Ecteinascidin synthetic analogues: a new class of selective inhibitors of transcription, exerting immunogenic cell death in refractory malignant pleural mesothelioma.

Background: Malignant pleural mesothelioma (MPM) is a highly chemo-refractory and immune-evasive tumor that presents a median overall survival of 12-14 months when treated with chemotherapy and immunotherapy. New anti-tumor therapies as well as the concomitant reactivation of immune destruction are urgently needed to treat patients with this tumor. The aim of this work is to investigate the potential effect of ecteinascidin derivatives as lurbinectedin as new first-line treatment option in MPM, alone and in combination with immunotherapy.

Infant mice fed soy-based formulas exhibit alterations in anxiety-like behaviours and the 5-HT system.

Genistein (GEN) is a phytoestrogen with oestrogen-like activity found in many plants. Classified as an endocrine disruptor, GEN is potentially hazardous, particularly during developmental stages. It induces alterations in anxious behaviour, fertility, and energy metabolism, alongside modifications in specific brain circuits.

Lymph node ratio (LNR) and lymph node yield (LNY) in head and neck cancer: A systematic review and meta-analysis.

Introduction: A growing amount of evidence points at lymph node yield (LNY) and lymph node ratio (LNR) as useful indicators in the prognostic evaluation of patients affected by head and neck squamous cell carcinoma (HNSCC) who require neck dissection. The aim of this study was to assess the importance of LNY and LNR in the prognostic evaluation of head and neck cancer patients.

Materials And Methods: Included studies were those examining LNY and/or LNR in head and neck cancer patients.

Genetic variants in DDX53 contribute to autism spectrum disorder associated with the Xp22.11 locus.

Autism spectrum disorder (ASD) exhibits an ∼4:1 male-to-female sex bias and is characterized by early-onset impairment of social/communication skills, restricted interests, and stereotyped behaviors. Disruption of the Xp22.11 locus has been associated with ASD in males.

Hafnium-Based Metal-Organic Framework Nanosystems Entrapping Squaraines for Efficient NIR-Responsive Photodynamic Therapy.

In this study, we present for the first time the incorporation of two distinct nonsymmetrical squaraines (SQ) into hierarchically porous Hafnium-based UiO-66 Metal-Organic Frameworks (MOFs), each functionalized with various moieties, for application as photosensitizers in photodynamic therapy. SQs are meticulously designed to feature COOH moieties for interaction with the MOF's metallic cluster and bromine atoms to enhance intersystem crossing and reactive oxygen species (ROS) production. The distinct central functionalizations, one with squaric acid and the other with a dicyanovinyl-substituted squaric acid derivative, result in unique geometric conformations.

Age- and sex-related variations in extracellular vesicle profiling for the assessment of cardiovascular risk: the EVaging index.

Extracellular vesicles (EVs) offer valuable diagnostic and prognostic insights for cardiovascular (CV) diseases, but the influence of age-related chronic inflammation ("inflammaging") and sex differences on EV profiles linked to CV risk remains unclear. This study aimed to use EV profiling to predict age and stratify patients by CV risk. We developed an EVaging index by analyzing surface antigen profiles of serum EVs from 625 participants, aged 20 to 94 years, across varying CV risk groups.

The carbonyl nucleobase adduct MAde is a potent antigen for adaptive polyclonal MR1-restricted T cells.

The major histocompatibility complex (MHC) class I-related molecule MHC-class-I-related protein 1 (MR1) presents metabolites to distinct MR1-restricted T cell subsets, including mucosal-associated invariant T (MAIT) and MR1T cells. However, self-reactive MR1T cells and the nature of recognized antigens remain underexplored. Here, we report a cell endogenous carbonyl adduct of adenine (8-(9H-purin-6-yl)-2-oxa-8-azabicyclo[3.

In vitro activity and genomic characterization of KPC-producing Klebsiella pneumoniae clinical blood culture isolates resistant to ceftazidime/avibactam, meropenem/vaborbactam, imipenem/relebactam: an Italian nationwide multicentre observational study (2022-23).

