Effect of a Novel Food Rich in Miraculin on the Intestinal Microbiome of Malnourished Patients with Cancer and Dysgeusia.

Background/objectives: Dysgeusia contributes to malnutrition and worsens the quality of life of patients with cancer. Despite the different strategies, there is no effective treatment for patients suffering from taste disorders provided by the pharmaceutical industry. Therefore, we developed a novel strategy for reducing side effects in cancer patients by providing a novel food supplement with the taste-modifying glycoprotein miraculin, which is approved by the European Union, as an adjuvant to medical-nutritional therapy.

Exploration of transfer learning techniques for the prediction of PM.

Modelling of pollutants provides valuable insights into air quality dynamics, aiding exposure assessment where direct measurements are not viable. Machine learning (ML) models can be employed to explore such dynamics, including the prediction of air pollution concentrations, yet demanding extensive training data. To address this, techniques like transfer learning (TL) leverage knowledge from a model trained on a rich dataset to enhance one trained on a sparse dataset, provided there are similarities in data distribution.

A single gene orchestrates androgen variation underlying male mating morphs in ruffs.

Androgens are pleiotropic and play pivotal roles in the formation and variation of sexual phenotypes. We show that differences in circulating androgens between the three male mating morphs in ruff sandpipers are linked to 17-beta hydroxysteroid dehydrogenase 2 (HSD17B2), encoded by a gene within the supergene that determines the morphs. Low-testosterone males had higher expression in blood than high-testosterone males, as well as in brain areas related to social behaviors and testosterone production.

Muscarinic receptor agonists and positive allosteric modulators in animal models of psychosis: protocol for a systematic review and meta-analysis.

Background: Muscarinic receptor agonism and positive allosteric modulation is a promising mechanism of action for treating psychosis, not present in most D2R-blocking antipsychotics. Xanomeline, an M1/M4-preferring agonist, has shown efficacy in late-stage clinical trials, with more compounds being investigated. Therefore, we aim to synthesize evidence on the preclinical efficacy of muscarinic receptor agonists and positive allosteric modulators in animal models of psychosis to provide unique insights and evidence-based information to guide drug development.

ARID1A mutations protect follicular lymphoma from FAS-dependent immune surveillance by reducing RUNX3/ETS1-driven FAS-expression.

The cell death receptor FAS and its ligand (FASLG) play crucial roles in the selection of B cells during the germinal center (GC) reaction. Failure to eliminate potentially harmful B cells via FAS can lead to lymphoproliferation and the development of B cell malignancies. The classic form of follicular lymphoma (FL) is a prototypic GC-derived B cell malignancy, characterized by the t(14;18)(q32;q21)IGH::BCL2 translocation and overexpression of antiapoptotic BCL2.

The Co-IMPACT Consortium: Integrating Prostate-specific Membrane Antigen Positron Emission Tomography and Radiotherapy in Prostate Cancer Care.

The Co-IMPACT consortium addresses knowledge gaps in prostate-specific membrane antigen positron emission tomography-guided radiotherapy for prostate cancer by establishing a global database (46 centres from 16 countries) to standardise and analyse data across four distinguished clinical scenarios. A collaborative model with the Advanced Prostate Cancer Consensus Conference aligns urgent clinical needs with actionable research insights.

Chronic intermittent fasting impairs β cell maturation and function in adolescent mice.

Intermittent fasting (IF) is a nutritional lifestyle intervention with broad metabolic benefits, but whether the impact of IF depends on the individual's age is unclear. Here, we investigated the effects of IF on systemic metabolism and β cell function in old, middle-aged, and young mice. Short-term IF improves glucose homeostasis across all age groups without altering islet function and morphology.

The clinical-stage drug BTZ-043 accumulates in murine tuberculosis lesions and efficiently acts against Mycobacterium tuberculosis.

The development of granulomas with central necrosis harboring Mycobacterium tuberculosis (Mtb) is the hallmark of human tuberculosis (TB). New anti-TB therapies need to effectively penetrate the cellular and necrotic compartments of these lesions and reach sufficient concentrations to eliminate Mtb. BTZ-043 is a novel antibiotic showing good bactericidal activity in humans in a phase IIa trial.

Longitudinal association between DNA methylation and type 2 diabetes: findings from the KORA F4/FF4 study.

Background: Type 2 diabetes (T2D) has been linked to changes in DNA methylation levels, which can, in turn, alter transcriptional activity. However, most studies for epigenome-wide associations between T2D and DNA methylation comes from cross-sectional design. Few large-scale investigations have explored these associations longitudinally over multiple time-points.

Construction of brain age models based on structural and white matter information.

Brain aging is an inevitable process in adulthood, yet there is a lack of objective measures to accurately assess its extent. This study aims to develop brain age prediction model using magnetic resonance imaging (MRI), which includes structural information of gray matter and integrity information of white matter microstructure. Multiparameter MRI was performed on two population cohorts.

Retrovirus-based manufacturing of chimeric antigen receptor-modified T cells for cancer therapy research.

Treatment with autologous chimeric antigen receptor (CAR)-modified T cells can achieve outstanding clinical response rates in heavily pretreated patients with B and plasma cell malignancies. However, relapses occur, and they limit the efficacy of this promising treatment approach. The complex GMP-compliant production and high treatment costs cause that CAR T cells cannot yet be used in a broad population.

Multi-Targeting Macrocyclic Peptides as Nanomolar Inhibitors of Self- and Cross-Seeded Amyloid Self-Assembly of α-Synuclein.

Amyloid self-assembly of α-synuclein (αSyn) is linked to the pathogenesis of Parkinson's disease (PD). Type 2 diabetes (T2D) has recently emerged as a risk factor for PD. Cross-interactions between their amyloidogenic proteins may act as molecular links.

