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Background: Cardiac rehabilitation programs provide a valuable opportunity to promote the adoption of healthy lifestyle behaviors in patients with atherosclerotic cardiovascular diseases (ASCVDs) and metabolic comorbidities, including metabolic syndrome and prediabetes. However, strategies to reverse these conditions remain to be explored. The DIABEPIC-1 study aimed to assess the feasibility of an enhanced 6-month cardiac rehabilitation program for patients with ASCVD while investigating prediabetes and metabolic syndrome remission. Methods: The study combined exercise training with a comprehensive nutritional intervention, emphasizing reduction in intake of ultraprocessed foods, adoption of a Mediterranean diet, and implementation of time-restricted eating. Baseline, 3-month, and 6-month assessments included segmental body-composition measurements, blood analysis, maximal exercise testing, nutritional diaries recorded with the Keenoa AI app, and lifestyle questionnaires. Remission criteria included a return to an HbA1c level of < 5.7%, and < 3 National Cholesterol Education Program Adult Treatment Panel III (NCEP/ATP-III) criteria for prediabetes and metabolic syndrome, respectively. Results: A total of 36 participants were recruited. The study demonstrated completion rates of 94.4% at 3 months, and 88.9% at 6 months, and a mean compliance rate of 92.5% for planned clinical appointments. Significant reductions in waist circumference (–9.2 cm, P < 0.001) and weight (–8.0 kg, P < 0.001) were observed. Improvement in glycemic and lipid profiles, insulin-resistance marker levels, and liver health were noted. Participants enhanced their cardiorespiratory fitness, reduced their consumption of ultraprocessed food, and increased their adherence to the Mediterranean diet and time-restricted eating. Notably, 50% achieved prediabetes remission, and 70% with metabolic syndrome at baseline achieved remission. Conclusions: The study demonstrates the possibility of enhancing cardiac rehabilitation with an intensive nutritional intervention, yielding clinically significant outcomes, including remission of key risk factors in a substantial number of ASCVD patients. Clinical Trial Registration: ClinicalTrials.gov, NCT05459987. Résumé: Contexte: Les programmes de réadaptation cardiaque offrent une occasion précieuse de promouvoir l'adoption d'un mode de vie sain chez les patients atteints de maladies cardiovasculaires athéroscléreuses (MCVA) et de comorbidités métaboliques, notamment le syndrome métabolique et le prédiabète. Cependant, les stratégies visant à inverser ces conditions restent à explorer. L'étude DIABEPIC-1 visait à évaluer la faisabilité d'un programme de réadaptation cardiaque renforcé de 6 mois pour les patients atteints de MCVA tout en examinant la rémission du prédiabète et du syndrome métabolique. Méthodes: L'étude a combiné un entraînement physique avec une intervention nutritionnelle complète, mettant l'accent sur la réduction de la consommation d'aliments ultra-transformés, l'adoption d'un régime méditerranéen et la mise en œuvre d'une alimentation restreinte dans le temps. Les évaluations de base, à 3 mois et à 6 mois, comprenaient des mesures de la composition corporelle par segments, des analyses sanguines, des tests d'exercice maximal, la tenue de journaux nutritionnels enregistrés avec l'application Keenoa AI et des questionnaires sur le mode de vie. Les critères de rémission comprenaient un retour à un niveau d'hémoglobine glyquée HbA1c < 5,7 %, et < 3 critères de la table du « National Cholesterol Education Program Adult Treatment Panel III » (NCEP/ATP-III) pour le prédiabète et le syndrome métabolique, respectivement. Résultats: Au total, 36 participants ont été recrutés. L'étude a montré des taux d'achèvement de 94,4 % à 3 mois et de 88,9 % à 6 mois, ainsi qu'un taux de conformité moyen de 92,5 % pour les rendez-vous cliniques planifiés. Des réductions significatives du tour de taille (-9,2 cm, p < 0,001) et du poids (-8,0 kg, p < 0,001) ont été observées. Une amélioration des profils glycémiques et lipidiques, des niveaux de marqueurs de résistance à l'insuline et de la santé hépatique a été constatée. Les participants ont amélioré leur condition cardiorespiratoire, réduit leur consommation d'aliments ultra-transformés et augmenté leur adhésion au régime méditerranéen et à l'alimentation restreinte dans le temps. Notamment, 50 % des participants ont obtenu une rémission du prédiabète et 70 % des participants atteints du syndrome métabolique au début de l'étude ont atteint la rémission. Conclusions: L'étude démontre la possibilité d'améliorer la réadaptation cardiaque par une intervention nutritionnelle intensive, produisant des résultats cliniquement significatifs, y compris la rémission des principaux facteurs de risque chez un nombre substantiel de patients atteints de MCVA. Enregistrement de l'essai clinique: ClinicalTrials.gov, NCT05459987.

Abstract Background Type 2 diabetes mellitus (T2DM) is a major risk factor for heart failure with preserved ejection fraction and cardiac arrhythmias. Precursors of these complications, such as diabetic cardiomyopathy, remain incompletely understood and underdiagnosed. Detection of early signs of cardiac deterioration in T2DM patients is critical for prevention. Our goal is to quantify T2DM-driven abnormalities in ECG and cardiac imaging biomarkers leading to cardiovascular disease. Methods We quantified ECG and cardiac magnetic resonance imaging biomarkers in two matched cohorts of 1781 UK Biobank participants, with and without T2DM, and no diagnosed cardiovascular disease at the time of assessment. We performed a pair-matched cross-sectional study to compare cardiac biomarkers in both cohorts, and examined the association between T2DM and these biomarkers. We built multivariate multiple linear regression models sequentially adjusted for socio-demographic, lifestyle, and clinical covariates. Results Participants with T2DM had a higher resting heart rate (66 vs. 61 beats per minute, p