Objectives: To evaluate the in vitro activity of ceftazidime/avibactam, meropenem/vaborbactam, imipenem/relebactam and comparators against KPC-producing Klebsiella pneumoniae (KPC-Kp) clinical isolates collected from a multicentre study in Italy (2022-23) and genomic characterization of the molecular mechanisms causing resistance.

Methods: Consecutive KPC-Kp isolates from blood cultures (n = 264) were collected from 14 hospital centres in the period 2022-23. Antimicrobial susceptibility testing was performed using broth microdilution.

Off-Target Inhibition of Human Dihydroorotate Dehydrogenase (DHODH) Highlights Challenges in the Development of Fat Mass and Obesity-Associated Protein (FTO) Inhibitors.

FTO, an -methyladenosine (mA) and ,2'--dimethyladenosine (mA) RNA demethylase, is a promising target for treating acute myeloid leukemia (AML) due to the significant anticancer activity of its inhibitors in preclinical models. Here, we demonstrate that the FTO inhibitor FB23-2 suppresses proliferation across both AML and CML cell lines, irrespective of FTO dependency, indicating an alternative mechanism of action. Metabolomic analysis revealed that FB23-2 induces the accumulation of dihydroorotate (DHO), a key intermediate in pyrimidine nucleotide synthesis catalyzed by human dihydroorotate dehydrogenase (DHODH).

Human Exposure to Asbestos in Central Asian Countries and Health Effects: A Narrative Review.

The discovery of the detrimental effects of asbestos on human health came long after its widespread use, with the first scientific evidence of asbestos-related diseases emerging in the late 19th and early 20th centuries. Despite efforts to ban its use, asbestos continues to be mined and used in Central Asia (as well as in Russia, China, and other countries). To gain a deeper understanding of the situation in Central Asia, we have conducted a systematic review of scientific literature on the use of asbestos, exposure assessment, and health consequences of asbestos exposure in this geographic area.

Quantification and time course of subjective psychotropic and somatic effects of tetrahydrocannabinol - a prospective, single-blind, placebo-controlled exploratory trial in healthy volunteers.

Background: Cannabis is increasingly used and debates about the legalisation of the recreational use of cannabis are ongoing. In this prospective, placebo-controlled study in healthy volunteers not regularly consuming cannabis, subjective psychotropic and somatic effects after a single dose of intravenous THC were assessed and quantified over 48 h.

Methods: Twenty-five healthy volunteers received a single IV bolus of THC and 6 received normal saline.

Lupus and SARS-CoV-2: What have we learned after the pandemic?

After the end of the COVID-19 public health emergency, we analysed the relationship between Systemic Lupus Erythematosous (SLE) and COVID-19 from the virologist's perspective based on recent findings. SLE and COVID-19 co-morbidity present unique challenges, as individuals with SLE may be at increased risk for severe COVID-19 illness due to immune system abnormalities and ongoing therapies. Effective management of both diseases requires careful monitoring, adherence to vaccination programs, preventive measures and approved and patient-tailored therapies.

Nature or nurture: genetic and environmental predictors of adiposity gain in adults.

Background: Previous prediction models for adiposity gain have not yet achieved sufficient predictive ability for clinical relevance. We investigated whether traditional and genetic factors accurately predict adiposity gain.

Methods: A 5-year gain of ≥5% in body mass index (BMI) and waist-to-hip ratio (WHR) from baseline were predicted in mid-late adulthood individuals (median of 55 years old at baseline).

Three Decades of Adolescent Health: Unveiling Global Trends Across 41 Countries in Psychological and Somatic Complaints (1994-2022).

Objectives: This study examined (non-)monotonic time trends in psychological and somatic complaints among adolescents, along with gender differences.

Methods: Repeated cross-sectional Health Behaviour in School-aged Children (HBSC) data from 1994 to 2022 covering 15-year-old adolescents from 41 countries (N = 470,797) were analysed. Three polynomial logistic regression models (linear, quadratic, cubic) were tested for best fit, including separate analyses by gender and health complaints dimension.

