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The development of nuclear fusion as a safe and virtually limitless power source is receiving growing attention in the context of looming energy crisis and climate change. ITER project stands as the flagship international initiative and is advancing steadily. The construction of the Tokamak Complex is nearly finished, and the assembly of core components has begun on site. Simultaneously, the design is being finalized, and the safety case is becoming more concrete. Current approaches to radiation safety demonstration using 3D nuclear analysis with the Monte Carlo code MCNP require sophisticated artifacts to sew together simulations in separate models for the Tokamak and the rest of the facility. This results in cumbersome studies and, consequently, challengeable conclusions. To address this issue, we have built the an integral MCNP model of the ITER facility: the ITER full model. Along with improvements to the D1SUNED code, we illustrate its computational practicality and pertinence in two meaningful simulations for ITER safety case. This work represents the culmination of a two-decade-long effort of ITER modelling aiming to demonstrate adequate radiation safety. Beyond supporting the remaining design tasks, this model simplifies the corresponding 3D nuclear analysis and improves the robustness of the ITER safety case. In this work, authors present an integral MCNP model of the ITER facility for radiation transport, addressing limitations of separate models for the Tokamak and Tokamak Complex. This model streamlines safety simulations, enhancing the robustness and simplicity of radiation safety analysis. [ABSTRACT FROM AUTHOR]

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The sustainable synthesis of urea from ammonia (NH3) and carbon dioxide (CO2) using ultraporous permanently polarized hydroxyapatite (upp-HAp) as catalyst has been explored as an advantageous CO2-revalorization strategy. As the simultaneous activation of N2 and CO2 (single-step) demands an increase of the reaction conditions, we have re-visited the industrial two-step Bazarov reaction. upp-HAp has been designed as a stable multifunctional catalyst capable of promoting both CO2 and NH3 adsorption for their subsequent C-N bond formation. Herein we report the synthesis of 1 mmol/gcat of urea with a selectivity of 97% under strictly mild conditions (95-120 ºC and 1 bar of CO2; without applying any electrical currents or UV irradiation) which represents an efficiency of ~2% and ~30% with respect to the NH3 and CO2 content, respectively. The study of the NH3 content, products adsorbed in the catalyst, presence of intermediates and temperature of the reaction allows unveiling the great potential of upp-HAp as a green catalyst for sustainable Bazarov reactions. Results suggest that the double-step approach could be more advantageous for both synthesizing urea and as a CO2-revalorization strategy, which in turn promotes the development of specific technologies for the independent synthesis of green NH3., (© 2024 Wiley‐VCH GmbH.)

Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is one of the most efficient therapeutic options available to cure many hematological malignancies. However, severe complications derived from this procedure, including graft-versus-host disease (GVHD) and infections, can limit its success and negatively impact survival. Previous studies have shown that alterations in the microbiome are associated with the development of allo-HSCT-derived complications. However, most studies relied on single techniques that can only analyze a unique aspect of the microbiome, which hinders our ability to understand how microbiome alterations drive allo-HSCT-associated diseases., Results: Here, we have applied multiple "omic" techniques (16S rRNA and shotgun sequencing, targeted and un-targeted metabolomics) in combination with machine learning approaches to define the most significant microbiome changes following allo-HSCT at multiple modalities (bacterial taxa, encoded functions, and derived metabolites). In addition, multivariate approaches were applied to study interactions among the various microbiome modalities (the interactome). Our results show that the microbiome of transplanted patients exhibits substantial changes in all studied modalities. These include depletion of beneficial microbes, mainly from the Clostridiales order, loss of their bacterial encoded functions required for the synthesis of key metabolites, and a reduction in metabolic end products such as short chain fatty acids (SCFAs). These changes were followed by an expansion of bacteria that frequently cause infections after allo-HSCT, including several Staphylococcus species, which benefit from the reduction of bacteriostatic SCFAs. Additionally, we found specific alterations in all microbiome modalities that distinguished those patients who subsequently developed GVHD, including depletion of anti-inflammatory commensals, protective reactive oxygen detoxifying enzymes, and immunoregulatory metabolites such as acetate or malonate. Moreover, extensive shifts in the homeostatic relationship between bacteria and their metabolic products (e.g., Faecalibacterium and butyrate) were detected mainly in patients who later developed GVHD., Conclusions: We have identified specific microbiome changes at different modalities (microbial taxa, their encoded genes, and synthetized metabolites) and at the interface between them (the interactome) that precede the development of complications associated with allo-HSCT. These identified microbial features provide novel targets for the design of microbiome-based strategies to prevent diseases associated with stem cell transplantation. Video Abstract., (© 2024. The Author(s).)