Abstract Background Diagnosis of dementia with Lewy bodies (DLB) is challenging, especially in the earlier stages of the disease, owing to the clinical overlap with other neurodegenerative diseases such as Alzheimer’s (AD) and Parkinson’s disease (PD). We aimed to identify the transcranial sonography (TCS) parameters that can help us to detect early DLB patients. Methods In this cross-sectional study, we prospectively recruited newly diagnosed DLB patients with less than 3 years from the onset of cognitive symptoms. For comparison purposes, we also included AD and PD patients, with a disease duration of less than 3 years, and a control group. TCS was performed to assess the substantia nigra (SN) echogenicity, the width of the third ventricle, and the frontal horns of the lateral ventricles. Subsequently, TCS images were analyzed with the medical image viewer Horos in order to quantify the intensity of the echogenicity of the SN. Univariate analysis and a logistic regression model were used to identify which variables can predict the diagnosis of DLB. Results One hundred and seven participants were included (23 DLB, 26 AD, 27 PD and 31 controls). The median age of DLB patients was 75(72–77) years, with a disease duration of 2 years. DLB and PD patients showed higher SN hyperechogenicity rates (72.73% and 81.82%, respectively) and a greater area of the SN compared to AD patients and controls (p

Abstract Background Besides the high prevalence of HIV and HCV infections, people who inject drugs (PWID) have a cumulative risk of acquiring skin and soft tissue infections (SSTI) from, among other things, social precariousness, homelessness/unstable housing, and unhygienic injecting practices. We propose to evaluate whether a two-component educational hand hygiene intervention which combines training in hand-washing with the supply of a single-use alcohol-based hand rub, called MONO-RUB, is effective in reducing injection-related abscesses in the PWID population. Specifically, we shall implement a nationwide, two-arm, multi-centre, cluster randomised controlled trial to evaluate the effectiveness and cost-effectiveness of this intervention in PWID. Methods HAWA is a community-based participatory research study to be conducted in 22 harm reduction centres (HR) in France (not yet recruiting); the latter will be randomised into two clusters: centres providing standard HR services and the intervention (i.e., intervention group) and those providing standard HR services only (i.e., control group). After randomization, each cluster will include 220 PWID, with an inclusion period of 12 months and an individual follow-up period of 6 months. For each participant, we will collect data at M0, M3 and M6 from photos of injection sites on the participant’s body, a face-to-face injection-related SSTI questionnaire, and a CATI questionnaire. The primary outcome is the reduction in abscess prevalence between M0 and M6, which will be compared between the control and intervention arms, and measured from observed (photographs) and self-declared (SSTI questionnaire) data. We will also assess the cost-effectiveness of the intervention. Discussion The HAWA trial will be the first cluster randomized controlled trial to improve hand hygiene among PWID with a view to reducing SSTI. If effective and cost-effective, the intervention combined with the distribution of MONO-RUBs (or a similar cleaning product) may prove to be an important HR tool, helping to reduce the enormous burden of infection-related deaths and diseases in PWID. Trial Registration NCT06131788, received on 2 January 2024.

Abstract The genetic landscape underlying the transformation of splenic diffuse red pulp small B‐cell lymphoma (SDRPL) is not well understood. The present study aimed to unravel the genomic alterations involved in the progression and transformation of SDRPL. We performed genetic studies on both SDRPL and subsequent or synchronous diffuse large B cell lymphoma (DLBCL) samples in three SDRPL patients who eventually developed DLBCL. Our findings revealed that SDRPL cases progressing to DLBCL acquired genomic alterations in genes related to the cell cycle (CDKN2A/B, TP53, MYC and CCND3) and B cell development (BCL6).

Abstract A 54-year-old female presented with recurrent abdominal pain and new onset chest pain. Chest computed-tomography angiogram detected a thoracic aortic aneurysm with suspected Type A intramural hematoma (IMH) versus aortitis. Initially, conservative management was pursued while awaiting a definitive diagnosis. Differential workup was negative, while additional imaging modalities favored IMH, prompting expedited surgical intervention. During ascending aortic and hemiarch replacement, severe aortitis was unexpectedly discovered without evidence of IMH. Histopathological examination of the aortic specimens identified transmural aortic inflammation with lymphoplasmacytic infiltrate and irregular fibrosis. Numerous IgG4-positive plasma cells were present with IgG4/IgG ratio of 40–50% suggesting IgG4-related disease (IgG4-RD). Subsequent analysis revealed B cells positive for clonal IgH gene rearrangement, and bone marrow biopsy then revealed the same clonal B cells. She was ultimately diagnosed with CLL, the most common phenotype of monoclonal B-cell lymphocytosis, thought to account for the IgG4-predominant plasma cells causing aortitis. Although rare, this case highlights the importance of considering IgG4-related disease (IgG4-RD) as a cause of aortitis when assessing symptomatic patients with aortic pathologies, emphasizing the complexities involved in diagnosing due to a variety of imaging presentation, differentiating, and managing large-vessel vasculitides. Moreover, it underscores the importance of Multidisciplinary Aortic Team care and the use of multiple diagnostic modalities in evaluating ambiguous aortic pathologies.

