A NOTCH3 pathogenic variant influences osteogenesis and can be targeted by antisense oligonucleotides in induced pluripotent stem cells.

Lateral Meningocele Syndrome (LMS), a disorder associated with NOTCH3 pathogenic variants, presents with neurological, craniofacial and skeletal abnormalities. Mouse models of the disease exhibit osteopenia that is ameliorated by the administration of Notch3 antisense oligonucleotides (ASO) targeting either Notch3 or the Notch3 mutation. To determine the consequences of LMS pathogenic variants in human cells and whether they can be targeted by ASOs, induced pluripotent NCRM1 and NCRM5 stem (iPS) cells harboring a NOTCH36692-93insC insertion were created.

Patterns of platelet use evaluated in EHR networks of the Biologics Effectiveness and Safety Initiative, 2012-2018.

Background: U.S. FDA's Center for Biologics Evaluation and Research (CBER) Biologics Effectiveness and Safety (BEST) Initiative leverages large electronic health records and administrative claims data to conduct active surveillance for CBER-regulated products.

Predictors of quality of life and resilience in patients with ovarian cancer during the COVID-19 pandemic: a cross-sectional study.

Purpose: The aim of this cross-sectional study was to investigate the psychosocial burdens of patients with ovarian cancer during the COVID-19 pandemic.

Methods: Ovarian cancer patients answered a quantitative survey assessing their resilience (BRS) and quality of life (FACT-G7) as well as clinical (first- vs. ≥ second-line treatment), demographic (age < 65 vs.

Value sets and the problem of redundancy in value set repositories.

Objective: Crafting high-quality value sets is time-consuming and requires a range of clinical, terminological, and informatics expertise. Despite widespread agreement on the importance of reusing value sets, value set repositories suffer from clutter and redundancy, greatly complicating efforts at reuse. When users encounter multiple value sets with the same name or ostensibly representing the same clinical condition, it can be difficult to choose amongst them or determine if any differences among them are due to error or intentional decision.

A NOTCH2 pathogenic variant and HES1 regulate osteoclastogenesis in induced pluripotent stem cells.

Hajdu Cheney Syndrome (HCS), a monogenic disorder associated with NOTCH2 pathogenic variants, presents with neurological, craniofacial and skeletal abnormalities. Mouse models of the disease exhibit osteopenia. To determine the consequences of a HCS pathogenic variant in human cells, induced pluripotent NCRM1 and NCRM5 stem (iPS) cells harboring a NOTCH2 mutation or null for HES1 alleles were created.

Guidelines for the use and interpretation of Alzheimer's disease biomarkers in clinical practice in Brazil: recommendations from the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology.

In recent years, the diagnostic accuracy of Alzheimer's disease has been enhanced by the development of different types of biomarkers that indicate the presence of neuropathological processes. In addition to improving patient selection for clinical trials, biomarkers can assess the effects of new treatments on pathological processes. However, there is concern about the indiscriminate and poorly supported use of biomarkers, especially in asymptomatic individuals or those with subjective cognitive decline.

Use of anti-amyloid therapies for Alzheimer's disease in Brazil: a position paper from the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology.

Novel therapies for Alzheimer's disease, particularly anti-amyloid drugs like lecanemab and donanemab, have shown modest clinical benefits but also significant risks. The present paper highlights the challenges of access to diagnosis, cost-effectiveness, safety, and the need for more representation of diverse populations in clinical trials. Recommendations include careful patient selection, risk-benefit analysis, and the importance of proven amyloid pathology for treatment.

TNFα has differential effects on the transcriptome profile of selected populations in murine cartilage.

Objective: To further our understanding of the role of tumor necrosis factor (TNF)α on the inflammatory response in chondrocytes.

Design: We explored the effects of TNFα on the transcriptome of epiphyseal chondrocytes from newborn C57BL/6 mice at the total and single cell (sc) resolution.

