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).

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.

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.

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.

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.

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.

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.

Endothelial Damage in JAK2V617F Myeloproliferative Neoplasms with Splanchnic Vein Thrombosis.

Background:  V617F-mutated myeloproliferative neoplasms (MPN) exhibit abnormal proliferation of bone marrow progenitors and increased risk of thrombosis, specifically in splanchnic veins (SVT). The contribution of the endothelium to the development of the prothrombotic phenotype was explored.

Material And Methods:  Plasma and serum samples from V617F MPN patients with (n=26) or without (n=7) thrombotic debut and different treatments, were obtained (n=33).

Cardiovascular Risk Prediction Models in People Living with Human Immunodeficiency Virus under Antiretroviral Therapy in Northern Mexico.

Background: The effective use of combination antiretroviral therapy (ART) has significantly improved the life expectancy of people living with the human immunodeficiency virus (HIV). However, complications have shifted from opportunistic infections to issues such as drug toxicity and resistance, as well as an increase in premature cardiovascular diseases (CVD). These conditions are attributed to chronic immune activation and persistent inflammation caused by HIV, along with lipid abnormalities and insulin resistance.

Prenatal Exercise Decreases Urinary Incontinence in Late Pregnancy and Three Months Postpartum: A Randomized Controlled Trial.

Purpose: This study aimed to evaluate the impact of a supervised exercise program, including Pelvic Floor Muscle Training (PFMT), throughout pregnancy on Urinary Incontinence (UI).

Methods: A randomized clinical trial (NCT04563065) was conducted. Initially, 600 pregnant women were screened for eligibility, with data from 356 participants eventually analyzed.

Humoral and cellular immune responses after 6 months of a heterologous SARS-CoV-2 booster with the protein-based PHH-1V vaccine in a phase IIb trial.

The HIPRA-HH-2 was a multicentre, randomized, active-controlled, double-blind, non-inferiority phase IIb clinical trial comparing the immunogenicity and safety of the PHH-1V adjuvanted recombinant vaccine as a heterologous booster against homologous booster with BNT162b2. Interim results demonstrated strong humoral and cellular immune response against the SARS-CoV-2 Wuhan-Hu-1 strain and the Beta, Delta, and Omicron BA.1 variants up to day 98 post-dosing.

Mapping alterations in the local synchrony of the cerebral cortex in Prader Willi syndrome.

Individuals with Prader Willi syndrome (PWS) often exhibit behavioral difficulties characterized by deficient impulse regulation and obsessive-compulsive features resembling those observed in obsessive-compulsive disorder. The genetic configuration of PWS aligns with molecular and neurophysiological findings suggesting dysfunction in the inhibitory gamma-aminobutyric acid (GABA) interneuron system may contribute to its clinical manifestation. In the cerebral cortex, this dysfunction is expressed as desynchronization of local neural activity.

Accelerating the Future of Oncology Drug Development: The Role of Consortia in the Delivery of Precision Oncology Early Phase Clinical Trials.

Purpose: Over the past 15 years, the landscape of early phase clinical trials (EPCTs) has undergone a remarkable expansion in both quantity and intricacy. The proliferation of sites, trials, sponsors, and contract research organizations has surged exponentially, marking a significant shift in research conduct. However, EPCT operations suffer from numerous inefficiencies, such as cumbersome start-up processes, which are particularly critical when drug safety and the recommended phase II dose need to be established in a timely manner.

Identifying depression subtypes and investigating their consistency and transitions in a 1-year cohort analysis.

Major depressive disorder (MDD) is defined by an array of symptoms that make it challenging to understand the condition at a population level. Subtyping offers a way to unpick this phenotypic diversity for improved disorder characterisation. We aimed to identify depression subtypes longitudinally using the Inventory of Depressive Symptomatology: Self-Report (IDS-SR).

Effect of the PakCat program on nutrition status, dietary pattern and nutrition knowledge and skills of Pakistani women living in Catalonia evaluated by a mixed-method randomized control trial (RCT).

Background: Pakistani women are among the most affected groups by obesity and heart failure in Catalonia. Due to cultural and linguistic barriers, their participation in standard health promotion programs is limited. To address this issue, we implemented a culturally and linguistically appropriate food education program called the PakCat Program.

Interpretable machine learning models for COPD ease of breathing estimation.

Chronic obstructive pulmonary disease (COPD) is a leading cause of death worldwide and greatly reduces the quality of life. Utilizing remote monitoring has been shown to improve quality of life and reduce exacerbations, but remains an ongoing area of research. We introduce a novel method for estimating changes in ease of breathing for COPD patients, using obstructed breathing data collected via wearables.

Contributions of short- and long-range white matter tracts in dynamic compensation with aging.

Optimal brain function is shaped by a combination of global information integration, facilitated by long-range connections, and local processing, which relies on short-range connections and underlying biological factors. With aging, anatomical connectivity undergoes significant deterioration, which affects the brain's overall function. Despite the structural loss, previous research has shown that normative patterns of functions remain intact across the lifespan, defined as the compensatory mechanism of the aging brain.

Ovarian Carcinomas: Clinicopathologic and Molecular Features With Comments on 2014 FIGO Staging.

According to histopathology and molecular genetics, there are 5 major subtypes of ovarian carcinomas: high-grade serous (70%), endometrioid (10%), clear cell (10%), mucinous (3% to 4%), and low-grade serous (<5%) carcinomas. These tumors, which constitute over 95% of cases, represent distinct diseases with different prognoses and therapy. This review outlines contemporary advances in molecular pathology, which have expanded our knowledge of the biology of epithelial ovarian cancer and are also important to patient management.