Elisabetta Bugianesi,1 Luca Miele,2,3 Giovanna Donnarumma,4 Katrine Grau,5 Mariarosaria Mancuso,4 Preethy Prasad,5 Andrea Leith,6 Victoria Higgins6 1Division of Gastroenterology, Department of Medical Sciences, University of Torino, AOU Città della Salute e della Scienza, Torino, Italy; 2Dipartimento di Scienze Mediche e Chirurgiche Addominali ed Endocrino Metaboliche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy; 3Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy; 4Novo Nordisk SpA, Rome, Italy; 5Novo Nordisk A/S, Søborg, Denmark; 6Adelphi Real World, Bollington, Cheshire, UKCorrespondence: Elisabetta Bugianesi, Email elisabetta.bugianesi@unito.itBackground: Although the estimated prevalence of non-alcoholic steatohepatitis (NASH) in Italy is 4– 6%, little is known about patient characteristics and care pathways.Aim: To describe patient characteristics and management approaches for patients with NASH or suspected NASH in Italy.Methods: Data were drawn from the Adelphi Real World NASH Disease Specific Programme™, a cross-sectional survey of endocrinologists and gastroenterologists in Italy from January to March 2018. Physicians completed questionnaires for their next five consecutively consulting patients with NASH or suspected NASH. Analyses were descriptive.Results: Seventy-six physicians provided data on 380 patients. The mean age was 58.5 ± 11.1 years and the mean body mass index was 31.8 ± 5.5 kg/m2. A total of 231 patients (61%) had no/non-advanced fibrosis as evaluated by liver biopsy or non-invasive tests. Common diagnostic assessments were cholesterol, hemoglobin A1c, absence of viral hepatitis, and alcohol assessment. At diagnosis, 87% (n=322/372) and 45% (n=169/372) of patients received an ultrasound and liver biopsy, respectively. Overall, 88% of patients were referred from primary to secondary care. Obesity (81%) and type 2 diabetes (62%) were the most commonly recorded comorbidities, with 70% of patients having ≥ 3 comorbidities. Vitamin E (13%) and GLP-1 receptor agonists (13%) were the most prescribed guideline-recommended treatments for all patients.Conclusion: Patients with NASH in Italy had high levels of obesity and comorbidities, while diagnosis and treatment frequently were not according to guidelines. Our data show an unmet need for more targeted diagnosis and treatment in Italian patients with NASH, in order to optimize outcomes.Plain language summary: Fat buildup in the liver, known as fatty liver disease, affects around 4-6% of people in Italy, and can lead to complications if left untreated. However, little is known about how doctors manage people with this disease. Fatty liver disease can only be diagnosed by a liver biopsy, but we found this is only performed in 45% of people, making accurate diagnosis difficult. We also found that 28% of people receive a recommended medication. Overall, increasing doctor awareness of fatty liver medical guidelines may help improve the diagnosis and treatment for people living with fatty liver disease in Italy.Keywords: NASH diagnosis, NASH treatment, NASH resource utilization

Background: The consortium project INTEGRATE-ADHD compared administrative data on the presence of attention-deficit/hyperactivity disorder (ADHD) in children and adolescents with the results of a parent survey and a comprehensive clinical assessment based on the S3 guideline of the Association of the Scientific Medical Societies in Germany (AWMF). Due to the COVID-19 pandemic, the clinical assessment was carried out online. Methods: The article describes how a guideline-based clinical assessment of ADHD can be implemented in an online setting. A specially developed diagnostic matrix is presented to illustrate the assessment procedures and the diagnostic decision-making process. The matrix is intended to help the diagnostician to gain an overview of the numerous individual findings that have been collected using different assessment perspectives and methods (e.g. diagnostic interviews, rating scales, performance tests) in order to make a well-founded and transparent diagnostic decision. Discussion: The consortium project INTEGRATE-ADHD has shown that an online assessment can be implemented in a guideline-compliant manner and allows a valid clinical decision. The diagnostic strategy is discussed with reference to international guidelines and recommendations for online diagnostics (e.g. aspects of feasibility, acceptability and safety of the assessment procedures). The challenges and opportunities of using online assessments in clinical practice are also described.

Background: The study examines the psychometric properties of the ADHD section of the semi-structured diagnostic interview ILF-EXTERNAL, which was conducted online via video chat. Methods: As part of the INTEGRATE-ADHD research project, 202 children and adolescents (age M = 12.87 years, SD = 3.04, 28.2 % female) with an administrative diagnosis of ADHD registered with their health insurance company were clinically assessed for the presence of ADHD according to the German ADHD S3 guideline. Using the ILF-EXTERNAL, one parent and, from the age of eight, also the children themselves were interviewed. A proxy rating by a parent was made using the German FBB-ADHS rating scale. In a subsample (n = 65), an independent blind interviewer rated the videorecordings of the ILF-EXTERNAL parent interview to determine the interrater reliability of the ILF-EXTERNAL. Results: All ADHD symptom scales of the ILF-EXTERNAL showed good to excellent internal consistency (α = 0.89 to 0.93). Interrater reliability was high for both categorical and dimensional analyses (κ = 0.78 and κ = 0.81; ICC(1,1) = 0.97 and 0.98). High correlations of the ILF-EXTERNAL parent interview with the FBB-ADHS (r = 0.79 to r = 0.85) and with the ILF-EXTERNAL child interview (r = 0.60 to r = 0.71) demonstrated convergent validity. Conclusions: Sound psychometric properties of the ILF-EXTERNAL were also confirmed for its use in an online setting. High interrater reliabilities demonstrate the quality of the ADHD diagnostics carried out in the consortium project INTEGRATE-ADHD.

Abstract Soil-transmitted helminth (STH) infections account for a significant global health burden, necessitating mass drug administration with benzimidazole-class anthelmintics, such as albendazole (ALB), for morbidity control. However, ALB efficacy shows substantial variability, presenting challenges for achieving consistent treatment outcomes. We have explored the potential impact of the baseline gut microbiota on ALB efficacy in hookworm-infected individuals through microbiota profiling and machine learning (ML) techniques. Our investigation included 89 stool samples collected from hookworm-infected individuals that were analyzed by microscopy and quantitative PCR (qPCR). Of these, 44 were negative by microscopy for STH infection using the Kato-Katz method and qPCR 21 days after treatment, which entails a cure rate of 49.4%. Microbiota characterization was based on amplicon sequencing of the V3–V4 16S ribosomal RNA gene region. Alpha and beta diversity analyses revealed no significant differences between participants who were cured and those who were not cured, suggesting that baseline microbiota diversity does not influence ALB treatment outcomes. Furthermore, differential abundance analysis at the phylum, family and genus levels yielded no statistically significant associations between bacterial communities and ALB efficacy. Utilizing supervised ML models failed to predict treatment response accurately. Our investigation did not provide conclusive insights into the relationship between gut microbiota and ALB efficacy. However, the results highlight the need for future research to incorporate longitudinal studies that monitor changes in the gut microbiota related to the infection and the cure with ALB, as well as functional metagenomics to better understand the interaction of the microbiome with the drug, and its role, if there is any, in modulating anthelmintic treatment outcomes in STH infections. Interdisciplinary approaches integrating microbiology, pharmacology, genetics and data science will be pivotal in advancing our understanding of STH infections and optimizing treatment strategies globally. Graphical Abstract