Results: Gene set enrichment analysis of total RNA-Seq from TNFα-treated chondrocytes revealed enhanced response to biotic stimulus, defense and immune response and cytokine signaling and suppressed cartilage and skeletal morphogenesis and development.

The Leaders in Informatics, Quality, and Systems (LInQS) Fellowship.

Background:  Leaders in Informatics, Quality, and Systems (LInQS) is a non-ACGME (Accreditation Council for Graduate Medical Education)-accredited 2-year training program developed to enhance training in the fields of health care delivery, quality improvement (QI), clinical informatics, and leadership.

Methods:  This single-institution 2-year longitudinal training program grounded in QI and informed by leadership and clinical informatics includes didactics, coaching, and mentorship, all centered around individualized QI projects. The program has been available to sub-specialty fellows, advanced practice providers, and physicians.

Linkability measures to assess the data characteristics for record linkage.

Objectives: Accurate record linkage (RL) enables consolidation and de-duplication of data from disparate datasets, resulting in more comprehensive and complete patient data. However, conducting RL with low quality or unfit data can waste institutional resources on poor linkage results. We aim to evaluate data linkability to enhance the effectiveness of record linkage.

Sex-specific differences in brain activity dynamics of youth with a family history of substance use disorder.

An individual's risk of substance use disorder (SUD) is shaped by a complex interplay of potent biosocial factors. Current neurodevelopmental models posit vulnerability to SUD in youth is due to an overreactive reward system and reduced inhibitory control. Having a family history of SUD is a particularly strong risk factor, yet few studies have explored its impact on brain function and structure prior to substance exposure.

Making Science Computable Using Evidence-Based Medicine on Fast Healthcare Interoperability Resources: Standards Development Project.

Background: Evidence-based medicine (EBM) has the potential to improve health outcomes, but EBM has not been widely integrated into the systems used for research or clinical decision-making. There has not been a scalable and reusable computer-readable standard for distributing research results and synthesized evidence among creators, implementers, and the ultimate users of that evidence. Evidence that is more rapidly updated, synthesized, disseminated, and implemented would improve both the delivery of EBM and evidence-based health care policy.

Altered Structural Connectivity and Functional Brain Dynamics in Individuals With Heavy Alcohol Use Elucidated via Network Control Theory.

Background: Heavy alcohol use and its associated conditions, such as alcohol use disorder, impact millions of individuals worldwide. While our understanding of the neurobiological correlates of alcohol use has evolved substantially, we still lack models that incorporate whole-brain neuroanatomical, functional, and pharmacological information under one framework.

Methods: Here, we utilized diffusion and functional magnetic resonance imaging to investigate alterations to brain dynamics in 130 individuals with a high amount of current alcohol use.

Improving Maternal Health Care Quality and Outcomes: Evaluation of a Pregnancy Medical Home.

Current maternal care recommendations in the United States focus on monitoring fetal development, management of pregnancy complications, and screening for behavioral health concerns. Often missing from these recommendations is support for patients experiencing socioeconomic or behavioral health challenges during pregnancy. A Pregnancy Medical Home (PMH) is a multidisciplinary maternal health care team with nurse navigators serving as patient advocates to improve the quality of care a patient receives and health outcomes for both mother and infant.

Patterns of red blood cell utilization: Harnessing electronic health records data from the Information Standard for Blood and Transplant (ISBT) 128 system within the Biologics Effectiveness and Safety (BEST) initiative.

Background: Current hemovigilance methods generally rely on survey data or administrative claims data utilizing billing and revenue codes, each of which has limitations. We used electronic health records (EHR) linked to blood bank data to comprehensively characterize red blood cell (RBC) utilization patterns and trends in three healthcare systems participating in the U.S.

Spatiotemporal Release of Singlet Oxygen in Low Molecular Weight Organo-Gels Upon Thermal or Photochemical External Stimuli.

The first example of a material capable of spatiotemporal catch and release of singlet oxygen (O) in gel phase is presented. Several low molecular weight organogelators based around an oxotriphenylhexanoate (OTHO) core are developed and optimized with regard to; their gelation properties, and ability of releasing O upon thermal and/or photochemical external stimuli, in both gel phase and solution. Remarkably, reversible phase transitioning between the gel and solution phase are also demonstrated.

