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Abstract Current quantum key distribution (QKD) networks focus almost exclusively on transporting secret keys at the highest possible rate. Consequently, they are built as mostly fixed, ad hoc, logically, and physically isolated infrastructures designed to avoid any penalty to the quantum channel. This architecture is neither scalable nor cost-effective and future, real-world deployments will differ considerably. The structure of the MadQCI QKD network presented here is based on disaggregated components and modern paradigms especially designed for flexibility, upgradability, and facilitating the integration of QKD in the security and telecommunications-networks ecosystem. These underlying ideas have been tested by deploying many QKD systems from several manufacturers in a real-world, multi-tenant telecommunications network, installed in production facilities and sharing the infrastructure with commercial traffic. Different technologies have been used in different links to address the variety of situations and needs that arise in real networks, exploring a wide range of possibilities. Finally, a set of realistic use cases has been implemented to demonstrate the validity and performance of the network. The testing took place during a period close to three years, where most of the nodes were continuously active.

Abstract Background While sex-based differences in various health scenarios have been thoroughly acknowledged in the literature, we lack sufficient tools and methods that allow for an in-depth analysis of sex as a variable in biomedical research. To fill this knowledge gap, we created MetaFun as an easy-to-use web-based tool to meta-analyze multiple transcriptomic datasets with a sex-based perspective to gain major statistical power and biological soundness. Description MetaFun is a complete suite that allows the analysis of transcriptomics data and the exploration of the results at all levels, performing single-dataset exploratory analysis, differential gene expression, gene set functional enrichment, and finally, combining results in a functional meta-analysis. Which biological processes, molecular functions or cellular components are altered in a common pattern in different transcriptomic studies when comparing male and female patients? This and other biological questions of interest can be answered with the use of MetaFun. This tool is available at https://bioinfo.cipf.es/metafun while additional help can be found at https://gitlab.com/ubb-cipf/metafunweb/-/wikis/Summary . Conclusions Overall, Metafun is the first open-access web-based tool to identify consensus biological functions across multiple transcriptomic datasets, helping to elucidate sex differences in numerous diseases. Its use will facilitate the generation of novel biological knowledge that can be used in the research and application of Personalized Medicine considering the sex of patients.

Abstract Background Schizophrenia is a severe neuropsychiatric disorder characterized by altered perception, mood, and behavior that profoundly impacts patients and society despite its relatively low prevalence. Sex-based differences have been described in schizophrenia epidemiology, symptomatology and outcomes. Different studies explored the impact of schizophrenia in the brain transcriptome, however we lack a consensus transcriptomic profile that considers sex and differentiates specific cerebral regions. Methods We performed a systematic review on bulk RNA-sequencing studies of post-mortem brain samples. Then, we fulfilled differential expression analysis on each study and summarized their results with regions-specific meta-analyses (prefrontal cortex and hippocampus) and a global all-studies meta-analysis. Finally, we used the consensus transcriptomic profiles to functionally characterize the impact of schizophrenia in males and females by protein-protein interaction networks, enriched biological processes and dysregulated transcription factors. Results We discovered the sex-based dysregulation of 265 genes in the prefrontal cortex, 1.414 genes in the hippocampus and 66 genes in the all-studies meta-analyses. The functional characterization of these gene sets unveiled increased processes related to immune response functions in the prefrontal cortex in male and the hippocampus in female schizophrenia patients and the overexpression of genes related to neurotransmission and synapses in the prefrontal cortex of female schizophrenia patients. Considering a meta-analysis of all brain regions available, we encountered the relative overexpression of genes related to synaptic plasticity and transmission in females and the overexpression of genes involved in organizing genetic information and protein folding in male schizophrenia patients. The protein-protein interaction networks and transcription factors activity analyses supported these sex-based profiles. Conclusions Our results report multiple sex-based transcriptomic alterations in specific brain regions of schizophrenia patients, which provides new insight into the role of sex in schizophrenia. Moreover, we unveil a partial overlapping of inflammatory processes in the prefrontal cortex of males and the hippocampus of females.

