Plasma S100β is a predictor for pathology and cognitive decline in Alzheimer's disease.

Background: Blood-brain barrier dysfunction is one characteristic of Alzheimer's disease (AD) and is recognized as both a cause and consequence of the pathological cascade leading to cognitive decline. The goal of this study was to assess markers for barrier dysfunction in postmortem tissue samples from research participants who were either cognitively normal individuals (CNI) or diagnosed with AD at the time of autopsy and determine to what extent these markers are associated with AD neuropathologic changes (ADNC) and cognitive impairment.

Methods: We used postmortem brain tissue and plasma samples from 19 participants: 9 CNI and 10 AD dementia patients who had come to autopsy from the University of Kentucky AD Research Center (UK-ADRC) community-based cohort; all cases with dementia had confirmed severe ADNC.

snRNA-seq stratifies multiple sclerosis patients into distinct white matter glial responses.

Poor understanding of the cellular and molecular basis of clinical and genetic heterogeneity in progressive multiple sclerosis (MS) has hindered the search for new effective therapies. To address this gap, we analyzed 632,000 single-nucleus RNA sequencing profiles from 156 brain tissue samples of MS and control donors to examine inter- and intra-donor heterogeneity. We found distinct cell type-specific gene expression changes between MS gray and white matter, highlighting clear pathology differences.

Improvement of variant reclassification in genetic neurodevelopmental conditions.

Purpose: Limited knowledge about disease mechanisms, few published cases, and the lack of functional assessment of variants for neurodevelopmental genetic disorders challenge diagnostic classification for variants and increase the frequency of variants of uncertain significance (VUS). Because inheritance patterns aid in variant interpretation for neurodevelopmental conditions, genetic testing including only the proband leads to larger numbers of VUS than testing strategies that include the parents.

Methods: We reinterpreted genetic variants submitted to the Simons Searchlight research registry using American College of Medical Genetics and Genomics variant interpretation guidelines, familial cascade testing, and literature curation with annual VUS reevaluation.

Novel loci and biomedical consequences of iron homoeostasis variation.

Iron homoeostasis is tightly regulated, with hepcidin and soluble transferrin receptor (sTfR) playing significant roles. However, the genetic determinants of these traits and the biomedical consequences of iron homoeostasis variation are unclear. In a meta-analysis of 12 cohorts involving 91,675 participants, we found 43 genomic loci associated with either hepcidin or sTfR concentration, of which 15 previously unreported.

Suppression of ADP-ribosylation reversal triggers cell vulnerability to alkylating agents.

The ADP-ribosyl hydrolases PARG and ARH3 counteract PARP enzymatic activity by removing ADP-ribosylation. PARG and ARH3 activities have a synthetic lethal effect; however, the specific molecular mechanisms underlying this response remain unknown. Here, we show that the PARG and ARH3 synthetic lethality is enhanced further in the presence of DNA alkylating agents, suggesting that the inability to revert ADP-ribosylation primarily affects the repair of alkylated DNA bases.

Challenges for the veterinary profession: A grounded theory study of veterinarians' experiences of caring for older horses.

Background: In Great Britain, owners are keeping their horses into increasingly older age, reflecting societal changes in human-animal relationships. The uptake of routine veterinary services is reported to reduce as horses age. Horse owners seek information regarding their animal's health from alternative sources before and/or following veterinary involvement.

A framework for counterfactual analysis, strategy evaluation, and control of epidemics using reproduction number estimates.

During pandemics, countries, regions, and communities develop various epidemic models to evaluate spread and guide mitigation policies. However, model uncertainties caused by complex transmission behaviors, contact-tracing networks, time-varying parameters, human factors, and limited data present significant challenges to model-based approaches. To address these issues, we propose a novel framework that centers around reproduction number estimates to perform counterfactual analysis, strategy evaluation, and feedback control of epidemics.

A modeling study on SARS-CoV-2 transmissions in primary and middle schools in Illinois.

Background: The global pandemic caused by the SARS-CoV-2 virus led to a statewide lockdown in Illinois starting in March 2020. To ensure students' and employees' safety for school reopening, protective measures, such as a statewide mask mandate and weekly testing, were in place in Illinois from Spring 2021 to Spring 2022. The study objective is to 1) estimate the in-school and external transmission of SARS-CoV-2 in elementary and middle schools under mask mandate and weekly surveillance and 2) estimate the impacts of protective measures such as testing and mask proportion and testing frequency on SARS-CoV-2 transmission.

We Are on the Verge of Breakthrough Cures for Type 1 Diabetes, but Who Are the 2 Million Americans Who Have It?

Two million Americans have type 1 diabetes (T1DM). Innovative treatments have standardized insulin delivery and improved outcomes for patients, but patients' access to such technologies depends on social determinants of health, including insurance coverage, proper diagnosis, and appropriate patient supports. Prior estimates of US prevalence, incidence, and patient characteristics have relied on data from select regions and younger ages and miss important determinants.

Collaboration strategies affecting implementation of a cross-systems intervention for child welfare and substance use treatment: a mixed methods analysis.

Background: Collaboration strategies refer to policies and practices used to align operations and services across organizations or systems. These strategies can influence implementation of cross-system interventions focused on improving integration of care, but remain under-specified and under-examined. This study identifies collaboration strategies and the conditions under which they affected implementation of Sobriety Treatment and Recovery Teams (START), an evidence-based intervention focused on integrating child welfare and behavioral health services for families involved with both systems.

Software-driven chronic disease management: Algorithm design and implementation in a community-based blood pressure control pilot.

Background: Optimal guideline-directed medical therapy is rarely attained in practice, resulting in inadequate control of diseases such as hypertension, with poorer results in under-resourced communities. Technology, including artificial intelligence-driven decision support and software-driven workflow transformation, can potentially improve disease outcomes at a reduced cost, although it must be integrated with a holistic approach.

Methods: We describe the design of a software platform that enables rapid iterative remote management of >20 conditions across cardiac-kidney-metabolic disease.

Patient Perceptions on the Follow-Up of Abnormal Cancer Screening Test Results.

Background: Timely follow-up after an abnormal cancer screening test result is needed to maximize the benefits of screening, but is frequently not achieved. Little is known about patient experiences with the process of following up abnormal screening results.

Objective: Assess patient experiences and perceptions regarding the process of a diagnostic workup following abnormal breast, cervical, or colorectal cancer screening results.

Emergency Department Management of Maxillofacial Trauma.

Patients with maxillofacial trauma require careful evaluation due to the anatomical proximity of the maxillofacial region to the head and neck. Facial trauma can lead to life-threatening airway compromise or hemorrhage, or permanent facial deformity. Although the Advanced Trauma Life Support guidelines provide a framework for the management of trauma patients, they do not provide a detailed reference for many subtle or complex facial injuries.

Experiences with home monitoring technology in older adults with traumatic brain injury: a qualitative study.

Background: Home monitoring systems utilising artificial intelligence hold promise for digitally enhanced healthcare in older adults. Their real-world use will depend on acceptability to the end user i.e.

Closing Gaps or Holding Steady? The Affordable Care Act, Medicaid Expansion, & Racial Disparities in Coverage, 2010-2021.

Context: The Affordable Care Act's (ACA) Medicaid expansion produced major gains in coverage. However, findings on racial and ethnic disparities are mixed and may depend on how disparities are measured. This study examines both absolute and relative changes in uninsurance from 2010-2021 by race and ethnicity, stratified by Medicaid expansion status.

Author Correction: PARP14 and PARP9/DTX3L regulate interferon-induced ADP-ribosylation.

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