Abstract Background Polygenic risk scores (PRS) derived from European individuals have reduced portability across global populations, limiting their clinical implementation at worldwide scale. Here, we investigate the performance of a wide range of PRS models across four ancestry groups (Africans, Europeans, East Asians, and South Asians) for 14 conditions of high-medical interest. Methods To select the best-performing model per trait, we first compared PRS performances for publicly available scores, and constructed new models using different methods (LDpred2, PRS-CSx and SNPnet). We used 285 K European individuals from the UK Biobank (UKBB) for training and 18 K, including diverse ancestries, for testing. We then evaluated PRS portability for the best models in Europeans and compared their accuracies with respect to the best PRS per ancestry. Finally, we validated the selected PRS models using an independent set of 8,417 individuals from Biobank of the Americas-Genomelink (BbofA-GL); and performed a PRS-Phewas. Results We confirmed a decay in PRS performances relative to Europeans when the evaluation was conducted using the best-PRS model for Europeans (51.3% for South Asians, 46.6% for East Asians and 39.4% for Africans). We observed an improvement in the PRS performances when specifically selecting ancestry specific PRS models (phenotype variance increase: 1.62 for Africans, 1.40 for South Asians and 0.96 for East Asians). Additionally, when we selected the optimal model conditional on ancestry for CAD, HDL-C and LDL-C, hypertension, hypothyroidism and T2D, PRS performance for studied populations was more comparable to what was observed in Europeans. Finally, we were able to independently validate tested models for Europeans, and conducted a PRS-Phewas, identifying cross-trait interplay between cardiometabolic conditions, and between immune-mediated components. Conclusion Our work comprehensively evaluated PRS accuracy across a wide range of phenotypes, reducing the uncertainty with respect to which PRS model to choose and in which ancestry group. This evaluation has let us identify specific conditions where implementing risk-prioritization strategies could have practical utility across diverse ancestral groups, contributing to democratizing the implementation of PRS.

Durante los últimos 40 años, las élites económicas y políticas de Costa Rica han implementado consistentemente políticas laborales neoliberales. Este texto se propone reconstruir ese camino de cuatro décadas alrededor de tres aspectos de la política que siguen teniendo vigencia en el debate laboral actual: la política de empleo público, la flexibilización de la jornada laboral y la política del Estado costarricense hacia los sindicatos. El análisis que se presenta en este texto, combina una sistematización de estudios realizados principalmente sobre las dos primeras décadas de estudio, con un análisis propio de la autora basado en fuentes primarias: proyectos de leyes, discursos políticos y prensa de las dos últimas décadas. Se concluye que el antisindicalismo ha sido el componente estratégico de la política laboral neoliberal en Costa Rica, por lo que se plantea la necesidad urgente de revalorizar y fortalecer la organización independiente de la clase trabajadora para poder revertir la lógica neoliberal en el ámbito laboral.

Abstract Purpose To determine the factors influencing the likelihood of biochemical pregnancy loss (BPL) after transfer of a euploid embryo from preimplantation genetic testing for aneuploidy (PGT-A) cycles. Methods The study employed an observational, retrospective cohort design, encompassing 6020 embryos from 2879 PGT-A cycles conducted between February 2013 and September 2021. Trophectoderm biopsies in day 5 (D5) or day 6 (D6) blastocysts were analyzed by next generation sequencing (NGS). Only single embryo transfers (SET) were considered, totaling 1161 transfers. Of these, 49.9% resulted in positive pregnancy tests, with 18.3% experiencing BPL. To establish a predictive model for BPL, both classical statistical methods and five different supervised classification machine learning algorithms were used. A total of forty-seven factors were incorporated as predictor variables in the machine learning models. Results Throughout the optimization process for each model, various performance metrics were computed. Random Forest model emerged as the best model, boasting the highest area under the ROC curve (AUC) value of 0.913, alongside an accuracy of 0.830, positive predictive value of 0.857, and negative predictive value of 0.807. For the selected model, SHAP (SHapley Additive exPlanations) values were determined for each of the variables to establish which had the best predictive ability. Notably, variables pertaining to embryo biopsy demonstrated the greatest predictive capacity, followed by factors associated with ovarian stimulation (COS), maternal age, and paternal age. Conclusions The Random Forest model had a higher predictive power for identifying BPL occurrences in PGT-A cycles. Specifically, variables associated with the embryo biopsy procedure (biopsy day, number of biopsied embryos, and number of biopsied cells) and ovarian stimulation (number of oocytes retrieved and duration of stimulation), exhibited the strongest predictive power.

