Clinical follow-up of 2 families with glomerulopathy caused by gene variants and literature review.

Background: Primary coenzyme Q10 (CoQ10) deficiency is an autosomal recessive genetic disease caused by mitochondrial dysfunction. Variants in Coenzyme Q8B () can cause primary CoQ10 deficiency. -related glomerulopathy is a recently recognized glomerular disease that most often presents as steroid-resistant nephrotic syndrome (SRNS) in childhood.

Quality of care delivery in patients with acute heart failure: insights from the international REPORT-HF registry.

Background: Heart Failure (HF) quality of care (QoC) is associated with clinical outcomes. Therefore, we investigated differences in HF QoC across worldwide regions (with differing national income) and the association of quality indicators with outcomes.

Methods: We examined the quality of care (QoC) in acute heart failure (HF) patients across different regions using quality indicators (QIs) from the European Society of Cardiology (ESC) and the American Heart Association (AHA) to evaluate QoC.

Achievement of guideline-based lipid goals among very-high-risk patients with atherosclerotic cardiovascular disease and type 2 diabetes: results in 213,380 individuals from the cvMOBIUS2 registry.

Objective: Lowering lipid to reach guideline-indicated goals significantly reduces cardiovascular outcomes in very-high-risk (VHR) patients with atherosclerotic cardiovascular disease (ASCVD) and type 2 diabetes (DM2). How well VHR patients currently achieve these goals in community practice is unknown.

Methods: VHR patients with ASCVD and DM2 were identified across 14 US healthcare systems using electronic health records between 1/1/2021-12/31/2022.

Context-specific eQTLs provide deeper insight into causal genes underlying shared genetic architecture of critically ill COVID-19 and idiopathic pulmonary fibrosis.

Most genetic variants identified through genome-wide association studies (GWAS) are suspected to be regulatory in nature, but only a small fraction colocalize with expression quantitative trait loci (eQTLs, variants associated with expression of a gene). Therefore, it is hypothesized but largely untested that integration of disease GWAS with context-specific eQTLs will reveal the underlying genes driving disease associations. We used colocalization and transcriptomic analyses to identify shared genetic variants and likely causal genes associated with critically ill COVID-19 and idiopathic pulmonary fibrosis.

Practical management of adverse events in patients receiving tarlatamab, a delta-like ligand 3-targeted bispecific T-cell engager immunotherapy, for previously treated small cell lung cancer.

Tarlatamab is a bispecific T-cell engager immunotherapy targeting delta-like ligand 3 (DLL3) and the cluster of differentiation 3 (CD3) molecule. In the phase 2 DeLLphi-301 trial of tarlatamab for patients with previously treated small cell lung cancer, tarlatamab 10 mg every 2 weeks achieved durable responses and encouraging survival outcomes. Analyses of updated safety data from the DeLLphi-301 trial demonstrated that the most common treatment-emergent adverse events were cytokine release syndrome (53%), pyrexia (38%), decreased appetite (36%), dysgeusia (32%), and an emia (30%).

Species- and strain-specific microbial modulation of interferon, innate immunity, and epithelial barrier in 2D air-liquid interface respiratory epithelial cultures.

Background: The microbiome regulates the respiratory epithelium's immunomodulatory functions. To explore how the microbiome's biodiversity affects microbe-epithelial interactions, we screened 58 phylogenetically diverse microbes for their transcriptomic effect on human primary bronchial air-liquid interface (ALI) cell cultures.

Results: We found distinct species- and strain-level differences in host innate immunity and epithelial barrier response.

Association between chiropractic spinal manipulation for sciatica and opioid-related adverse events: A retrospective cohort study.

Background: Patients receiving chiropractic spinal manipulation (CSM) for spinal pain are less likely to be prescribed opioids, and some evidence suggests that these patients have a lower risk of any type of adverse drug event. We hypothesize that adults receiving CSM for sciatica will have a reduced risk of opioid-related adverse drug events (ORADEs) over a one-year follow-up compared to matched controls not receiving CSM.

