Multiplexed single-cell imaging reveals diverging subpopulations with distinct senescence phenotypes during long-term senescence induction.

Cellular senescence is a phenotypic state that contributes to the progression of age-related disease through secretion of pro-inflammatory factors known as the senescence-associated secretory phenotype (SASP). Understanding the process by which healthy cells become senescent and develop SASP factors is critical for improving the identification of senescent cells and, ultimately, understanding tissue dysfunction. Here, we reveal how the duration of cellular stress modulates the SASP in distinct subpopulations of senescent cells.

Design features of the rotating head total hip arthroplasty by Weber-Huggler- a forgotten technical solution to reduce wear.

Total hip arthroplasty (THA) is a very successful operation. Once the problem of implant fixation was solved with the use of bone cement, the next development steps focused on improving the bearing. Weber, a Swiss surgeon, introduced the first modular heads in THA.

Computational design of highly signalling-active membrane receptors through solvent-mediated allosteric networks.

Protein catalysis and allostery require the atomic-level orchestration and motion of residues and ligand, solvent and protein effector molecules. However, the ability to design protein activity through precise protein-solvent cooperative interactions has not yet been demonstrated. Here we report the design of 14 membrane receptors that catalyse G protein nucleotide exchange through diverse engineered allosteric pathways mediated by cooperative networks of intraprotein, protein-ligand and -solvent molecule interactions.

Erector spinae plane block for management of acute opioid withdrawal in the emergency department: A case report.

Background: Gastrointestinal symptoms of acute opioid withdrawal are distressing for patients and are often difficult to manage with conventional therapies. Insufficiently managed opioid withdrawal symptoms may lead patients to leave against medical advice, which can increase their risk of relapse and result in poor outcomes from untreated conditions. We assessed the impact of an erector spinae plane block on the acute gastrointestinal symptoms of opioid withdrawal.

KDIGO 2025 clinical practice guideline for the evaluation, management, and treatment of autosomal dominant polycystic kidney disease (ADPKD): executive summary.

The Kidney Disease: Improving Global Outcomes (KDIGO) 2025 Clinical Practice Guideline for the Evaluation, Management, and Treatment of Autosomal Dominant Polycystic Kidney Disease (ADPKD) represents the first KDIGO guideline on this subject. Its scope includes nomenclature, diagnosis, prognosis, and prevalence; kidney manifestations; chronic kidney disease (CKD) management and progression, kidney failure, and kidney replacement therapy; therapies to delay progression of kidney disease; polycystic liver disease; intracranial aneurysms and other extrarenal manifestations; lifestyle and psychosocial aspects; pregnancy and reproductive issues; pediatric issues; and approaches to the management of people with ADPKD. The guideline has been developed with patient partners, clinicians, and researchers around the world, with the goal to generate a useful resource for healthcare providers and patients by providing actionable recommendations.

How Do Clinicians Use Quotations in Goals of Care Notes?

Background: Quoting patients in electronic medical record (EMR) notes is controversial. Quotations may be used to promote accuracy in documentation. However they also may be used to cast skepticism on patient speech.

Development of a health equity tool in resuscitation sciences and application to current research in extracorporeal cardiopulmonary resuscitation for cardiac arrest.

Background: Extracorporeal cardiopulmonary resuscitation (ECPR) is increasingly used for adults with cardiac arrest (CA) refractory to Advanced Cardiovascular Life Support (ACLS). Concerns exist that adding ECPR could worsen health inequities, defined as differences in health outcomes that are unfair or unjust. Current guidelines do not explicitly address this issue.

Cost-effectiveness Analysis of Uterus Transplantation versus Gestational Carrier for Treatment of Absolute Uterine Factor Infertility.

Importance: Patients with uterine factor infertility (UFI) have few options for family building. Uterus transplant is a feasible treatment for some patients; however, cost remains a significant concern.

Objective: To compare the cost effectiveness of treatment for patients with absolute uterine factor infertility to achieve 1-2 singleton births by gestational carrier or uterus transplant DESIGN: Decision analysis from the United States healthcare sector perspective, with time horizons to achieve one or two singleton births.

Survival Among Patients Treated with Total Mesorectal Excision or Selective Watch-and-Wait After Total Neoadjuvant Therapy: A Pooled Analysis of the CAO/ARO/AIO-12 and OPRA Randomized Phase II Trials.

Background: Prospective data comparing watch-and-wait (WW) to mandatory total mesorectal excision (TME) in patients with locally advanced rectal cancer (LARC) remains limited, as randomized control trials assessing these two treatment approaches are considered impractical. This pooled analysis of the CAO/ARO/AIO-12 and OPRA trials analyzes survival outcomes among LARC patients managed with either a selective WW or mandatory TME strategy following total neoadjuvant therapy (TNT).

Patients And Methods: The CAO/ARO/AIO-12 and OPRA trials were multicenter, phase II trials that randomized patients with stage II/III rectal cancer to receive either induction or consolidation chemotherapy as part of TNT.

Utility of Hybrid Angio-CT in Interventional Radiology: Case-Based Examples.

Although cone-beam computed tomography (CBCT) is the predominant cross-sectional imaging modality used by interventional radiologists, advancements in hybrid angiography-computed tomography (Angio-CT) technology have demonstrated a strong potential for increased utilization in the angiography suite. The benefits of increased workflow efficiency, decreased relative cost, multipurpose utility, and most importantly improved patient care, may encourage institutions to accept the higher upfront cost of Angio-CT rooms for potential long-term benefits. Hybrid Angio-CT setups are less prone to motion and streak artifacts and may provide superior image quality compared to CBCT.