Abstract Background To investigate the reproducibility of automated volumetric bone mineral density (vBMD) measurements from routine thoracoabdominal computed tomography (CT) assessed with segmentations by a convolutional neural network and automated correction of contrast phases, on diverse scanners, with scanner-specific asynchronous or scanner-agnostic calibrations. Methods We obtained 679 observations from 278 CT scans in 121 patients (77 males, 63.6%) studied from 04/2019 to 06/2020. Observations consisted of two vBMD measurements from Δdifferent reconstruction kernels (n = 169), Δcontrast phases (n = 133), scan Δsessions (n = 123), Δscanners (n = 63), or Δall of the aforementioned (n = 20), and observations lacking scanner-specific calibration (n = 171). Precision was assessed using root-mean-square error (RMSE) and root-mean-square coefficient of variation (RMSCV). Cross-measurement agreement was assessed using Bland-Altman plots; outliers within 95% confidence interval of the limits of agreement were reviewed. Results Repeated measurements from Δdifferent reconstruction kernels were highly precise (RMSE 3.0 mg/cm3; RMSCV 1.3%), even for consecutive scans with different Δcontrast phases (RMSCV 2.9%). Measurements from different Δscan sessions or Δscanners showed decreased precision (RMSCV 4.7% and 4.9%, respectively). Plot-review identified 12 outliers from different scan Δsessions, with signs of hydropic decompensation. Observations with Δall differences showed decreased precision compared to those lacking scanner-specific calibration (RMSCV 5.9 and 3.7, respectively). Conclusion Automatic vBMD assessment from routine CT is precise across varying setups, when calibrated appropriately. Low precision was found in patients with signs of new or worsening hydropic decompensation, what should be considered an exclusion criterion for both opportunistic and dedicated quantitative CT. Relevance statement Automated CT-based vBMD measurements are precise in various scenarios, including cross-session and cross-scanner settings, and may therefore facilitate opportunistic screening for osteoporosis and surveillance of BMD in patients undergoing routine clinical CT scans. Key Points Artificial intelligence-based tools facilitate BMD measurements in routine clinical CT datasets. Automated BMD measurements are highly reproducible in various settings. Reliable, automated opportunistic osteoporosis diagnostics allow for large-scale application. Graphical Abstract

Often, Latin America conservation policy implicitly assumes past references to define worth-conserving ecosystems. However, the Pleistocene/pre-human reference is based on biophysical conditions impossible to be restored; the early Holocene reference overlooks that early humans likely caused massive extinctions; pre-European references fail to acknowledge that indigenous societies were often unsustainable and that many valuable ecosystems are in part a colonial legacy; pre-industrial references underplay the role of biological invasions, modern technology and socioeconomic development to preserve, increase or generate biodiversity. The Anthropocene rapid dynamics requires forward-looking policies that incorporate change as a source of biodiversity and resilience, actively accept that urbanization and modern agriculture can play a key role in conservation, challenge the prevalence of nativism and eco-alarmism, and emphasize that research should focus on shaping future socio-ecological scenarios, that would necessarily differ from the past.

Abstract Background Comprehensive cancer care requires effective collaboration by interprofessional healthcare teams. The need to develop educational initiatives to improve interprofessional collaboration is increasingly recognised. However, there is no agreement regarding the interprofessional competencies required for effective cancer care leading to much variation on the focus of research, planning and managing change. A scoping review was conducted to identify the current status of IPE in cancer care and to summarise the results of previous research in order to guide the development of interprofessional education in cancer care. Methods The JBI Scoping Review guidelines were used to guide the process of the review. A search of the available literature was conducted in CINAHL, MEDLINE (Ovid), PubMed, PsycInfo, Scopus databases from January 2012 to March 2023 to investigate IPE for health professional clinicians working in cancer care. Results Of the 825 initial references and 153 studies imported for screening, a total of 28 studies were included in the final review. From those studies, seven focused on the need for IPE and interprofessional competence for oncology healthcare professionals, four reviewed existing IPE programs and 17 described the development and evaluation of interprofessional education. Findings show variation and lack of concept definitions underpinning research in IPE in cancer care settings. Variation also exists in the range of research activities in IPE, most notably related to communication, teamwork and the development of interprofessional practice. The evaluation of impact of IPE is mainly focused on health care professionals’ self-evaluation and general feedback. Impact on patient care was only evaluated in one study. Conclusions Based on the results, interprofessional education research in the field of cancer care is limited in Europe. Thus, there is a significant increase in publications in the last five years. A more systematic focus on the theoretical framework and definition of concepts would be of value. Research and programme development should be based on a shared understanding on what constitutes the interprofessional competences and IPE. Programmes to develop interprofessional practice should be developed and implemented systematically with inclusion of validated assessment methods, and evaluated and improved regularly.

Abstract Bike-sharing systems have emerged as a significant element of urban mobility, providing an environmentally friendly transportation alternative. With the increasing integration of electric bikes alongside mechanical bikes, it is crucial to illuminate distinct usage patterns and their impact on maintenance. Accordingly, this research aims to develop a comprehensive understanding of mobility dynamics, distinguishing between different mobility modes, and introducing a novel predictive maintenance system tailored for bikes. By utilising a combination of trip information and maintenance data from Barcelona’s bike-sharing system, Bicing, this study conducts an extensive analysis of mobility patterns and their relationship to failures of bike components. To accurately predict maintenance needs for essential bike parts, this research delves into various mobility metrics and applies statistical and machine learning survival models, including deep learning models. Due to their complexity, and with the objective of bolstering confidence in the system’s predictions, interpretability techniques explain the main predictors of maintenance needs. The analysis reveals marked differences in the usage patterns of mechanical bikes and electric bikes, with a growing user preference for the latter despite their extra costs. These differences in mobility were found to have a considerable impact on the maintenance needs within the bike-sharing system. Moreover, the predictive maintenance models proved effective in forecasting these maintenance needs, capable of operating across an entire bike fleet. Despite challenges such as approximated bike usage metrics and data imbalances, the study successfully showcases the feasibility of an accurate predictive maintenance system capable of improving operational costs, bike availability, and security.

