Consensus recommendations for measuring the impact of contraception on the menstrual cycle in contraceptive clinical trials.

Objective: We sought to develop consensus recommendations for measurement and analysis of data on contraceptive-induced menstrual changes (CIMCs) in contraceptive clinical trials. We built upon previous standardization efforts over the last 50 years and prioritized input from a variety of global experts and current regulatory authority guidance on patient-reported outcomes.

Study Design: We completed a formal consensus-building process with an interdisciplinary group of 57 experts from 30 organizations and 14 countries in five global regions who work across academia, nonprofit research organizations, the pharmaceutical industry, and funding agencies.

A quantitative intracellular peptide binding assay reveals recognition determinants and context dependence of short linear motifs.

Transient protein-protein interactions play key roles in controlling dynamic cellular responses. Many examples involve globular protein domains that bind to peptide sequences known as Short Linear Motifs (SLiMs), which are enriched in intrinsically disordered regions of proteins. Here we describe a novel functional assay for measuring SLiM binding, called Systematic Intracellular Motif Binding Analysis (SIMBA).

Human organotypic colon in vitro microtissue: unveiling a new window into colonic drug disposition.

The purpose of this study was to evaluate EpiColon, a novel human organotypic 3D colon microtissue prototype, developed to assess colonic drug disposition, with a particular focus on permeability ranking, and compare its performance to Caco-2 monolayers. EpiColon was characterized for barrier function using transepithelial electrical resistance (TEER), morphology via histology and immunohistochemistry, and functionality through drug transport studies measuring apparent permeability (P). Cutoff thresholds for the permeability of FITC-dextran 4 kDa (FD4), FITC-dextran 10 kDa (FD10S), and [C]mannitol were established to monitor microtissue integrity.

Association of Chronic Limb Ischemia Rutherford Classification with Clinical Outcomes Following Lower Extremity Revascularization.

Introduction: The Rutherford Classification for chronic limb-threatening ischemia (CLTI) is used to categorize peripheral artery disease severity through history and physical examination. This study investigated whether higher Rutherford Classification correlates with worse clinical outcomes and could serve as a predictive tool.

Methods: In this prospective single-center study , 252 patients undergoing lower extremity revascularization were followed for three years (2020-2023).

Prescription Stimulant Dispensing to US Children: 2017-2023.

Objective: To evaluate changes in prescription stimulant dispensing to children aged 5 to 17 years associated with the COVID-19 pandemic and the shortage of immediate-release mixed amphetamine salts (Adderall), which was announced in October 2022.

Methods: We analyzed the 2017 to 2023 IQVIA Longitudinal Prescription Database, which captures 92% of US prescriptions. Using an interrupted time series design, we evaluated level and slope changes in the monthly stimulant-dispensing rate (number of children with stimulant dispensing per 100 000 children) in March 2020 and October 2022.

A Bitter Pill: The Ethics of Involuntary Treatment of Adolescents With Severe Eating Disorders.

Severe eating disorders (EDs) are a common and increasing threat to normal adolescent health and development. Major clinical challenges include longstanding malnutrition potentially complicated by emergent electrolyte disorders and cardiac dysfunction. The care of adolescents with severe EDs can lead to challenging decisions regarding the initiation of involuntary feeding with restraints.

Proxy-reported outcomes accurately reflect objective patient-reported outcomes in older adult patients with traumatic orthopaedic injuries.

Background: Older adults make up an increasing portion of orthopedic trauma care. Proxy reports are particularly valuable when patients face difficulties formulating answers due to pre-existing or temporary cognitive impairment, and provide critical insights into patient well-being.

Questions/purposes: This study examines the agreement between patient- and proxy-reported outcome measures across various health domains of older adult orthopedic trauma patients, including those with mild cognitive impairment.

Characterizing the relationship between personality dimensions and psychosis-specific clinical characteristics.

Background: Past studies associating personality with psychosis have been limited by small nonclinical samples and a focus on general symptom burden. This study uses a large clinical sample to examine personality's relationship with psychosis-specific features and compare personality dimensions across clinically and neurobiologically defined categories of psychoses.

Methods: A total of 1352 participants with schizophrenia, schizoaffective disorder, and bipolar with psychosis, as well as 623 healthy controls (HC), drawn from the Bipolar-Schizophrenia Network for Intermediate Phenotypes (BSNIP-2) study, were included.

Identification of an ANCA-associated vasculitis cohort using deep learning and electronic health records.

Background: ANCA-associated vasculitis (AAV) is a rare but serious disease. Traditional case-identification methods using claims data can be time-intensive and may miss important subgroups. We hypothesized that a deep learning model analyzing electronic health records (EHR) can more accurately identify AAV cases.

"I Won't Put Myself or My Family Through That": Decision Preferences, Family Experiences, and Kidney Disease Decision-Making.

Background And Objectives: Chronic kidney disease (CKD) is a major public health concern that uniquely impacts older Black Americans, a population also likely to have family members also diagnosed with CKD. This study aimed to (1) describe how participants viewed their decision preferences considering the experiences of family, and friends previously diagnosed with CKD, and (2) to understand how these social complexities informed their own decisions for future CKD care.

Research Design And Methods: Utilizing a phenomenologically-informed approach, this study explored participants' perceptions of how patients and their family members' experiences with CKD influenced treatment-related decision-making.

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.

Towards device technologies non-invasive to our daily lives.

Recent advances in non-invasive technologies have shown disruptive potential for biomedical applications. However, while surgically non-invasive, they may introduce other types of limitations which interfere with the patient’s quality of life, from impracticalities and discomfort in daily life to social stigma.

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.