Efficacy and safety of antibody-drug conjugates in pretreated HER2-low metastatic breast cancer: A systematic review and network meta-analysis.

Introduction: Antibody-drug conjugates (ADCs) trastuzumab-deruxtecan (T-DXd) and sacituzumab-govitecan (SG) provided significant progression-free survival (PFS) and overall survival (OS) improvements over chemotherapy (CT) in pretreated hormone receptor-positive (HR+) and triple-negative (TN)/HER2-low metastatic breast cancer (MBC). However, no direct comparison between the two exists, nor with the more recent datopotamab-deruxtecan (Dato-DXd).

Methods: We conducted a network meta-analysis (NMA) to compare efficacy and safety of T-DXd and SG in CT-pretreated HR+ and TN/HER2-low MBC and assess their benefit over standard CT, exploring also a comparison with Dato-DXd.

The International Bathymetric Chart of the Arctic Ocean Version 5.0.

Knowledge about seafloor depth, or bathymetry, is crucial for various marine activities, including scientific research, offshore industry, safety of navigation, and ocean exploration. Mapping the central Arctic Ocean is challenging due to the presence of perennial sea ice, which limits data collection to icebreakers, submarines, and drifting ice stations. The International Bathymetric Chart of the Arctic Ocean (IBCAO) was initiated in 1997 with the goal of updating the Arctic Ocean bathymetric portrayal.

Accuracy of freehand surgery, static and dynamic computer assisted surgery on zygomatic implant placement: A systematic review and meta-analyses.

Real-time surgical navigation systems (dynamic computer-aided surgery, d-CAIS) and static guided surgery (static computer-aided surgery, s-CAIS) have been shown to enhance the accuracy of zygomatic implant (ZI) placement. The objective of this systematic review was to evaluate and compare the accuracy and risk of complications associated with d-CAIS and s-CAIS in ZI placement. A systematic review of published studies involving more than 4 patients was conducted to assess and compare the accuracy of d-CAIS and s-CAIS in zygomatic implant placement.

Synergic Integration of the miRNome, Machine Learning and Bioinformatics for the Identification of Potential Disease-Modifying Agents in Obstructive Sleep Apnea.

Introduction: Understanding the diverse pathogenetic pathways in obstructive sleep apnea (OSA) is crucial for improving outcomes. microRNA (miRNA) profiling is a promising strategy for elucidating these mechanisms.

Objective: To characterize the pathogenetic pathways linked to OSA through the integration of miRNA profiles, machine learning (ML) and bioinformatics.

Detecting occult hemorrhage and retroperitoneal bleeding using a new protocol called the UFOH protocol: Ultrasound focused occult hemorrhage.

Point-of-care abdominal ultrasound (US) has emerged as a powerful tool for clinicians and is becoming a routine bedside tool to rapidly diagnose, manage hemodynamics, monitor fluid status, and guide procedures in emergency and critical care. Extended focused assessment with sonography for trauma (eFAST), is commonly used to detect free intraperitoneal blood in the trauma setting and may also be an option in non-trauma patients. However, it has significant limitations for detecting gastrointestinal or retroperitoneal bleeding.

Novel Digital Anomalies, Hippocampal Atrophy, and Mutations Expand the Genotypic and Phenotypic Spectra of CNKSR2 in the Houge Type of X-Linked Syndromic Intellectual Development Disorder (MRXSHG).

The Houge type of X-linked syndromic intellectual developmental disorder (MRXSHG) encompasses a spectrum of neurodevelopmental disorders characterized by intellectual disability (ID), language/speech delay, attention issues, and epilepsy. These conditions arise from hemizygous or heterozygous deletions, along with point mutations, affecting CNKSR2, a gene located at Xp22.12.

Randomized trial investigating the utility of a liver tissue transcriptional biomarker in identifying adult liver transplant recipients not requiring maintenance immunosuppression.

The maintenance of stable allograft status in the absence of immunosuppression, known as operational tolerance, can be achieved in a small proportion of liver transplant recipients, but we lack reliable tools to predict its spontaneous development. We conducted a prospective, multi-center, biomarker-strategy design, immunosuppression withdrawal clinical trial to determine the utility of a predictive biomarker of operational tolerance. The biomarker test, originally identified in a patient cohort with high operational tolerance prevalence, consisted of a 5-gene transcriptional signature measured in liver tissue collected before initiating immunosuppression weaning.

Prognostic value of residual disease (RD) biology and gene expression changes during the neoadjuvant treatment in patients with HER2+ early breast cancer (EBC).