Highlights: • Some archaeological results obtained using SAR-X images received through the PAZ satellite and applied to a part of what was called Ager Cosanus are shown in this article. • The study has been completed with the analysis of multispectral images TripleSAT and Sentinel-2A and the historical aerial photos from 1944 and 1954. • The possibilities of using PAZ images treated multi-temporally as a high-resolution panchromatic image applicable to multispectral optical images of the type Sentinel-2 were tested. Abstract: Some archaeological results are shown in this article, which have been generated from the use of Synthetic Aperture Radar (SAR)-X images obtained from the PAZ satellite and applied to part of what was called Ager Cosanus, that is, the territory of the city of Cosa, which was one of the first maritime colonies of Rome in the heart of Etruscan territory. Our study has been carried out mainly based on previous works in which a set of images was used to improve the quality of the resulting image, reducing the noise caused by the speckle of the radar images and maintaining the quality of the spatial resolution that can be obtained from these images (1.25 m/pixel). More specifically, a set of images obtained between 2019 and 2021 was used. The study has been completed with the analysis of multispectral images TripleSAT and Sentinel-2A, the historical aerial photos taken from 1944 and 1954, and the use of the historical cadastre of Tuscany, prepared at the beginning of the 19th century. As an addition, the Digital Terrain Model (DTM) Light Detection And Ranging (LiDAR) of the Region of Tuscany was used, on which various functions of the Relief Visualization Tool (RVT) programme have been applied, complementing or contrasting the results. It can be confirmed that the multi-temporal treatment of SAR PAZ images provides better results than an individualised analysis of the image. Finally, it is of great interest to verify the results of studies using new technologies, where it was previously possible to resort only to prospecting on the ground and to analogical aerial photography in black and white. In this case, the Sinistra Decumano I (SDI) structure was seen, which Castagnoli observed in the aerial photography, but of which he only located materials on the ground and it was visualised both in individualised PAZ images and in Sentinel-2.

Background: Epidemic intelligence (EI) ensures early detection, assessment, and communication of public health threats. Threat reporting defines priorities and mobilize resources for surveillance, prevention, and control. In Portugal, the Directorate-General of Health (DGS) is responsible for EI and publishes a weekly public health threat report (RONDA). Changes in threats in regular threat reports since COVID-19 have not been previously described. We analysed changes in non-COVID threat reporting in the weekly threat report. Methods: Using the DGS Emergency Operations Centre’s threat reporting database, we compared threats reported in RONDAs from 2016 to 2022 in three sequential periods: P1 before COVID-19 (January 2016–March 2020), P2 during acute COVID-19 restrictions (April 2020–February 2022), and P3 in post-acute COVID-19 phase (February 2022–September 2022). We described the monthly average frequency of reports on non-COVID-19 threats in those periods considering different disease groups, geographical focus, and information sources. We estimated expected non-COVID-19 reports on threats using a forecast model fitted to the time series until March 2020 and compared observed and expected values. Results: Non-COVID-19 threats had a decrease in the monthly average frequency of reporting in period 2 (x¯1: 4.7 vs. x¯: 2.3, p < 0.001) compared to period 1. Using the forecast methods, there were 114 fewer non-COVID threats than the 162 expected (−70%) in period 2. In period 3, there were 105 more threats than expected (+256%). The ECDC and the WHO were the most frequent sources of information followed by national Public Health sources. Conclusions: During COVID-19, there was a decrease in reports on non-COVID threats in Portugal. COVID-19 possibly affected global EI, by shifting attention and resources from other threats to the pandemic. However, the number of threats that warrant follow-up and communication is increasing. Further research is necessary to inform the EI research and development agenda, to ensure that all relevant threats are detected, accessed, and communicated according to evolving EI objectives and priorities while resources and preparedness are guaranteed.

Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a growing health concern due to its increasing prevalence worldwide. Metabolic homeostasis encompasses the stable internal conditions vital for efficient metabolism. This equilibrium extends to the intestinal microbiota, whose metabolic activities profoundly influence overall metabolic balance and organ health. The metabolites derived from the gut microbiota metabolism can be defined as microbiota-related co-metabolites. They serve as mediators between the gut microbiota and the host, influencing various physiological processes. The recent redefinition of the term MASLD has highlighted the metabolic dysfunction that characterize the disease. Metabolic dysfunction encompasses a spectrum of abnormalities, including impaired glucose regulation, dyslipidemia, mitochondrial dysfunction, inflammation, and accumulation of toxic byproducts. In addition, MASLD progression has been linked to dysregulation in the gut microbiota and associated co-metabolites. Short-chain fatty acids (SCFAs), hippurate, indole derivatives, branched-chain amino acids (BCAAs), and bile acids (BAs) are among the key co-metabolites implicated in MASLD progression. In this review, we will unravel the relationship between the microbiota-related metabolites which have been associated with MASLD and that could play an important role for developing effective therapeutic interventions for MASLD and related metabolic disorders.