Introduction. Systemic antibacterial treatment in patients with infected pancreatic necrosis often fails to resolve the infection due to impaired penetration in necrotic areas. The endoscopic step-up approach based on endoscopic transmural drainage followed, if necessary, by endoscopic necrosectomy has become the standard of care in patients who do not respond to systemic antibiotics. The additional local administration of antibiotics may increase their concentration in necrotic tissue. Aim. To evaluate the efficacy of local infusion of antibacterial agents to the site of infection in addition to systemic treatment after endoscopic drainage to resolve the infection and decrease the need for necrosectomy in patients with walled-off infected pancreatic necrosis. Materials and methods. Major databases were searched for clinical studies assessing the efficacy of local perfusion of antibiotics for the treatment of infected pancreatic necrosis. Results. Four studies were included, two cohort studies and two single-case reports. The majority of patients with infected pancreatic necrosis developed polymicrobial infection. More than one-third of patients additionally had fungal infection. Local irrigation of antibiotics in patients with infected pancreatic necrosis resulted in the eradication of bacteria and fungi, avoiding necrosectomy in almost half of cases. No local or systemic side effects were reported with this strategy. Conclusions. Evidence evaluating the efficacy of local antibiotics for the treatment of infected pancreatic necrosis is scarce. Simultaneous local and systemic administration of antibiotics after endoscopic drainage could reduce the need for necrosectomy. Randomized clinical trials are needed to evaluate the impact of adding local to systemic antibiotics in the prognosis of patients with infected pancreatic necrosis.

Abstract The integration of new Internet of Things (IoT) applications and services heavily relies on task offloading to external devices due to the constrained computing and battery resources of IoT devices. Up to now, Cloud Computing (CC) paradigm has been a good approach for tasks where latency is not critical, but it is not useful when latency matters, so Multi-access Edge Computing (MEC) can be of use. In this work, we propose a distributed Deep Reinforcement Learning (DRL) tool to optimize the binary task offloading decision, this is, the independent decision of where to execute each computing task, depending on many factors. The optimization goal in this work is to maximize the Quality-of-Experience (QoE) when performing tasks, which is defined as a metric related to the battery level of the UE, but subject to satisfying tasks’ latency requirements. This distributed DRL approach, specifically an Actor-Critic (AC) algorithm running on each User Equipment (UE), is evaluated through the simulation of two distinct scenarios and outperforms other analyzed baselines in terms of QoE values and/or energy consumption in dynamic environments, also demonstrating that decisions need to be adapted to the environment’s evolution.

Objective: The application of the Zentangle® Method in relation to relaxation and well-being has not been tested in patients with borderline personality disorder (BPD). This study was to analyze the practising Zentangle® experience in patients with BPD. Methods: With a phenomenological interpretative approach, this qualitative study conducted semi-structured interviews with patients who participated in a 6-session Zentangle® program accomplished monthly over six months in a Personality Disorders Unit. A total of 15 patients were interviewed for this study. Smith, Flowers & Larkin method was applied for evaluation in the data analysis. Results: Based on our findings, three categories were extracted: As you sow, so shall you reap (participants reported improvements in concentration, relaxation, interpersonal relationships, and interaction with their environment as well as positive experiences toward acceptance and change); Many hands make light work (patients admitted feeling better in a group and developed group membership. They described how a group environment influences individual behavior); Drawing your own path (this method provides a medium for self-expression and self-knowledge through drawing, improving well-being through emotional expression, enhancing creativity, and increasing self-confidence). Conclusions: By practicing Zentangle®, patients achieve behavioral responses such as flexibility and adaptability, reaching greater emotional well-being through anxiety management, impulse control, learning to cope with problems, or improving self-esteem or concentration. Mental health nursing plays a critical active role in the comprehensive treatment of BPD, as well as the mobilization and coordination of complementary and diverse interventions.