Background: In HER2+ early breast cancer (EBC), we investigated tumor and immune changes during neoadjuvant treatment and their impact on residual disease (RD) biology and prognostic implications across 4 neoadjuvant studies of trastuzumab with or without lapatinib, and with or without chemotherapy: CALGB 40601, PAMELA, NeoALTTO and NSABP B-41.

Patients And Methods: We compared tumor and immune gene expression changes during neoadjuvant treatment and their association with with event-free survival (EFS) by uni- and multivariable Cox regression models in different cohorts and timepoints: 452 RD samples at baseline including 169 with a paired RD, and biomarker changes during neoadjuvant therapy, evaluating model performance via the c-index.

Results: Analysis of 169 paired tumor samples revealed a shift in intrinsic subtype proportions from HER2-Enriched at baseline (50.

Tile by tile: capturing the evolutionary mosaic of human conditions.

The collection of Homo sapiens anatomical hallmarks hypothesized to support the 'human condition' did not appear at one specific time and place, but gradually, creating a reticulate evolutionary trajectory. The recent reconstruction of migration patterns and gene flows across different hominin species and populations draws a mosaic that we contend can be illuminated by genomic comparisons and specific experiments. Here, we first review key discoveries that could allow this experimental endeavor by describing recent advances in a variety of fields, stressing the importance of charting the current human neurodiversity as an interpretive substrate for evolutionary changes.

Endocervical Brush Cytology After Cervical Conization as a Predictor of Treatment Failure: A Prospective Cohort Study.

Objective: Endocervical curettage (ECC) is the gold standard for predicting the persistence of high-grade squamous intraepithelial lesions (HSIL) after cervical conization. However, ECC has a high rate of unsatisfactory samples and may be uncomfortable for women. Endocervical sampling with brush (ECB) has been proposed as an alternative to ECC, which, in addition to the cytological evaluation, allows performing HPV testing using the same sample.

LRH-1/NR5A2 targets mitochondrial dynamics to reprogram type 1 diabetes macrophages and dendritic cells into an immune tolerance phenotype.

Background: The complex aetiology of type 1 diabetes (T1D), characterised by a detrimental cross-talk between the immune system and insulin-producing beta cells, has hindered the development of effective disease-modifying therapies. The discovery that the pharmacological activation of LRH-1/NR5A2 can reverse hyperglycaemia in mouse models of T1D by attenuating the autoimmune attack coupled to beta cell survival/regeneration prompted us to investigate whether immune tolerisation could be translated to individuals with T1D by LRH-1/NR5A2 activation and improve islet survival.

Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from individuals with and without T1D and derived into various immune cells, including macrophages and dendritic cells.

ESR Essentials: gadolinium-wise MRI-practice recommendations by the European Society for Magnetic Resonance in Medicine and Biology.

The Gadolinium Research and Education Committee (GREC) is a working group of the European Society for Magnetic Resonance in Medicine and Biology (ESMRMB), established in 2016. The aim of the committee is to monitor scientific evidence for a continuous quality and safety improvement of enhanced MRI using gadolinium-based contrast agents (GBCAs), and also assess potential alternatives. The scope of the present article is to describe the level of evidence concerning safety beyond the single patient (access to community and environmental impact), justification and optimization of the use of GBCAs beyond dosage (appropriateness and influence on clinical decision making), dose reduction with the use of AI (benefits and pitfalls), the advent of next-generation GBCAs (based on currently available data).

Carvedilol vs. propranolol for the prevention of decompensation and mortality in patients with compensated and decompensated cirrhosis.

Background And Aims: Data on the effectiveness of classical non-selective beta-blockers (cNSBB, i.e., propranolol and nadolol) versus carvedilol in patients with cirrhosis are scarce.

Endoretinal biopsy outcomes in suspected vitreoretinal lymphoma after inconclusive vitreous cytology.

Objective: To review the clinical utility of endoretinal biopsies in diagnostically undefined cases of vitreoretinal lymphoma (VRL) with negative vitreous cytology.

Methods: Retrospective case series including all consecutive patients who underwent endoretinal biopsies in a tertiary care center, Hospital Clinic of Barcelona (Spain), between 2014 and 2020.

Results: A total of 5 patients were included in this study.

European consensus-based interdisciplinary guideline for melanoma. Part 1: Diagnostics - Update 2024.

This guideline was developed in close collaboration with multidisciplinary experts from the European Association of Dermato-Oncology (EADO), the European Dermatology Forum (EDF) and the European Organization for Research and Treatment of Cancer (EORTC). Recommendations for the diagnosis and treatment of melanoma were developed on the basis of systematic literature research and consensus conferences. Cutaneous melanoma (CM) is the most dangerous form of skin tumor and accounts for 90 % of skin cancer mortality.