Introducción. La pandemia por COVID-19 interrumpe la educación presencial y de manera abrupta obliga a los sistemas educativos a transicionar hacia la educación remota de emergencia (ERE). En este modelo educativo se observan diversos efectos negativos, entre ellos el bajo nivel de aprendizaje de los estudiantes y las barreras para acceder a la educación para quienes están en situación de vulnerabilidad, considerando en dicho grupo a la niñez migrante. Metodología. Estudio cualitativo de tipo descriptivo exploratorio. Se realizaron entrevistas semiestructurada a 26 estudiantes de entre 6 y 11 años de edad, y a 6 profesionales de la educación. El objetivo es reconstruir la experiencia de estudiar de manera remota de emergencia (ERE) durante los años 2020-2021, desde la subjetividad de estudiantes de familias migrantes y profesionales de la educación pública. Resultados. La transición hacia la ERE para los estudiantes y profesores fue sumamente compleja. Muchos niños(as) migrantes debieron estudiar en condiciones que no eran óptimas, lo que es debido a fenómenos como el hacinamiento y la brecha digital. Por otro lado, según los profesores, en muchos casos hubo un bajo nivel de apoyo familiar, producto de la necesidad de trabajar para subsistir y también por el bajo nivel de escolaridad de los familiares. Así también, se observó que los profesionales entrevistados prestaron un importante apoyo a sus estudiantes, el cual tuvo un carácter pedagógico, pero también de acompañamiento. Discusión. La escuela cumple una función crucial como espacio de socialización para niños(as) migrantes, quienes aprenden en la escuela a interactuar con otros grupos que difieren en tradiciones, costumbres o creencias. El proceso de aprendizaje en los escenarios presenciales permite conocer las distintas realidades de los estudiantes, y posibilita que los profesores reconozcan los trastornos que afectan el aprendizaje de los estudiantes. A raíz de la ERE, la evidente pérdida de aprendizaje en estudiantes, que es tan aguda como generalizada, vislumbra que la presencialidad es un elemento insustituible para contrarrestar los efectos del deterioro en el ritmo de aprendizaje. Esta situación es especialmente preocupante si se considera además el importante papel que puede ocupar la escuela en la adquisición de herramientas de un/a niño(a), las cuales determinan gran parte de las trayectorias de vida. Frente a lo anterior, para fortalecer el compromiso escolar, y promover la permanencia en el sistema educativo de los estudiantes, es clave el apoyo de profesores y sus familias. Conclusiones. Este periodo ha sido uno de los más desafiantes para la política educacional chilena. En lo relativo a la población migrante, y más allá del contexto de pandemia, que no hizo más que develar una realidad que había permanecido oculta, se requiere el desarrollo de políticas educativas con énfasis en la interculturalidad, junto con un trabajo interdisciplinario y en red, que fortalezca el involucramiento de las familias en las trayectorias educativas de sus hijos(as). Y en esto el Trabajo Social tiene mucho que aportar, trabajando tanto a nivel de prevención como de intervención en la exclusión educativa y en una posible deserción escolar de la niñez migrante.

The use of Unmanned Aerial Vehicles (UAV) has increased in the last decade, using these technologies for many different topics, such as infrastructure inspection or biodiversity monitoring. The main advantages of these systems are its reduced cost and its ability to navigate on hard-accessible areas, what makes it possible to acquire aerial data with a reduced cost. The new technological developments and the progress in the definition of the regulations applicable to these vehicles have allowed the first BVLOS (Beyond Visual Line of Sight) operations to begin to be carried out at a professional level, which has meant a great advance for the UAV sector. In this field, Telespazio Ibérica SLU is leading a project called GEOSUB, which objective is the development of a UAV integral solution for biodiversity monitoring. The project has two main parts. The first one is the evolution and improvement of a fixed-wing and multicopter UAV, equipped with four different sensors: RGB camera, multispectral camera, thermographic camera, and a LiDAR sensor. The second part focused on the development of a geoinformation processing platform for both the mission planification and monitoring, and the data processing to obtain the final product. This work presents the preliminary results of the project and goes in depth with the developments made.

Abstract Background Continued dietary treatment since early diagnosis through newborn screening programs usually prevents brain-related complications in phenylketonuria (PKU). However, subtle neurocognitive and brain alterations may be observed in some adult patients despite early treatment. Nevertheless, neuropsychological and neuroimaging studies in the field remain scarce. Objectives This work aimed to determine possible neuropsychological and structural brain alterations in treated adult patients with PKU. Methods Thirty-five patients with PKU and 22 healthy controls (HC) underwent neuropsychological assessment and T1-weighted magnetic resonance imaging on a 3 T scanner. FreeSurfer (v.7.1) was used to obtain volumetric measures and SPSS (v27.0.1.0) was used to analyze sociodemographic, neuropsychological, volumetric, and clinical data (p

Abstract Background The high rate of stoma placement during emergency laparotomy for secondary peritonitis is a paradigm in need of change in the current fast-track surgical setting. Despite growing evidence for the feasibility of primary bowel reconstruction in a peritonitic environment, little data substantiate a surgeons’ choice between a stoma and an anastomosis. The aim of this retrospective analysis is to identify pre- and intraoperative parameters that predict the leakage risk for enteric sutures placed during source control surgery (SCS) for secondary peritonitis. Methods Between January 2014 and December 2020, 497 patients underwent SCS for secondary peritonitis, of whom 187 received a primary reconstruction of the lower gastro-intestinal tract without a diverting stoma. In 47 (25.1%) patients postoperative leakage of the enteric sutures was directly confirmed during revision surgery or by computed tomography. Quantifiable predictors of intestinal suture outcome were detected by multivariate analysis. Results Length of intensive care, in-hospital mortality and failure of release to the initial home environment were significantly higher in patients with enteric suture leakage following SCS compared to patients with intact anastomoses (p

Abstract Aim Acute respiratory distress syndrome or ARDS is an acute, severe form of respiratory failure characterised by poor oxygenation and bilateral pulmonary infiltrates. Advancements in signal processing and machine learning have led to promising solutions for classification, event detection and predictive models in the management of ARDS. Method In this review, we provide systematic description of different studies in the application of Machine Learning (ML) and artificial intelligence for management, prediction, and classification of ARDS. We searched the following databases: Google Scholar, PubMed, and EBSCO from 2009 to 2023. A total of 243 studies was screened, in which, 52 studies were included for review and analysis. We integrated knowledge of previous work providing the state of art and overview of explainable decision models in machine learning and have identified areas for future research. Results Gradient boosting is the most common and successful method utilised in 12 (23.1%) of the studies. Due to limitation of data size available, neural network and its variation is used by only 8 (15.4%) studies. Whilst all studies used cross validating technique or separated database for validation, only 1 study validated the model with clinician input. Explainability methods were presented in 15 (28.8%) of studies with the most common method is feature importance which used 14 times. Conclusion For databases of 5000 or fewer samples, extreme gradient boosting has the highest probability of success. A large, multi-region, multi centre database is required to reduce bias and take advantage of neural network method. A framework for validating with and explaining ML model to clinicians involved in the management of ARDS would be very helpful for development and deployment of the ML model.

