Characterisation of the tumour microenvironment and PD-L1 granularity reveals the prognostic value of cancer-associated myofibroblasts in non-invasive bladder cancer.

High-risk non-muscle-invasive bladder cancer (NMIBC) presents high recurrence and progression rates. Despite the use of Bacillus Calmette-Guérin gold-standard immunotherapy and the recent irruption of anti-PD-1/PD-L1 drugs, we are missing a comprehensive understanding of the tumor microenvironment (TME) that may help us find biomarkers associated to treatment outcome. Here, we prospectively analyzed TME composition and PD-L1 expression of tumor and non-tumoral tissue biopsies from 73 NMIBC patients and used scRNA-seq, transcriptomic cohorts and tissue micro-array to validate the prognostic value of cell types of interest.

Psychosocial hybrid interventions for weight and sedentary behavior management among patients with severe mental disorders: A systematic review and meta-analysis.

Background: Severe mental disorders, such as schizophrenia, bipolar disorders, and other psychosis have been associated with risk of premature mortality, predominantly due to cardiovascular diseases and metabolic syndrome. The aim of this systematic review and meta-analysis was to examine the efficacy of hybrid psychosocial interventions combining face-to-face and eHealth components for patients with severe mental disorders on reduction of weight and waist circumference.

Method: The electronic search on PubMED, PsycINFO, EMBASE, Web of Science were conducted, and data were extracted twice.

The Evidence Base for Circulating Tumor DNA-Methylation in Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis.

: Non-Small Cell Lung Cancer (NSCLC) remains a challenging disease to manage with effectiveness. Early detection and precise monitoring are crucial for improving patient outcomes. Circulating tumor DNA (ctDNA) offers a non-invasive cancer detection and monitoring method.

Assessing interactions between antibiotics and triazine porous organic polymeric sorbents by photophysics.

This study purposes three triazine-based porous organic polymers (T-POPs 1-3) as advanced platforms for the early detection of antibiotic-polluted environments and effective water decontamination, in order to mitigate water pollution and antimicrobial resistance, which are two huge current problems damaging ecosystems and human health. T-POPs exhibited good performances as adsorbents for the removal of sulfamethazine (SMT) and tetracycline (TC) from water, with efficiencies up to 97% and 96%, and maximum adsorption capacities between (0.36-0.

Association of adverse childhood experiences and overweight or obesity in adolescents: A systematic review and network analysis.

This systematic review with meta-analysis assessed the effects of adverse childhood experiences (ACEs) linked to overweight or obesity in adolescents. Twenty-eight studies (cross-sectional, case-control, or cohort) were included, which described individuals with a history of ACE or adverse family experiences, such as physical, emotional, or psychological abuses; neglect; exposure to domestic violence or peer violence; and sexual abuse. Body mass index (BMI) or BMI z score was used by the study to define adolescents with overweight or obesity.

Charge-switchable cell-penetrating peptides for rerouting nanoparticles to glioblastoma treatment.

Glioblastoma (GB) is one of the most lethal types of neoplasms with unique anatomic, physiologic, and pathologic features that usually persist after exposure to standard therapeutic modalities. It is biologically aggressive, and the existence of the blood-brain barrier (BBB) limits the efficacy of standard therapies. In this work, we hypothesize the potential of surface-functionalized ultra-small nanostructured lipid carriers (usNLCs) with charge-switchable cell-penetrating peptides (CPPs) to overcome this biological barrier and improve targeted delivery to brain tumor tissues.

Modulation of tumor microenvironment by targeting histone acetylation in bladder cancer.

Alterations in the epigenetic machinery in both tumor and immune cells contribute to bladder cancer (BC) development, constituting a promising target as an alternative therapeutic option. Here, we have explored the effects of a novel histone deacetylase (HDAC) inhibitor CM-1758, alone or in combination with immune checkpoint inhibitors (ICI) in BC. We determined the antitumor effects of CM-1758 in various BC cell lines together with the induction of broad transcriptional changes, with focus on the epigenetic regulation of PD-L1.

Selective, broad-spectrum antiviral photodynamic disinfection with dicationic imidazolyl chlorin photosensitizers.

The COVID-19 pandemic exposes our vulnerability to viruses that acquire the ability to infect our cells. Classical disinfection methods are limited by toxicity. Existing medicines performed poorly against SARS-CoV-2 because of their specificity to targets in different organisms.

Reactivity of ethyl nitrosoacrylate toward pyrrole, indole and pyrrolo[3,2-]carbazole: an experimental and theoretical study.