The Inventory of Complicated Grief (ICG) is the most widely used instrument to measure complicated grief (CG), but its psychometric properties have hardly been examined in relatives of those who died by violent means. The objective of this study was to obtain evidence of validity of the ICG in a relatives of those who died due to terrorist attacks in Spain. The factorial structure, internal consistency, and relationship with depression, anxiety, and post-traumatic stress were analyzed in a Spanish sample of 211 relatives of people who died in terrorist attacks. The ICG presented a one-factor structure that supports the validity of its total score. This score showed excellent internal consistency indices (alpha = .927; omega = .932) and adequate correlation indices with depression, anxiety, and post-traumatic stress ( r = .71, .63 and .76, respectively). The ICG provides reliable and valid measures of CG in adults who have lost a family member due to violent death., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The association of graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) effects after allogeneic stem-cell transplantation (SCT) is well-established but was not confirmed in the modern era and following post-transplant cyclophosphamide (PTCy). We assessed GVHD/ GVL association in AML patients following HLA-matched SCT with standard calcineurin-based (n = 12,653, 57% with additional in-vivo T-cell depletion) or PTCy-based (n = 508) GVHD prophylaxis. Following standard prophylaxis, acute GVHD grade II-IV and III-IV, chronic GVHD, and extensive chronic GVHD rates were 23.8%, 7.5%, 37.0%, and 16.3%, respectively. Acute GVHD grade II and III-IV were associated with lower relapse [hazard-ratio (HR) 0.85, P = 0.002; HR 0.76, P = 0.003, respectively)], higher non-relapse mortality (NRM) (HR 1.5, P < 0.001; HR 6.21, P < 0.001) and lower overall survival (OS) (HR 1.49, P < 0.001; HR 6.1, P < 0.001). Extensive chronic GVHD predicted lower relapse (HR 0.69, P < 0.001), higher NRM (HR 2.83, P < 0.001), and lower OS (HR 2.74, P < 0.001). Following PTCy, GVHD rates were 22.8%, 6.2%, 35.5%, and 17.7%, respectively. Acute GVHD was not associated with relapse (HR 1.37, P = 0.15) but predicted higher NRM (HR 3.34, P < 0.001) and lower OS (HR 1.92, P = 0.001). Chronic GVHD was not prognostic for these outcomes. In conclusion, GVHD and GVL are strongly associated with contemporary SCT. However, following PTCy, GVHD is not associated with reduced relapse., (© 2024. The Author(s).)

To enable transmission of information in the brain, synaptic vesicles fuse to presynaptic membranes, liberating their content and exposing transiently a myriad of vesicular transmembrane proteins. However, versatile methods for quantifying the synaptic translocation of endogenous proteins during neuronal activity remain unavailable, as the fast dynamics of synaptic vesicle cycling difficult specific isolation of trafficking proteins during such a transient surface exposure. Here, we developed a novel approach using synaptic cleft proximity labeling to capture and quantify activity-driven trafficking of endogenous synaptic proteins at the synapse. We show that accelerating cleft biotinylation times to match the fast dynamics of vesicle exocytosis allows capturing endogenous proteins transiently exposed at the synaptic surface during neural activity, enabling for the first time the study of the translocation of nearly every endogenous synaptic protein. As proof-of-concept, we further applied this technology to obtain direct evidence of the surface translocation of noncanonical trafficking proteins, such as ATG9A and NPTX1, which had been proposed to traffic during activity but for which direct proof had not yet been shown. The technological advancement presented here will facilitate future studies dissecting the molecular identity of proteins exocytosed at the synapse during activity, helping to define the molecular machinery that sustains neurotransmission in the mammalian brain., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Pascual-Caro, de Juan-Sanz. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Gastrointestinal bleeding (GIB) is a serious complication following allogeneic hematopoietic stem cell transplantation (HSCT), with limited data on its incidence and characteristics, particularly for upper gastrointestinal bleeding (UGIB) of gastric origin. We aimed to evaluate the incidence, clinical, endoscopic, and histopathologic features, and outcomes of UGIB, with a focus on gastric vascular ectasias (GVEs) in patients undergoing HSCT with graft-versus-host disease (GVHD) prophylaxis using post-transplant cyclophosphamide (PTCY), sirolimus or calcineurin inhibitors, and mycophenolate mofetil. This retrospective, single-center study included all adult patients who underwent allogeneic HSCT at a single institution between January 2017 and December 2023. Data were collected on transplant procedures, complications, and GIB incidents, with UGIB cases undergoing endoscopic and histologic examination. Out of 559 patients, 38 (6.6%) experienced UGIB, with 27 cases (70%) attributed to GVE. GVE typically presented as melena or hematemesis at a median time of 68 d (range, 29 to 125) after transplant. Endoscopy revealed diffuse oozing from gastric antral mucosa without distinct lesions, while histology showed vascular congestion and mild foveolar hyperplasia. The 6-mo cumulative incidence of GVE was 5.1%. Older age (≥60 yr) and diagnosis of myelodysplastic/myeloproliferative neoplasm were significant risk factors. All cases resolved with no attributable mortality with supportive measures including transfusions, proton-pump inhibitors, and sirolimus withdrawal in some cases. GVE is a notable cause of UGIB in HSCT recipients on PTCY-based GVHD prophylaxis, presenting significant morbidity but favorable outcomes with appropriate management. The potential role of sirolimus and conditioning agents in GVE pathogenesis warrants further investigation., (Copyright © 2024. Published by Elsevier Inc.)

