Small-molecule MMRi36 induces apoptosis in p53-mutant lymphomas by targeting MDM2/MDM4/XIAP for degradation.

Rituximab combined with systemic chemotherapy significantly improves the rate of complete response in B-cell lymphomas. However, acquired rituximab resistance develops in most patients leading to relapse. The mechanisms underlying rituximab resistance are not well-understood.

Climate change, migration, and health: perspectives from Latin America and the Caribbean.

This article delves into the complex relationship between climate change, migration patterns, and health outcomes in Latin America and the Caribbean (LAC). While the severe impact of climate change on health in LAC is widely acknowledged, the article sheds light on the often-overlooked multiple effects on migration and the well-being of migrants. These impacts encompass poverty, food and water insecurity, and adverse physical and mental health outcomes.

Maximising efficiency with exoscopic surgery: a versatile approach for transoral laryngeal and oropharyngeal procedures.

Objectives: Several devices have been developed to improve head and neck surgery. 3D exoscopes provide surgeons a viable alternative to microscopes. We propose our setting for transoral exoscopic oropharyngeal (TOEOS) and transoral exoscopic laryngeal surgery (TOELS).

Attitudes towards mental health professionals in social media: infodemiology study.

Background: Negative perceptions of mental health professionals can deter individuals from seeking mental healthcare. Given the high burden of mental health globally, it is essential to understand attitudes towards mental health professionals. Social media platforms like Twitter/X provide valuable insights into the views of the general population.

Exploring Gender-Based Disparities in Finalist Technical-Tactical Actions: A Study of Amateur and Professional Padel Players.

Our aim in this study was to analyze gender differences across amateur and professional padel players related to the last shot of each rally. We analyzed a total of 180 games per category (professional and amateur), with 90 games for each gender. We performed descriptive and inferential analyses, including the Chi-square (χ2) statistical test, the Cramer's V coefficient (Vc), subsequent Z-tests and corrected standard residuals (CSR).

First report of peach-associated luteovirus (PaLV) infecting almond trees () in Spain.

Peach-associated luteovirus (PaLV) belongs to the genus Luteovirus, family Tombusviridae. To date, PaLV has only been reported in peach (Prunus persica) and its presence detected in the Republic of Georgia (Wu et al., 2017), China (Zhou et al.

Visible-Light-Mediated Deaminative Alkylation of Primary Amines with Silacarboxylic Acids via Isonitrile Formation.

The functionalization of the C-N bond of amines is a straightforward strategy for the construction of complex scaffolds or for the late-stage functionalization of pharmaceuticals. Herein, we describe a photoredox-catalyzed strategy for the deaminative alkylation of primary amine-derived isonitriles that provides unnatural amino acid derivatives under mild conditions. The use of silacarboxylic acids as silyl radical precursors enables the generation of carbon-centered radicals that allow the construction of Csp-Csp bonds via a Giese-type addition, avoiding the undesired hydrodeamination product.

G9a an Epigenetic Therapeutic Strategy for Neurodegenerative Conditions: From Target Discovery to Clinical Trials.

This review provides a comprehensive overview of the role of G9a/EHMT2, focusing on its structure and exploring the impact of its pharmacological and/or gene inhibition in various neurological diseases. In addition, we delve into the advancements in the design and synthesis of G9a/EHMT2 inhibitors, which hold promise not only as a treatment for neurodegeneration diseases but also for other conditions, such as cancer and malaria. Besides, we presented the discovery of dual therapeutic approaches based on G9a inhibition and different epigenetic enzymes like histone deacetylases, DNA methyltransferases, and other lysine methyltransferases.

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.

Printed Models for Better Prediction of Surgery in Patients with Double Outlet Right Ventricle.

The complex and variable anatomy of complex double outlet right ventricle makes it imperative to understand the spatial anatomic structures to determine whether it is feasible to repair the anomaly in a biventricular or univentricular fashion. Biventricular repair should be aimed for but is not always feasible. Choosing the correct surgical technique is of great importance in surgical planning of biventricular repair.

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.

Details on the transport of European eel larvae through the Strait of Gibraltar into the Mediterranean Sea.

Numbers of European glass eels (Anguilla anguilla) monitored along the Atlantic and Mediterranean coasts of Europe currently serve as the main stock indicator in assessment of this critically endangered species. Spawning, however, takes place exclusively in the Sargasso Sea, several thousand kilometers away. The beginning of its complex lifecycle is characterized by a distant and lengthy larval drift, before the young-of-the-year reach the monitoring stations at the European coasts.

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.