Targeting of the G9a, DNMT1 and UHRF1 epigenetic complex as an effective strategy against pancreatic ductal adenocarcinoma.

Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with limited treatment options and a poor prognosis. The critical role of epigenetic alterations such as changes in DNA methylation, histones modifications, and chromatin remodeling, in pancreatic tumors progression is becoming increasingly recognized. Moreover, in PDAC these aberrant epigenetic mechanisms can also limit therapy efficacy.

TP53 germline testing and hereditary cancer: how somatic events and clinical criteria affect variant detection rate.

Background: Germline heterozygous pathogenic variants (PVs) in TP53 cause Li-Fraumeni syndrome (LFS), a condition associated with increased risk of multiple tumor types. As the associated cancer risks were refined over time, clinical criteria also evolved to optimize diagnostic yield. The implementation of multi-gene panel germline testing in different clinical settings has led to the identification of TP53 PV carriers outside the classic LFS-associated cancer phenotypes, leading to a broader cancer phenotypic redefinition and to the renaming of the condition as "heritable TP53-related cancer syndrome" (hTP53rc).

Metabolic and inflammatory status in prepuberty and early adulthood for individuals with a history of extrauterine growth restriction: a cohort study.

Background: Perinatal growth and nutrition have been shown to be determinants in the programming of different tissues, such as adipose tissue, predisposing individuals to metabolic alterations later in life. Previous studies have documented an increased risk of metabolic disturbances and low-grade inflammation in prepubertal children with a history of extrauterine growth restriction (EUGR). The aim of this study was to evaluate possible alterations resulting from impaired growth during early childhood and their impact on young adult health.

Quantitative proteomic analysis unveils a critical role of VARS1 in hepatocellular carcinoma aggressiveness through the modulation of MAGI1 expression.

Background: Hepatocellular carcinoma (HCC) genetic/transcriptomic signatures have been widely described. However, its proteomic characterization is incomplete. We performed non-targeted quantitative proteomics of HCC samples and explored its clinical, functional, and molecular consequences.

Multiplex genome editing eliminates lactate production without impacting growth rate in mammalian cells.

The Warburg effect, which describes the fermentation of glucose to lactate even in the presence of oxygen, is ubiquitous in proliferative mammalian cells, including cancer cells, but poses challenges for biopharmaceutical production as lactate accumulation inhibits cell growth and protein production. Previous efforts to eliminate lactate production in cells for bioprocessing have failed as lactate dehydrogenase is essential for cell growth. Here, we effectively eliminate lactate production in Chinese hamster ovary and in the human embryonic kidney cell line HEK293 by simultaneous knockout of lactate dehydrogenases and pyruvate dehydrogenase kinases, thereby removing a negative feedback loop that typically inhibits pyruvate conversion to acetyl-CoA.

Impact of irrelevant speech and non-speech sounds on serial recall of verbal and spatial items in children and adults.

Short-term memory for sequences of verbal items such as written words is reliably impaired by task-irrelevant background sounds, a phenomenon known as the "Irrelevant Sound Effect" (ISE). Different theoretical accounts have been proposed to explain the mechanisms underlying the ISE. Some of these assume specific interference between obligatory sound processing and phonological or serial order representations generated during task performance, whereas other posit that background sounds involuntarily divert attention away from the focal task.

The modulating effect of circulating carbohydrate antigen 125 on ST2 and long-term recurrent morbidity burden.

Soluble ST2 (sST2) is released in response to vascular congestion, inflammation, and pro-fibrotic stimuli. In heart failure (HF), elevated levels of sST2 are associated with a higher risk of adverse clinical outcomes. Emerging evidence suggests that carbohydrate antigen 125 (CA125) may act as a ligand that modulates the inflammatory response.

Analysis of sex-specific disease patterns associated with human lifespan.

Disability and multimorbidity increase with aging and constitute a challenge for the health system. However, different individuals display different aging trajectories, and understanding the underlying relationships between lifespan and disease is fundamental for identifying the different patterns in human lifespan. A previous study explored associations between lifespan and age of onset of diseases of different organ systems, prevalence of escapers, and percentage of life free of disease (health span), comparing them between genders in Catalonian population.

Transarterial Radioembolisation with Y90 Resin Microspheres and the Effect of Reimbursement Criteria in France: Final Results of the CIRT-FR Prospective Observational Study.

Purpose: This analysis of the CIRSE Registry for SIR-Spheres Therapy in France, CIRT-FR, reports on real-world outcomes of transarterial radioembolisation (TARE) with Y90 resin microspheres for hepatocellular carcinoma (HCC) and colorectal cancer liver metastases (CRLM) patients in France, focusing on safety, effectiveness and health-related quality of life (HRQoL). Results on patients treated based on national reimbursement criteria are discussed here.

Methods: Prospective, multicentre, observational study of HCC and CRLM patients treated between August 2017 and July 2020 with TARE Y90 resin microspheres.

Comprehensive dataset from high resolution UAV land cover mapping of diverse natural environments in Serbia.

This study highlights the vital role of high-resolution (HR), open-source land cover maps for food security, land use planning, and environmental protection. The scarcity of freely available HR datasets underscores the importance of multi-spectral HR aerial images. We used unmanned aerial vehicle (UAV) to capture images for a centimeter-level orthomosaics, facilitating advanced remote sensing and spatial analysis.

Soil erosion susceptibility maps and raster dataset for the hydrological basins of North Africa.

Soil erosion in North Africa modulates agricultural and urban developments as well as the impacts of flash floods. Existing investigations and associated datasets are mainly performed in localized urban areas, often representing a limited part of a watershed. The above compromises the implementation of mitigation measures for this vast area under accentuating extremes and continuous hydroclimatic fluctuations.

