Repression of PFKFB3 sensitizes ovarian cancer to PARP inhibitors by impairing homologous recombination repair.

Background: Ovarian cancer (OC), particularly high-grade serous ovarian carcinoma (HGSOC), is the leading cause of mortality from gynecological malignancies worldwide. Despite the initial effectiveness of treatment, acquired resistance to poly(ADP-ribose) polymerase inhibitors (PARPis) represents a major challenge for the clinical management of HGSOC, highlighting the necessity for the development of novel therapeutic strategies. This study investigated the role of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), a pivotal regulator of glycolysis, in PARPi resistance and explored its potential as a therapeutic target to overcome PARPi resistance.

Amelioration of premature aging in Werner syndrome stem cells by targeting SHIP/AKT pathway.

Background: Pathogenic or null mutations in WRN helicase is a cause of premature aging disease Werner syndrome (WS). WRN is known to protect somatic cells including adult stem cells from premature senescence. Loss of WRN in mesenchymal stem cells (MSCs) not only drives the cells to premature senescence but also significantly impairs the function of the stem cells in tissue repair or regeneration.

Theory-informed refinement and tailored implementation of a quality improvement program in maternity care to reduce unwarranted clinical variation across a health service network.

Background: Unwarranted clinical variation presents a major challenge in contemporary healthcare, indicating potential inequalities and inefficiencies, and unrealised potential for better outcomes. Despite an increasing focus on unwarranted clinical variation, and consideration of efforts to address this challenge, evidence-based strategies which achieve this are limited. Audit and feedback of healthcare processes (process auditing) and clinician engagement are important tools which may help to reduce unwarranted clinical variation, however their application in maternity care is yet to be thoroughly explored.

Prospective association between breakfast consumption frequency and BMI z-score among European school-aged children. The Feel4Diabetes Study.

Background: The long-term effects of breakfast on childhood z-BMI remain inconclusive.

Objective: To prospectively assess the impact of stable and altered breakfast consumption habits on z-BMI change over two years, in school-aged children across six European countries.

Methods: Data of 6,528 children (8.

Dissociating social reward learning and behavior in alcohol use disorder.

Background: Alcohol use disorder (AUD) is associated with deficits in social cognition and behavior, but why these deficits are acquired is unknown. We hypothesized that a reduced association between actions and outcomes for others, i.e.

Supramolecular discrimination and diagnosis-guided treatment of intracellular bacteria.

Pathogenic intracellular bacteria pose a significant threat to global public health due to the barriers presented by host cells hindering the timely detection of hidden bacteria and the effective delivery of therapeutic agents. To address these challenges, we propose a tandem diagnosis-guided treatment paradigm. A supramolecular sensor array is developed for simple, rapid, accurate, and high-throughput identification of intracellular bacteria.

Kinetics of recovery and normalization of running biomechanics following aerobic-based exercise-induced muscle damage in recreational male runners.

Objectives: The study aimed to examine the effects of exercise-induced muscle damage on running kinetics.

Design: Twenty-six adult recreational male runners performed 60 min of downhill running (-10 %) at 65 % of maximal heart rate. Running gait changes, systemic and localized muscle damage markers were assessed pre - and post-exercise induced muscle damage protocol.

Impact of SARS-CoV-2 spike antibody positivity on infection and hospitalisation rates in immunosuppressed populations during the omicron period: the MELODY study.

Background: In the UK, booster COVID-19 vaccinations have been recommended biannually to people considered immune vulnerable. We investigated, at a population level, whether the absence of detectable anti-SARS-CoV-2 spike protein IgG antibody (anti-S Ab) following three or more vaccinations in immunosuppressed individuals was associated with greater risks of infection and severity of infection.

Methods: In this prospective cohort study using UK national disease registers, we recruited participants with solid organ transplants (SOTs), rare autoimmune rheumatic diseases (RAIRDs), and lymphoid malignancies.

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.

Spatiotemporal metabolic mapping of ex-situ preserved hearts subjected to dialysis by integration of bio-SPME sampling with non-targeted metabolipidomic profiling.