Mechanistic Insights and Technical Challenges in Sulfur-Based Batteries: A Comprehensive / Monitoring Toolbox.

Batteries based on sulfur cathodes offer a promising energy storage solution due to their potential for high performance, cost-effectiveness, and sustainability. However, commercial viability is challenged by issues such as polysulfide migration, volume changes, uneven phase nucleation, limited ion transport, and sluggish sulfur redox kinetics. Addressing these challenges requires insights into the structural, morphological, and chemical evolution of phases, the associated volume changes and internal stresses, and ion and polysulfide diffusion within the battery.

Internet gaming disorder and the alternative five factor personality model: a study in a Spanish community sample.

Background: This study was designed to examine the prevalence and relationships between the Internet gaming disorder (IGD) behaviors, suggested by the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), and personality traits.

Participants And Procedure: A sample community of 1,548 subjects, 707 men and 841 women, with a mean age of 40.90 and 38.

Sex differences in patients with Non-Small Cell Lung Cancer harboring driver fusions treated with tyrosine kinase inhibitors: a systematic review.

Background: While targeted therapies have transformed the treatment landscape of oncogene-addicted non-small cell lung cancer (NSCLC), the influence of sex on treatment outcomes remains insufficiently understood.

Objectives: This systematic review aimed to investigate the impact of sex on clinical outcomes in patients with NSCLC harboring driver fusions treated with targeted therapies enrolled in clinical trials.

Data Sources And Methods: A comprehensive literature search was conducted using PubMed, Embase, and relevant conference abstracts to identify phase III randomized and early clinical trials that reported sex-specific data, including progression-free survival (PFS), overall survival (OS), overall response rate, and adverse events (AEs), in patients with fusion-positive NSCLC treated with tyrosine kinase inhibitors (TKIs).

Effects of alcohol-related problems on the costs of frequent emergency department use: an economic analysis of a case-control study in Spain.

Introduction: Alcohol-related problems increase the probability of frequent emergency department (ED) use. In this study, we compared the direct healthcare expenses incurred during a single visit among frequent and non-frequent ED users and analyzed the impact of alcohol-related issues in healthcare costs arising from ED usage.

Methods: The study relied on secondary analyses of economic data from a 1:1 matched case-control study with the primary aim of identifying the clinical characteristics of hospital ED frequent users in a Mediterranean European environment with a public, universal, and tax-funded health system.

Applicability of machine learning methods for classifying lightweight pigs in commercial conditions.

The varying growth rates within a group of pigs present a significant challenge for the current all-in-all-out systems in the pig industry. This study evaluated the applicability of statistical methods for classifying pigs at risk of growth retardation at different production stages using a robust dataset collected under commercial conditions. Data from 26,749 crossbred pigs (Yorkshire × Landrace) with Duroc at weaning (17 to 27 d), 15,409 pigs at the end of the nursery period (60 to 78 d), and 4996 pigs at slaughter (151 to 161 d) were analyzed under three different cut points (lowest 10%, 20%, and 30% weights) to characterize light animals.

PPARβ/δ upregulates the insulin receptor β subunit in skeletal muscle by reducing lysosomal activity and EphB4 levels.

Background: The increased degradation of the insulin receptor β subunit (InsRβ) in lysosomes contributes to the development of insulin resistance and type 2 diabetes mellitus. Endoplasmic reticulum (ER) stress contributes to insulin resistance through several mechanisms, including the reduction of InsRβ levels. Here, we examined how peroxisome proliferator-activated receptor (PPAR)β/δ regulates InsRβ levels in mouse skeletal muscle and C2C12 myotubes exposed to the ER stressor tunicamycin.

Alterations of the IKZF1-IKZF2 tandem in immune cells of schizophrenia patients regulate associated phenotypes.

Schizophrenia is a complex multifactorial disorder and increasing evidence suggests the involvement of immune dysregulations in its pathogenesis. We observed that IKZF1 and IKZF2, classic immune-related transcription factors (TFs), were both downregulated in patients' peripheral blood mononuclear cells (PBMCs) but not in their brain. We generated a new mutant mouse model with a reduction in Ikzf1 and Ikzf2 to study the impact of those changes.

Sphingolipid profiling as a biomarker of type 2 diabetes risk: evidence from the MIDUS and PREDIMED studies.

Background: Type 2 diabetes (T2D) has become a worldwide pandemic. While ceramides may serve as intermediary between obesity-related lipotoxicity and T2D, the relationship with simple glycosphingolipids remains uncertain. The aim of this study was to characterize the associations between blood glycosphingolipid and ceramide species with T2D and to identify a circulating sphingolipid profile that could serve as novel biomarker for T2D risk.