Nitrosoalkenes react with 8-methyl-1,6-dihydropyrrolo[3,2-]carbazole to give both 2- and 3-alkylated products via hetero-Diels-Alder reaction followed by the cycloadduct ring-opening. Quantum chemical calculations, at DFT level of theory, were carried out to investigate the regioselectivity of the cycloaddition of ethyl nitrosoacrylate with 1,6-dihydropyrrolo[3,2-]carbazoles as well as with pyrrole and indole, allowing a more comprehensive analysis of the reactivity pattern of nitrosoalkenes with five-membered heterocycles. Furthermore, theoretical calculations confirmed that ethyl nitrosoacrylate reacts with these heterocycles via a LUMO-HOMO controlled cycloaddition.

Fluorinated Mn(III)/(II)-Porphyrin with Redox-Responsive H and F Relaxation Properties.

A new fluorinated manganese porphyrin, (Mn-TPP-p-CF ) is reported capable of providing, based on the Mn(III)/Mn(II) equilibrium, dual H relaxivity and F NMR response to redox changes. The physical-chemical characterization of both redox states in DMSO-d /H O evidenced that the H relaxometric and F NMR properties are appropriate for differential redox MRI detection. The Mn(III)-F distance (d =9.

A descriptive analysis of hospitalized adolescents facing chronic illnesses with different durations of disease.

Objectives: To assess characteristics of hospitalized adolescents facing chronic diseases, correlating the perceptions of their illness, quality of life and the prevalence of risk behaviors, considering gender and the diseases' durations.

Methods: The sample consisted of 61 adolescents, aged between 10 and 19 years, with chronic diseases, hospitalized at the University Hospital of the State University of Londrina. They answered a questionnaire and the scales World Health Organization Quality of Life (WHOQOL-BREF) and Illness Perception Questionnaire (IPQ).

Cognitive impairment, childhood trauma, sedentary behaviour, and elevated C-reactive protein levels in major affective disorders.

Elevated C-reactive protein (CRP) levels were associated with cognitive decline, sedentary behaviour, and childhood trauma in patients with major affective disorders. This study aims to examine the association of peripheral CRP levels, cognitive function, childhood trauma, sedentary behaviour, and quality of life in individuals with major affective disorders, including bipolar disorder (BD), major depressive disorder (MDD), and individuals without mood disorders (controls). We included outpatients with BD (n = 42), MDD (n = 27), and healthy controls (n = 40).

Pilot project. Resveratrol intake by physical active and sedentary older adult women and blood pressure.

Objective: Although the use of resveratrol is widespread, there is a lack of studies concerning its use in older adults who practice regular physical activity. The present study aimed to evaluate how resveratrol influenced anthropometric parameters, heart measures, blood analytes in women participants, aged 60 to 80 years old, distributed in four groups consisting of those who regularly exercise or not, and those who were under resveratrol treatment or not. The older adult women exercised in a Community Center.

Impact of rs1344706 or rs1006737 polymorphisms on cognition in patients with severe mental disorders: A systematic review and meta-analysis.

Objectives: This systematic review and meta-analysis focussed on insights into the relationship between -rs1006737 and -rs1344706 polymorphisms and cognitive performance in schizophrenia (SCZ) spectrum and bipolar disorder (BD) and provide some contributions for clinical practice.

Methods: We searched the websites databases (PubMED, PsycINFO, Web of Science, EMBASE and Cochrane Library) using eligibility and exclusion criteria to capture all potential studies, based on PICO model and according to the PRISMA.

Results: Eight articles were included in this systematic review (five referring to -rs1006737 and three related to -rs1344706 polymorphisms), with a total of 5759 participants (1751 SCZ patients, 348 BD patients, 3626 controls and 34 first-degree relatives).

Hybrid and Remote Psychosocial Interventions Focused on Weight and Sedentary Behavior Management Among Patients with Severe Mental Illnesses: a Systematic Review.

Severe mental illness could be defined through its diagnosis, disability, and duration, and one of their main characteristics is the high prevalence of some clinical conditions such as obesity and metabolic syndrome. Although the promotion of a healthier lifestyle has been demonstrated as an effective strategy to reduce both body mass index and abdominal circumference in this population, there is a lack of studies focusing on digital intervention in this population. The aim of this systematic review was to evaluate the efficacy of studies that used digital technologies to reduce weight, body mass index (BMI) and abdominal circumference in individuals with severe mental illness.

Toward Tumor Fight and Tumor Microenvironment Remodeling: PBA Induces Cell Cycle Arrest and Reduces Tumor Hybrid Cells' Pluripotency in Bladder Cancer.