Background: Normothermic ex situ heart perfusion (ESHP) has emerged as a valid modality for advanced cardiac allograft preservation and conditioning prior to transplantation though myocardial function declines gradually during ESHP thus limiting its potential for expanding the donor pool. Recently, the utilization of dialysis has been shown to preserve myocardial and coronary vasomotor function. Herein, we sought to determine the changes in myocardial metabolism that could support this improvement.

Monitoring for 5-aminosalicylate nephrotoxicity in adults with inflammatory bowel disease: prognostic model development and validation using data from the Clinical Practice Research Datalink.

Objective: To develop and validate a prognostic model for risk-stratified monitoring of 5-aminosalicylate nephrotoxicity.

Methods: This UK retrospective cohort study used data from the Clinical Practice Research Datalink Aurum and Gold for model development and validation respectively. It included adults newly diagnosed with inflammatory bowel disease and established on 5-aminosalicylic acid (5-ASA) treatment between 1 January 2007 and 31 December 2019.

A review of pharmacological mechanisms, challenges and prospects of macromolecular glycopeptides.

Macromolecular glycopeptides are natural products derived from various sources, distinguished by their structural diversity, multifaceted biological activities, and low toxicity. These compounds exhibit a wide range of biological functions, such as immunomodulation, antitumor effects, anti-inflammatory properties, antioxidant activity, and more. However, limited understanding of natural glycopeptides has hindered their development and practical application.

Novel Hsp90α inhibitor inhibits HSV-1 infection by suppressing the Akt/β-catenin pathway.

The prevalence of herpes simplex virus type 1 (HSV-1) infection and the emergence of drug-resistant HSV-1 strains posts a significant global health challenge, necessitating the urgent development of effective anti-HSV-1 drugs. As one of the most prevalent molecular chaperones, heat shock protein 90 α (Hsp90α) has been extensively demonstrated to regulate a range of viral infections, thus representing a promising antiviral target. In this study, we identified JD-13 as a novel Hsp90α inhibitor and explored its capability in inhibiting HSV-1 infection.

Upright versus recumbent lumbar spine MRI: Do findings differ systematically, and which correlates better with pain? A systematic review.

Background Context: Recumbent MRI is the most widely used image modality in people with low back pain (LBP), however, it has been proposed that upright (standing) MRI has advantages over recumbent MRI because of its ability to assess the effects of being weight-bearing. It has been suggested that this produces systematic differences in MRI parameters and differences in the correlation between MRI parameters and pain or disability in patients thus, potentially adding clinically helpful information.

Purpose: This paper aims to review and summarize the available empirical evidence for or against these two hypotheses.

P3 site-directed mutagenesis: An efficient method based on primer pairs with 3'-overhangs.

Site-directed mutagenesis is a fundamental tool indispensable for protein and plasmid engineering. An important technological question is how to achieve the efficiency at the ideal level of 100%. Based on complementary primer pairs, the QuickChange method has been widely used, but it requires significant improvements due to its low efficiency and frequent unwanted mutations.

Association between prenatal depressive symptoms and receipt of recommended maternal and infant care postpartum.

Background: Maternal mental health can impact health care access and utilization for both the birthing parent and infant. We examined the association between prenatal depressive symptoms (episodic and chronic) and receipt of the postpartum 6-week visit and infant vaccinations in the first year postpartum.

Methods: Postpartum individuals (N = 672) who attended Expect With Me group prenatal care in Nashville, Tennessee and Detroit, Michigan completed surveys during the second and third trimesters of pregnancy, as well as 6- and 12- months postpartum.

Deciphering the phenotypic, inflammatory, and endocrine disrupting impacts of e-waste plastic-associated chemicals.

As the volume of plastic waste from electrical and electronic equipment (WEEE) continues to rise, a significant portion is disposed of in the environment, with only a small fraction being recycled. Both disposal and recycling pose unknown health risks that require immediate attention. Existing knowledge of WEEE plastic toxicity is limited and mostly relies on epidemiological data and association studies, with few insights into the underlying toxicity mechanisms.

Long-term exposure to air pollution and greenness in association with respiratory emergency room visits and hospitalizations: The Life-GAP project.