Methods: We searched a United States (US) claims-based data resource (Diamond Network, TriNetX, Inc.

Cognitive variation reflects amyloid, tau, and neurodegenerative biomarkers in Alzheimer's disease.

In Alzheimer's disease (AD), the accumulation of neuropathological markers such as amyloid-β plaques, neurofibrillary tangles, and cortical neurodegeneration occurs over many years before overt manifestation of cognitive impairment. There is thus a need for neuropsychological markers that are indicative of pathological changes in the early stages of the disease. Intra-individual cognitive variability (IICV), defined as the variation of an individual's performance across cognitive domains, is a promising neuropsychological marker measuring heterogeneous changes in cognition that may reflect these early pathological changes.

Glucose-6-phosphate dehydrogenase regulates mitophagy by maintaining PINK1 stability.

Glucose-6-phosphate dehydrogenase (G6PD) is the rate-limiting enzyme in the pentose phosphate pathway (PPP) in glycolysis. Glucose metabolism is closely implicated in the regulation of mitophagy, a selective form of autophagy for the degradation of damaged mitochondria. The PPP and its key enzymes such as G6PD possess important metabolic functions, including biosynthesis and maintenance of intracellular redox balance, while their implication in mitophagy is largely unknown.

Development and Delivery of Enhanced Implementation Support to Disseminate a National Caregiver Skills Training Program.

Background And Objectives: As the population ages there is an increasing need for caregiver training programs, but little is known about how to deliver implementation support for diverse sites in large-scale implementation efforts. External group-based implementation facilitation may be one promising approach. This study's objective is to detail the development and delivery of a pragmatic implementation facilitation approach to support the national rollout of caregiver training, Caregivers FIRST, at over 140 Veterans Health Administration (VHA) sites.

Environment scan of generative AI infrastructure for clinical and translational science.

This study reports a comprehensive environmental scan of the generative AI (GenAI) infrastructure in the national network for clinical and translational science across 36 institutions supported by the CTSA Program led by the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health (NIH) at the United States. Key findings indicate a diverse range of institutional strategies, with most organizations in the experimental phase of GenAI deployment. The results underscore the need for a more coordinated approach to GenAI governance, emphasizing collaboration among senior leaders, clinicians, information technology staff, and researchers.

Identifying enablers and barriers to teleultrasound use for remote settings: A scoping review.

Introduction/purpose: Teleultrasound connects expert point-of-care ultrasound (POCUS) users with remote community and rural sites. Evolving technologies including handheld devices, upgraded image quality, and the ability to transmit over low bandwidth connections increase POCUS education, accessibility, and clinical integration. Potential teleultrasound venues include low-resource settings, prehospital care, and austere environments (high altitudes, microgravity, conflict zones, etc.

Striving for early effective glycaemic and weight management in type 2 diabetes: A narrative review.

Despite the recognition by key guidelines that achieving early glycaemic control has important benefits in individuals with type 2 diabetes (T2D) and that addressing excess adiposity is one of the central components of comprehensive person-centred T2D care, a substantial proportion of individuals with T2D do not meet their metabolic treatment goals. Prior treatment paradigms were limited by important treatment-associated risks such as hypoglycaemia and body weight gain. Therefore, a more conservative, sequential approach to treatment was typically utilized.

Research Best Practices for Eye Stroke Vision Rehabilitation: A Qualitative Study.

Purpose: Central retinal artery occlusion, also known as an eye stroke, results in visual impairment and functional challenges. Our study objectives were to identify meaningful measures and factors that indicate or enable successful recovery after eye stroke and to determine optimal processes to support research, including exploring barriers and facilitators to successful research participation.

Methods: We used qualitative methods including the 5Ts Framework (target population identification, team composition, time considerations, tips to accommodate older adults, tools for inclusive enrollment of older adults) to provide a guide to the development of the semi-structured interviews and to help facilitate the research process such as the set-up of interviews.