Understanding the spread of agriculture in the Western Mediterranean (6th-3rd millennia BC) with Machine Learning tools.

The first Neolithic farmers arrived in the Western Mediterranean area from the East. They established settlements in coastal areas and over time migrated to new environments, adapting to changing ecological and climatic conditions. While farming practices and settlements in the Western Mediterranean differ greatly from those known in the Eastern Mediterranean and central Europe, the extent to which these differences are connected to the local environment and climate is unclear.

Multi-omics architecture of childhood obesity and metabolic dysfunction uncovers biological pathways and prenatal determinants.

Childhood obesity poses a significant public health challenge, yet the molecular intricacies underlying its pathobiology remain elusive. Leveraging extensive multi-omics profiling (methylome, miRNome, transcriptome, proteins and metabolites) and a rich phenotypic characterization across two parts of Europe within the population-based Human Early Life Exposome project, we unravel the molecular landscape of childhood obesity and associated metabolic dysfunction. Our integrative analysis uncovers three clusters of children defined by specific multi-omics profiles, one of which characterized not only by higher adiposity but also by a high degree of metabolic complications.

Effectiveness of positive allosteric modulators of metabotropic glutamate receptor 2/3 (mGluR2/3) in animal models of schizophrenia.

Schizophrenia (SZ) is a deleterious brain disorder characterised by its heterogeneity and complex symptomatology consisting of positive, negative and cognitive deficits. Current antipsychotic drugs ameliorate the positive symptomatology, but are inefficient in treating the negative symptomatology and cognitive deficits. The neurodevelopmental glutamate hypothesis of SZ has opened new avenues in the development of drugs targeting the glutamatergic system.

A diagnostic host-specific transcriptome response for Mycoplasma pneumoniae pneumonia to guide pediatric patient treatment.

Mycoplasma pneumoniae causes atypical pneumonia in children and young adults. Its lack of a cell wall makes it resistant to beta-lactams, which are the first-line treatment for typical pneumonia. Current diagnostic tests are time-consuming and have low specificity, leading clinicians to administer empirical antibiotics.

Achieving Language Justice in Pediatric Hematology-Oncology: A Multinational Perspective for Language-Concordant Equitable Patient- and Family-Centered Care and Research Inclusion.

Language-discordant healthcare encounters-when the patient/caregiver and clinician are not able to communicate directly in the patient's/caregiver's preferred language-are associated with worse quality of care, increased adverse events, and research exclusion. Here, we describe the current state of language justice in clinical practice and research in the United States, Canada, and Spain, discuss the role of social determinants of health and language, in patient safety and health outcomes and review an example of culturally and linguistically concordant interventions to increase research participation. We close with practical and global strategies to increase multilingual research participation and to provide equitable patient- and family-centered care in pediatric hematology-oncology.

Gut microbial alteration in chronic spontaneous urticaria unresponsive to second generation antihistamines and its correlation with disease characteristics- a cross-sectional case-control study.

Background: Gut microbial involvement has been speculated in chronic spontaneous urticaria (CSU). The aim of the study was to compare the gut microbiome composition and diversity in CSU patients uncontrolled with second-generation antihistamines (sgAHs) and healthy individuals, as well as to explore any association between gut microbiome and disease characteristics.

Methods: A cross-sectional case-control study including 20 CSU patients unresponsive to standard doses of sgAHs, and 15 age-and-sex matched healthy controls was conducted.

Global, regional and national burden of depressive disorders and attributable risk factors, from 1990 to 2021: results from the 2021 Global Burden of Disease study.

Background: Depressive disorders pose a significant global public health challenge, yet evidence on their burden remains insufficient.

Aims: To report the global, regional and national burden of depressive disorders and their attributable risk factors from 1990 to 2021.

Methods: Data from the Global Burden of Disease 2021 were analyzed for 204 countries and territories from 1990 to 2021.

Transcatheter edge-to-edge repair in severe mitral regurgitation following acute myocardial infarction - aetiology-based analysis.

Aims: To evaluate the association between transcatheter edge-to-edge repair (TEER) and outcomes in patients with significant mitral regurgitation (MR) following acute myocardial infarction (MI), focusing on the aetiology of acute post-MI MR in high-risk surgical patients.

Methods And Results: The International Registry of MitraClip in Acute Mitral Regurgitation following Acute Myocardial Infarction (IREMMI) includes 187 patients with severe MR post-MI managed with TEER. Of these, 176 were included in the analysis, 23 (13%) patients had acute papillary muscle rupture (PMR) and 153 (87%) acute secondary MR.

Risk Factors and Outcomes Associated With Polymicrobial Infection in Community-Acquired Pneumonia.

Background: Polymicrobial pneumonia is a concern for clinicians due to its association with increased disease severity. Determining the prevalence of polymicrobial pneumonia and identifying patients who have an increased risk of this aetiology is important for the management of CAP patients. Here we describe the clinical characteristics and outcomes of adult hospitalized patients with CAP, and identify the risk factors related to polymicrobial pneumonia and specifically to 30-day mortality.

Belatacept in Kidney Transplantation: A Single-center Experience.

Belatacept was introduced as an immunosuppressant for kidney transplantation in 2010, but its use in Spain remains limited. Since its commercialization, 15 kidney transplant recipients have received immunosuppressive treatment with belatacept at the Cruces University Hospital. This observational and retrospective study analyzes the reasons for switching to belatacept, its impact on kidney function, and the drug's safety profile.

Br(e)aking the tomato fruit size-sweetness trade-off.

The study by Zhang et al. demonstrated that two kinases (SlCDPK27 and SlCDPK26) regulate the sugar content in tomato fruits with little impact on morphology. They act as sugar breaks by phosphorylating a sucrose synthase, promoting its degradation and unveiling the mechanism by which sugar content can be increased without yield penalty.