Regular human insulins versus rapid-acting insulin analogues in children and adolescents with type 1 diabetes: a protocol for a systematic review with meta-analysis and Trial Sequential Analysis.

Background: Type 1 diabetes is a serious, chronic disorder with an increasing incidence among children and adolescents. Glycemic control in individuals with type 1 diabetes is better managed through a basal-bolus regimen with either regular human or rapid-acting insulin analogues administered as a bolus at mealtimes. Rapid-acting insulin analogues have been hypothesized to cause optimal glycemic control and less risk of hypoglycemic episodes compared to regular human insulins.

Effects of Alzheimer's disease plasma marker levels on multilayer centrality in healthy individuals.

Background: Changes in amyloid beta (Aβ) and phosphorylated tau brain levels are known to affect brain network organization but very little is known about how plasma markers can relate to these measures. We aimed to address the relationship between centrality network changes and two plasma pathology markers: phosphorylated tau at threonine 231 (p-tau231), a proxy for early Aβ change, and neurofilament light chain (Nfl), a marker of axonal degeneration.

Methods: One hundred and four cognitively unimpaired individuals were divided into a high pathology load (33 individuals; HP) group and a low pathology (71 individuals; LP) one.

Deep analysis of the major histocompatibility complex genetic associations using covariate analysis and haploblocks unravels new mechanisms for the molecular etiology of Elite Control in AIDS.

Introduction: We have reanalyzed the genomic data from the International Collaboration for the Genomics of HIV (ICGH), focusing on HIV-1 Elite Controllers (EC).

Methods: A genome-wide association study (GWAS) was performed, comparing 543 HIV-1 EC individuals with 3,272 uninfected controls (CTR) of European ancestry. 8 million single nucleotide polymorphisms (SNPs) and HLA class I and class II gene alleles were imputed to compare EC and CTR.

Associations between physical activity, brain health, cognitive function, and circulating GPLD1 in healthy older (65-85 years) individuals.

Declines in physical and cognitive function are common in older adults. The circulating enzyme glycosylphosphatidylinositol (GPI)-specific phospholipase D1 (GPLD1) is elevated after exercise and has been associated with improved cognitive function when administered to aged mice. The purpose of this study was to investigate the relationship between GPLD1 and both cognitive function and brain structure/function in older adults with either high or low levels of physical activity.

Immunotherapy for advanced-stage squamous cell lung cancer: the state of the art and outstanding questions.

Immune-checkpoint inhibitors (ICIs) have transformed the treatment paradigm for advanced-stage squamous non-small-cell lung cancer (LUSC), a histological subtype associated with inferior outcomes compared with lung adenocarcinoma. However, only a subset of patients derive durable clinical benefit. In the first-line setting, multiple ICI regimens are available, including anti-PD-(L)1 antibodies as monotherapy, in combination with chemotherapy, or with an anti-CTLA4 antibody with or without chemotherapy.

Autogene cevumeran with or without atezolizumab in advanced solid tumors: a phase 1 trial.

Effective targeting of somatic cancer mutations to enhance the efficacy of cancer immunotherapy requires an individualized approach. Autogene cevumeran is a uridine messenger RNA lipoplex-based individualized neoantigen-specific immunotherapy designed from tumor-specific somatic mutation data obtained from tumor tissue of each individual patient to stimulate T cell responses against up to 20 neoantigens. This ongoing phase 1 study evaluated autogene cevumeran as monotherapy (n = 30) and in combination with atezolizumab (n = 183) in pretreated patients with advanced solid tumors.

Patients with dementia with Lewy bodies display a signature alteration of their cognitive connectome.

Cognition plays a central role in the diagnosis and characterization of dementia with Lewy bodies (DLB). However, the complex associations among cognitive deficits in different domains in DLB are largely unknown. To characterize these associations, we investigated and compared the cognitive connectome of DLB patients, healthy controls (HC), and Alzheimer's disease patients (AD).

Isolation and characterization of a new Leptobacillium species promoting tomato plant growth.

Endophytes can be a promising alternative for sustainable agronomic practices. In this study, we report for the first time a root-colonizing fungal strain (Sl27) of the genus Leptobacillium as a tomato (Solanum lycopersicum) endophyte, with no clear homology to any known species. Performed analyses and assays, including morphological and physiological characterization of the fungal isolate, provided insights into the ecological niche and potential agronomical and industrial applications of the fungal isolate.

Validation and accuracy of the Hyfe cough monitoring system: a multicenter clinical study.

Background: The ability to passively and continuously monitor coughing for prolonged periods of time would significantly improve cough management and research. To date there is no automated clinically validated cough monitor that can be routinely used in clinical care and research. Here we describe the validation of such an automated cough monitor.

Rapid climate action is needed: comparing heat vs. COVID-19-related mortality.

The impacts of climate change on human health are often underestimated or perceived to be in a distant future. Here, we present the projected impacts of climate change in the context of COVID-19, a recent human health catastrophe. We compared projected heat mortality with COVID-19 deaths in 38 cities worldwide and found that in half of these cities, heat-related deaths could exceed annual COVID-19 deaths in less than ten years (at + 3.

MAT2A inhibitor AG-270/S095033 in patients with advanced malignancies: a phase I trial.

