Basic Science and Pathogenesis.

Background: The presence of Tau pathology is strongly associated with the clinical symptoms and cognitive decline found in Alzheimer's disease (AD), suggesting that targeting pathological tau may be a more effective therapeutic approach. Microglia have been implicated in tauopathies as their activation is strongly related to the progression of tau phosphorylation and aggregation potentially due to dysfunctional lysosomal activity. Cannabinoid type 2 receptors (CB2) are highly expressed in immune cells and upregulated in activated microglia under conditions of neurologic disease, such as AD.

Basic Science and Pathogenesis.

Background: Previously, we developed a co-calibrated and harmonized brain pathology score (BPS) across prospective cohort studies with research brain donation that incorporates multiple forms of postmortem neuropathology, using confirmatory factor analysis. We sought to identify genetic loci associated with BPS using a systems-biology approach, combining data from participants in the Adult Changes in Thought (ACT), the Religious Orders Study, and Rush Memory and Aging Project (ROSMAP) autopsy cohorts.

Method: We used PLINK in each cohort separately for genome-wide association studies (GWAS) of BPS using HRC imputed data from European ancestry participants, adjusting for age at death, sex, and population substructure.

Clinical Manifestations.

Background: Subjective Cognitive Decline (SCD) may represent the initial symptom of Alzheimer's disease (AD), but SCD may be absent and/or unrelated to actual cognitive decline. Objective Subtle Cognitive Decline (obj-SCD) can be identified through longitudinal standardized neuropsychological tests in individuals not yet meeting criteria for Mild Cognitive Impairment (MCI). We argue that the relationship between SCD and obj-SCD might help to inform clinical and research criteria in pre-MCI stages.

Clinical Manifestations.

Background: Mild behavioral impairment (MBI) is associated with all-cause dementia. Little is known about MBI's effects on cognitive function among individuals in earlier disease stages, particularly in racially diverse samples. We examined relationships between MBI and cognitive decline in a richly characterized sample of white and African American (AA) older-middle aged adults.

Clinical Manifestations.

Background: Judgment is an aspect of executive functioning that is critical to many aspects of daily functioning, and often affected in older adults with cognitive decline. The Test of Practical Judgement (TOP-J) evaluates judgment related real-world issues that may arise in aging populations. The current study investigates the incremental validity of the TOP-J-i.

Clinical Manifestations.

Background: Each year, millions of Americans experience mild traumatic brain injury (mTBI). Current research on the long-term effects of mTBI vary considerably. Several mechanisms linking mTBI to dementia have been proposed including amyloid plaque formation and cerebrovascular injury following mTBI.

Family Caregivers' Experiences of Long-Term Care Residents Living With Dementia During the COVID-19 Pandemic: An International Grounded Theory Study.

Aims: Caution around the COVID-19 pandemic resulted in visitation restrictions to prevent the spread of the virus among vulnerable older persons living in long-term care (LTC), which posed a threat to individual well-being and family togetherness across the globe. The purpose of this study was to explore family caregiver's experience of having a person who is living with dementia residing in a long-term care facility during the COVID-19 pandemic.

Design: Qualitative descriptive study using constructivist grounded theory (GT) methodology.

Early Onset Active Inflammatory Bowel Disease Is Associated With Psychiatric Comorbidities: A Multi-Network Propensity-Matched Cohort Study.

Background: Psychiatric disease burden in patients with Inflammatory bowel disease (IBD) has risen substantially over the past few decades. However, there is limited data on the relationship between IBD disease activity and the incidence of psychiatric comorbidities. We sought to conduct a population-based study to investigate the impact of early onset disease activity in newly diagnosed IBD patients on psychiatric disease diagnoses and medication usage.

Structural and kinetic characterization of DUSP5 with a Di-phosphorylated tripeptide substrate from the ERK activation loop.

