Loss of the Endothelial Glycocalyx Component EMCN Leads to Glomerular Impairment.

Background: EMCN (endomucin), an endothelial-specific glycocalyx component, was found to be highly expressed by the endothelium of the renal glomerulus. We reported an anti-inflammatory role of EMCN and its involvement in the regulation of VEGF (vascular endothelial growth factor) activity through modulating VEGFR2 (VEGF receptor 2) endocytosis. The goal of this study is to investigate the phenotypic and functional effects of EMCN deficiency using the first global EMCN knockout mouse model.

A 25-Year Retrospective of Health IT Infrastructure Building: The Example of the Catalonia Region.

Over the past decades, health care systems have significantly evolved due to aging populations, chronic diseases, and higher-quality care expectations. Concurrently with the added health care needs, information and communications technology advancements have transformed health care delivery. Technologies such as telemedicine, electronic health records, and mobile health apps promise enhanced accessibility, efficiency, and patient outcomes, leading to more personalized, data-driven care.

A phase 2, multicenter, clinical trial of CPX-351 in older patients with secondary or high-risk acute myeloid leukemia: PETHEMA-LAMVYX.

Background: LAMVYX was a multicenter, single-arm, phase 2 trial designed to validate the safety and efficacy of CPX-351 in patients aged 60-75 years with newly diagnosed, secondary acute myeloid leukemia and to generate evidence on key issues not addressed in the preceding regulatory pivotal trial.

Methods: The primary end point of the study was the complete remission (CR)/CR with incomplete hematologic recovery (CRi) rate after induction. Eligible patients were recommended to undergo allogeneic hematopoietic stem cell transplantation after the first consolidation cycle.

Identification of pharmacological inducers of a reversible hypometabolic state for whole organ preservation.

Drugs that induce reversible slowing of metabolic and physiological processes would have great value for organ preservation, especially for organs with high susceptibility to hypoxia-reperfusion injury, such as the heart. Using whole-organism screening of metabolism, mobility, and development in , we identified an existing drug, SNC80, that rapidly and reversibly slows biochemical and metabolic activities while preserving cell and tissue viability. Although SNC80 was developed as a delta opioid receptor activator, we discovered that its ability to slow metabolism is independent of its opioid modulating activity as a novel SNC80 analog (WB3) with almost 1000 times less delta opioid receptor binding activity is equally active.

Unique genetic and risk-factor profiles in clusters of major depressive disorder-related multimorbidity trajectories.

The heterogeneity and complexity of symptom presentation, comorbidities and genetic factors pose challenges to the identification of biological mechanisms underlying complex diseases. Current approaches used to identify biological subtypes of major depressive disorder (MDD) mainly focus on clinical characteristics that cannot be linked to specific biological models. Here, we examined multimorbidities to identify MDD subtypes with distinct genetic and non-genetic factors.

Deletion of the endothelial glycocalyx component endomucin leads to impaired glomerular structure and function.

Background: Endomucin (EMCN), an endothelial-specific glycocalyx component, was found to be highly expressed by the endothelium of the renal glomerulus. We reported an anti-inflammatory role of EMCN and its involvement in the regulation of vascular endothelial growth factor (VEGF) activity through modulating VEGF receptor 2 (VEGFR2) endocytosis. The goal of this study is to investigate the phenotypic and functional effects of EMCN deficiency using the first global EMCN knockout mouse model.

Toward Sustainable Adoption of Integrated Care for Prevention of Unplanned Hospitalizations: A Qualitative Analysis.

Introduction: Complex chronic patients are prone to unplanned hospitalizations leading to a high burden on healthcare systems. To date, interventions to prevent unplanned admissions show inconclusive results. We report a qualitative analysis performed into the EU initiative JADECARE (2020-2023) to design a digitally enabled integrated care program aiming at preventing unplanned hospitalizations.

Retrospective analysis of hospitalization costs using two payment systems: the diagnosis related groups (DRG) and the Queralt system, a newly developed case-mix tool for hospitalized patients.

Background: Hospital services are typically reimbursed using case-mix tools that group patients according to diagnoses and procedures. We recently developed a case-mix tool (i.e.