NOTCH2 promotes osteoclast maturation and metabolism and modulates the transcriptome profile during osteoclastogenesis.

Notch signaling plays a key regulatory role in bone remodeling and NOTCH2 enhances osteoclastogenesis, an effect that is mostly mediated by its target gene Hes1. In the present study, we explored mechanisms responsible for the enhanced osteoclastogenesis in bone marrow-derived macrophages (BMM) from Notch2, harboring a NOTCH2 gain-of-function mutation, and control mice. Notch2 mice are osteopenic and have enhanced osteoclastogenesis.

Exploring Spoken Discourse and Its Neural Correlates in Women With Alzheimer's Disease With Low Levels of Education and Socioeconomic Status.

Purpose: Early impairments in spoken discourse abilities have been identified in Alzheimer's disease (AD). However, the impact of AD on spoken discourse and the associated neuroanatomical correlates have mainly been studied in populations with higher levels of education, although preliminary evidence seems to indicate that socioeconomic status (SES) and level of education have an impact on spoken discourse. The purpose of this study was to analyze microstructural variables in spoken discourse in people with AD with low-to-middle SES and low level of education and to study their association with gray matter (GM) density.

Lessons Learned: Evaluation of Fracture Liaison Service Quality Improvement Efforts in a Large Academic Healthcare System.

Background: The Fracture Liaison Service (FLS) care model, a care coordination program for patients experiencing a fragility fracture, is proven to improve management of patients with an osteoporotic fracture, but treatment initiation gaps persist.

Objective: We describe the evolution of a centralized FLS within a university-based healthcare system, including impact of adding clinical pharmacist consultation, and describe circumstances surrounding continued care gaps.

Design: Cohort analysis of osteoporosis medication initiation before FLS, after initial implementation, and after addition of pharmacist consultation.

Altered structural connectivity and functional brain dynamics in individuals with heavy alcohol use.

Heavy alcohol use and its associated conditions, such as alcohol use disorder (AUD), impact millions of individuals worldwide. While our understanding of the neurobiological correlates of AUD has evolved substantially, we still lack models incorporating whole-brain neuroanatomical, functional, and pharmacological information under one framework. Here, we utilize diffusion and functional magnetic resonance imaging to investigate alterations to brain dynamics in = 130 individuals with a high amount of current alcohol use.

Neuropsychiatric Symptoms and Microglial Activation in Patients with Alzheimer Disease.

Importance: Neuropsychiatric symptoms are commonly encountered and are highly debilitating in patients with Alzheimer disease. Understanding their underpinnings has implications for identifying biomarkers and treatment for these symptoms.

Objective: To evaluate whether glial markers are associated with neuropsychiatric symptoms in individuals across the Alzheimer disease continuum.

Patient Perception and Impact of Home Test Kits on Health Care Utilization for Urinary Tract Infection.

Urinary tract infection (UTI) is a common reason for emergency department (ED) utilization that could potentially be treated by a primary care provider (PCP). This study assessed patient perceived value of a home UTI test kit plus educational materials and its impact on ED utilization for a UTI symptom episode. Women aged 18-75 years with Medicaid insurance and a history of 1-3 uncomplicated UTIs in the past year were prospectively identified and randomized to the intervention, intervention plus (intervention plus a patient portal message before its delivery), or standard of care group.

Automatic Assessment of Connected Speech and Its Relation to Memory in Alzheimer's Disease in Low Education.

Introduction: Discourse is one of the main linguistic aspects affected by Alzheimer's disease (AD), and its relationship with memory needs to be further studied, mainly in low education and low socioeconomic status groups. The present study aimed to investigate differences in the recall of short narratives between participants with mild AD and a control group (CG) of typical older adults (CG) with the use of automatic assessment.

Methods: Seventeen older adults diagnosed with AD (mean age 76.