Computational Insights into Membrane Disruption by Cell-Penetrating Peptides.

Cell-penetrating peptides (CPPs) can translocate into cells without inducing cytotoxicity. The internalization process implies several steps at different time scales ranging from microseconds to minutes. We combine adaptive Steered Molecular Dynamics (aSMD) with conventional Molecular Dynamics (cMD) to observe nonequilibrium and equilibrium states to study the early mechanisms of peptide-bilayer interaction leading to CPPs internalization.

Gender and sex differences in colorectal cancer screening, diagnosis and treatment.

Males have a higher incidence and mortality rate from colorectal cancer (CRC) compared with females. This review examines the reasons for these differences, including risk factors, screening participation, interpretation of screening tests, presentation and tumour types, pathophysiology (particularly the impact of sex hormones on tumour-related gene expression, microsatellite instability, micro-RNA expression, and the tumour microenvironment), and the efficacy and toxicity of treatment. Sex differences in hormones and body composition are responsible for some of the sexual dimorphism in CRC incidence and outcomes, particularly the pathophysiology, CRC presentation, the pharmacokinetics of cytotoxic therapies, and the impact of treatment on outcomes.

Mild acute biliary pancreatitis: still a surgical disease. A post-hoc analysis of the MANCTRA-1 international study.

Background: The current standard of care for mild acute biliary pancreatitis (MABP) involves early laparoscopic cholecystectomy (ELC) to reduce the risk of recurrence. The MANCTRA-1 project revealed a knowledge-to-action gap and higher recurrence rates in patients admitted to medical wards, attributable to fewer ELCs being performed. The project estimated a 35% to 70% probability of narrowing this gap by 2025.

Robotic hiatus hernia surgery: learning curve and lessons learned.

New procedures like the robotic approach require proficiency to ensure patient safety and satisfactory functional results. Hiatal hernia surgery serves as a suitable training procedure for upper gastrointestinal tract surgeons transitioning to the robotic approach. This study aims to evaluate the outcomes of implementing the robotic approach in hiatal hernia surgery at a tertiary hospital and to assess the associated learning curve.

Pregnancy entails a U-shaped trajectory in human brain structure linked to hormones and maternal attachment.

Growing evidence places the gestational period as a unique moment of heightened neuroplasticity in adult life. In this longitudinal study spanning pre, during, and post pregnancy, we unveil a U-shaped trajectory in gray matter (GM) volume, which dips in late pregnancy and partially recovers during postpartum. These changes are most prominent in brain regions associated with the Default Mode and Frontoparietal Network.

The Human Microglia Atlas (HuMicA) unravels changes in disease-associated microglia subsets across neurodegenerative conditions.

Dysregulated microglia activation, leading to neuroinflammation, is crucial in neurodegenerative disease development and progression. We constructed an atlas of human brain immune cells by integrating nineteen single-nucleus RNA-seq and single-cell RNA-seq datasets from multiple neurodegenerative conditions, comprising 241 samples from patients with Alzheimer's disease, autism spectrum disorder, epilepsy, multiple sclerosis, Lewy body diseases, COVID-19, and healthy controls. The integrated Human Microglia Atlas (HuMicA) included 90,716 nuclei/cells and revealed nine populations distributed across all conditions.

Effect of the Number of Vaccine Doses Before Starting Anti-CD20 Therapy on Seroprotection Rates Against Hepatitis B Virus in People With MS.

Background And Objectives: Hepatitis B vaccination (HBV) requires 6 months to complete and is recommended for patients with multiple sclerosis (PWMS), particularly those who are candidates for anti-CD20 therapy. However, limited data exist on HBV immunogenicity in PWMS receiving disease-modifying therapies (DMTs) and the impact of starting anti-CD20 therapy during immunization. We aimed to evaluate HBV immunogenicity in PWMS starting anti-CD20 therapy during vaccination, focusing on the number of doses received before anti-CD20 initiation.

Real-World Experience in Tricuspid Transcatheter Edge-to-Edge Repair: Transcatheter Tricuspid Valve Repair in Spain Registry.