Introduction: Dual specific phosphatases (DUSPs) are mitogen-activated protein kinase (MAPK) regulators, which also serve as drug targets for treating various vascular diseases. Previously, we have presented mechanistic characterizations of DUSP5 and its interaction with pERK, proposing a dual active site.

Methods: Herein, we characterize the interactions between the DUSP5 phosphatase domain and the pT-E-pY activation loop of ERK2, with specific active site assignments.

Understanding the experience of Latinas in medical education: A qualitative study.

Background: Despite increased recruitment of Latina medical students, the percentage of Latina physicians has remained stagnant, suggesting unique retentive barriers affecting this population. Discriminatory experiences involving bias may contribute to difficulties in the retention and advancement of Latinas in medicine. This qualitative analysis aimed to explore thematic barriers prevalent among Latinas throughout their medical training in the United States.

A proof-of-concept study in small and large animal models for coupling liver normothermic machine perfusion with mesenchymal stromal cell bioreactors.

To fully harness mesenchymal-stromal-cells (MSCs)' benefits during Normothermic Machine Perfusion (NMP), we developed an advanced NMP platform coupled with a MSC-bioreactor and investigated its bio-molecular effects and clinical feasibility using rat and porcine models. The study involved three work packages: 1) Development (n = 5): MSC-bioreactors were subjected to 4 h-liverless perfusion; 2) Rat model (n = 10): livers were perfused for 4 h on the MSC-bioreactor-circuit or with the standard platform; 3) Porcine model (n = 6): livers were perfused using a clinical device integrated with a MSC-bioreactor or in its standard setup. MSCs showed intact stem-core properties after liverless-NMP.

Cigarette smoking and symptom burden: baseline results from 9 ECOG-ACRIN cancer clinical trials.

Context: Approximately 11% of cancer survivors smoke post-diagnosis.

Objective: Understanding the relationship between smoking and perceived cancer-related symptoms may inform tobacco treatment interventions for this population.

Methods: From 2017-2021, 740 adults in 9 ECOG-ACRIN trials provided baseline data.

Geriatrics Connect: countering ageism in first-year medical students with longitudinal telephonic relationships.

The authors created Geriatrics Connect (GeriConnect), a program for first-year medical students at NYU Grossman School of Medicine to learn about healthy aging by developing a 7-month long telephonic relationship with an older adult living in the community. : Early exposure to geriatrics and older adults is instrumental to preparing future physicians to care for the aging population. The objective of this study was to evaluate how the GeriConnect program affected students' attitudes on aging and ageism.

Transplant-Free Approach in Relapsed Hodgkin Lymphoma in Children, Adolescents, and Young Adults: A Nonrandomized Clinical Trial.

Importance: Retrieval strategies for children, adolescents, and young adults with relapsed classic Hodgkin lymphoma (cHL) aim to maintain efficacy while minimizing long-term toxic effects. Children, adolescents, and young adults with low-risk, relapsed cHL may benefit from replacing high-dose chemotherapy and autologous stem cell transplant with less intensive involved-site radiotherapy (ISRT).

Objective: To evaluate a risk-stratified, response-adapted, transplant-free approach for treatment of children, adolescents, and young adults with low-risk relapsed cHL with nivolumab plus brentuximab vedotin (BV) followed by BV plus bendamustine for patients with suboptimal response and ISRT (30.

Updating probability of pathogenicity for RYR1 and CACNA1S exon variants in individuals without malignant hyperthermia after exposure to triggering anesthetics.

Objectives: We aimed to classify genetic variants in RYR1 and CACNA1S associated with malignant hyperthermia using biobank genotyping data in patients exposed to triggering anesthetics without malignant hyperthermia phenotype.

Methods: We identified individuals who underwent surgery and were exposed to triggering anesthetics without malignant hyperthermia phenotype and who had RYR1 or CACNA1S genotyping data available in our biobank. We classified all variants in the cohort using a Bayesian framework of the American College of Medical Genetics and Genomics and the Association of Molecular Pathologists guidelines for variant classification and updated the posterior probabilities from this model with the new information from our biobank cohort.

