Cancer risk in carriers of TP53 germline variants grouped into different functional categories.

Li-Fraumeni syndrome is a cancer predisposition syndrome caused by pathogenic TP53 germline variants and associated with a high lifelong cancer risk. We analysed the German LFS registry that contains data on 304 individuals. Cancer phenotypes were correlated with variants grouped according to their ability to transactivate target genes in a yeast assay using a traditional (non-functional, partially-functional) and a novel (clusters A, B, C) classification of variants into different groups.

Posterior cruciate ligament resection increases intraoperative lateral and medial flexion laxity during total knee arthroplasty.

Purpose: This study reports the relationship between posterior cruciate ligament (PCL) retention vs resection and soft tissue laxity and balance throughout flexion using a robotically controlled ligament tensioner.

Methods: 55 robotic-assisted TKAs (Total knee arthroplasty) were retrospectively reviewe. The robotic ligament tensioner collected laxity data both before and after PCL resection.

Small-Angle and Quasi-Elastic Neutron Scattering from Polydisperse Oligolamellar Vesicles Containing Glycolipids.

Glycolipids are known to stabilize biomembrane multilayers through preferential sugar-sugar interactions that act as weak transient membrane cross-links. Here, we use small-angle and quasi-elastic neutron scattering on oligolamellar phospholipid vesicles containing defined glycolipid fractions in order to elucidate the influence of glycolipids on membrane mechanics and dynamics. Small-angle neutron scattering (SANS) reveals that the oligolamellar vesicles (OLVs) obtained by extrusion are polydisperse with regard to the number of lamellae, , which renders the interpretation of the quasi-elastic neutron spin echo (NSE) data nontrivial.

Larsucosterol for the Treatment of Alcohol-Associated Hepatitis.

Background: Larsucosterol is a DNA methyltransferase inhibitor in development for alcohol-associated hepatitis (AH), a disease for which there is no approved therapy.

Methods: In this phase 2b trial, patients with severe AH were randomly assigned 1:1:1 to receive 30 mg or 90 mg of larsucosterol or placebo; a second dose was administered after 72 hours if the patient remained hospitalized. All patients received supportive care as determined by investigators.

Catalytic H/D exchange of (hetero)arenes with early-late polyhydride heterobimetallic complexes: impact of transition metal pairs.

Metal-catalyzed hydrogen isotope exchange (HIE) has become a valuable method for incorporating deuterium and tritium into organic molecules, with applications in a wide range of scientific fields. This study explores the role of transition metal cooperativity in enhancing catalytic hydrogen/deuterium (H/D) exchange using early-late heterobimetallic polyhydride (ELHB) complexes. A series of four ELHB complexes, of general formula [M(CHBu)(H)M'Cp*], combining early transition metals (M = Hf, Ta) with late metals (M' = Ir, Os), were synthesized and evaluated for their catalytic activity in HIE of (hetero)arenes.

Insulitis and exocrinitis in autoantibody-positive non-diabetic individuals: role of HLA genotypes.

Context: Type 1 diabetes (T1D) is characterized by the presence of autoantibodies on a genetic background largely determined by HLA class II haplotypes. Stage 1 T1D is characterized by the presence of multiple autoantibodies and normoglycemia.

Objective: To investigate the prevalence of high-risk HLA-DQB1 haplotypes and the extent of islet autoimmunity in pancreatic tissues from non-diabetic organ donors with autoantibodies.

Reshaping computational neuropsychiatry beyond synaptopathy.

Computational neuropsychiatry is a leading discipline to explain psychopathology in terms of neuronal message passing, distributed processing, and belief propagation in neuronal networks. Active Inference (AI) has been one of the ways of representing this dysfunctional signal processing. It involves that all neuronal processing and action selection can be explained by maximizing Bayesian model evidence, or minimizing variational free energy.

An intelligent decision-making system for embryo transfer in reproductive technology: a machine learning-based approach.

Infertility has emerged as a significant public health concern, with assisted reproductive technology (ART) is a last-resort treatment option. However, ART's efficacy is limited by significant financial cost and physical discomfort. The aim of this study is to build Machine learning (ML) decision-support models to predict the optimal range of embryo numbers to transfer, using data from infertile couples identified through literature reviews.

