A Comprehensive Atlas of AAV Tropism in the Mouse.

Gene therapy with Adeno-Associated Virus (AAV) vectors requires knowledge of their tropism within the body. Here we analyze the tropism of ten naturally occurring AAV serotypes (AAV3B, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAVrh8, AAVrh10 and AAVrh74) following systemic delivery into male and female mice. A transgene expressing ZsGreen and Cre recombinase was used to identify transduction in a cell-dependent manner based on fluorescence.

Mitochondrial Dysfunction in HFpEF: Potential Interventions Through Exercise.

HFpEF is a prevalent and complex type of heart failure. The concurrent presence of conditions such as obesity, hypertension, hyperglycemia, and hyperlipidemia significantly increase the risk of developing HFpEF. Mitochondria, often referred to as the powerhouses of the cell, are crucial in maintaining cellular functions, including ATP production, intracellular Ca regulation, reactive oxygen species generation and clearance, and the regulation of apoptosis.

Osilodrostat improves blood pressure and glycemic control in patients with Cushing's disease: a pooled analysis of LINC 3 and LINC 4 studies.

Purpose: To evaluate the effect of osilodrostat and hypercortisolism control on blood pressure (BP) and glycemic control in patients with Cushing's disease.

Methods: Pooled analysis of two Phase III osilodrostat studies (LINC 3 and LINC 4), both comprising a 48-week core phase and an optional open-label extension. Changes from baseline in systolic and diastolic BP (SBP and DBP), fasting plasma glucose (FPG), and glycated hemoglobin (HbA) were evaluated during osilodrostat treatment in patients with/without hypertension or diabetes at baseline.

Comparison of the diagnostic performance of non-contrast MR angiography and planar V/Q scintigraphy for pulmonary embolism: a systematic review and meta-analysis.

Objectives: To conduct a meta-analysis of the diagnostic performance of non-contrast magnetic resonance pulmonary angiography (NC-MRPA) and ventilation-perfusion (V/Q) scintigraphy for the detection of acute pulmonary embolism (PE).

Materials And Methods: Systematic searches of electronic databases were conducted from 2000 to 2024. Primary outcomes were per-patient sensitivity and specificity of NC-MRPA and V/Q scintigraphy.

Liquid-based encapsulation for implantable bioelectronics across broad pH environments.

Wearable and implantable bioelectronics that can interface for extended periods with highly mobile organs and tissues across a broad pH range would be useful for various applications in basic biomedical research and clinical medicine. The encapsulation of these systems, however, presents a major challenge, as such devices require superior barrier performance against water and ion penetration in challenging pH environments while also maintaining flexibility and stretchability to match the physical properties of the surrounding tissue. Current encapsulation materials are often limited to near-neutral pH conditions, restricting their application range.

Nonlinearity of the post-spinel transition and its expression in slabs and plumes worldwide.

Phase transitions in the mantle control its internal dynamics and structure. The post-spinel transition marks the upper-lower mantle boundary, where ringwoodite dissociates into bridgmanite plus ferropericlase, and its Clapeyron slope regulates mantle flow across it. This interaction has previously been assumed to have no lateral spatial variations, based on the assumption of a linear post-spinel boundary in pressure and temperature.

Anthracyclines disaggregate and restore mutant p63 function: a potential therapeutic approach for AEC syndrome.

Ankyloblepharon-Ectodermal Defects-Cleft Lip/Palate (AEC) syndrome is a rare genetic disorder caused by mutations in the TP63 gene, which encodes a transcription factor essential for epidermal gene expression. A key feature of AEC syndrome is chronic skin erosion, for which no effective treatment currently exists. Our previous studies demonstrated that mutations associated with AEC syndrome lead to p63 protein misfolding and aggregation, exerting a dominant-negative effect.

The importance of Ombudsman programs in supporting the transition from medicare-medicaid plans to dual special needs plans.

In this paper, we examine the critical role of Ombudsman programs in facilitating the transition from Medicare-Medicaid Plans (MMPs) to Dual Special Needs Plans (D-SNPS) for dual-eligible members. As states implement this federally mandated transition, Ombudsman programs serve as essential supports for the dual-eligible population who are navigating complex healthcare changes. Through analysis of Ombudsman programs in California, Massachusetts, Rhode Island, and Michigan, we highlight how these services address beneficiary concerns, resolve access issues, and provide valuable insights to policymakers.

Protocol for a systematic review and individual participant data meta-analysis for risk factors for lung cancer in individuals with lung nodules identified by low-dose CT screening.

Background: Worldwide, lung cancer (LC) is the second most frequent cancer and the leading cause of cancer related mortality. Low-dose CT (LDCT) screening reduced LC mortality by 20-24% in randomised trials of high-risk populations. A significant proportion of those screened have nodules detected that are found to be benign.

AGA Clinical Practice Guideline on the Prevention and Treatment of Hepatitis B Virus Reactivation in At-Risk Individuals.

Background & Aims: Hepatitis B reactivation (HBVr) can occur due to a variety of immune-modulating exposures, including multiple drug classes and disease states. Antiviral prophylaxis can be effective in mitigating the risk of HBVr. In select cases, clinical monitoring without antiviral prophylaxis is sufficient for managing the risk of HBVr.

Menstrual cycle characteristics across the reproductive lifespan and cognitive function in midlife women.

Background: Menstrual cycle characteristics are potential indicators of hormonal exposures and may also signal cardiovascular disease risk factors, both of which are relevant to cognitive health. However, there is scarce epidemiological evidence on the association between cycle characteristics and cognitive function.

