissection with malperfusion.

Impact of maternal antenatal nutrition and infection treatment interventions on Longitudinal Infant Development and Growth in rural Ethiopia: protocol of the LIDG child follow-up study.

Introduction: Maternal undernutrition and inflammation in utero may significantly impact the neurodevelopmental potential of offspring. However, few studies have investigated the effects of pregnancy interventions on long-term child growth and development. This study will examine the effects of prenatal nutrition and infection management interventions on long-term growth and neurodevelopmental outcomes of offspring.

Negative valence in Obsessive-Compulsive Disorder: A worldwide mega-analysis of task-based functional neuroimaging data of the ENIGMA-OCD consortium.

Objective: Obsessive-compulsive disorder (OCD) is associated with altered brain function related to processing of negative emotions. To investigate neural correlates of negative valence in OCD, we pooled fMRI data of 633 individuals with OCD and 453 healthy controls from 16 studies using different negatively-valenced tasks across the ENIGMA-OCD Working-Group.

Methods: Participant data were processed uniformly using HALFpipe, to extract voxelwise participant-level statistical images of one common first-level contrast: negative vs.

Sex and Gender Considerations in Orthopaedic Research: Existing Barriers, What's Needed by Institutions and Research Departments, and How to Guide Junior Investigators and Faculty.

JBJS convened a symposium to discuss the reporting of sex and gender in research studies as an imperative to improve research methods and results to benefit all patients. Barriers to improved reporting include a lack of societal and cultural acceptance of its need; a lack of education regarding appropriate terminology and appropriate statistical methods and efficient study designs; a need for increased research funding to support larger group sizes; unknown concordance of cell and animal models with humans to reflect biologic variables such as sex; and a lack of understanding of key considerations of gender, race, and other social determinants of health and how these factors intersect. Attention to developing and disseminating best-practice statistical methods and to educating investigators (at all career levels), reviewers, funders, editors, and staff in their proper implementation will aid reporting.

Towards an Understanding of the Dentate Gyrus Hilus.

For many years, the hilus of the dentate gyrus (DG) was a mystery because anatomical data suggested a bewildering array of cells without clear organization. Moreover, some of the anatomical information led to more questions than answers. For example, it had been identified that one of the major cell types in the hilus, the mossy cell, innervates granule cells (GCs).

Reproductive rights at the U.S. state level and medication access for pregnant women with opioid use.

Despite the rise in chronic, untreated opioid use among pregnant women, their rate of receiving medications for opioid use disorder (MOUD) has remained stagnant since the mid-1990s. Using retrospective cross-sectional substance use treatment admissions data from 2015 to 2019, we examined access to treatment for opioid use by pregnant adults across 48 U.S.

Cell-type-specific auditory responses in the striatum are shaped by feedforward inhibition.

The posterior "tail" region of the striatum receives dense innervation from sensory brain regions and is important for behaviors that require sensorimotor integration. The output neurons of the striatum, D1 and D2 striatal projection neurons (SPNs), which make up the direct and indirect pathways, are thought to play distinct functional roles, although it remains unclear if these neurons show cell-type-specific differences in their response to sensory stimuli. Here, we examine the strength of synaptic inputs onto D1 and D2 SPNs following the stimulation of upstream auditory pathways.

Multidimensional Effects of Stress on Neuronal Exosome Levels and Simultaneous Transcriptomic Profiles.

Background: An excess of exosomes, nanovesicles released from all cells and key regulators of brain plasticity, is an emerging therapeutic target for stress-related mental illnesses. The effects of chronic stress on exosome levels are unknown; even less is known about molecular drivers of exosome levels in the stress response.

Methods: We used our state-of-the-art protocol with 2 complementary strategies to isolate neuronal exosomes from plasma, ventral dentate gyrus, basolateral amygdala, and olfactory bulbs of male mice to determine the effects of chronic restraint stress (CRS) on exosome levels.

3D chromatin hubs as regulatory units of identity and survival in human acute leukemia.

Cancer progression involves genetic and epigenetic changes that disrupt chromatin 3D organization, affecting enhancer-promoter interactions and promoting growth. Here, we provide an integrative approach, combining chromatin conformation, accessibility, and transcription analysis, validated by in silico and CRISPR-interference screens, to identify relevant 3D topologies in pediatric T cell leukemia (T-ALL and ETP-ALL). We characterize 3D hubs as regulatory centers for oncogenes and disease markers, linking them to biological processes like cell division, inflammation, and stress response.

Targeted degradation of oncogenic KRASG12V triggers antitumor immunity in lung cancer models.

KRAS is the most frequently mutated oncogene in lung adenocarcinoma, with G12C and G12V being the most predominant forms. Recent breakthroughs in KRASG12C inhibitors have transformed the clinical management of patients with G12C mutation and advanced our understanding of its function. However, little is known about the targeted disruption of KRASG12V, partly due to a lack of specific inhibitors.

Simultaneous Bilateral T, T, and T Relaxation Mapping of Hip Joint With 3D-MRI Fingerprinting.

Background: Three-dimensional MR fingerprinting (3D-MRF) has been increasingly used to assess cartilage degeneration, particularly in the knee joint, by looking into multiple relaxation parameters. A comparable 3D-MRF approach can be adapted to assess cartilage degeneration for the hip joint, with changes to accommodate specific challenges of hip joint imaging.

Purpose: To demonstrate the feasibility and repeatability of 3D-MRF in the bilateral hip jointly we map proton density (PD), T, T, T, and ∆B in clinically feasible scan times.

surtvep: An R package for estimating time-varying effects.

The surtvep package is an open-source software designed for estimating time-varying effects in survival analysis using the Cox non-proportional hazards model in R. With the rapid increase in large-scale time-to-event data from national disease registries, detecting and accounting for time-varying effects in medical studies have become crucial. Current software solutions often face computational issues such as memory limitations when handling large datasets.

Optimal Antithrombotic Regimen After Cryptogenic Stroke: A Systematic Review and Network Meta-Analysis.

Although several antithrombotic strategies have been investigated for the management of cryptogenic strokes, ie, ischemic strokes without known etiologies, an optimal antithrombotic strategy for cryptogenic strokes is unknown. We aim to assess oral antithrombotic agents' comparative efficacy and safety after cryptogenic stroke to identify an optimal treatment.A systematic review and meta-analysis synthesizing evidence from randomized controlled trials (RCTs) obtained from PubMed, Embase Cochrane, Scopus, and Web of Science until February 2024.

In Search of Transcriptomic Correlates of Neuronal Firing-Rate Adaptation across Subtypes, Regions and Species: A Patch-seq Analysis.

Can the transcriptomic profile of a neuron predict its physiological properties? Using a Patch-seq dataset of the primary visual cortex, we addressed this question by focusing on spike rate adaptation (SRA), a well-known phenomenon that depends on small conductance calcium (Ca)-dependent potassium (SK) channels. We first show that in parvalbumin-expressing (PV) and somatostatin-expressing (SST) interneurons (INs), expression levels of genes encoding the ion channels underlying action potential generation are correlated with the half-width (HW) of spikes. Surprisingly, the SK encoding gene is not correlated with the degree of SRA (dAdap).