Physiologically Based Pharmacokinetic Modeling and Simulation to Support a Change in the FDA-Labeled Dosing Frequency of RHB-105 Low-Dose Rifabutin Triple Therapy for Helicobacter pylori Eradication.

Patient adherence is vital for Helicobacter pylori eradication. Simplifying therapy dosing schedules may promote patient adherence, enhance treatment success rates, and help mitigate the development of antibiotic resistance. We aimed to assess plasma and intragastric rifabutin, amoxicillin, and omeprazole concentrations comparing two dosing schedules of RHB-105 (every 8 h and a more flexible three-times daily schedule, at 8 a.

Engraft: A Collaborative Learning Health Network for Enhanced Transplant and Cellular Therapy Outcomes.

The Engraft Learning Health Network (LHN) aims to improve outcomes for patients undergoing transplant and cellular therapy (TCT) through a collaborative, data-driven approach. Engraft brings together diverse stakeholders, including clinicians, patients, caregivers, and institutions, to standardize best practices and accelerate the dissemination of innovations in TCT care. By establishing a multicenter, real-world clinical registry focused on rapid-cycle quality improvement (QI) and implementation research, Engraft seeks to reduce variability in clinical practice to improve TCT outcomes across centers.

Utility of color Doppler imaging in patients with retinoblastoma treated by intra-arterial chemotherapy.

Background: There are no clinical parameters that predict response to intra-arterial chemotherapy (IAC), which is a first-line treatment for primary and recurrent unilateral retinoblastoma. We evaluated the utility of ophthalmic ultrasound with color Doppler imaging to predict retinoblastoma response to IAC treatment.

Methods: The medical records of 14 retinoblastoma patients (20 eyes) treated with IAC were reviewed retrospectively.

Have Degree, Will Travel? Geography and Orthopaedic Surgery Residency Match.

Introduction: The paucity of objective data on the residency application is challenging to Orthopedic Surgery residency programs when selecting candidates to interview and to rank. Qualifying or quantifying the effect of geography on match results will help programs screen and rank candidates more effectively. The aim of this study is to describe the geographic background of current Orthopedic Surgery residents in the United States relative to their current residency program.

Quantifying the Diagnostic Utility of Baseline Testing in Concussion Management: An Analysis of Collegiate Athletes From the NCAA-DoD CARE Consortium Dataset.

Background: Although preseason baseline testing is a commonly recommended part of the concussion management process, its "value-added" contribution to the diagnosis of acute concussion compared with normative reference values remains in question.

Purpose: This research aimed to evaluate the diagnostic benefits of baseline testing in acute concussion assessment compared with normative reference values and characterize the athletes who receive the most diagnostic utility from baseline testing.

Study Design: Cohort study (Diagnosis); Level of evidence, 2.

Impact of a Quality Cardiopulmonary Resuscitation Coach on Pediatric Intensive Care Unit Resuscitation Teams.

Background: The quality cardiopulmonary resuscitation (CPR) coach role was developed for hospital-based resuscitation teams. This supplementary team member (CPR coach) provides real-time, verbal feedback on chest compression quality to compressors during a cardiac arrest.

Objectives: To evaluate the impact of a quality CPR coach training intervention on resuscitation teams, including presence of coaches on teams and physiologic metrics of quality CPR delivery in real compression events.

Sustained growth-promoting effects of vosoritide in children with achondroplasia from an ongoing phase 3 extension study.

Background: Vosoritide is a C-type natriuretic peptide analog that addresses an underlying pathway causing reduced bone growth in achondroplasia. Understanding the vosoritide treatment effect requires evaluation over an extended duration and comparison with outcomes in untreated children.

Methods: After completing ≥6 months of a baseline observational growth study and 52 weeks in a double-blind, placebo-controlled study (ClinicalTrials.