Contribution of hypoxia-inducible factor 1alpha to pathogenesis of sarcomeric hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) caused by autosomal-dominant mutations in genes coding for structural sarcomeric proteins, is the most common inherited heart disease. HCM is associated with myocardial hypertrophy, fibrosis and ventricular dysfunction. Hypoxia-inducible transcription factor-1α (Hif-1α) is the central master regulators of cellular hypoxia response and associated with HCM.

Nanocarrier imaging at single-cell resolution across entire mouse bodies with deep learning.

Efficient and accurate nanocarrier development for targeted drug delivery is hindered by a lack of methods to analyze its cell-level biodistribution across whole organisms. Here we present Single Cell Precision Nanocarrier Identification (SCP-Nano), an integrated experimental and deep learning pipeline to comprehensively quantify the targeting of nanocarriers throughout the whole mouse body at single-cell resolution. SCP-Nano reveals the tissue distribution patterns of lipid nanoparticles (LNPs) after different injection routes at doses as low as 0.

Insights into the molecular underpinning of type 2 diabetes complications.

Type 2 diabetes (T2D) complications pose a significant global health challenge. Omics technologies have been employed to investigate these complications and identify the biological pathways involved. In this review, we focus on four major T2D complications: diabetic kidney disease, diabetic retinopathy, diabetic neuropathy, and cardiovascular complications.

Prognostic significance of immune reconstitution following CD19 CAR T-cell therapy for relapsed/refractory B-cell lymphoma.

Immune deficits after CD19 chimeric antigen receptor (CAR) T-cell therapy can be long-lasting, predisposing patients to infections and non-relapse mortality. In B-cell non-Hodgkin lymphoma (B-NHL), the prognostic impact of immune reconstitution (IR) remains ill-defined, and detailed cross-product comparisons have not been performed to date. In this retrospective observational study, we longitudinally characterized lymphocyte subsets and immunoglobulin levels in 105 B-NHL patients to assess patterns of immune recovery arising after CD19 CAR-T.

Nonlinear exposure-response associations of daytime, nighttime, and day-night compound heatwaves with mortality amid climate change.

Heatwaves are commonly simplified as binary variables in epidemiological studies, limiting the understanding of heatwave-mortality associations. Here we conduct a multi-country study across 28 East Asian cities that employed the Cumulative Excess Heatwave Index (CEHWI), which represents excess heat accumulation during heatwaves, to explore the potentially nonlinear associations of daytime-only, nighttime-only, and day-night compound heatwaves with mortality from 1981 to 2010. Populations exhibited high adaptability to daytime-only and nighttime-only heatwaves, with non-accidental mortality risks increasing only at higher CEHWI levels (75th-90th percentiles).

Hypoxia Regulates Brown Adipocyte Differentiation and Stimulates miR-210 by HIF-1α.

MicroRNAs (miRNAs) are short sequences of single-stranded non-coding RNAs that target messenger RNAs, leading to their repression or decay. Interestingly, miRNAs play a role in the cellular response to low oxygen levels, known as hypoxia, which is associated with reactive oxygen species and oxidative stress. However, the physiological implications of hypoxia-induced miRNAs ("hypoxamiRs") remain largely unclear.

Safety, bactericidal activity, and pharmacokinetics of the antituberculosis drug candidate BTZ-043 in South Africa (PanACEA-BTZ-043-02): an open-label, dose-expansion, randomised, controlled, phase 1b/2a trial.

Background: The broad use of bedaquiline and pretomanid as the mainstay of new regimens to combat tuberculosis is a risk due to increasing bedaquiline resistance. We aimed to assess the safety, bactericidal activity, and pharmacokinetics of BTZ-043, a first-in-class DprE1 inhibitor with strong bactericidal activity in murine models.

Methods: This open-label, dose-expansion, randomised, controlled, phase 1b/2a trial was conducted in two specialised tuberculosis sites in Cape Town, South Africa.

Consuming a modified Mediterranean ketogenic diet reverses the peripheral lipid signature of Alzheimer's disease in humans.

Background: Alzheimer's disease (AD) is a major neurodegenerative disorder with significant environmental factors, including diet and lifestyle, influencing its onset and progression. Although previous studies have suggested that certain diets may reduce the incidence of AD, the underlying mechanisms remain unclear.

Method: In this post-hoc analysis of a randomized crossover study of 20 elderly adults, we investigated the effects of a modified Mediterranean ketogenic diet (MMKD) on the plasma lipidome in the context of AD biomarkers, analyzing 784 lipid species across 47 classes using a targeted lipidomics platform.

Effects of time-of-day on the noradrenaline, adrenaline, cortisol and blood lipidome response to an ice bath.

While the effect of time-of-day (morning versus evening) on hormones, lipids and lipolysis has been studied in relation to meals and exercise, there are no studies that have investigated the effects of time-of-day on ice bath induced hormone and lipidome responses. In this crossover-designed study, a group of six women and six men, 26 ± 5 years old, 176 ± 7 cm tall, weighing 75 ± 10 kg, and a BMI of 23 ± 2 kg/mhad an ice bath (8-12 °C for 5 min) both in the morning and evening on separate days. Absence from intense physical exercise, nutrient intake and meal order was standardized in the 24 h prior the ice baths to account for confounders such as diet or exercise.

Exposure to Cadmium and Other Trace Elements Among Individuals with Mild Cognitive Impairment.

Background: A limited number of studies have investigated the role of environmental chemicals in the etiology of mild cognitive impairment (MCI). We performed a cross-sectional study of the association between exposure to selected trace elements and the biomarkers of cognitive decline.

Methods: During 2019-2021, we recruited 128 newly diagnosed patients with MCI from two Neurology Clinics in Northern Italy, i.