Oocytes with impaired meiotic maturation contain increased mtDNA deletions.

Purpose: Induction of meiotic competence is a major goal of the controlled ovarian stimulation used in ART. Do factors intrinsic to the oocyte contribute to oocyte maturation? Deletions in mtDNA accumulate in long-lived post mitotic tissues and are found in human oocytes. If oogenesis cleanses the germline of deleterious deletions in mtDNA, meiotically competent oocytes should contain lower levels of mtDNA deletions vs.

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.

Targeting aldehyde dehydrogenase ALDH3A1 increases ferroptosis vulnerability in squamous cancer.

Ferroptosis is a unique modality of regulated cell death induced by excessive lipid peroxidation, playing a crucial role in tumor suppression and providing potential therapeutic strategy for cancer treatment. Here, we find that aldehyde dehydrogenase-ALDH3A1 tightly links to ferroptosis in squamous cell carcinomas (SCCs). Functional assays demonstrate the enzymatic activity-dependent regulation of ALDH3A1 in protecting SCC cells against ferroptosis through catalyzing aldehydes and mitigating lipid peroxidation.

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.

Histopathology and proteomics are synergistic for high-grade serous ovarian cancer platinum response prediction.

Patients with High-Grade Serous Ovarian Cancer (HGSOC) exhibit varied responses to treatment, with 20-30% showing de novo resistance to platinum-based chemotherapy. While hematoxylin-eosin (H&E)-stained pathological slides are used for routine diagnosis of cancer type, they may also contain diagnostically useful information about treatment response. Our study demonstrates that combining H&E-stained whole slide images (WSIs) with proteomic signatures using a multimodal deep learning framework significantly improves the prediction of platinum response in both discovery and validation cohorts.

Joint association of objective and subjective aging with premature mortality.

Objective and subjective aging indicators reflect diverse biological and psychosocial processes, yet their combined association with premature mortality remains underexplored. This study aimed to investigate the association between a multidomain framework of aging indicators and premature mortality, addressing gaps in understanding cumulative effects. We included 369,741 UK Biobank participants initially free of cardiovascular disease (CVD) and cancer, followed until December 31, 2022.

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.

Fast single atom imaging for optical lattice arrays.

High-resolution fluorescence imaging of ultracold atoms and molecules is paramount to performing quantum simulation and computation in optical lattices and tweezers. Imaging durations in these experiments typically range from a millisecond to a second, significantly limiting the cycle time. In this work, we present fast, 2.

CHD6 has poly(ADP-ribose)- and DNA-binding domains and regulates PARP1/2-trapping inhibitor sensitivity via abasic site repair.

To tolerate oxidative stress, cells enable DNA repair responses often sensitive to poly(ADP-ribose) (PAR) polymerase 1 and 2 (PARP1/2) inhibition-an intervention effective against cancers lacking BRCA1/2. Here, we demonstrate that mutating the CHD6 chromatin remodeler sensitizes cells to PARP1/2 inhibitors in a manner distinct from BRCA1, and that CHD6 recruitment to DNA damage requires cooperation between PAR- and DNA-binding domains essential for nucleosome sliding activity. CHD6 displays direct PAR-binding, interacts with PARP-1 and other PAR-associated proteins, and combined DNA- and PAR-binding loss eliminates CHD6 relocalization to DNA damage.

High-resolution fleezers reveal duplex opening and stepwise assembly by an oligomer of the DEAD-box helicase Ded1p.

DEAD-box RNA-dependent ATPases are ubiquitous in all domains of life where they bind and remodel RNA and RNA-protein complexes. DEAD-box ATPases with helicase activity unwind RNA duplexes by local opening of helical regions without directional movement through the duplexes and some of these enzymes, including Ded1p from Saccharomyces cerevisiae, oligomerize to effectively unwind RNA duplexes. Whether and how DEAD-box helicases coordinate oligomerization and unwinding is not known and it is unclear how many base pairs are actively opened.

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.

Quantitative and Visual Benefits of Data-Driven Motion Correction on Oncologic PET/CT: A Prospective Cross-sectional Study.

Rationale And Objective: Conventional positron emission tomography (PET) respiratory gating utilizes a fraction of acquired PET counts (i.e., optimal gate [OG]), whereas elastic motion correction with deblurring (EMCD) utilizes all PET counts to reconstruct motion-corrected images without increasing image noise.

Establishing functionally segregated dopaminergic circuits.

Despite accounting for only ~0.001% of all neurons in the human brain, midbrain dopaminergic neurons control numerous behaviors and are associated with many neuropsychiatric disorders that affect our physical and mental health. Dopaminergic neurons form various anatomically and functionally segregated pathways.