Comparison of Acute and Protracted Gamma Irradiation Effects During Perinatal Development in Beagle Dogs.

Ionizing radiation exposure during perinatal development can produce various biological effects on the developing offspring. These effects are dependent on a number of factors, including total dose, dose rate and the developmental processes occurring at the time of irradiation. The present study conducted an analysis of historical radiobiological archived data involving 60Co-gamma irradiation of beagle dogs at specific periods of prenatal or postnatal development.

Semaglutide in obesity-related heart failure with preserved ejection fraction and type 2 diabetes across baseline HbA levels (STEP-HFpEF DM): a prespecified analysis of heart failure and metabolic outcomes from a randomised, placebo-controlled trial.

Background: About half of patients with heart failure with mildly reduced or preserved ejection fraction (HFpEF) have type 2 diabetes. In the STEP-HFpEF DM trial of adults with obesity-related HFpEF and type 2 diabetes, subcutaneous once weekly semaglutide 2·4 mg conferred improvements in heart failure-related symptoms and physical limitations, bodyweight, and other heart failure outcomes. We aimed to determine whether these effects of semaglutide differ according to baseline HbA.

Integration of 168,000 samples reveals global patterns of the human gut microbiome.

The factors shaping human microbiome variation are a major focus of biomedical research. While other fields have used large sequencing compendia to extract insights requiring otherwise impractical sample sizes, the microbiome field has lacked a comparably sized resource for the 16S rRNA gene amplicon sequencing commonly used to quantify microbiome composition. To address this gap, we processed 168,464 publicly available human gut microbiome samples with a uniform pipeline.

Validation of the Portuguese version of the Movement Disorder Society non-motor rating scale (MDS-NMS) in Parkinson's disease.

Background: The Movement Disorder Society Non-Motor Rating Scale (MDS-NMS) serves as a comprehensive clinical assessment tool for non-motor symptoms in Parkinson's disease (PD) OBJECTIVES: This study aims to validate the Portuguese version of the MDS-NMS, addressing the critical need for culturally adapted rating scales in Portuguese-speaking populations.

Methods: This multicenter, cross-sectional study engaged native Portuguese-speaking PD patients from 16 Movement Disorders Centers across Portugal and Brazil. We conducted a meticulous translation process into Portuguese, including forward-backward translation and cognitive pretesting.

Association of anti-phosphatidylserine/prothrombin antibodies with adverse in vitro fertilization outcomes.

Anti-phosphatidylserine/prothrombin antibodies (aPS/PT) are classified as non-criteria antiphospholipid antibodies (aPL), and are strongly associated with thrombosis and pregnancy complications linked to antiphospholipid syndrome (APS). This study aimed to investigate whether aPS/PT positivity is associated with adverse outcomes in vitro fertilization (IVF). The study included infertile women who tested positive aPS/PT and underwent IVF cycles, as well as infertile controls with pure tubal etiology.

The expression of chromosome 19 miRNA cluster members during insulin sensitivity changes in pregnancy.

Hypothesis: Declines in insulin sensitivity during pregnancy important for fetal growth are associated with impairments in skeletal muscle post-receptor insulin signaling. The primary initiator of these changes is unknown but believed to originate in the placenta. We hypothesize that placental miRNAs are associated with maternal sensitivity changes and impact insulin-sensitive mechanisms in target tissues in vitro.

Influence of birthplace and age at migration on cognitive aging among Hispanic/Latino populations in the U.S.: Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA).

Background And Objectives: While Hispanic/Latino populations in the U.S. are remarkably diverse in terms of birthplace and age at migration, we poorly understand how these factors are associated with cognitive aging.

Genetic ancestry superpopulations show distinct prevalence and outcomes across pediatric central nervous system tumors from the PBTA and PNOC.

Background: Central nervous system (CNS) tumors lead to cancer-related mortality in children. Genetic ancestry-associated cancer prevalence and outcomes have been studied, but is limited.

Methods: We performed genetic ancestry prediction in 1,452 pediatric patients with paired normal and tumor whole genome sequencing from the Open Pediatric Cancer (OpenPedCan) project to evaluate the influence of reported race and ethnicity and ancestry-based genetic superpopulations on tumor histology, molecular subtype, survival, and treatment.

Distribution of opioid analgesics by community racial/ethnic and socioeconomic profiles, 2011-2021.

Rapid declines in opioid analgesics dispensed in American communities since 2011 raise concerns about inadequate access to effective pain management among patients for whom opioid therapies are appropriate, especially for those living in racial/ethnic minority and socioeconomically deprived communities. Using 2011 to 2021 national data from the Automated Reports and Consolidated Ordering System and generalized linear models, this study examined quarterly per capita distribution of oxycodone, hydrocodone, and morphine (in oral morphine milligram equivalents [MMEs]) by communities' racial/ethnic and socioeconomic profiles. Communities (defined by 3-digit-zip codes areas) were classified as "majority White" (≥50% self-reported non-Hispanic White population) vs "majority non-White.

Spatially resolved transcriptomics of benign and malignant peripheral nerve sheath tumors.

Background: Peripheral nerve sheath tumors (PNSTs) encompass entities with different cellular differentiation and degrees of malignancy. Spatial heterogeneity complicates diagnosis and grading of PNSTs in some cases. In malignant PNST (MPNST) for example, single cell sequencing data has shown dissimilar differentiation states of tumor cells.