Differential encoding of odor and place in mouse piriform and entorhinal cortex.

The integration of olfactory and spatial information is critical for guiding animal behavior. The lateral entorhinal cortex (LEC) is reciprocally interconnected with cortical areas for olfaction and the hippocampus and thus ideally positioned to encode odor-place associations. Here, we used mini-endoscopes to record neural activity in the mouse piriform cortex (PCx) and LEC.

APMAT analysis reveals the association between CD8 T cell receptors, cognate antigen, and T cell phenotype and persistence.

Elucidating the relationships between a class I peptide antigen, a CD8 T cell receptor (TCR) specific to that antigen, and the T cell phenotype that emerges following antigen stimulation, remains a mostly unsolved problem, largely due to the lack of large data sets that can be mined to resolve such relationships. Here, we describe Antigen-TCR Pairing and Multiomic Analysis of T-cells (APMAT), an integrated experimental-computational framework designed for the high-throughput capture and analysis of CD8 T cells, with paired antigen, TCR sequence, and single-cell transcriptome. Starting with 951 putative antigens representing a comprehensive survey of the SARS-CoV-2 viral proteome, we utilize APMAT for the capture and single cell analysis of CD8 T cells from 62 HLA A*02:01 COVID-19 participants.

Risk of Severe Hypoglycemia After Initiation of Noninsulin Glucose-Lowering Therapies in Adults With Type 2 Diabetes at Moderate Cardiovascular Disease Risk.

In this emulated comparative effectiveness target trial of glucagon-like peptide 1 (GLP-1) receptor agonist, sodium-glucose cotransporter 2 (SGLT2) inhibitor, dipeptidyl peptidase 4 (DPP-4) inhibitor, and sulfonylurea therapy among adults with type 2 diabetes at moderate cardiovascular disease risk, sulfonylurea use was associated with a significantly higher risk of hypoglycemia requiring emergency department or hospital care than treatment with DPP-4 inhibitors, GLP-1 receptor agonists, or SGLT2 inhibitors. This consideration can guide the choice of glucose-lowering therapy in this highly prevalent patient population, in whom avoidance of hypoglycemia is important, yet among whom the risk of severe hypoglycemia has not been examined previously.

Preliminary effects of oral ANS-6637, an ALDH2 inhibitor, on cue-induced craving, safety and alcohol consumption among adults with alcohol use disorder: a proof-of-concept, randomized, human laboratory trial.

Aims: We evaluated the safety, efficacy, and patient adherence to oral ANS-6637, a selective, reversible inhibitor of aldehyde dehydrogenase 2 (ALDH2), for treating alcohol use disorder (AUD).

Methods: A 3-arm, double-blind, randomized, proof-of-concept human laboratory study embedded in a 5-week multisite clinical trial tested 200 mg and 600 mg daily doses of ANS-6637 compared to placebo in treatment-seeking adults with AUD. After 1 week of medication, participants completed an alcohol cue reactivity session.

Craniosynostosis: Quantifying Differences in Skull Architecture.

Craniosynostosis, a condition marked by the premature fusion of one or more cranial sutures, exhibits diverse phenotypes. This study aims to advance the understanding of these phenotypes beyond the conventional 2-dimensional analysis by focusing on identifying indicators of increased intracranial pressure (ICP) such as bony thinning or irregularities in skull morphology. A retrospective review was conducted for all pediatric patients with midline craniosynostosis who presented to our tertiary academic center for evaluation.

Prenatally Diagnosed Absent Septum Pellucidum and Septo-Optic Dysplasia: A Narrative Review and Practical Recommendations for Pediatric Neurologists.

Evaluation of the cavum septum pellucidum is required in standard second-trimester screening fetal anatomy ultrasound scans. The absence of septum pellucidum triggers further evaluation and referral for subspecialty counseling. Absence of septum pellucidum is linked to other midline anomalies including septo-optic dysplasia.

Disparities in utilization of novel cancer therapies in advanced stage III and IV melanoma and variance in outcomes.

Introduction: Significant gains in advanced melanoma have been made through immunotherapy trials. Factors influencing equitable access and survival impact of these novel therapies are not well-defined.

Method: Retrospective analysis using National Cancer Database of patients with advanced stage III and IV melanoma from 2004 to 2021.

Influence of positive consequences on subsequent incentive ratings and drinking quantity.

Alcohol use is prevalent among young adults, with significant rates of binge drinking and frequent reports of both positive and negative consequences. The current study investigates how positive drinking consequences influence subsequent incentives ratings and drinking behavior. Utilizing mobile daily diary data from 104 young adults over two weeks (event N = 507), we assessed the impact of event-specific positive consequences on future incentive ratings and drinking quantity.