Inpp5e Is Critical for Photoreceptor Outer Segment Maintenance.

In humans, inositol polyphosphate-5-phosphatase e (INPP5E) mutations cause retinal degeneration as part of Joubert and MORM syndromes and can also cause non-syndromic blindness. In mice, mutations cause a spectrum of brain, kidney, and other anomalies and prevent the formation of photoreceptor outer segments. To further explore the function of Inpp5e in photoreceptors, we generated conditional and inducible knockouts of mouse Inpp5e where the gene was deleted either during outer segment formation or after outer segments were fully formed.

Assessing Family Caregiver Readiness for Hospital Discharge of Patients With Serious or Life-Limiting Illness Using Electronic Health Record (EHR) and Self-Reported Data.

Objective: To assess how patient and caregiver factors influence caregiver readiness for hospital discharge in palliative care patients.

Study Setting And Design: This transitional care study uses cross-sectional data from a randomized controlled trial conducted from 2018 to 2023 testing an intervention for caregivers of hospitalized adult patients with a serious or life-limiting illness who received a palliative care consult prior to transitioning out of the hospital.

Data Sources And Analytical Sample: Caregiver readiness was measured with the Family Readiness for Hospital Discharge Scale (n = 231).

Alu-Sc-mediated exonization generated a mitochondrial LKB1 gene variant found only in higher order primates.

The tumor suppressor LKB1/STK11 plays important roles in regulating cellular metabolism and stress responses and its mutations are associated with various cancers. We recently identified a novel exon 1b within intron 1 of human LKB1/STK11, which generates an alternatively spliced, mitochondria-targeting LKB1 isoform important for regulating mitochondrial oxidative stress. Here we examined the formation of this novel exon 1b and uncovered its relatively late emergence during evolution.

CellREADR: An ADAR-based RNA sensor-actuator device.

RNAs are central mediators of genetic information flow and gene regulation that underlie diverse cell types and cell states across species. Thus, methods that can sense and respond to RNA profiles in living cells will have broad applications in biology and medicine. CellREADR - Cell access through RNA sensing by Endogenous ADAR (adenosine deaminase acting on RNA), is a programmable RNA sensor-actuator technology that couples the detection of a cell-defining RNA to the translation of an effector protein to monitor and manipulate the cell.

Radiographic Soft Tissue Thickness is not a Risk Factor for Infection after Primary Total Ankle Arthroplasty.

As the incidence of total ankle arthroplasty (TAA) for the management of end-stage arthritis is on the rise, identification of risk factors for periprosthetic joint infection (PJI) is essential. There has been limited research exploring the use of radiographic soft tissue thickness in TAA despite its predictive value in other forms of arthroplasty. This study evaluated the predictive capabilities of radiographic soft-tissue thickness for PJI following TAA.

Norman B. Anderson (1955-2024).

Memorializes Norman B. Anderson (1924-2024). Norman B.

Comprehensive guide for epigenetics and transcriptomics data quality control.

Host response to environmental exposures such as pathogens and chemicals can include modifications to the epigenome and transcriptome. Improved signature discovery, including the identification of the agent and timing of exposure, has been enabled by advancements in assaying techniques to detect RNA expression, DNA base modifications, histone modifications, and chromatin accessibility. The interrogation of the epigenome and transcriptome cascade requires analyzing disparate datasets from multiple assay types, often at single-cell resolution, derived from the same biospecimen.

Case management in emergency care: impact evaluation of the CARED Program.

Background: Hospitals face mounting pressure to reduce unplanned utilization amid rising healthcare demands from an aging population. The Case management for At-Risk patients in the Emergency Department (CARED) program is among the first ED transitional care strategies to focus on both frail older adults and emergency department (ED) re-attenders to reduce acute hospital utilization. This study aims to evaluate the effectiveness of the CARED program in reducing hospital (re)admissions and ED re-attendances within 30- and 60 days post-discharge.