Olaparib as treatment for platinum-sensitive relapsed ovarian cancer by BRCA mutation and homologous recombination deficiency: Phase 2 LIGHT study final overall survival analysis.

Background: LIGHT (oLaparib In HRD-Grouped Tumor types; NCT02983799) prospectively evaluated olaparib treatment in patients with platinum-sensitive relapsed ovarian cancer (PSROC) assigned to cohorts by known BRCA mutation (BRCAm) and homologous recombination deficiency (HRD) status: germline BRCAm (gBRCAm), somatic BRCAm (sBRCAm), HRD-positive non-BRCAm, and HRD-negative. At the primary analysis, olaparib treatment demonstrated activity across all cohorts, with greatest efficacy in terms of objective response rate and progression-free survival observed in the g/sBRCAm cohorts. The authors report final overall survival (OS).

Trifunctional lipid derivatives: PE's mitochondrial interactome.

Phosphatidylethanolamine (PE) is a ubiquitous lipid species in higher eukaryotes. Here, we synthesized a multifunctionalized PE derivative (1) designed to identify PE-binding proteins in intact cells through photo-crosslinking and subsequent isolation and proteomic analysis of the PE-protein conjugates. We show that the tool is also useful for tracking PE translocation to mitochondria after uncaging.

Coexisting Calcific Aortic Stenosis and Transthyretin Cardiac Amyloidosis: Real-World Evaluation of Clinical Characteristics and Outcomes.

Background: The coexistence of transthyretin cardiac amyloidosis (ATTR-CA) and aortic stenosis (AS) is increasingly recognized, but the clinical consequences are unclear. We aimed to characterize clinical outcomes in AS plus ATTR-CA compared with only AS or ATTR-CA.

Methods And Results: In a retrospective cohort study, patients with AS only, ATTR-CA only, or AS plus ATTR-CA were identified using all-payer claims data (2015-2021).

Welfare Status in Dairy Cows during Confined and Grazing Periods in the North American Pacific Northwest using Blood Parameters and Visual Assessments.

Grazing is usually associated with higher well-being in dairy cows. However, current research on the welfare of grazing cows lacks validation via blood profiling. We monitored four dairy farms that seasonally graze in the temperate North American Pacific Northwest, USA, to address this gap.

Electrical Heterogeneity in Hispanic Background Subpopulations: The HCHS/SOL.

Background: The Hispanic/Latino population is not uniform. Prevalence and clinical outcomes of cardiac arrhythmias in ethnic background subgroups are variable, but the reasons for differences are unclear. Vectorcardiographic Global Electrical Heterogeneity (GEH) has been shown to be associated with adverse cardiovascular outcomes.

Ground Reaction Forces and Joint Moments Predict Metabolic Cost in Physical Performance: Harnessing the Power of Artificial Neural Networks.

Understanding metabolic cost through biomechanical data, including ground reaction forces (GRFs) and joint moments, is vital for health, sports, and rehabilitation. The long stabilization time (2-5 min) of indirect calorimetry poses challenges in prolonged tests. This study investigated using artificial neural networks (ANNs) to predict metabolic costs from the GRF and joint moment time series.

Divergent Transport Dynamics of Alkylated versus Unsubstituted Polycyclic Aromatic Hydrocarbons at the Air-Water and Sediment-Water Interfaces at a Legacy Creosote Site.

Alkylated polycyclic aromatic hydrocarbons (PAHs) are abundant constituents of many PAH mixtures and contribute to risk at contaminated sites. Despite their abundance, the movement of alkylated PAHs remains understudied relative to unsubstituted PAHs. In the present study, passive sampling devices were deployed in the air, water, and sediments at 11 locations across multiple seasons to capture spatial and temporal variability in the abundance and movement of alkylated PAHs at a Brownsfield creosote site in Oregon, USA.

The potential role of tumor deposits in the prognosis and TNM staging for colorectal cancer.

Background: Tumor deposits (TDs) can impact proper staging of cancer, which is crucial for discussing prognosis and determining the appropriate treatment plan. Our study aimed to correlate how TDs influence prognosis of resected colorectal cancer (CRC) and how to optimize tumor-node-metastasis (TNM) staging with respect to TDs for clinical decision-making.

Methods: A retrospective analysis was performed on 611 patients with CRC treated in Jiangsu Cancer Hospital from January 1, 2010 to December 31, 2020 among whom 197 had TDs.

Cognitive Remediation to Facilitate Independent Living in Persons With Serious Mental Illness.

Many people with serious mental illness (SMI) experience cognitive disabilities and poor independent living skills which limit their ability to live independently in the community. This study examined the feasibility and initial effectiveness of integrating a new cognitive remediation program, Thinking Skills for Life (TSL), into independent living skills training programs in four secure residential treatment facilities (SRTFs) to facilitate discharge to more independent living situations. Participants were 30 individuals in the SRTF, of whom 11 were forensically committed to the SRTF.

An Expert Consensus Statement for Implementing Cognitive Behavioral Therapy for Nightmares in Adults.