Multicentric Assessment of a Multimorbidity-Adjusted Disability Score to Stratify Depression-Related Risks Using Temporal Disease Maps: Instrument Validation Study.

Background: Comprehensive management of multimorbidity can significantly benefit from advanced health risk assessment tools that facilitate value-based interventions, allowing for the assessment and prediction of disease progression. Our study proposes a novel methodology, the Multimorbidity-Adjusted Disability Score (MADS), which integrates disease trajectory methodologies with advanced techniques for assessing interdependencies among concurrent diseases. This approach is designed to better assess the clinical burden of clusters of interrelated diseases and enhance our ability to anticipate disease progression, thereby potentially informing targeted preventive care interventions.

Toward Adoption of Health Risk Assessment in Population-Based and Clinical Scenarios: Lessons From JADECARE.

Introduction: Health risk assessment (HRA) strategies are cornerstone for health systems transformation toward value-based patient-centred care. However, steps for HRA adoption are undefined. This article analyses the process of transference of the Adjusted Morbidity Groups (AMG) algorithm from the Catalan Good Practice to the Marche region (IT) and to Viljandi Hospital (EE), within the JADECARE initiative (2020-2023).

Iadademstat in combination with azacitidine in patients with newly diagnosed acute myeloid leukaemia (ALICE): an open-label, phase 2a dose-finding study.

Background: Iadademstat is a potent, selective, oral inhibitor of both the enzymatic and scaffolding activities of the transcriptional repressor lysine-specific demethylase 1 (LSD1; also known as KDM1A) that showed promising early activity and safety in a phase 1 trial and strong preclinical synergy with azacitidine in acute myeloid leukaemia cell lines. Therefore, we aimed to investigate the combination of iadademstat and azacitidine for the treatment of adult patients with newly diagnosed acute myeloid leukaemia.

Methods: The open-label, phase 2a, dose-finding ALICE study was conducted at six hospitals in Spain and enrolled patients aged 18 years or older with newly diagnosed acute myeloid leukaemia not eligible for intensive chemotherapy and an ECOG performance status of 0-2.

Impact of gene-by-trauma interaction in MDD-related multimorbidity clusters.

Background: Major depressive disorder (MDD) is considerably heterogeneous in terms of comorbidities, which may hamper the disentanglement of its biological mechanism. In a previous study, we classified the lifetime trajectories of MDD-related multimorbidities into seven distinct clusters, each characterized by unique genetic and environmental risk-factor profiles. The current objective was to investigate genome-wide gene-by-environment (G × E) interactions with childhood trauma burden, within the context of these clusters.

Novel portable hypothermic machine perfusion preservation device enhances cardiac viability of donated human hearts.

Introduction: Heart transplant remains the gold standard treatment for patients with advanced heart failure. However, the list of patients waiting for a heart transplant continues to increase. We have developed a portable hypothermic oxygenated machine perfusion device, the VP.

The value of admission avoidance: cost-consequence analysis of one-year activity in a consolidated service.

Background: Many advantages of hospital at home (HaH), as a modality of acute care, have been highlighted, but controversies exist regarding the cost-benefit trade-offs. The objective is to assess health outcomes and analytical costs of hospital avoidance (HaH-HA) in a consolidated service with over ten years of delivery of HaH in Barcelona (Spain).

Methods: A retrospective cost-consequence analysis of all first episodes of HaH-HA, directly admitted from the emergency room (ER) in 2017-2018, was carried out with a health system perspective.

Endomucin selectively regulates vascular endothelial growth factor receptor-2 endocytosis through its interaction with AP2.

The endothelial glycocalyx, located at the luminal surface of the endothelium, plays an important role in the regulation of leukocyte adhesion, vascular permeability, and vascular homeostasis. Endomucin (EMCN), a component of the endothelial glycocalyx, is a mucin-like transmembrane glycoprotein selectively expressed by venous and capillary endothelium. We have previously shown that knockdown of EMCN impairs retinal vascular development in vivo and vascular endothelial growth factor 165 isoform (VEGF165)-induced cell migration, proliferation, and tube formation by human retinal endothelial cells in vitro and that EMCN is essential for VEGF165-stimulated clathrin-mediated endocytosis and signaling of VEGF receptor 2 (VEGFR2).