Sex and Body Mass Index Differences in Changes in Skin Temperature After Repeated Sessions of Whole-Body Cryostimulation.

: Whole-body cryostimulation (WBC) involves exposure to extremely low temperatures to reduce inflammation and pain and to enhance recovery. Despite its growing popularity and the importance of the magnitude of WBC-induced skin cooling in triggering the cascade of effects, limited research has focused on skin temperature changes in individuals with severe obesity, where body composition and sex may influence outcomes. : To examine differences in the cooling response based on sex and BMI, we conducted an observational study comparing patients with obesity to normal-weight individuals after repeated WBC sessions.

Nurse-Led Interventions for Improving Medication Adherence in Chronic Diseases: A Systematic Review.

: Poor medication adherence results in negative health outcomes and increased healthcare costs. Several healthcare professionals provide interventions to improve medication adherence, with the effectiveness of nurse-led interventions in people with chronic diseases remaining unclear. : This study sought to evaluate the effectiveness of nurse-led interventions for improving medication adherence in adults with chronic conditions.

A UV-Protective Textile Coating Based on Recycled Poly(vinyl butyral) (PVB): A New Life for a Waste Polymer.

Polyvinyl butyral (PVB) is a high-performance thermoplastic polymer, commonly used as an interlayer material in laminated safety glass for the automotive and architectural sectors. Currently, there is no end-of-life cycle program for a substantial amount of PVB film, which mainly ends up in landfills. According to a circular approach, PVB can be revalorized after efficient separation and recovery from glass.

Enhancing Permanence of Corrosion Inhibitors Within Acrylic Protective Coatings for Outdoor Bronze Using Green Nanocontainers.

Outdoor bronze statues are constantly exposed to weather conditions and reactive compounds in the atmosphere that can interact with their surfaces. To avoid these interactions, a commonly used method is the application of coatings with corrosion inhibitors. However, a significant limitation of these inhibitors is their gradual loss over time.

Molecular and Clinical Features of Adrenocortical Tumors in Beckwith-Wiedemann Spectrum.

Background/objectives: Adrenocortical tumors (ACTs), including adrenocortical adenoma (ACA) and carcinoma (ACC), represent 0.3-0.4% of pediatric tumors.

Albi score predicts overall survival (OS) in patients with hepatocellular carcinoma (HCC) treated with selective internal radiation therapy (SIRT).

Purpose: We aimed to evaluate the prognostic impact of baseline clinical features and treatment procedure, including liver function measured with albumin-bilirubin (ALBI) formula and dosing methods in HCC patients treated with SIRT.

Material And Methods: The study includes 82 consecutive patients with liver-dominant HCC treated with SIRT (Y glass microspheres, TheraSphereTM) between October 2014 and September 2023. Twenty-five patients were treated with standard dosimetry, while for remaining patients, multi-compartment dosimetry was performed using Simplicit90YTM software.

Schwann Cell-Specific Ablation of Beclin 1 Impairs Myelination and Leads to Motor and Sensory Neuropathy in Mice.

The core component of the class III phosphatidylinositol 3-kinase complex, Beclin 1, takes part in different protein networks, thus switching its role from inducing autophagy to regulating autophagosomal maturation and endosomal trafficking. While assessed in neurons, astrocytes, and microglia, its role is far less investigated in myelinating glia, including Schwann cells (SCs), responsible for peripheral nerve myelination. Remarkably, the dysregulation in endosomal trafficking is emerging as a pathophysiological mechanism underlying peripheral neuropathies, such as demyelinating Charcot-Marie-Tooth (CMT) diseases.

Social play in African savannah elephants may inform selection against aggression.

In social groups, competition for individual advantage is balanced with cooperation, for the collective benefit. Selection against aggression has favored cooperation and non-aggressive competitive strategies. Because social play is a behavioral system that fluctuates between cooperation and competition, selection against aggression might have especially influenced this behavior.