Objectives: Research supports cognitive behavioral therapies for nightmares (CBT-N) in adults. However, the nuances of implementation and unstandardized nomenclature for treatment components has created confusion in the field. To provide clarification, an expert consensus panel convened to review treatment manual components and to develop guidelines for the standardized implementation and terminology of CBT-N.

Causal analysis for multivariate integrated clinical and environmental exposures data.

Electronic health records (EHRs) provide a rich source of observational patient data that can be explored to infer underlying causal relationships. These causal relationships can be applied to augment medical decision-making or suggest hypotheses for healthcare research. In this study, we explored a large-scale EHR dataset on patients with asthma or related conditions (N = 14,937).

The human and non-human primate developmental GTEx projects.

Many human diseases are the result of early developmental defects. As most paediatric diseases and disorders are rare, children are critically underrepresented in research. Functional genomics studies primarily rely on adult tissues and lack critical cell states in specific developmental windows.

Massively parallel characterization of transcriptional regulatory elements.

The human genome contains millions of candidate cis-regulatory elements (cCREs) with cell-type-specific activities that shape both health and many disease states. However, we lack a functional understanding of the sequence features that control the activity and cell-type-specific features of these cCREs. Here we used lentivirus-based massively parallel reporter assays (lentiMPRAs) to test the regulatory activity of more than 680,000 sequences, representing an extensive set of annotated cCREs among three cell types (HepG2, K562 and WTC11), and found that 41.

Addition of an NK1 receptor antagonist to standard antiemetic prophylaxis in patients with B-cell lymphoma receiving EPOCH.

Introduction: Data on the optimal management of patients with hematologic malignancies and chemotherapy-induced nausea and vomiting (CINV) are lacking, particularly for multiday chemotherapy regimens. We report our institutional experience in patients with B-cell lymphoma receiving multiday dose-adjusted R-EPOCH chemotherapy utilizing two CINV prophylaxis strategies.

Methods: We performed a retrospective, single-center, cohort study evaluating hospitalized patients with aggressive non-Hodgkin B-cell lymphoma receiving DA-R-EPOCH (April 2016 to October 2022).

Maternal derived antibodies and avian β-defensins expression patterns and their correlation in the yolk sac tissue of different chicken breeds (Gallus gallus).

The expression of maternal derived antibodies (MDAs) and avian β-defensins (AvBDs) in yolk sac tissue may be age-specific and influenced by breed, thereby immunological window difference in hatchlings. This study investigated the mRNA expression of MDAs and AvBDs in the yolk sac tissues of Beijing You and Hy-Line Gray chickens from the embryonic day (ED)7 to 3 days after hatch (DAH). Hy-Line showed a higher embryo bodyweight and a lower residual yolk weight at ED17 (P < 0.

Enhanced mercury deposition in Arctic Alaskan lake sediments coincides with early Holocene hydroclimate shift.

Substantial amounts of mercury (Hg) are projected to be released into Arctic watersheds as permafrost thaws amid warmer and wetter conditions. This may have far-reaching consequences because the highly toxic methylated form of Hg biomagnifies rapidly in ecosystems. However, understanding how climate change affects Hg dynamics in permafrost regions is limited due to the lack of long-term Arctic Hg records.

Gait during community ambulation and laboratory-based walking in people with mild traumatic brain injury.

Background: Gait impairments are common in individuals with mild traumatic brain injury (mTBI), presenting in the acute phase and often persisting in subtle ways over time. Despite the prominence of laboratory gait evaluations, a comprehensive understanding of gait deficits post-mTBI necessitates the examination of various gait domains in real-world environments. Assessing gait during a community ambulation task (CAT) may capture real-world challenges and influence focused interventions or rehabilitation in individuals with mTBI.

Sex differences in the maximal metabolic steady state of fitness matched women and men.

We tested the hypothesis that power at maximal metabolic steady state is similar between fitness matched men and women. Eighteen participants (9 men, 9 women) performed a cycling graded exercise test for maximal oxygen consumption (V̇O). Men and women were matched for V̇O normalized to fat free mass (FFM), which was 50.

A histochemical approach to activity-based copper sensing reveals cuproplasia-dependent vulnerabilities in cancer.

Copper is an essential nutrient for sustaining vital cellular processes spanning respiration, metabolism, and proliferation. However, loss of copper homeostasis, particularly misregulation of loosely bound copper ions which are defined as the labile copper pool, occurs in major diseases such as cancer, where tumor growth and metastasis have a heightened requirement for this metal. To help decipher the role of copper in the etiology of cancer, we report a histochemical activity-based sensing approach that enables systematic, high-throughput profiling of labile copper status across many cell lines in parallel.

Outcomes of mechanical thrombectomy for medium vessel occlusion in acute ischemic stroke patients with ASPECTS 4-5 vs. 6-7: a retrospective, multicenter, and multinational study.

Introduction: Mechanical thrombectomy (MT) efficacy in medium vessel occlusion (MeVO) stroke, particularly in patients with low Alberta Stroke Program Early Computed Tomography Score (ASPECTS), remains less explored.

Methods: This retrospective study analyzed data from 443 AIS patients treated with MT for MeVO and low ASPECTS (4-7) at 37 centers across North America, Asia, and Europe, from September 2017 to July 2021. Patients were categorized into ASPECTS of 4-5 and 6-7.