Background: Significant tricuspid regurgitation (TR) is associated with increased morbidity and mortality. The development of transcatheter valve repair therapies has opened a wide range of opportunities for treatment of patients with high surgical risk. Real-world data might improve patient selection and outcome.

Left ventricular elastance with resting volumetric transthoracic echocardiography identifies different phenotypes in heart failure with preserved ejection fraction: A retrospective analysis of a multicenter prospective observational study.

Background: Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous entity including patients with different phenotypes of near normal, normal, and supernormal left ventricular (LV) function.

Objectives: To assess the value of resting LV elastance (also known as force) with transthoracic echocardiography (TTE) to identify HFpEF phenotypes.

Methods: In a prospective, observational, multicenter study, 2380 HFpEF patients were recruited from July 2016 to May 2024.

Survival of viruses in water microcosms.

Human enteric viruses and emerging viruses such as severe acute respiratory syndrome coronavirus 2, influenza virus and monkeypox virus, are frequently detected in wastewater. Human enteric viruses are highly persistent in water, but there is limited information available for non-enteric viruses. The present study evaluated the stability of hepatitis A virus (HAV), murine norovirus (MNV), influenza A virus H3N2 (IAV H3N2), human coronavirus (HCoV) 229E, and vaccinia virus (VACV) in reference water (RW), effluent wastewater (EW) and drinking water (DW) under refrigeration and room temperature conditions.

HEBE: A novel chimeric chronokine for ameliorating memory deficits in Alzheimer's disease.

Alzheimer's disease (AD) is a prevalent neurodegenerative disorder characterized by amyloid-β and Tau protein depositions, with treatments focusing on single proteins have shown limited success due to the complexity of pathways involved. This study explored the potential of chronokines -proteins that modulate aging-related processes- as an alternative therapeutic approach. Specifically, we focused on a novel pleiotropic chimeric protein named HEBE, combining s-KL, sTREM2 and TIMP2, guided by bioinformatic analyses to ensure the preservation of each protein's conformation, crucial for their functions.

Long-term outcome and risk stratification in compensated advanced chronic liver disease after HCV-cure.

Background And Aims: Around 750,000 patients per year will be cured of HCV infection until 2030. Those with compensated advanced chronic liver disease remain at risk for hepatic decompensation and de novo HCC. Algorithms have been developed to stratify risk early after cure; however, data on long-term outcomes and the prognostic utility of these risk stratification algorithms at later time points are lacking.

A Homozygous ATP2A2 Variant Alters Sarcoendoplasmic Reticulum Ca-ATPase 2 Function in Skeletal Muscle and Causes a Novel Vacuolar Myopathy.

Aims: Sarcoendoplasmic reticulum Ca-ATPase 2 (SERCA2), encoded by ATP2A2, is a key protein involved in intracellular Ca homeostasis. The SERCA2a isoform is predominantly expressed in cardiomyocytes and type I myofibres. Variants in this gene are related to Darier disease, an autosomal dominant dermatologic disorder, but have never been linked to myopathy.

Incidental Findings Identified by Prenatal Microarray Analysis and Consensus Reporting Criteria of the Catalan Public Health Network XIGENICS.

Objective: The study aimed to evaluate the frequency of pathogenic copy number variants (CNVs) classified as incidental findings (IFs) in prenatal diagnosis and to develop consensus recommendations for standardizing their reporting across six centers within the Catalan public health system (XIGENICS network).

Method: A retrospective review of 4219 consecutive prenatal microarrays performed within the network from 2018 to 2023 was conducted, including all referral reasons. To develop consensus recommendations, several discussion meetings were held along with an extensive review of the existing literature.

Autologous haematopoietic stem cell transplantation for treatment of multiple sclerosis and neuromyelitis optica spectrum disorder - recommendations from ECTRIMS and the EBMT.