Development and Evaluation of a Presenter Coaching Program at an Academic Surgical Conference.

Objective: Presenting at academic conferences is an important means of disseminating research, networking, and building a professional reputation, but the quality of presentations at conferences is often suboptimal. This project describes the design, implementation, and evaluation of a presentation coaching program offered by an academic surgical society to presenters at its annual meeting.

Design: Oral presenters were paired with a coach and encouraged to meet independently, yet coaching was unstructured.

Developing emergency medical care policy across Kenya: A framework for policy development.

Background And Objectives: The Kenya Emergency Medical Care (EMC) Policy 2020-2030 was created to guide the advancement of EMC throughout Kenya. This report describes and maps the ongoing EMC policy development process across Kenya's 47 counties, serving as a real-world example of EMC policy development within a decentralized healthcare system in a low-or middle-income country (LMIC).

Methods: This report evaluates the development of county-specific EMC policies using the Kenya Institute for Public Policy Research and Analysis (KIPPRA) six stages for policy development: 1) problem identification, 2) agenda setting, 3) policy design, 4) approval, 5) implementation, and 6) monitoring and evaluation.

Highly Efficient Compositional and Compound Specific Isotopic Analysis of Volatile Primary Amines and Ammonia in the Murchison Meteorite Using SPME On-Fiber Derivatization: Optimization for Bennu Sample Analyses.

Rationale: Extraterrestrial amines and ammonia are critical ingredients for the formation of astrobiologically important compounds such as amino acids and nucleobases. However, conventional methods for analyzing the composition and isotopic ratios of volatile amines suffer from lengthy derivatization and purification procedures, high sample mass consumption, and chromatographic interferences from derivatization reagents and non-target compounds.

Methods: Here we demonstrate a highly efficient method to analyze the composition and compound specific isotopic ratios of C to C amines as well as ammonia based on solid phase micro-extraction (SPME) on-fiber derivatization.

Psychosocial Support Needs and Preferences Among Family Caregivers of ICU Patients with Severe Acute Brain Injury: A Qualitative Thematic Analysis.

Background: Family caregivers of patients with severe acute brain injury (SABI) are at risk for clinically significant chronic emotional distress, including depression, anxiety, and posttraumatic stress. Existing psychosocial interventions for caregivers of intensive care unit (ICU) patients are not tailored to the unique needs of caregivers of patients with SABI, do not demonstrate long-term efficacy, and may increase caregiver burden. In this study, we explored the needs and preferences for psychosocial services among SABI caregivers to inform the development and adaptation of interventions to reduce their emotional distress during and after their relative's ICU admission.

Neural Variability and Cognitive Control in Individuals With Opioid Use Disorder.

Importance: Opioid use disorder (OUD) impacts millions of people worldwide. Prior studies investigating its underpinning neural mechanisms have not often considered how brain signals evolve over time, so it remains unclear whether brain dynamics are altered in OUD and have subsequent behavioral implications.

Objective: To characterize brain dynamic alterations and their association with cognitive control in individuals with OUD.

Expanded Naloxone Distribution by Opioid Overdose Prevention Programs to High-Need Populations and Neighborhoods in New York City.

From 2014 to 2017, the drug overdose death rate per 100,000 in New York City (NYC) increased by 81%, with 57% of overdoses in 2017 involving the opioid fentanyl. In response, overdose education and naloxone dispensing (OEND) efforts were expanded in NYC, informed by neighborhood-level and population-level opioid overdose fatality rates. We describe the demographic and geographical distribution of naloxone by NYC opioid overdose prevention programs (OOPPs; the primary distributor of naloxone to laypersons in NYC) as OEND was expanded in NYC.

Skin cancer treatment environment and survivorship resources among sexual and gender minority patients: results of the OUT National Cancer Survey.

Sexual and gender minority (SGM) cancer survivors face unmet care needs in accessing cancer health information and social support despite high satisfaction with treatment. SGM patients often delay care due to concerns of discrimination in healthcare settings, though the care experiences of SGM skin cancer survivors are less known. SGM individuals, particularly sexual minority men, report higher skin cancer prevalence and related risk behaviors than heterosexual men.

Consolidation in an Era of Population Health and Value-Based Care: Implications For Effectiveness, Costs, and Equity.

Consolidation of health care providers, and vertical integration of physicians with hospitals and/or payers has accelerated over the past 15 years. Although there is potential for consolidation to improve patient care, efficiencies and reduce overhead costs, participants in our conference identified that almost all research on consolidation has shown increased cost without improvement in outcomes or the experience of care. To provide a framework for considering the impact of consolidation, future research and analysis we offer 4 themes: (1) to move forward, we need to look back at historical drivers, value creation, and unintended consequences; (2) not all consolidation is created equally; (3) real-time, continuous evaluation is critical for improvement; and (4) a policy blueprint is desperately needed.