Background: Age represents a significant risk factor for the development of Alzheimer's disease (AD); however, recent research has documented an influencing role of sex in several features of AD. Understanding the impact of sex on specific molecular mechanisms associated with AD remains a critical challenge to creating tailored therapeutic interventions. Methods: The exploration of the sex-based differential impact on disease (SDID) in AD used a systematic review to first select transcriptomic studies of AD with data regarding sex in the period covering 2002 to 2021 with a focus on the primary brain regions affected by AD - the cortex (CT) and the hippocampus (HP). A differential expression analysis for each study and two tissue-specific meta-analyses were then performed. Focusing on the CT due to the presence of significant SDID-related alterations, a comprehensive functional characterization was conducted: protein-protein network interaction and over-representation analyses to explore biological processes and pathways and a VIPER analysis to estimate transcription factor activity. Results: We selected 8 CT and 5 HP studies from the Gene Expression Omnibus (GEO) repository for tissue-specific meta-analyses. We detected 389 significantly altered genes in the SDID comparison in the CT. Generally, female AD patients displayed more affected genes than males; we grouped said genes into six subsets according to their expression profile in female and male AD patients. Only subset I (repressed genes in female AD patients) displayed significant results during functional profiling. Female AD patients demonstrated more significant impairments in biological processes related to the regulation and organization of synapsis and pathways linked to neurotransmitters (glutamate and GABA) and protein folding, Aβ aggregation, and accumulation compared to male AD patients. These findings could partly explain why we observe more pronounced cognitive decline in female AD patients. Finally, we detected 23 transcription factors with different activation patterns according to sex, with some associated with AD for the first time. All results generated during this study are readily available through an open web resource Metafun-AD (https://bioinfo.cipf.es/metafun-ad/). Conclusion: Our meta-analyses indicate the existence of differences in AD-related mechanisms in female and male patients. These sex-based differences will represent the basis for new hypotheses and could significantly impact precision medicine and improve diagnosis and clinical outcomes in AD patients.

BackgroundsAlthough allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative therapy for hematological malignancies, it can be associated with relevant post-transplant complications. Several reports have shown that polymorphisms in immune system genes are correlated with the development of post-transplant complications. Within this context, this work focuses on identifying novel polymorphisms in cytokine genes and developing predictive models to anticipate the risk of developing graft-versus-host disease (GVHD), transplantation-related mortality (TRM), relapse and overall survival (OS).MethodsOur group developed a 132-cytokine gene panel which was tested in 90 patients who underwent an HLA-identical sibling-donor allo-HSCT. Bayesian logistic regression (BLR) models were used to select the most relevant variables. Based on the cut-off points selected for each model, patients were classified as being at high or low-risk for each of the post-transplant complications (aGVHD II-IV, aGVHD III-IV, cGVHD, mod-sev cGVHD, TRM, relapse and OS).ResultsA total of 737 polymorphisms were selected from the custom panel genes. Of these, 41 polymorphisms were included in the predictive models in 30 cytokine genes were selected (17 interleukins and 13 chemokines). Of these polymorphisms, 5 (12.2%) were located in coding regions, and 36 (87.8%) in non-coding regions. All models had a statistical significance of p

Speciation and diversification patterns in angiosperms are frequently shaped by niche evolution. Centaurium Hill is a Mediterranean genus with ca. 25 species, of which 60% are polyploids (tetra- and hexaploids), distributed mainly in the Mediterranean Basin and in areas with temperate and arid climates of Asia, Europe, North-Central Africa and North America. The evolutionary history of this genus has been studied using morphological, biogeographical and molecular approaches, but its climatic niche characterization and its relation with genome evolution (chromosome number and ploidy level) has not been addressed yet. Thus, this study aims to identify the role of the evolution of climatic niche, ploidy level, life cycle and floral traits in the diversification of Centaurium. Climatic niche characterization involved estimating present climate preferences using quantitative data and reconstructing ancestral niches to evaluate climatic niche shifts. The evolution of climatic niche towards selective optima determined by ploidy level (three ploidy levels) and different binary traits (polyploidy, floral size, floral display, herkogamy and life cycle) was addressed under the Ornstein-Uhlenbeck model. Chromosome number evolution was inferred using the ChromoSSE model, testing if changes are clado- or anagenetic. Chromosome number evolution and its link with cladogenesis, life cycle and floral traits was modeled on the phylogeny. The reconstruction of the ancestral niches shows that Centaurium originated in a mild climate and diversified to both humid and cold as well as to dry and warmer climates. Niche conservatism was estimated in the climatic niche of the ancestors, while the climatic niche of the current taxa experienced transitions from their ancestors’ niche. Besides, the evolution of climatic niche towards multiple selective optima determined by the studied traits was supported, life cycle optima receiving the highest support. The reconstruction of chromosome number transitions shows that the rate of speciation process resulting from chromosomal changes (chromosomal cladogenesis) is similar to that of non-chromosomal cladogenesis. Additionally, dependent evolution of floral size, floral display and herkogamy with chromosome number variation was supported. In conclusion, polyploidization is a crucial process in the Mediterranean region that assisted speciation and diversification into new areas with different climates, entailing niche shifts and evolution of reproductive strategies.