Bladder cancer (BC) is the second most frequent cancer of the genitourinary system. The most successful therapy since the 1970s has consisted of intravesical instillations of (BCG) in which the tumor microenvironment (TME), including macrophages, plays an important role. However, some patients cannot be treated with this therapy due to comorbidities and severe inflammatory side effects.

Artificial Intelligence and Quantum Computing as the Next Pharma Disruptors.

Artificial intelligence (AI) consists of a synergistic assembly of enhanced optimization strategies with wide application in drug discovery and development, providing advanced tools for promoting cost-effectiveness throughout drug life cycle. Specifically, AI brings together the potential to improve drug approval rates, reduce development costs, get medications to patients faster, and help patients complying with their treatments. Accelerated pharmaceutical development and drug product approval rates can further benefit from the quantum computing (QC) technology, which will ultimately enable larger profits from patent-protected market exclusivity.

Key Factors for Implementing Magnetic NDT Method on Thin UHPFRC Bridge Elements.

This paper provides an overview of the use of the magnetic NDT method for estimating the fibre content, and fibre orientation and efficiency factors in thin UHPFRC elements/layers, along any two orthogonal directions. These parameters are of utmost importance for predicting the post-cracking tensile strength in the directions of interest. After establishing meaningful correlations at the lab-specimen scale, this NDT method can be effectively implemented into quality control protocols at the industrial production scale.

Increased nitro-oxidative toxicity in association with metabolic syndrome, atherogenicity and insulin resistance in patients with affective disorders.

Background: There is a strong comorbidity between mood disorders and metabolic syndrome (MetS). Increased levels of reactive oxygen and nitrogen species (RONS) and nitro-oxidative stress toxicity (NOSTOX) partially underpin this comorbidity.

Aims: To examine the associations of RONS/NOSTOX biomarkers with MetS after adjusting for the significant effects of mood disorders (major depression, and bipolar type 1 and 2), generalized anxiety disorder (GAD), tobacco use disorder (TUD), and male sex.

Cognition-immune interactions between executive function and working memory, tumour necrosis factor-alpha (TNF-alpha) and soluble TNF receptors (sTNFR1 and sTNFR2) in bipolar disorder.

Objectives: This study examined cognition-immune interactions, specifically executive function, working memory, peripheral levels of tumour necrosis factor-alpha (TNF-α), and soluble tumour necrosis factor receptors-1 and -2 (sTNFR1 and 2) levels in bipolar disorder (BD) patients in comparison with controls.

Methods: Thirty-one BD participants and twenty-seven controls participated in the study. The neurocognitive assessment was performed through three of CogState Research Battery tasks for executive function and working memory.

Tackling tumor microenvironment through epigenetic tools to improve cancer immunotherapy.

Background: Epigenetic alterations are known contributors to cancer development and aggressiveness. Additional to alterations in cancer cells, aberrant epigenetic marks are present in cells of the tumor microenvironment, including lymphocytes and tumor-associated macrophages, which are often overlooked but known to be a contributing factor to a favorable environment for tumor growth. Therefore, the main aim of this review is to give an overview of the epigenetic alterations affecting immune cells in the tumor microenvironment to provoke an immunosuppressive function and contribute to cancer development.

Towards a new model and classification of mood disorders based on risk resilience, neuro-affective toxicity, staging, and phenome features using the nomothetic network psychiatry approach.

Current diagnoses of mood disorders are not cross validated. The aim of the current paper is to explain how machine learning techniques can be used to a) construct a model which ensembles risk/resilience (R/R), adverse outcome pathways (AOPs), staging, and the phenome of mood disorders, and b) disclose new classes based on these feature sets. This study was conducted using data of 67 healthy controls and 105 mood disordered patients.

Increased nitro-oxidative stress toxicity as a major determinant of increased blood pressure in mood disorders.

Background: Hypertension, atherogenicity and insulin resistance are major risk factors of cardiovascular disorder (CVD), which shows a strong comorbidity with major depression (MDD) and bipolar disorder (BD). Activated oxidative and nitrosative stress (O&NS), inflammatory pathways, and increased atherogenicity are shared pathways underpinning CVD and mood disorders.

Methods: The current study examined the effects of lipid hydroperoxides (LOOH), superoxide dismutase (SOD), nitric oxide metabolites (NOx), advanced oxidation protein products (AOPP), and malondialdehyde (MDA) on systolic (SBP) and diastolic (DBP) blood pressure in 96 mood disordered patients and 60 healthy controls.