Autologous haematopoietic stem cell transplantation (AHSCT) is a treatment option for relapsing forms of multiple sclerosis (MS) that are refractory to disease-modifying therapy (DMT). AHSCT after failure of high-efficacy DMT in aggressive forms of relapsing-remitting MS is a generally accepted indication, yet the optimal placement of this approach in the treatment sequence is not universally agreed upon. Uncertainties also remain with respect to other indications, such as in rapidly evolving, severe, treatment-naive MS, progressive MS, and neuromyelitis optica spectrum disorder (NMOSD).

Clinical expression of radiographic axial spondyloarthritis and its association with HLA-B27 in European and Ibero-American populations.

Objective: To compare the clinical and sociodemographic characteristics of Ibero-American patients with radiographic axial spondyloarthritis (r-axSpA) to those of European patients, with a particular focus on the influence of HLA-B27.

Methods: This was an observational, cross-sectional, and multicentre study of patients who fulfilled the European Spondyloarthropathy Study Group (ESSG) criteria for SpA from the REGISPONSER and RESPONDIA registries. Univariate and multivariate analyses between European and Ibero-American populations stratified by HLA-B27 status were conducted.

The impact of neoadjuvant therapy in patients with left-sided resectable pancreatic cancer: an international multicenter study.

Purpose: To assess the association between neoadjuvant therapy and overall survival (OS) in patients with left-sided resectable pancreatic cancer (RPC) compared to upfront surgery.

Background: Left-sided pancreatic cancer is associated with worse OS compared to right-sided pancreatic cancer. Although neoadjuvant therapy is currently seen as not effective in patients with RPC, current randomized trials included mostly patients with right-sided RPC.

Impact of the COVID-19 pandemic on mHealth adoption: Identification of the main barriers through an international comparative analysis.

Background: The COVID-19 pandemic greatly challenged health systems worldwide. The adoption and application of mHealth technology emerged as a critical response. However, the permanent implementation and use of such technology faces several barriers, which vary by each country's innovation level and specific health policies.

Insights on the evolution and adaptation toward high-altitude and cold environments in the snow leopard lineage.

How snow leopard gradually adapted to the extreme environments in Tibet remains unexplored due to the scanty fossil record in Tibet. Here, we recognize five valid outside-Tibet records of the snow leopard lineage. Our results suggest that the snow leopard dispersed out of the Tibetan Plateau multiple times during the Quaternary.

Audiovisual analysis of the diagnostic video polysomnography in patients with isolated REM sleep behavior disorder.

Background: The diagnosis of isolated REM sleep behavior disorder (IRBD) requires video polysomnography (V-PSG) showing increased muscle activity and abnormal behaviors in REM sleep.

Objective: To describe in IRBD the behavioral manifestations occurring during REM sleep in the diagnostic V-PSG.

Methods: This is a systematic audiovisual V-PSG analysis of consecutive IRBD patients.

Clinical and imaging spectrum of non-congenital dominant ACTN2 myopathy.

Background: Alpha-actinin-2, a protein with high expression in cardiac and skeletal muscle, is located in the Z-disc and plays a key role in sarcomere stability. Mutations in ACTN2 have been associated with both hypertrophic and dilated cardiomyopathy and, more recently, with skeletal myopathy.

Methods: Genetic, clinical, and muscle imaging data were collected from 37 patients with an autosomal dominant ACTN2 myopathy belonging to 11 families from Spain and Belgium.

Vascularized Periosteal Grafts for Bone Union in Children: A Systematic Review.

Background: The periosteum is the main organ responsible for bone regeneration. Vascularized Periosteal Grafts (VPG) have demonstrated exceptional efficacy and speed in facilitating bone union among children with challenging bone healing conditions. Despite their promising results, the overall impact of these interventions has yet to be comprehensively evaluated through systematic review.

Safety Assessment of Graphene-Based Materials.

Graphene is the first 2D atomic crystal, and its isolation heralded a new era in materials science with the emergence of several other atomically thin materials displaying multifunctional properties. The safety assessment of new materials is often something of an afterthought, but in the case of graphene, the initial isolation and characterization of the material was soon followed by the assessment of its potential impact on living systems. The Graphene Flagship project addressed the health and environmental aspects of graphene and other 2D materials, providing an instructive lesson in interdisciplinarity - from materials science to biology.