El LAB.PAP Laboratorio de Paisaje Arquitectónico, Patrimonial y Cultural es un Grupo de Investigación Reconocido de la Escuela Técnica Superior de Arquitectura de la Universidad de Valladolid. Está integrado por profesores arquitectos cuyo trabajo es la realización de proyectos de intervención en los paisajes patrimoniales de Castilla y León, con especial dedicación a los paisajes arqueológicos, elaborando para ello una metodología específica y unos mecanismos personales, fruto de la larga experiencia. A lo largo de los últimos años se ha ocupado de proyectos en lugares tan emblemáticos como la ciudad romana de Colonia Clunia Sulpicia en Burgos, la ciudad celtíbero-romana de Tiermes en Soria, el Paisaje Cultural de Las Médulas en León, así como en villas y calzadas romanas. El objetivo de sus proyectos y actuaciones es hacer visible un patrimonio muy rico, pero de una gran fragilidad, para su conservación e investigación y también para hacerlo más comprensible para el turismo cultural de calidad.

Calcium hexaluminate (CaAl12O19) is the most alumina-rich intermediate compound of the CaO-Al2O3 system. The formation of this aluminate is produced by the reaction between calcium oxide and alumina with the consequent formation of intermediates compounds with lower alumina content with increasing temperature (CaAl2O4, CaAl4O7…). In this study we studied the variation of sintering parameters for obtaining dense and pure calcium hexaluminate by reaction sintering by Spark Plasma Sintering (SPS). A mixing of Al2O3 and CaCO3 were used as reactive. Final densities close to the theoretical and phase transformation over 93% were achieved by this method.El hexaluminato de calcio (CaAl12O19 o CA6) es el material más rico en Al2O3 entre los compuestos intermedios en el sistema CaO-Al2O3. La formación de este aluminato se produce por la reacción entre el CaO y la Al2O3 con la consecuente formación de compuestos intermedios con menores contenidos en Al2O3 con el aumento de la temperatura (CaAl2O4, CaAl4O7,…). En este trabajo se ha estudiado la variación de los parámetros de sinterización para la obtención de hexaluminato de calcio (CA6) denso y puro por sinterización reactiva mediante Spark Plasma Sintering (Sinterización mediante corriente eléctrica pulsada o SPS), utilizando como reactivos Al2O3 y CaCO3 para su formación. Se han obtenido densidades cercanas a las teóricas y transformaciones superiores al 93% por este método.

We describe the curation, annotation methodology, and characteristics of the dataset used in an artificial intelligence challenge for detection and localization of COVID-19 on chest radiographs. The chest radiographs were annotated by an international group of radiologists into four mutually exclusive categories, including typical, indeterminate, and atypical appearance for COVID-19, or negative for pneumonia, adapted from previously published guidelines, and bounding boxes were placed on airspace opacities. This dataset and respective annotations are available to researchers for academic and noncommercial use.