Resistance Analyses in Heavily Treatment-Experienced People with HIV Treated with the Novel HIV Capsid Inhibitor Lenacapavir After 2 years.

Background: Lenacapavir is a highly potent first-in-class inhibitor of HIV-1 capsid approved for the treatment of heavily treatment-experienced (HTE) people with HIV-1 (PWH) harboring multidrug resistant (MDR) virus, in combination with an optimized background regimen (OBR). Resistance analyses conducted after 2 years of lenacapavir treatment in the phase 2/3 CAPELLA study are described.

Methods: CAPELLA enrolled viremic HTE PWH with resistance to 2 or more drugs per class in at least 3 of the 4 main drug classes.

Co-Producing Peritoneal Dialysis Nursing Sensitive Indicators for Quality Care: A Multinational Consensus Building Design.

Background: Nursing sensitive indicators are a way of measuring aspects of patient care that are most affected by the actions of the nurse. Despite the existence of nursing sensitive indicators, these are largely not suitable to measure peritoneal dialysis nursing practice.

Objective: This project aimed to co-develop a set of peritoneal dialysis nursing-sensitive indicators.

Measurement of multidifferential cross sections for dijet production in proton-proton collisions at .

A measurement of the dijet production cross section is reported based on proton-proton collision data collected in 2016 at by the CMS experiment at the CERN LHC, corresponding to an integrated luminosity of up to 36.3 . Jets are reconstructed with the anti- algorithm for distance parameters of and 0.

Micro-Scale Topography Triggers Dynamic 3D Nuclear Deformations.

Navigating complex extracellular environments requires extensive deformation of cells and their nuclei. Most in vitro systems used to study nuclear deformations impose whole-cell confinement that mimics the physical crowding experienced by cells during 3D migration through tissues. Such systems, however, do not reproduce the types of nuclear deformations expected to occur in cells that line tissues such as endothelial or epithelial cells whose physical confinement stems principally from the topography of their underlying basement membrane.

Near-universal prevalence of central adiposity in heart failure with preserved ejection fraction: the PARAGON-HF trial.

Background And Aims: An expansion of fat mass is an integral feature of patients with heart failure and preserved ejection fraction (HFpEF). While body mass index (BMI) is the most common anthropometric measure, a measure of central adiposity-the waist-to-height ratio (WHtR)-focuses on body fat content and distribution; is not distorted by bone or muscle mass, sex, or ethnicity; and may be particularly relevant in HFpEF.

Methods: The PARAGON-HF trial randomized 4796 patients with heart failure and ejection fraction ≥45% to valsartan or sacubitril/valsartan.

Efficacy and Safety of Mechanical Thrombectomy in Distal Medium Middle Cerebral Artery Occlusion Ischemic Stroke Patients on Low-Dose Aspirin.

Background: Acute ischemic stroke (AIS) from distal medium vessel occlusion (DMVO) presents unique treatment challenges. Mechanical thrombectomy (MT) is emerging as a viable option for these patients, yet the role of pre-stroke aspirin treatment is unclear. This study evaluates the impact of pre-stroke low-dose aspirin on outcomes in DMVO patients undergoing MT.

A Novel Polymersome Nanocarrier Promotes Anti-Tumour Immunity by Improved Priming of CD8 T Cells.

Cancer is one of the leading causes of death worldwide. In recent years, immune checkpoint inhibitor therapies, in addition to standard immuno- or chemotherapy and surgical approaches, have massively improved the outcome for cancer patients. However, these therapies have their limitations and improved strategies, including access to reliable cancer vaccines, are needed.

Nickel-Catalyzed Selective Reduction of Carbon Monoxide with Magnesium Alkyl Compounds.

