Expert Perspective: Management of Relapses in Giant Cell Arteritis.

Giant cell arteritis (GCA) is a relapsing large-vessel vasculitis with risk of serious ischemic manifestations including vision loss and vascular damage in the form of large-artery stenosis, aneurysms and dissections. Approximately 50% of patients treated with glucocorticoid (GC) monotherapy and 30% of patients receiving adjunctive therapy with tocilizumab experience disease relapses, often during the first 2 years after diagnosis. Although most relapses in GCA do not involve life- or organ-threatening presentations and can be controlled successfully, frequent relapses may lead to increased use of GC and consequent treatment-related morbidity, in addition to risk of further vascular damage.

Differential impact of impaired steryl ester biosynthesis on the metabolome of tomato fruits and seeds.

Steryl esters (SE) are a storage pool of sterols that accumulates in cytoplasmic lipid droplets and helps to maintain plasma membrane sterol homeostasis throughout plant growth and development. Ester formation in plant SE is catalyzed by phospholipid:sterol acyltransferase (PSAT) and acyl-CoA:sterol acyltransferase (ASAT), which transfer long-chain fatty acid groups to free sterols from phospholipids and acyl-CoA, respectively. Comparative mass spectrometry-based metabolomic analysis between ripe fruits and seeds of a tomato (Solanum lycopersicum cv Micro-Tom) mutant lacking functional PSAT and ASAT enzymes (slasat1xslpsat1) shows that disruption of SE biosynthesis has a differential impact on the metabolome of these organs, including changes in the composition of free and glycosylated sterols.

HER2DX genomic test in early-stage HER2-positive breast cancer.

Therapies targeting human epidermal growth factor receptor 2 (HER2)-positive breast cancer significantly impact patient outcomes, quality of life, and health care systems. While chemotherapy and trastuzumab improve survival in early-stage HER2-positive breast cancer, variability in clinical and biological characteristics leads to different response to therapies and outcomes. Clinical guidelines provide general recommendations, but significant uncertainty persists in identifying an optimal treatment plan for individual patients.

Association between Driving Pressure, Systemic Inflammation and Non-pulmonary Organ Dysfunction in Patients with Acute Respiratory Distress Syndrome, a Prospective Pathophysiological Study.

Background: Driving pressure is thought to determine the effect of low tidal ventilation on survival in patients with acute respiratory distress syndrome. The leading cause of mortality in these patients is non-pulmonary multiorgan dysfunction, which is believed to worsen due to the biological response to mechanical ventilation (biotrauma). Therefore, we aimed to analyze the association between driving pressure, biotrauma, and non-pulmonary multiorgan dysfunction.

Consistent acidogenic co-fermentation of waste activated sludge and food waste under thermophilic conditions.

Acidogenic co-fermentation of waste activated sludge (WAS) and food waste (FW) under thermophilic conditions enhances process consistency, while overcoming the problem of acetic acid consumption due to growing methanogens. Two long-term continuous co-fermentation experiments were carried out with a WAS:FW mixture (70:30 % in VS) at organic loading rate of 8 gVS/(L·d). Experiment 1 assessed the impact of temperature (35 °C and 55 °C) and WAS origin (WAS_A and WAS_B) in two collection periods.

Effect of BMP15 and GDF9 in the IVM medium on subsequent oocyte competence and embryo development of prepubertal goats.

Oocyte-secreted factors (OSFs), such as BMP15 and GDF9, are soluble paracrine factors that drive cumulus cell differentiation and function, sustaining oocyte competence acquisition and embryo development. This study aimed to assess the effect of BMP15 and GDF9 on IVM medium of prepubertal goat oocytes. COCs were in vitro matured in absence (control group) or presence of 100 ng/mL of BMP15, GDF9, or both.

European consensus-based interdisciplinary guideline for melanoma. Part 2: Treatment - Update 2024.

A unique collaboration of multi-disciplinary experts from the European Association of Dermato-Oncology (EADO), the European Dermatology Forum (EDF), and the European Organization of Research and Treatment of Cancer (EORTC) was formed to make recommendations on cutaneous melanoma diagnosis and treatment, based on systematic literature reviews and the experts' experience. Cutaneous melanomas are excised with one to two-centimeter safety margins. For a correct stage classification and treatment decision, a sentinel lymph node biopsy shall be offered in patients with tumor thickness ≥ 1.

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.