In-capillary enzymatic digestion beyond trypsin for the sensitive targeted bottom-up analysis of protein biomarkers by capillary electrophoresis-mass spectrometry.

Background: Targeted bottom-up proteomics is of great interest for the straightforward, accurate, and sensitive measurement of specific protein biomarkers from surrogate peptide fragments. However, this approach typically relies on off-line enzymatic digestion with trypsin, a time-consuming step that may be inadequate for covering certain sequence regions containing important post-translational modifications (PTMs).

Results: In this study, we present an in-line enzymatic digestion strategy for the targeted bottom-up analysis of α-synuclein (α-syn), which is a protein biomarker of Parkinson's disease (PD).

Integrated metagenomic, culture-based, and whole genome sequencing analyses of antimicrobial resistance in wastewater and drinking water treatment plants in Barcelona, Spain.

The misuse and overuse of antimicrobials drive the emergence of antimicrobial resistance (AMR), a critical global health concern. While wastewater treatment plants (WWTPs) are essential for removing microorganisms and contaminants, they also serve as hotspots for antibiotic-resistant bacteria (ARB) and antimicrobial resistance genes (ARGs), facilitating their persistence and dissemination. This study investigated AMR in two WWTPs and one drinking water treatment plant (DWTP) in the Baix Llobregat area of Barcelona, Spain.

HER2DX ERBB2 score in advanced HER2-positive gastric cancer treated with trastuzumab and chemotherapy.

Background: Response to trastuzumab combined with chemotherapy (T-chemo) in human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer (AGC) varies widely, highlighting the need for more precise biomarkers beyond conventional HER2 assessment with immunohistochemistry (IHC) and in situ hybridization (ISH). The HER2DX ERBB2 messenger RNA (mRNA) assay, a clinically validated genomic test initially developed for early-stage HER2-positive breast cancer, quantitatively measures ERBB2 expression and may improve patient selection for T-chemo in AGC.

Patients And Methods: In a retrospective cohort of 134 patients with AGC, including 58 who received T-chemo, we evaluated whether the HER2DX ERBB2 score defines more accurately HER2 status and correlates with treatment response and survival outcomes in HER2-positive AGC, compared with standard pathology-based methods.

Prevention of Tuberculosis in Patients Treated With Biological Therapies: Twenty Years' Experience in a Specialised Tuberculosis Clinic in a Low-prevalence Country.

Background: This study builds on previous evidence to assess the risk of tuberculosis (TB) in patients treated with biologic therapies (BioT), the role of the interferon-γ-release assay (IGRA) QuantiFERON-TB (QFT) Gold as a stand-alone screening test, and whether periodic re-testing is warranted for patients with a negative pre-BioT screening.

Methods: A total of 1,368 patients starting BioT were screened for TB infection using four screening strategies over four consecutive periods: (1) two-step tuberculin skin test (TST); (2) two-step TST plus QFT Gold In-Tube; (3) single-step TST plus QFT Gold In-Tube; and (4) QFT Gold In-Tube (or QFT Gold Plus) alone. All patients with TB infection were offered preventive therapy.

Forms of interventions for problematic usage of the internet: A scoping review.

Background And Aims: This scoping review aims to identify current forms of interventions for Problematic Usage of the Internet (PUI) to inform more effective intervention and policy-making initiatives grounded in robust empirical evidence.

Methods: The search was conducted in the PubMed, Scopus, and PsycINFO databases until October 12, 2024. Empirical research presenting data on interventions for PUI and written in English was included without restrictions of age groups, types of interventions, or types of PUI.

Sentinel node detection and imaging concordance in Early-Stage ovarian cancer: A MELISA trial analysis of tracer, timing, and intraoperative gamma camera.

Purpose: To evaluate the detection rate of sentinel lymph node (SLN) mapping in early-stage ovarian cancer using [Tc]Tc-nanocolloid and indocyanine green (ICG), and the added value of an intraoperative gamma camera.

Methods: This was a prospective single-center trial of 63 patients with suspected early-stage epithelial ovarian cancer who underwent SLN mapping with combined tracers. [Tc]Tc-nanocolloid was injected into the ovarian ligaments before adnexectomy, and if malignancy was confirmed on intraoperative frozen section, ICG was administered after adnexectomy in immediate staging cases.

Effects of 6-week flywheel resistance training on tennis serve velocity and accuracy.

Background: This study analyzed the impact of a 6-week joint-specific flywheel-based resistance training program on serve velocity (SV) and serve accuracy (SA) in junior tennis players.

Methods: Fourteen participants were assigned to either an experimental group (FG; N.=7) training with an inertial conical pulley or a control group (CG; N.

Pediatric cofactor-enhanced food anaphylaxis: A narrative review of epidemiology, pathophysiology, and clinical phenotypes.

Cofactors are external factors that can lower the threshold dose of an allergen and amplify the severity of allergic reactions, turning mild or moderate responses into severe anaphylaxis. These include exercise, nonsteroidal anti-inflammatory drugs (NSAIDs), alcohol, menstruation, and infections. Initially described in relation to food allergens and physical activity or NSAIDs, these reactions have been labeled under various terms, such as food-dependent exercise-induced anaphylaxis (FDEIA), wheat-dependent exercise-induced anaphylaxis (WDEIA), and food-dependent NSAID-induced anaphylaxis (FDNIA).

The unexploited potential of data systems tracking medicines utilization: an opportunity to improve access to oncology combination therapies.

Background: While progress has been made in oncology treatments, including the introduction of combination therapies, barriers affect patient access. There are approaches that could improve access including combination-specific pricing that allow the price to reflect whether a product is used in monotherapy or in combination. The feasibility of this solution requires data on the utilization of combination therapies.