Homozygous MTAP deletion occurs in ~15% of cancers, making them vulnerable to decreases in the concentration of S-adenosylmethionine (SAM). AG-270/S095033 is an oral, potent, reversible inhibitor of methionine adenosyltransferase 2 A (MAT2A), the enzyme primarily responsible for the synthesis of SAM. We report results from the first-in-human, phase 1 trial of AG-270/S095033 as monotherapy in patients with advanced malignancies (ClinicalTrials.

Association of novel ERLIN2 gene variants with hereditary spastic paraplegia.

Two ERLIN2 variants (NM_007175.8:c.660delA and NM_007175.

Spatial tumor immune heterogeneity facilitates subtype co-existence and therapy response in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) displays a high degree of spatial subtype heterogeneity and co-existence, linked to a diverse microenvironment and worse clinical outcome. However, the underlying mechanisms remain unclear. Here, by combining preclinical models, multi-center clinical, transcriptomic, proteomic, and patient bioimaging data, we identify an interplay between neoplastic intrinsic AP1 transcription factor dichotomy and extrinsic macrophages driving subtype co-existence and an immunosuppressive microenvironment.

Key elements for designing effective second victim support interventions: a focus group study in European clinical settings.

Background: The second victim (SV) experience limits the performance of health and care workers and places patients at risk. Peer support is recognised as the most effective, feasible and acceptable intervention to mitigate its impact.

Objective: To define a set of success factors when designing interventions to support SVs in health and care facilities based on expertise in different European countries.

Pathophysiological characterization of the ApoE mouse: A model of diabetes and atherosclerosis.

The high prevalence of type 2 diabetes and atherosclerosis makes essential the availability of in vivo experimental models that accurately replicate the pathophysiological mechanisms of these diseases. Apolipoprotein E knockout mice (ApoE) have been used in atherosclerosis studies, and the db/db mice show hyperphagia and obesity. Mice harbouring both alterations (i.

Pediococcus acidilactici CECT 9879 (pA1c®) and heat inactivated pA1c® (pA1c® HI) ameliorate gestational diabetes mellitus in mice.

Aims: Gestational diabetes mellitus (GDM) is the most common complication of pregnancy and is known to be associated with an increased risk of postpartum metabolic disease. Based on the important role that the intestinal microbiota plays in blood glucose regulation and insulin sensitivity, supplementation of probiotic and postbiotic strains could improve glucose metabolism and tolerance in GDM.

Main Methods: 56 4-week-old female C57BL/6J-mice were divided into 4 groups (n = 14 animals/group): control (CNT), high-fat/high-sucrose (HFS), pA1c® alive (pA1c®) and heat-inactivated pA1c® (pA1c®HI).

Structural and Functional Insights into UDP-N-acetylglucosamine-enolpyruvate Reductase (MurB) from Brucella ovis.

The peptidoglycan biosynthetic pathway involves a series of enzymatic reactions in which UDP-N-acetylglucosamine-enolpyruvate reductase (MurB) plays a crucial role in catalyzing the conversion of UDP-N-acetylglucosamine-enolpyruvate (UNAGEP) to UDP-N-acetylmuramic acid. This reaction relies on NADPH and FAD and, since MurB is not found in eukaryotes, it is an attractive target for the development of antimicrobials. MurB from Brucella ovis, the causative agent of brucellosis in sheep, is characterized here.

Effects of prenatal exposure to multiple heavy metals on infant neurodevelopment: a multi-statistical approach.

Prenatal exposure to heavy metals poses risks to fetal brain development, yet the joint effects of these metals remain unclear, with inconsistent findings across statistical models. This study investigates the joint effect of prenatal exposure to cadmium (Cd), nickel (Ni), mercury (Hg), and lead (Pb) on infant neurodevelopment using various statistical approaches. The study included 400 mother-infant pairs.

PRAME Immunostaining in BAP-1-Inactivated Melanocytic Tumors: Unraveling Diagnostic Complexity and Exploring Germline Mutation Associations.

Background: Cutaneous melanocytic tumors with BAP-1 inactivation (BIMTs), linked to mutations in the BAP-1 gene, present diagnostic challenges due to their morphological similarities with other melanocytic lesions. The search for reliable diagnostic markers, including PRAME, holds potential to significantly improve the accuracy of differential diagnoses.

Methods: A retrospective analysis of 32 BIMTs from 25 patients, collected between 2018 and 2022, involved histologic examination and immunostaining for BAP-1 and PRAME.

Conceptual Contextualization of Neutrophilic Dermatoses.

Neutrophilic dermatoses are defined as inflammatory skin diseases characterized by sterile infiltration of polymorphonuclear neutrophils into various cutaneous layers. Although, in many cases, neutrophilic dermatoses represent the cutaneous counterpart of autoinflammatory diseases, this is not always the case, and there are other causes associated with this group of diseases, such as the administration of certain drugs or an underlying tumor. However, understanding the autoinflammatory context in which most of these entities develop, as well as their close relationship with autoimmunity, is key to comprehending their pathogenesis.

Biomechanical perspectives on traumatic brain injury in the elderly: A comprehensive review.

Traumatic brain injuries (TBIs) pose a significant health concern among the elderly population, influenced by age-related physiological changes and the prevalence of neurodegenerative diseases. Understanding the biomechanical dimensions of TBIs in this demographic is vital for developing effective preventive strategies and optimizing clinical management. This comprehensive review explores the intricate biomechanics of TBIs in the elderly, integrating medical and aging studies, experimental biomechanics of head tissues, and numerical simulations.