Research on CO activation and homologation is pivotal for promoting sustainable chemistry and the construction of Cn molecular blocks. This work reports the nickel-catalyzed reduction of CO by magnesium alkyl compounds utilizing a bimetallic Mg/Ni synergistic strategy. The exposure of β-diketiminato ligand-supported magnesium monoalkyl compounds LMgR (L = [(DippNCMe)2CH]-, Dipp = 2,6-iPr2C6H3; R = nBu, CH3, C5H9) to 1 bar of CO in the presence of 10 mol% Ni(COD)2 (COD: 1,5-cyclooctadiene) selectively afforded the CO single-insertion product [LMg(CHO)C5H8], the dimerization product [(LMg)2(μ-C2O2)(CH3)2], and the linear trimerization product [(LMg)2(μ-C3O3)(nBu)2], respectively, depending on the R group.

Previous treatment with anthracycline does not affect the course of sepsis in cancer patients: Retrospective cohort study.

Background: Cancer patients who are exposed to sepsis and had previous chemotherapy may have increased severity. Among chemotherapeutic agents, anthracyclines have been associated with cardiac toxicity. Like other chemotherapeutic agents, they may cause endothelial toxicity.

Nebulized aminoglycosides for ventilator-associated pneumonia: Methodological considerations and lessons from experimental studies.

Aminoglycosides are concentration-dependent antibiotics exerting a bactericidal effect when concentrations at the site of infection are equal to or greater than 5 times the minimum inhibitory concentrations (MIC). When administered intravenously, they exhibit poor lung penetration and high systemic renal and ototoxicity, imposing to restrict their administration to 5 days. Experimental studies conducted in anesthetized and mechanically ventilated sheep and pigs provide evidence that high doses of nebulized aminoglycosides induce a rapid and potent bacterial killing in the infected lung parenchyma.

New drugs for acute kidney injury.

Acute kidney injury (AKI) presents a significant challenge in the management of critically ill patients, as it is associated with increased mortality, prolonged hospital stays, and increased healthcare costs. In certain conditions, such as during sepsis or after cardiac surgery, AKI is one of the most frequent complications, affecting 30%-50% of patients. Over time, even after the resolution of AKI, it can evolve into chronic kidney disease, a leading global cause of mortality, and cardiovascular complications.

Correlates of Protection Against Symptomatic COVID-19: The CORSER 5 Case-Control Study.

Background: Establishing correlates of protection often requires large cohorts. A rapid and adaptable case-control study design can be used to identify antibody correlates of protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in serum and saliva.

Methods: We designed a case-control study to compare antibody levels between cases of SARS-CoV-2 infection within 5 days of symptom onset and uninfected controls.

Learning From Full Characterization of HIV Proviruses in People Receiving Long-Acting Cabotegravir/Rilpivirine With a History of Replication on the Antiretroviral Classes.

Background: To better understand factors associated with virologic response, we retrospectively characterized the HIV proviruses of 7 people with HIV who received long-acting cabotegravir/rilpivirine (CAB/RPV-LA) and were selected according to the following criteria: virologic control achieved despite a history of viral replication on 1 or both corresponding antiretroviral classes (n = 6) and virologic failure (VF) after CAB/RPV-LA initiation (n = 1).

Methods: Last available blood samples before the initiation of CAB/RPV-LA were analyzed retrospectively. Near full-length HIV DNA genome haplotypes were inferred from Nanopore sequencing by the in vivo Genome Diversity Analyzer to search for archived drug resistance mutations (DRMs) and evaluate the frequency and intactness of proviruses harboring DRMs.

Machine learning and deep learning to improve prevention of anastomotic leak after rectal cancer surgery.

Anastomotic leakage (AL) is a significant complication following rectal cancer surgery, adversely affecting both quality of life and oncological outcomes. Recent advancements in artificial intelligence (AI), particularly machine learning and deep learning, offer promising avenues for predicting and preventing AL. These technologies can analyze extensive clinical datasets to identify preoperative and perioperative risk factors such as malnutrition, body composition, and radiological features.

Using DIMet for Differential Analysis of Labeled Metabolomics Data: A Step-by-step Guide Showcasing the Glioblastoma Metabolism.

Stable-isotope resolved metabolomics (SIRM) is a powerful approach for characterizing metabolic states in cells and organisms. By incorporating isotopes, such as C, into substrates, researchers can trace reaction rates across specific metabolic pathways. Integrating metabolomics data with gene expression profiles further enriches the analysis, as we demonstrated in our prior study on glioblastoma metabolic symbiosis.