Improved healthcare utilization and economic outcomes of chronic subdural hematoma treatment with middle meningeal artery embolization compared to conventional surgical drainage.

Background: Middle meningeal artery embolization (MMAE) emerges as an alternative to conventional surgical drainage (CSD) for chronic subdural hematomas (cSDH). Several studies have suggested that MMAE improves the cost efficacy of cSDH treatment. However, further comprehensive analyses of the outcomes and healthcare costs of MMAE are necessary.

Photoelectron Imaging and Photodetachment Spectroscopy for the Cryogenically Cooled Cyanocyclopentadienide Anion.

The cyano-cyclopentadiene molecule (CN-CH) has attracted significant interest since its detection in the interstellar medium, but the radical (CN-CH) and anionic (CN-CH) forms of cyano-cyclopentadiene have not been studied. The cyano-cyclopentadienyl radical (CN-Cp) has a strong dipole moment, rendering it an ideal system for vibrational and rotational spectroscopy. We report an investigation of the cryogenically cooled cyano-cyclopentadienide anion (CN-Cp) using high-resolution photoelectron imaging, photodetachment spectroscopy, and resonant photoelectron imaging.

Science tells us that portable air filters reduce infection risk. It's time for public health authorities to make this clear.

Throughout the COVID-19 pandemic, Canadian public health advisors and politicians have shared mixed messages about the utility of portable air filters (PAFs) for mitigating the transmission of airborne infectious diseases. Some public health advisors and decision-makers have also suggested that PAFs are cumbersome or require expert advice. We take this opportunity to review evidence and address myths about PAFs.

Characteristics of older patients undergoing major oncological surgery: Insights from the Geriatric Surgery Verification Program.

Introduction: Studies outlining the unique burden of geriatric medical conditions and syndromes among older adults undergoing major oncological surgery are lacking, along with understanding of the goals of care for this population.

Materials And Methods: We conducted a single-institutional review of the initial 50 patients who enrolled in the American College of Surgeons' Geriatric Surgery Verification Program (GSV) program implemented for those ≥65 years undergoing major oncological surgery during the year 2023. Patient variables were categorized into four domains - somatic, functional, psychological, and social.

Olaparib as treatment for platinum-sensitive relapsed ovarian cancer by BRCA mutation and homologous recombination deficiency: Phase 2 LIGHT study final overall survival analysis.

Background: LIGHT (oLaparib In HRD-Grouped Tumor types; NCT02983799) prospectively evaluated olaparib treatment in patients with platinum-sensitive relapsed ovarian cancer (PSROC) assigned to cohorts by known BRCA mutation (BRCAm) and homologous recombination deficiency (HRD) status: germline BRCAm (gBRCAm), somatic BRCAm (sBRCAm), HRD-positive non-BRCAm, and HRD-negative. At the primary analysis, olaparib treatment demonstrated activity across all cohorts, with greatest efficacy in terms of objective response rate and progression-free survival observed in the g/sBRCAm cohorts. The authors report final overall survival (OS).

Safety and Efficacy of Toripalimab in Patients with Cholangiocarcinoma: An Open-Label, Phase 1 Study.

Introduction: This was the first phase 1 study conducted in the United States. It consisted of dose-escalation (part A) and multiple indication-specific cohort expansion (part B), investigating the safety and preliminary efficacy of toripalimab (anti-programmed cell death-1 inhibitor) in patients with advanced malignancies.

Methods: Patients with advanced malignancies that progressed after treatment with at least one prior line of standard systemic therapy, including the patients with advanced/recurrent cholangiocarcinoma (CCA), received toripalimab 240 mg every 3 weeks in part B.

Cardiomyocyte S1PR1 promotes cardiac regeneration via AKT/mTORC1 signaling pathway.

Lower vertebrates and some neonatal mammals are known to possess the ability to regenerate cardiomyocyte and fully recover after heart injuries within a limited period. Understanding the molecular mechanisms of heart regeneration and exploring new ways to enhance cardiac regeneration hold significant promise for therapeutic intervention of heart failure. Sphingosine 1-phospahte receptor 1 (S1PR1) is highly expressed in cardiomyocytes and plays a crucial role in heart development and pathological cardiac remodeling.

Barriers to Research Faced by High-Income Versus Low- and Middle-Income Country Otolaryngologists and Otolaryngology Residents.

Objective: This study aims to compare research productivity and barriers to research between high-income countries (HICs) and low- and middle-income countries (LMICs) otolaryngologists.

Study Design: Cross-sectional survey.

Setting: International survey.