Stromagenesis and cancer-associated fibroblast heterogeneity in primary tumors and metastasis: focus in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is the most common lung cancer type and one of the deadliest neoplasias worldwide. NSCLC is histologically classified into adenocarcinoma, squamous cell carcinoma, and other less frequent subtypes. Both subtypes and other solid tumors are increasingly regarded as abnormal organs, highlighting the critical role of the desmoplastic tumor stroma rich in cancer-associated fibroblasts (CAFs) in driving tumor progression and therapeutic resistance.

Identification of Neuritin 1 as a local metabolic regulator of brown adipose tissue.

Brown adipose tissue (BAT) plays a key role in metabolic homeostasis through its thermogenic effects and the secretion of regulatory molecules. Here we report that RAP250 haploinsufficiency stimulates BAT in mice, thus contributing to a decrease in fat accumulation. Local in vivo AAV-mediated RAP250 silencing in BAT reduces body weight and fat mass and enhances glucose oxidation, thereby indicating that RAP250 participates in the regulation of BAT metabolic activity.

Assessment of stigma in Spanish people with chronic pain using the 8-item Stigma Scale for Chronic Illnesses (SSCI-8).

Stigma is common in people with chronic pain. At present, however, the measurement of stigma in Spanish-speaking individuals remains a challenge due to a lack of validated measures in Spanish. The present study examines the psychometric properties of the Spanish version of the Stigma Scale for Chronic Illnesses 8-item version (SSCI-8) in people with chronic pain, focusing on dimensionality, factorial invariance, reliability (internal consistency and test-retest), and construct validity.

Current Situation of Solid Organ Transplantation from HIV-Positive Donors to HIV-Positive Recipients in Europe. The Spanish Perspective.

Objectives: There is limited information on the use of organs from HIV-positive donors (HIV D+) for HIV-positive recipients (HIV R+) in Europe. In some countries the use of HIV D+ organs is prohibited by law. This study aimed to assess the attitudes of Spanish kidney and liver transplant (KT/LT) teams towards HIV D+/R+ KT/LT through a nationwide survey, and to evaluate the current situation across Europe regarding legislation and reported cases.

Extra-Virgin Olive Oil and Additional Cardiovascular Outcomes in the PREDIMED Trial: An Outcome-Wide Perspective.

Background And Aims: Olive oil, increasingly consumed in the U.S., has been inversely associated with cardiovascular disease (CVD) risk.

Clinical validation of liquid biopsy-RECIST (LB-RECIST) in metastatic colorectal cancer (mCRC) patients: findings from the PLATFORM-B study.

Background: Circulating tumor DNA (ctDNA) variations predict tumor response to systemic treatment (so-called molecular response) earlier than radiological assessment. However, a standardized categorization of molecular response is an unmet clinical need. Liquid biopsy-RECIST (LB-RECIST), based on aggregate variant allele frequency (aggVAF; sum of all detected variant allele frequencies in a sample) variations, has been proposed to stratify molecular response.

Deep Learning Modeling to Differentiate Multiple Sclerosis From MOG Antibody-Associated Disease.

Background And Objectives: Multiple sclerosis (MS) is common in adults while myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is rare. Our previous machine-learning algorithm, using clinical variables, ≤6 brain lesions, and no Dawson fingers, achieved 79% accuracy, 78% sensitivity, and 80% specificity in distinguishing MOGAD from MS but lacked validation. The aim of this study was to (1) evaluate the clinical/MRI algorithm for distinguishing MS from MOGAD, (2) develop a deep learning (DL) model, (3) assess the benefit of combining both, and (4) identify key differentiators using probability attention maps (PAMs).

Cerebrovascular Reactivity at Rest and Its Association With Cognitive Function in People With Genetic Frontotemporal Dementia.

Background And Objectives: Cerebrovascular reactivity (CVR) is an indicator of cerebrovascular health, and its signature in familial frontotemporal dementia (FTD) remains unknown. The primary aim was to investigate CVR in genetic FTD using an fMRI index of vascular contractility termed resting-state fluctuation amplitudes (RSFAs) and to assess whether RSFA differences are moderated by age. A secondary aim was to study the relationship between RSFA and cognition.

Effectiveness of the FIBROWALK multicomponent therapy in online and outdoor formats for fibromyalgia: A randomized controlled trial (The On&Out study).

This study evaluated the effectiveness of FIBROWALK multicomponent intervention, delivered online (FIBRO-On) or outdoors (FIBRO-Out), compared to treatment as usual (TAU) in reducing fibromyalgia (FM) severity measured by FIQR, which assesses functional impairment, symptom intensity, and overall impact. A total of 225 individuals with FM were randomly assigned to 12 weeks of FIBRO-On (plus TAU), FIBRO-Out (plus TAU), or TAU alone. Assessments were conducted at baseline, mid-intervention (6 weeks), post-intervention (12 weeks), and 6-months (3 months post-intervention).

Economic evaluation of the FIBROWALK multicomponent intervention in online and outdoor formats for fibromyalgia (The On&Out Study).

Fibromyalgia (FM) is a chronic condition with substantial healthcare and societal costs. Although multicomponent interventions are widely available, evidence of their economic impact remains scarce. This study evaluated the cost-utility and cost-effectiveness of the FIBROWALK intervention in online (FIBRO-On) and outdoor (FIBRO-Out) formats, compared to treatment as usual (TAU), for individuals with FM.

Age-related differences in cardiogenic shock secondary to Takotsubo syndrome.

Background: Age-related differences in Takotsubo Syndrome (TTS) have been described, but there is limited information regarding TTS patients who develop cardiogenic shock (CS).

Methods And Results: We analysed data from 408 CS-TTS patients in the RETAKO registry. Patients were stratified into three age groups: ≤50 years (9%), 51-74 years (48%), and ≥75 years (43%).