Background/Objectives : The experience of the COVID-19 pandemic has turned the spotlight on the importance of public health measures and disease prevention. Despite this, the acceptance of influenza vaccination has remained low in most countries (and far from the 75% target set by the World Health Organization). The objective of this study has been to investigate how attitudes and behaviors regarding influenza vaccination in the Spanish adult population have changed over the last three years (from 2021 to 2024) in order to analyze trends in influenza vaccination. Methods : To this end, a cross-sectional study was conducted through 2206 telephone interviews, and the results were compared with those obtained in previous campaigns. Results : The findings indicate a significant decline in overall vaccination intent. Healthcare professionals remain the most influential factor in encouraging vaccination, yet there is a notable increase in the lack of vaccine recommendations, contributing to the decision not to vaccinate. This study also reveals low awareness of the influenza vaccine campaign, emphasizing the need for improved public health communication. Conclusions : To counteract these trends, this study recommends intensifying awareness campaigns, strengthening the role of healthcare providers in vaccine advocacy, and tailoring communication strategies. These efforts are crucial to enhancing vaccination coverage and protecting vulnerable populations against influenza.

We previously described a septal variant termed left atrial septal pouch (LASP). Present in a third of hearts, it results from incomplete fusion of the septum primum (SP) and septum secundum (SS). We assessed the prevalence of LASP using 64-section multidetector computed tomography and further characterized the different variants. Among 864 scans, 770 were of sufficient quality for assessment (428 male, aged 59.2 ± 11.7 years). They were classified on the basis of the degrees of fusion of the SP and SS into a completely fused septum (CFS), patent foramen ovale (PFO), or LASP. The lengths of the SS, SP, and overlapping SP, the maximal length of the foramen ovale (FO) floor, and the atrial dimensions were compared. A PFO was seen in 181 patients (23.5%), a LASP in 242 (31.4%), and a CFS in 339 (44.0%). There were significant differences in the length of the SS (PFO-13.6 ± 4.3 mm, LASP-17.6 ± 4.8 mm, CFS-14.3 ± 7.7 mm, p < 0.001). Hearts with LASPs had a longer overlapping SP than those with PFOs (PFO-6.3 ± 4.5 mm, LASP-13.1 ± 5.2 mm, p < 0.001). The maximal lengths of the FO floor showed differences in short axis (SAX) view (PFO-21.7 ± 4.5 mm, LASP-15.3 ± 4.3 mm, CFS-16.3 ± 4.3 mm, p < 0.001). Hearts with PFO and LASP showed similar SP lengths (27.3 ± 6.6 mm vs. 26.4 ± 6.6 mm, p = 0.10). There was a positive linear correlation between the length of the SS and the overlapping SP (R 2  = 0.28, p < 0.001) with a weaker negative correlation between the SS length and maximal length of the FO floor (R 2  = 0.02, p < 0.001). The groups showed similar atrial dimensions and volumes. Present in a third of patients, hearts with LASP have longer SS and overlapping SP., (© 2024 American Association of Clinical Anatomists and British Association of Clinical Anatomists.)

