Exome sequencing reveals a rare damaging variant in GRIN2C in familial late-onset Alzheimer's disease.

Background: Alzheimer's disease (AD) is a progressive neurodegenerative disorder with both genetic and environmental factors contributing to its pathogenesis. While early-onset AD has well-established genetic determinants, the genetic basis for late-onset AD remains less clear. This study investigates a large Italian family with late-onset autosomal dominant AD, identifying a novel rare missense variant in GRIN2C gene associated with the disease, and evaluates the functional impact of this variant.

F-Prostate-Specific Membrane Antigen PET/CT imaging for potentially resectable pancreatic cancer (PANSCAN-2): a phase I/II study.

Background: Current diagnostic imaging modalities have limited ability to differentiate between malignant and benign pancreaticobiliary disease, and lack accuracy in detecting lymph node metastases. F-Prostate-Specific Membrane Antigen (PSMA) PET/CT is an imaging modality used for staging of prostate cancer, but has incidentally also identified PSMA-avid pancreatic lesions, histologically characterized as pancreatic ductal adenocarcinoma (PDAC). This phase I/II study aimed to assess the feasibility of F-PSMA PET/CT to detect PDAC.

Lactate accumulation promotes immunosuppression and fibrotic transformation of bone marrow microenvironment in myelofibrosis.

Background: Clonal myeloproliferation and fibrotic transformation of the bone marrow (BM) are the pathogenetic events most commonly occurring in myelofibrosis (MF). There is great evidence indicating that tumor microenvironment is characterized by high lactate levels, acting not only as an energetic source, but also as a signaling molecule.

Methods: To test the involvement of lactate in MF milieu transformation, we measured its levels in MF patients' sera, eventually finding a massive accumulation of this metabolite, which we showed to promote the expansion of immunosuppressive subsets.

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.

Metabolically activated and highly polyfunctional intratumoral VISTA regulatory B cells are associated with tumor recurrence in early-stage NSCLC.

B cells have emerged as central players in the tumor microenvironment (TME) of non-small cell lung cancer (NSCLC). However, although there is clear evidence for their involvement in cancer immunity, scanty data exist on the characterization of B cell phenotypes, bioenergetic profiles and possible interactions with T cells in the context of NSCLC. In this study, using polychromatic flow cytometry, mass cytometry, and spatial transcriptomics we explored the intricate landscape of B cell phenotypes, bioenergetics, and their interaction with T cells in NSCLC.

Governance and resilience as entry points for transforming food systems in the countdown to 2030.

Due to complex interactions, changes in any one area of food systems are likely to impact-and possibly depend on-changes in other areas. Here we present the first annual monitoring update of the indicator framework proposed by the Food Systems Countdown Initiative, with new qualitative analysis elucidating interactions across indicators. Since 2000, we find that 20 of 42 indicators with time series have been trending in a desirable direction, indicating modest positive change.

Exploring the plant-growth promoting bacterium Herbaspirillum seropedicae as catalyst of microbiome remodeling and metabolic changes in wheat plants.

Inoculation with the PGPB Herbaspirillum seropedicae shapes both the structure and putative functions of the wheat microbiome and causes changes in the levels of various plant metabolites described to be involved in plant growth and health. Plant growth promoting bacteria (PGPB) can establish metabolic imprints in their hosts, contributing to the improvement of plant health in different ways. However, while PGPB imprints on plant metabolism have been extensively characterized, much less is known regarding those affecting plant indigenous microbiomes, and hence it remains unknown whether both processes occur simultaneously.

Neurophysiological correlates of ketamine-induced dissociative state in bipolar disorder: insights from real-world clinical settings.

Ketamine, a dissociative compound, shows promise in treating mood disorders, including treatment-resistant depression (TRD) and bipolar disorder (BD). Despite its therapeutic potential, the neurophysiological mechanisms underlying ketamine's effects are not fully understood. This study explored acute neurophysiological changes induced by subanesthetic doses of ketamine in BD patients with depression using electroencephalography (EEG) biomarkers.

Molecular dynamics-guided reaction discovery reveals endoperoxide-to-alkoxy radical isomerization as key branching point in α-pinene ozonolysis.

Secondary organic aerosols (SOAs) significantly impact Earth's climate and human health. Although the oxidation of volatile organic compounds (VOCs) has been recognized as the major contributor to the atmospheric SOA budget, the mechanisms by which this process produces SOA-forming highly oxygenated organic molecules (HOMs) remain unclear. A major challenge is navigating the complex chemical landscape of these transformations, which traditional hypothesis-driven methods fail to thoroughly investigate.

Intervalence plasmons in boron-doped diamond.

Doped semiconductors can exhibit metallic-like properties ranging from superconductivity to tunable localized surface plasmon resonances. Diamond is a wide-bandgap semiconductor that is rendered electronically active by incorporating a hole dopant, boron. While the effects of boron doping on the electronic band structure of diamond are well-studied, any link between charge carriers and plasmons has never been shown.

Intelligent in-cell electrophysiology: Reconstructing intracellular action potentials using a physics-informed deep learning model trained on nanoelectrode array recordings.

Intracellular electrophysiology is essential in neuroscience, cardiology, and pharmacology for studying cells' electrical properties. Traditional methods like patch-clamp are precise but low-throughput and invasive. Nanoelectrode Arrays (NEAs) offer a promising alternative by enabling simultaneous intracellular and extracellular action potential (iAP and eAP) recordings with high throughput.