Objectives: We studied the associations of menstrual cycle characteristics at three stages of a woman's reproductive lifespan with cognitive function in midlife.

Advancing long-read nanopore genome assembly and accurate variant calling for rare disease detection.

More than 50% of families with suspected rare monogenic diseases remain unsolved after whole-genome analysis by short-read sequencing (SRS). Long-read sequencing (LRS) could help bridge this diagnostic gap by capturing variants inaccessible to SRS, facilitating long-range mapping and phasing and providing haplotype-resolved methylation profiling. To evaluate LRS's additional diagnostic yield, we sequenced a rare-disease cohort of 98 samples from 41 families, using nanopore sequencing, achieving per sample ∼36× average coverage and 32-kb read N50 from a single flow cell.

A Comparative Study Between Cold Static Storage and Normothermic Ex-Situ Donor Heart Preservation in a Rat Model of Heterotopic Heart Transplantation.

Introduction: Cold static storage (CSS) and normothermic ex-situ preservation are the most widely used donor heart preservation techniques worldwide. The current study compares both CSS and normothermic ex-situ preservation methods in terms of graft performance, morphologic changes, and acute immune response in an experimental model.

Method And Materials: Twenty rats underwent heterotopic abdominal heart transplantation after 2 h of CSS (group 1; n = 10) or normothermic ex-situ perfusion (group 2; n = 10).

Associations of Serum Urate and Cardiovascular Events in a Clinical Trial of Interleukin-1β Blockade.

Background: Serum urate (SU) associates with cardiovascular (CV) events, mortality, and gout.

Objectives: The purpose of this study was to assess whether SU predicts CV risk in a trial of interleukin (IL)-1β inhibition with canakinumab, and whether IL-1β blockade, kidney function, or gout alter these associations.

Methods: This study is a subanalysis of the Canakinumab Antiinflammatory Thrombosis Outcome Study (CANTOS), which randomized 10,061 patients with prior myocardial infarction and elevated high-sensitivity C-reactive protein to 3 doses of canakinumab or placebo.

Management of renal cell carcinoma with ablation in comparison to nephrectomy: A 5-year analysis of inpatient procedural data to evaluate utilization disparities in the United States.

Purpose: To perform a nationwide analysis of ablation compared to partial and total nephrectomy for the management of renal cell carcinoma (RCC) to evaluate utilization trends and disparities in the USA.

Materials And Methods: The 2016-2020 National Inpatient Sample was analyzed. Using ICD-10, we identified the diagnosis of RCC then analyzed the utilization trends of ablation and nephrectomies (both partial and complete).

Emerging insights into the impact of systemic metabolic changes on tumor-immune interactions.

Tumors are inherently embedded in systemic physiology, which contributes metabolites, signaling molecules, and immune cells to the tumor microenvironment. As a result, any systemic change to host metabolism can impact tumor progression and response to therapy. In this review, we explore how factors that affect metabolic health, such as diet, obesity, and exercise, influence the interplay between cancer and immune cells that reside within tumors.

A-kinase anchor protein 12 promotes oligodendrogenesis and cognitive recovery in carbon monoxide therapy for traumatic brain injury.

Therapeutic drug development for central nervous system injuries, such as traumatic brain injury (TBI), presents significant challenges. TBI results in primary mechanical damage followed by secondary injury, leading to cognitive dysfunction and memory loss. Our recent study demonstrated the potential of carbon monoxide-releasing molecules (CORMs) to improve TBI recovery by enhancing neurogenesis.

'It is scary to pause treatment': perspectives on HIV cure-related research and analytical treatment interruptions from women diagnosed during acute HIV in Durban, South Africa.

Background: HIV remains a major challenge in KwaZulu-Natal, South Africa, particularly for young women who face disproportionate risks and barriers to prevention and treatment. Most HIV cure trials, however, occur in high-income countries.

Objective: To examine the perspectives of young women diagnosed with acute HIV in a longitudinal study, focusing on their perceptions on ATI-inclusive HIV cure trials and the barriers and facilitators to participation.

Use of the Adaptive Behaviour Dementia Questionnaire in a Down Syndrome Specialty Clinic.

Objective: To study the use of a dementia screening tool in our clinic cohort of adults with Down syndrome.

Study Design: A retrospective chart review of patients with Down syndrome was conducted to follow the use of the Adaptive Behaviour Dementia Questionnaire (ABDQ) in a dementia screening protocol. The ABDQ results for patients aged 40 years and older at a Down syndrome specialty clinic program were assessed.

Multicenter screening for ADHD among school-age pediatric patients with type 1 diabetes - study protocol.

Purpose: Attention-deficit hyperactivity disorder (ADHD) is a common neurodevelopmental condition that affects approximately 5% of the pediatric population, with increased prevalence among those with type 1 diabetes (T1D). Reports suggest that unrecognized and untreated ADHD impairs T1D control and that ADHD may be underdiagnosed in the Polish population. The International Society for Pediatric and Adolescent Diabetes recommends neurodevelopmental assessments in children with T1D, but specific guidelines on procedures and implementation are lacking.

Patterns of Treatment and Real-World Outcomes of Patients With Non-small Cell Lung Cancer With EGFR Exon 20 Insertion Mutations Receiving Mobocertinib: The EXTRACT Study.

Background: Real-world data regarding patients with non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion (ex20ins) mutations receiving mobocertinib are limited. This study describes these patients' characteristics and outcomes.

Methods: A chart review was conducted across three countries (Canada, France, and Hong Kong), abstracting data from eligible patients (NCT05207423).