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.

Identifying proteomic prognostic markers for Alzheimer's disease with survival machine learning: The Framingham Heart Study.

Background: Protein abundance levels, sensitive to both physiological changes and external interventions, are useful for assessing the Alzheimer's disease (AD) risk and treatment efficacy. However, identifying proteomic prognostic markers for AD is challenging by their high dimensionality and inherent correlations.

Methods: Our study analyzed 1128 plasma proteins, measured by the SOMAscan platform, from 858 participants 55 years and older (mean age 63 years, 52.

Ultra-processed food consumption and risk of dementia and Alzheimer's disease: The Framingham Heart Study.

Background: Ultra-processed food consumption is emerging as a risk factor for various cardiometabolic diseases, however its association with dementia and Alzheimer's disease has rarely been explored.

Objectives: We sought to examine whether ultra-processed food consumption is associated with risk of all-cause dementia and Alzheimer's disease among middle-age and older adults.

Design: A prospective cohort study.

High definition transcranial direct current stimulation as an intervention for cognitive deficits in Alzheimer's dementia: A randomized controlled trial.

Background: Recent disease-modifying treatments for Alzheimer's disease show promise to slow cognitive decline, but show no efficacy towards reducing symptoms already manifested.

Objectives: To investigate the efficacy of a novel noninvasive brain stimulation technique in modulating cognitive functioning in Alzheimer's dementia (AD).

Design: Pilot, randomized, double-blind, parallel, sham-controlled study SETTING: Clinical research site at UT Southwestern Medical Center PARTICIPANTS: Twenty-five participants with clinical diagnoses of AD were enrolled from cognition specialty clinics.

A Multivariate Analysis of a Modified Frailty Index on Perioperative Morbidity and Mortality Following Non-Emergent Endovascular Aortic Aneurysm Repair.

Objective: Frailty has become an increasingly recognized perioperative risk stratification tool. While frailty has been strongly correlated with worsening surgical outcomes, the individual determinants of frailty have rarely been investigated in the setting of aortic disease. The aim of this study was to examine the determinants of an 11-factor modified frailty index (mFI-11) on mortality and postoperative complications in patients undergoing endovascular aortic aneurysm repair (EVAR).

Differences in Postoperative Disposition by Kidney Disease Severity: A Population-Based Cohort Study.

Rationale & Objective: People with advanced kidney disease undergo more non-cardiac operations compared to the general population, with a higher risk of perioperative cardiac events and death. However, little is known about the associations between severity of preoperative kidney dysfunction with postoperative length of hospitalization and discharge disposition; these were the focus of this study.

Study Design: Population-based retrospective cohort.

ARCH: Large-scale knowledge graph via aggregated narrative codified health records analysis.

Objective: Electronic health record (EHR) systems contain a wealth of clinical data stored as both codified data and free-text narrative notes (NLP). The complexity of EHR presents challenges in feature representation, information extraction, and uncertainty quantification. To address these challenges, we proposed an efficient Aggregated naRrative Codified Health (ARCH) records analysis to generate a large-scale knowledge graph (KG) for a comprehensive set of EHR codified and narrative features.

Impella versus Non-Impella for Non-emergent High-Risk Percutaneous Coronary Intervention: Impella vs. Non-Impella for HR-PCI.

Background: The benefit of mechanical circulatory support (MCS) with Impella (Abiomed, Inc, Danvers, MA) for patients undergoing non-emergent, high-risk percutaneous coronary intervention (HR-PCI) is unclear and currently the subject of a large randomized clinical trial (RCT), PROTECT IV. While contemporary registry data from PROTECT III demonstrated improvement of outcomes with Impella when compared with historical data (PROTECT II), there is lack of direct comparison to the HR-PCI cohort that did not receive Impella support.

Methods: We retrospectively identified patients from our institution meeting PROTECT III inclusion criteria (left ventricular ejection fraction [LVEF] <35% with unprotected left main or last remaining vessel or LVEF <30% undergoing multivessel PCI), and compared this group (NonIMP) to the published outcomes data from the PROTECT III registry (IMP).

Prognostic performance of the two-step clinical care pathway in metabolic dysfunction-associated steatotic liver disease.

Background & Aims: Current guidelines recommend a 2-step approach for risk stratification in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) with Fibrosis-4 index (FIB-4) followed by liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE) or similar second-line tests. This study aimed to examine to prognostic performance of this approach.

Methods: The VCTE-Prognosis Study was a longitudinal study of patients with MASLD who had undergone VCTE examinations at 16 centres from the US, Europe and Asia with subsequent follow-up for clinical events.