Successful Pregnancies During Crizotinib Therapy for Anaplastic Lymphoma Kinase Positive Lymphoma.

Anaplastic lymphoma kinase positive (ALK+) anaplastic large cell lymphoma (ALCL) typically affects young individuals and, despite high responsiveness to cytotoxic drugs, relapses occur in over 50% of patients. Crizotinib has improved outcomes, but its management in patients desiring parenthood remains an issue. This study presents the first description of four successful pregnancies during crizotinib treatment for ALK+ALCL: a female patient achieving two pregnancies through assisted reproductive technologies (ART), temporarily discontinuing crizotinib and maintaining a complete remission (CR), and a male patient conceiving naturally while on continuous therapy.

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.

Safety and efficacy of a light antithrombotic regimen after left atrial appendage occlusion: Insights from the LOGIC (left atrial appendage occlusion in patients with gastrointestinal or IntraCranial bleeding) international multicenter registry.

Background: Antithrombotic therapy (AT) after left atrial appendage occlusion (LAAO) in patients with non-valvular atrial fibrillation (NVAF) has the purpose of preventing device related thrombosis (DRT), avoiding embolic events; nevertheless, the correct antithrombotic regimen after LAAO is still under debate.

Aims: Aim of this substudy of the observational LOGIC registry was to describe the efficacy and safety of a light antithrombotic regimen, comprising single antiplatelet therapy or none, compared to a standard antithrombotic regimen, after a successful LAAO.

Methods: Patients with NVAF that underwent LAAO were previously included in the LOGIC registry.

Inclusive basketball training for players with intellectual disability.

Objectives: To evaluate sport-specific basketball skills before and after 8 months of integrated and non-integrated basketball practice of participants with intellectual disability; in relation to the competitive basketball level and the degree of intellectual disability.

Design: Pre-test/training/post-test design.

Methods: Forty-one adult male players with intellectual disability were randomly divided into 21 athletes playing in the Integrated Basketball group together with 10 athletes without intellectual disability, and 20 athletes playing in the Non-integrated Basketball group.

TP53 gene status can promote sensitivity and resistance to chemotherapeutic drugs and small molecule signal transduction inhibitors.

TP53 is normally a tumor suppressor. However, it is mutated in at least 50% of human cancers. Usually, we assume that mutation of the TP53 is associated with loss of sensitivity to various drugs as in most cases wild type (WT) TP53 activity is lost.

Multiple Myeloma in Italy: An Epidemiological Model by Treatment Line and Refractoriness Status.

Background: Multiple myeloma (MM) clinical management is challenging owing to its relapse and refractoriness to treatment. Understanding the treatment patterns and refractory dynamics is crucial for optimizing patient care. This study aimed to estimate the evolution of MM according to the treatment line and refractoriness status in Italy.

N-Acetylcysteine and Liver Transplant. Advantages of its Administration in Multi-Organ Donors Especially During World-Economical-Crisis. Long-Term Sub-Group Analysis in a Randomized Study.

Background: Liver transplantation (LT) is the main indication for the treatment of end-stage liver disease but have to face organ shortages. Using marginal donors is an option to increase the donor pool. Previous studies showed that the graft procured using N-acetylcysteine (NAC) provides a longer survival compared to perfusion with standard solutions, especially in marginal liver donors.

Italian Vocal Fatigue Index: Cross-Cultural Adaptation and Validation.

Background: Vocal fatigue involves self-perceived vocal symptoms and reduced physiological capacity. This study aimed to adapt and validate the Vocal Fatigue Index (VFI), a tool originally designed to distinguish between patients with vocal fatigue and vocally healthy individuals, for Italian speakers.

Method: A four-step translation and validation process was employed.

Adiponectin removal by the human kidney: A preliminary study.

Background And Aims: The adipocyte-derived adiponectin (APN) has potent insulin-sensitizing and anti-inflammatory properties. The adipose tissue is known to be the main source for APN in the circulation, but sites and mechanisms which remove APN from blood are still unknown in humans.

Methods And Results: We reviewed APN data obtained in previous studies in which the inter-organ exchange of amino acids and cytokines was measured in our laboratory.

Preventing dementia in Italy: Estimations of modifiable risk factors and public health implications.

Background: Dementia is a major global public health challenge, with over 50 million cases in 2020, projected to reach 152 million by 2050. Effective prevention strategies are needed to reduce the impact of modifiable risk factors associated with dementia, particularly in countries with ageing populations like Italy. The Population Attributable Fraction (PAF) and Potential Impact Fraction (PIF) are key metrics for understanding and reducing dementia cases through targeted interventions.

The ADESTE trial: A phase 2 study of enibarcimab, a monoclonal antibody targeting adrenomedullin, in acute heart failure.

Aims: This study aimed to conduct a phase 2 proof-of-concept and safety study to evaluate the effect of ENIBARCIMAB (EN), a non-neutralizing humanized monoclonal antibody targeting the N-terminus of adrenomedullin (ADM), administered immediately after stabilization with standard of care (SoC) treatment, in patients hospitalized for acute heart failure (AHF).

Methods And Results: This prospective, open-label, controlled, interventional, multicenter, dose-escalation study was conducted at two cardiology sites in Indonesia. Patients were divided into two interventional groups sequentially receiving 0.