Transcriptomic Responses to Koi Herpesvirus in Isolated Blood Leukocytes from Infected Common Carp.

Koi herpesvirus (KHV, CyHV-3) causes severe economic losses in carp farms. Its eradication is challenging due to the establishment of latency in blood leukocytes and other tissues. To understand the molecular mechanisms leading to KHV infection in leukocytes, common carp were bath-exposed to KHV at 17 °C.

Loop-Mediated Isothermal Amplification for the Fast Detection of and in Flat Oysters.

The haplosporidian parasites (BO) and (BE) are serious oyster pathogens. Two independent laboratories evaluated fluorescence real-time loop-mediated isothermal amplification (LAMP) assays for rapidly detecting these parasites. Specific LAMP assays were designed on the BO and BE genes.

Five years of Hospital at Home adoption in Catalonia: impact, challenges, and proposals for quality assurance.

Background: Hospital at home (HaH) was increasingly implemented in Catalonia (7.7 M citizens, Spain) achieving regional adoption within the 2011-2015 Health Plan. This study aimed to assess population-wide HaH outcomes over five years (2015-2019) in a consolidated regional program and provide context-independent recommendations for continuous quality improvement of the service.

A sound mind in a sound body: a novel concept unravelling heterogeneity of depression.

Depression is a highly prevalent and debilitating condition, yet we still lack both in-depth knowledge concerning its etiopathology and sufficiently efficacious treatment options. With approximately one third of patients resistant to currently available antidepressants there is a pressing need for a better understanding of depression, identifying subgroups within the highly heterogeneous illness category and to understand the divergent underlying biology of such subtypes, to help develop and personalise treatments. The TRAJECTOME project aims to address such challenges by (1) identifying depression-related multimorbidity subgroups and shared molecular pathways based on temporal disease profiles from healthcare systems and biobank data using machine learning approaches, and by (2) characterising these subgroups from multiple aspects including genetic variants, metabolic processes, lifestyle and environmental factors.

SbSeI and SbSeBr micro-columnar solar cells by a novel high pressure-based synthesis process.

Van der Waals chalcogenides and chalcohalides have the potential to become the next thin film PV breakthrough, owing to the earth-abundancy and non-toxicity of their components, and their stability, high absorption coefficient and quasi-1D structure, which leads to enhanced electrical anisotropic properties when the material is oriented in a specific crystalline direction. However, quasi-1D semiconductors beyond Sb(S,Se), such as SbSeX chalcohalides, have been scarcely investigated for energy generation applications, and rarely synthesised by physical vapor deposition methodologies, despite holding the promise of widening the bandgap range (opening the door to tandem or semi-transparent devices), and showing enticing new properties such as ferroelectric behaviour and defect-tolerant nature. In this work, SbSeI and SbSeBr micro-columnar solar cells have been obtained for the first time by an innovative methodology based on the selective halogenation of SbSe thin films at pressure above 1 atm.

Experimental validation and characterization of putative targets of Escargot and STAT, two master regulators of the intestinal stem cells in Drosophila melanogaster.

Many organs contain adult stem cells (ASCs) to replace cells due to damage, disease, or normal tissue turnover. ASCs can divide asymmetrically, giving rise to a new copy of themselves (self-renewal) and a sister that commits to a specific cell type (differentiation). Decades of research have led to the identification of pleiotropic genes whose loss or gain of function affect diverse aspects of normal ASC biology.

Geometry and Microstructure Control of Remanufactured Metallic Parts by Cold Spray Additive Manufacturing.

Cold Spray Additive Manufacturing (CSAM) is a thermal spray technique that is typically used for the repair of metallic components. One of the challenges of CSAM is to improve the geometrical accuracy of the sprayed parts, along with overcoming the inferiority of the mechanical properties of the deposits by tailoring their microstructure with different deposition strategies. For this, Cu, Al, Ti, and Ti6Al4V substrates were reconstructed by two Cold Spray (CS) methods: Traditional (T) and a novel strategy, Metal Knitting (MK).