En este trabajo se analiza la autopresentación online auténtica (AOA): grado en que las personas se presentan de manera online de modo auténtico, sin distorsionar su modo de ser offline. Primero se diseñó una medida psicométrica para su operacionalización, y luego se estudió su asociación con aspectos psicológicos positivos (bienestar y satisfacción con la vida), negativos (síntomas psicológicos y uso problemático de internet) y rasgos de personalidad (normales, patológicos y positivos). Finalmente, se analizó un modelo explicativo en donde la AOA era mediadora entre la personalidad y aspectos psicológicos positivos. Se analizó una muestra de 384 participantes (46.6% hombres, 52.6% mujeres y 0.05% no binarios) con edad promedio de 28 años (DE = 5.92) y una muestra adicional para el análisis factorial confirmatorio de características similares. Se obtuvo buena evidencia de validez (e. g., CFI = .917, SMRS = .059) y confiabilidad (α = .79, ω = .85) para una medida de ocho elementos. La AOA se relaciona positivamente con el bienestar y la satisfacción con la vida, y negativamente con la sintomatología psicológica y el uso problemático de internet. Se encontraron asociaciones positivas con todos los rasgos positivos y con extraversión, agradabilidad y responsabilidad. Se hallaron relaciones negativas con desapego y desinhibición. Los rasgos positivos resultaron ser los más explicativos de la AOA. Se halló que la AOA media la relación entre el rasgo de integridad y la satisfacción con la vida y el bienestar. Se destaca el rol primordial de los rasgos positivos en este tipo de conducta online y con los aspectos positivos asociados a la AOA.

Abstract Fractured crystalline rocks have been chosen or are under consideration by several countries as host rock formations for deep geological repositories for spent nuclear fuel. In such geological formations, flow and solute transport are mostly controlled by a network of connected natural fractures, each of them being characterised by internal heterogeneity, also denoted as roughness. Fractures are, in turn, subject to variable load caused by various factors, such as the presence of thick ice sheets formed during glaciation periods. Understanding how coupled hydro-mechanical (HM) processes affect flow and transport at the scale of a single natural fracture is crucial for a robust parameterisation of large-scale discrete fracture network models, which are not only used for nuclear waste disposal applications but are also of interest to problems related to geothermics, oil and gas production or groundwater remediation. In this work, we analyse and model an HM experiment carried out in a single natural fracture and use the results of both, the experimental and the modelling work, to get insights into fundamental questions such as the applicability of local cubic law or the effect of normal load on channeling. The initial fracture aperture was obtained from laser scanning of the two fracture surfaces and an equivalent initial aperture was then defined by moving the two fracture surfaces together and comparing the results obtained using a Navier–Stokes based computational fluid dynamics (CFD) model with the experimental flowrate obtained for unloaded conditions. The mechanical effect of the different loading stages was simulated using a high-resolution contact model. The different computed fracture apertures were then used to run groundwater flow simulations using a modified Reynolds equation. The results show that, without correction, local cubic law largely overestimates flowrates. Instead, we show that by explicitly acknowledging the difference between the mechanical aperture and the hydraulic aperture and setting the latter equal to 1/5 of the former, cubic law provides a very reasonable approximation of the experimental flowrates over the entire loading cycle. A positive correlation between fluid flow channeling and normal load is also found.

Abstract The digitization of natural history specimens and the popularization of citizen science are creating an unprecedented availability of large amounts of biodiversity data. These biodiversity inventories can be severely affected by species misidentification, a source of taxonomic uncertainty that is rarely acknowledged in biodiversity data management. For these reasons, taxonomists debate the use of online repositories to address biological questions at the species level. Hedera L. (ivies) provides an excellent case study as it is well represented in both herbaria and online repositories with thousands of records likely to be affected by high taxonomic uncertainty. We analyze the sources and extent of taxonomic errors in the identification of the European ivy species by reviewing herbarium specimens and find a high misidentification rate (18% on average), which varies between species (maximized in H. hibernica: 55%; H. azorica: 48%; H. iberica: 36%) and regions (maximized in the UK: 38% and Spain: 27%). We find a systematic misidentification of all European ivies with H. helix behind the high misidentification rates in herbaria and warn of even higher rates in online records. We compile a spatial database to overcome the large discrepancies we observed in species distributions between online and morphologically reviewed records.

Abstract The interactions between tumor and immune cells along the course of breast cancer progression remain largely unknown. Here, we extensively characterize multiple sequential and parallel multiregion tumor and blood specimens of an index patient and a cohort of metastatic triple-negative breast cancers. We demonstrate that a continuous increase in tumor genomic heterogeneity and distinct molecular clocks correlated with resistance to treatment, eventually allowing tumors to escape from immune control. TCR repertoire loses diversity over time, leading to convergent evolution as breast cancer progresses. Although mixed populations of effector memory and cytotoxic single T cells coexist in the peripheral blood, defects in the antigen presentation machinery coupled with subdued T cell recruitment into metastases are observed, indicating a potent immune avoidance microenvironment not compatible with an effective antitumor response in lethal metastatic disease. Our results demonstrate that the immune responses against cancer are not static, but rather follow dynamic processes that match cancer genomic progression, illustrating the complex nature of tumor and immune cell interactions.