Deficiencies in the electron transport chain (ETC) lead to mitochondrial diseases. While mutations are distributed across the organism, cell and tissue sensitivity to ETC disruption varies, and the molecular mechanisms underlying this variability remain poorly understood. Here we show that, upon ETC inhibition, a non-canonical tricarboxylic acid (TCA) cycle upregulates to maintain malate levels and concomitant production of NADPH. Our findings indicate that the adverse effects observed upon CI inhibition primarily stem from reduced NADPH levels, rather than ATP depletion. Furthermore, we find that Pyruvate carboxylase (PC) and ME1, the key mediators orchestrating this metabolic reprogramming, are selectively expressed in astrocytes compared to neurons and underlie their differential sensitivity to ETC inhibition. Augmenting ME1 levels in the brain alleviates neuroinflammation and corrects motor function and coordination in a preclinical mouse model of CI deficiency. These studies may explain why different brain cells vary in their sensitivity to ETC inhibition, which could impact mitochondrial disease management., (© 2024. The Author(s).)

Introduction and Objectives: In patients with established chronic coronary syndrome (CCS), the significance of persistent angina is controversial. We aimed to evaluate the prognostic role of persistent angina in symptomatic CCS patients with abnormal stress cardiovascular magnetic resonance (CMR) and altered angiographic findings undergoing percutaneous revascularization., Methods: We analyzed 334 CCS patients with Canadian Cardiovascular Society angina class ≥2, perfusion deficits on stress CMR and severe lesions in angiography who underwent medical therapy optimization plus CMR-guided percutaneous revascularization. We investigated the association of persistent angina at 6 months postintervention with subsequent cardiac death, myocardial infarction, and hospital admission., Results: All patients had angina class ≥2 (mean: 2.8±0.7), abnormal stress CMR (mean ischemic burden: 5.8±2.7 segments), and severe angiographic lesions. The angina resolution rates were 81% at 6 months, and 81%, 81%, and 77% at 1, 2, and 5 years, respectively. During a median follow-up of 8.9 years, persistent angina was independently associated with higher rates of subsequent cardiac death (13% vs 4%; HR, 3.7; 95%CI, 1.5-9.2; P=.005), myocardial infarction (24% vs 6%; HR, 4.9; 95%CI, 2.4-9.9; P<.001), and hospital admission for heart failure (27% vs 13%; HR, 2.7; 95%CI, 1.5-5.2; P=.001)., Conclusions: In CCS patients with robust diagnostic evidence from symptoms, stress CMR, and angiography, persistent angina after percutaneous revascularization is a strong predictor of subsequent cardiac death, myocardial infarction, and hospital admission for heart failure., (Copyright © 2024 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction: We analyzed epidemiological, clinical characteristics, and the response to treatment in people living with HIV (PLHIV) who recently acquired hepatitis C (RAHC) in a multicentre study in Madrid (Spain)., Methods: Multicenter, ambispective, observational study of RAHC in men who have sex with men (MSM) infected with HIV. Clinical, epidemiological, and RAHC evolution were recorded prospectively in 2019 and 2020 and retrospectively in 2017 and 2018. In patients who received HCV treatment, sustained virological response (SVR) was provided 12 weeks after the end of treatment in an intention to treat analysis (ITT): all treated patients were included; and in analysis per-protocol (PP): missing patients were excluded., Results: Overall, 133 patients were included. Median (IQR) age was 40 (34.3-46.1) years, 90.9% had at least one previous sexual transmission disease (STD), and 33.6% had previously hepatitis C. More than half of the prospective sample included patients using chemsex related drugs (57.3%), 45.7% of them intravenously. The most prevalent genotype was G1a (66.2%), followed by G4 (11.3%). Ten of 90 patients evaluated for spontaneous cure (11%) cured the infection spontaneously, and 119 had treatment after a median time of 1.8 (0.7-4.6) months: sustained virological response (SVR) was achieved in 90.7% in the ITT and 94.7% in the PP analysis, with no differences regarding the direct-acting antiviral agents (DAA) combination used., Conclusions: MSM infected by HIV with a RAHC were exposed to high-risk sexual behavior. Spontaneous cure rate was low, while SVR after treatment was achieved by more than 90%., (Copyright © 2023 Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. Published by Elsevier España, S.L.U. All rights reserved.)