Background: Air pollution has been linked to respiratory diseases, while the effects of greenness remain inconclusive.

Objective: We investigated the associations between exposure to particulate matter (PM and PM), black carbon (BC), nitrogen dioxide (NO), ozone (O), and greenness (normalized difference vegetation index, NDVI) with respiratory emergency room visits and hospitalizations across seven Northern European centers in the European Community Respiratory Health Survey (ECRHS) study.

Methods: We used modified mixed-effects Poisson regression to analyze associations of exposure in 1990, 2000 and mean exposure 1990-2000 with respiratory outcomes recorded duing ECRHS phases II and III.

Atrial fibrillation versus. atrial myopathy in thrombogenesis: Two sides of the same coin?

Atrial fibrillation (AF) and atrial myopathy are recognized contributors to cardiovascular morbidity, particularly ischemic stroke. AF poses an elevated risk of thrombogenesis due to irregular heart rhythm leading to blood stasis and clot formation. Atrial myopathy, marked by structural and functional alterations in the atria, is emerging as a crucial factor influencing thromboembolic events, independently of AF.

Multifaceted interplays between the essential players and lipid peroxidation in ferroptosis.

Ferroptosis, a type of programmed cell death, represents a distinct paradigm in cell biology. It is characterized by the iron-dependent accumulation of reactive oxygen species, which induce lipid peroxidation (LPO), and is orchestrated by the interplay between iron, lipid peroxides, and glutathione. In this review, we emphasize the frequently overlooked role of iron in LPO beyond the classical iron-driven Fenton reaction in several crucial processes that regulate cellular iron homeostasis, including iron intake and export as well as ferritinophagy, and the emerging roles of endoplasmic reticulum-resident flavoprotein oxidoreductases, especially P450 oxidoreductases, in modulating LPO.

Safety and efficacy of satralizumab in patients with generalised myasthenia gravis (LUMINESCE): a randomised, double-blind, multicentre, placebo-controlled phase 3 trial.

Background: Evidence from preclinical studies suggests that IL-6 signalling has the potential to modulate immunopathogenic mechanisms upstream of autoantibody effector mechanisms in patients with generalised myasthenia gravis. We aimed to assess the safety and efficacy of satralizumab, a humanised monoclonal antibody targeting the IL-6 receptor, in patients with generalised myasthenia gravis.

Methods: LUMINESCE was a randomised, double-blind, placebo-controlled, multicentre, phase 3 study at 105 sites, including hospitals and clinics, globally.

Crossing the blood-brain barrier: emerging therapeutic strategies for neurological disease.

The blood-brain barrier is a physiological barrier that can prevent both small and complex drugs from reaching the brain to exert a pharmacological effect. For treatment of neurological diseases, drug concentrations at the target site are a fundamental parameter for therapeutic effect; thus, the blood-brain barrier is a major obstacle to overcome. Novel strategies have been developed to circumvent the blood-brain barrier, including CSF delivery, intracranial delivery, ultrasound-based methods, membrane transporters, receptor-mediated transcytosis, and nanotherapeutics.

Quantification and profiling of urine cells by integrated cytocentrifugation and infrared spectroscopy.

The presence of cells in urine and in particular White Blood Cells (WBCs) is often associated with Urinary Tract Infections (UTIs) and other diseases. Non-invasive screening of WBCs requires the development of cost-effective point of care diagnostic tools. Infrared (IR) spectroscopy has the potential to identify and quantify cells in urine.

Estrogenic and anti-estrogenic assessment of the flame retardant, 2-ethylhexyl diphenyl phosphate (EHDPP), and its metabolites: Evidence from in vitro, in silico, and transcriptome studies.

2-Ethylhexyl diphenyl phosphate (EHDPP) is a replacement flame-retardant commonly found in several environmental matrices and human biospecimens. Although some adverse effects of EHDPP have been identified, the endocrine-disrupting effects of EHDPP and its key metabolites on the human estrogen receptor (ER) are largely unknown. Herein, we report for the first time that EHDPP, at concentrations found in the environment and humans, significantly promoted estrogenic activity and synergized with 17β-estradiol-induced ER transactivation.