Abstract Background Neoantigens are patient- and tumor-specific peptides that arise from somatic mutations. They stand as promising targets for personalized therapeutic cancer vaccines. The identification process for neoantigens has evolved with the use of next-generation sequencing technologies and bioinformatic tools in tumor genomics. However, in-silico strategies for selecting immunogenic neoantigens still have very low accuracy rates, since they mainly focus on predicting peptide binding to Major Histocompatibility Complex (MHC) molecules, which is key but not the sole determinant for immunogenicity. Moreover, the therapeutic potential of neoantigen-based vaccines may be enhanced using an optimal delivery platform that elicits robust de novo immune responses. Methods We developed a novel neoantigen selection pipeline based on existing software combined with a novel prediction method, the Neoantigen Optimization Algorithm (NOAH), which takes into account structural features of the peptide/MHC-I interaction, as well as the interaction between the peptide/MHC-I complex and the TCR, in its prediction strategy. Moreover, to maximize neoantigens’ therapeutic potential, neoantigen-based vaccines should be manufactured in an optimal delivery platform that elicits robust de novo immune responses and bypasses central and peripheral tolerance. Results We generated a highly immunogenic vaccine platform based on engineered HIV-1 Gag-based Virus-Like Particles (VLPs) expressing a high copy number of each in silico selected neoantigen. We tested different neoantigen-loaded VLPs (neoVLPs) in a B16-F10 melanoma mouse model to evaluate their capability to generate new immunogenic specificities. NeoVLPs were used in in vivo immunogenicity and tumor challenge experiments. Conclusions Our results indicate the relevance of incorporating other immunogenic determinants beyond the binding of neoantigens to MHC-I. Thus, neoVLPs loaded with neoantigens enhancing the interaction with the TCR can promote the generation of de novo antitumor-specific immune responses, resulting in a delay in tumor growth. Vaccination with the neoVLP platform is a robust alternative to current therapeutic vaccine approaches and a promising candidate for future personalized immunotherapy.

Abstract Background The incidence of Alzheimer's disease (AD)—the most frequent cause of dementia—is expected to increase as life expectancies rise across the globe. While sex-based differences in AD have previously been described, there remain uncertainties regarding any association between sex and disease-associated molecular mechanisms. Studying sex-specific expression profiles of regulatory factors such as microRNAs (miRNAs) could contribute to more accurate disease diagnosis and treatment. Methods A systematic review identified six studies of microRNA expression in AD patients that incorporated information regarding the biological sex of samples in the Gene Expression Omnibus repository. A differential microRNA expression analysis was performed, considering disease status and patient sex. Subsequently, results were integrated within a meta-analysis methodology, with a functional enrichment of meta-analysis results establishing an association between altered miRNA expression and relevant Gene Ontology terms. Results Meta-analyses of miRNA expression profiles in blood samples revealed the alteration of sixteen miRNAs in female and 22 miRNAs in male AD patients. We discovered nine miRNAs commonly overexpressed in both sexes, suggesting a shared miRNA dysregulation profile. Functional enrichment results based on miRNA profiles revealed sex-based differences in biological processes; most affected processes related to ubiquitination, regulation of different kinase activities, and apoptotic processes in males, but RNA splicing and translation in females. Meta-analyses of miRNA expression profiles in brain samples revealed the alteration of six miRNAs in female and four miRNAs in male AD patients. We observed a single underexpressed miRNA in female and male AD patients (hsa-miR-767-5p); however, the functional enrichment analysis for brain samples did not reveal any specifically affected biological process. Conclusions Sex-specific meta-analyses supported the detection of differentially expressed miRNAs in female and male AD patients, highlighting the relevance of sex-based information in biomedical data. Further studies on miRNA regulation in AD patients should meet the criteria for comparability and standardization of information.

ObjectivesPrecise HDV-RNA detection and quantification are pivotal for diagnosis and monitoring of response to newly approved treatment. We evaluate the performance of three HDV RNA detection and quantification assays.MethodsHepatitis Delta RT-PCR system kit, EurobioPlex HDV assay, and RoboGene HDV RNA Quantification kit 2.0 were used for testing 151 HBsAg-positive samples, 90 HDV-RNA negative and 61 HDV-RNA positive. We also evaluated serial dilutions of the WHO international standard for HDV, PEI 7657/12. All HDV-RNA positive samples were genotyped using a next-generation sequencing strategy.ResultsQualitative results indicated a 100% concordance between tests. Quantitative results correlated well, r2 = 0.703 (Vircell-vs-Eurobio), r2 = 0.833 (Vircell-vs-RoboGene), r2 = 0.835 (Robogene-vs-Eurobio). Bias index was 2.083 (Vircell-vs-Eurobio), -1.283 (Vircell-vs-RoboGene), and -3.36 (Robogene-vs-Eurobio). Using the WHO IS, Vircell overestimated the viral load by 0.98 log IU/mL, Eurobio by 1.46 log IU/mL, and RoboGene underestimated it by 0.98 log IU/mL. Fifty-nine samples were successfully genotyped (Genotype 1, n=52; Genotype 5, n=7; Genotype 6, n=1), with similar results for correlation and bias.ConclusionThis study underscores the necessity of using reliable HDV-RNA detection and quantification assays, as evidenced by the high concordance rates in qualitative detection and the observed variability in quantitative results. These findings highlight the importance of consistent assay use in clinical practice to ensure accurate diagnosis and effective treatment monitoring of HDV infection.

IntroductionCarbapenemase-Producing Escherichia coli (CP-Eco) isolates, though less prevalent than other CP-Enterobacterales, have the capacity to rapidly disseminate antibiotic resistance genes (ARGs) and cause serious difficult-to-treat infections. The aim of this study is phenotypically and genotypically characterizing CP-Eco isolates collected from Spain to better understand their resistance mechanisms and population structure.MethodsNinety representative isolates received from 2015 to 2020 from 25 provinces and 59 hospitals Spanish hospitals were included. Antibiotic susceptibility was determined according to EUCAST guidelines and whole-genome sequencing was performed. Antibiotic resistance and virulence-associated genes, phylogeny and population structure, and carbapenemase genes-carrying plasmids were analyzed.Results and discussionThe 90 CP-Eco isolates were highly polyclonal, where the most prevalent was ST131, detected in 14 (15.6%) of the isolates. The carbapenemase genes detected were blaOXA-48 (45.6%), blaVIM-1 (23.3%), blaNDM-1 (7.8%), blaKPC-3 (6.7%), and blaNDM-5 (6.7%). Forty (44.4%) were resistant to 6 or more antibiotic groups and the most active antibiotics were colistin (98.9%), plazomicin (92.2%) and cefiderocol (92.2%). Four of the seven cefiderocol-resistant isolates belonged to ST167 and six harbored blaNDM. Five of the plazomicin-resistant isolates harbored rmt. IncL plasmids were the most frequent (45.7%) and eight of these harbored blaVIM-1. blaOXA-48 was found in IncF plasmids in eight isolates. Metallo-β-lactamases were more frequent in isolates with resistance to six or more antibiotic groups, with their genes often present on the same plasmid/integron. ST131 isolates were associated with sat and pap virulence genes. This study highlights the genetic versatility of CP-Eco and its potential to disseminate ARGs and cause community and nosocomial infections.

Abstract There are several overlapping clinical practice guidelines in acute pancreatitis (AP), however, none of them contains suggestions on patient discharge. The Hungarian Pancreatic Study Group (HPSG) has recently developed a laboratory data and symptom-based discharge protocol which needs to be validated. (1) A survey was conducted involving all members of the International Association of Pancreatology (IAP) to understand the characteristics of international discharge protocols. (2) We investigated the safety and effectiveness of the HPSG-discharge protocol. According to our international survey, 87.5% (49/56) of the centres had no discharge protocol. Patients discharged based on protocols have a significantly shorter median length of hospitalization (LOH) (7 (5;10) days vs. 8 (5;12) days) p