Introduction: Literacy of health professionals on patient safety aims to prevent and reduce risks and adverse events in healthcare. Objective: The objective of this study was to translate, adapt, and validate for Portugal of the World Health Organization Questionnaire to Assess the Implementation of the Multiprofessional Guide. Methodology: Following the cultural adaptation process, we carried out a psychometric analysis on a sample of 300 health professionals. The scale was tested for apparent and content validity. Psychometric properties were assessed using Cronbach’s alpha coefficient (α) through exploratory and confirmatory factor analysis, convergent validity, and discriminant validity. Results: Exploratory factor analysis led to a tetra factor structure that accounted for 43.0% of the variance and had an overall alpha of 0.759. The hypothesized structure was submitted to confirmatory factor analysis, and the following items were eliminated from factors 1, 2, and 3 and the respective items: 7; 5; and 3, 4, 5, and 6, due to multicollinearity problems. Overall good-of-fit indexes are reliable. Conclusions: The “KIT TOOL-S2 TEXT” scale presents a factor structure with satisfactory validity and reliability results, adequately representing the constructs in question.

Objective To evaluate the impact of coadministering statins with direct oral anticoagulants (DOACs) on the risk of major bleeding events in patients with venous thromboembolism (VTE).Design Observational cohort analysis based on a multicentre international registry.Setting Data were extracted from the Registro Informatizado de Enfermedad TromboEmbolica Registry, which involves 205 centres across 27 countries.Participants A total of 73 659 patients diagnosed with VTE were classified based on their anticoagulant therapy (DOACs) versus low-molecular-weight heparin (LMWH) or vitamin K antagonists (VKAs) and concurrent use of statins.Methods Multivariable Cox proportional hazards models adjusted for confounding variables to assess the risk of major bleeding events stratified by the type of anticoagulant use and statin use.Results From October 2013 to February 2023, 73 659 patients were recruited: 2573 were statin users on DOACs, 14 090 were statin users on LMWH or VKA therapy, 10 088 were non-statin users on DOACs and 46 908 were non-statin users on LMWH or VKA therapy. Statin users were 10 years older and more likely to have hypertension, diabetes, renal failure or prior artery disease. During anticoagulation (median, 187 days), 1917 patients (2.6%) suffered major bleeding. Rates of major bleeding per 100 patient-years were 2.33 (95% CI 1.72 to 3.09), 3.75 (95% CI 3.43 to 4.10), 1.39 (95% CI 1.13 to 1.69) and 3.10 (95% CI 2.93 to 3.27), respectively. On multivariable analysis, patients treated with DOACs had a significantly lower risk of major bleeding compared with those on LMWH or VKA therapy (adjusted HR 0.59; 95% CI 0.48 to 0.74). The adjusted HR in statin users versus non-users was 1.03 (95% CI 0.92 to 1.14), while in statin users on DOACs versus the rest of patients, it was 1.18 (95% CI 0.79 to 1.76).Conclusions In patients with VTE receiving statins, long-term anticoagulation with DOACs was associated with a reduced risk of major bleeding, regardless of the statin use. These findings support the safety profile of DOACs over VKAs or LMWH in the management of VTE in patients requiring statins.

Introducción: Este estudio explora los efectos toxicológicos de las nanopartículas de plata (AgNPs) y nanopartículas de óxido de hierro (Fe2O3NPs), que se utilizan como colorantes alimentarios (E-174 y E-172, respectivamente), al entrar en contacto con un medio acuoso que simula matrices alimentarias. Para ello se ha empleado el modelo biológico in vivo Caenorhabditis elegans. Metodología: Se evaluó el impacto de las NPs en parámetros fisicoquímicos, como el tamaño de partícula, el potencial zeta y la conductividad eléctrica. También se analizaron parámetros biológicos en C. elegans, incluyendo letalidad, estrés oxidativo y apoptosis o muerte celular. Resultados: El análisis fisicoquímico reveló cambios significativos en las propiedades de las NPs en contacto con el medio acuoso. Las AgNPs mostraron una mayor estabilidad, así como un aumento en su solubilización. Las Fe2O3NPs mostraron una mayor toxicidad aguda en comparación con las AgNPs, exponiendo tasas de letalidad más altas y mayor estrés oxidativo. El análisis de la apoptosis celular destacó aún más sus efectos tóxicos. Conclusiones: Los resultados del estudio mostraron el papel crítico de las características fisicoquímicas de las NPs y sus interacciones biológicas. Se demostró que las variaciones en la estabilidad de las NPs pueden aumentar su potencial tóxico cuando se utilizan como aditivos alimentarios. Los hallazgos requieren una investigación exhaustiva para comprender mejor el comportamiento de las NPs en las matrices alimentarias y los riesgos para la salud asociados, garantizando así la seguridad del consumidor. Financiación: Plan de Recuperación, Transformación y Resiliencia de la Comunidad Valenciana", a través del proyecto "Programa Investigo". Proyecto europeo "NAMS4NANO: Integración de Resultados de Nuevas Metodologías de Enfoque en Evaluaciones de Riesgo Químico: Estudios de Caso que Abordan Consideraciones a Escala Nanométrica", apoyado por la Agencia Europea de Seguridad Alimentaria (EFSA).

Abstract Testicular large B‐cell lymphoma (TLBCL) is an infrequent and aggressive lymphoma arising in an immune‐privileged site and has recently been recognized as a distinct entity from diffuse large B‐cell lymphoma (DLBCL). We describe the genetic features of TLBCL and compare them with published series of nodal DLBCL and primary large B‐cell lymphomas of the CNS (PCNSL). We collected 61 patients with TLBCL. We performed targeted next‐generation sequencing, copy number arrays, and fluorescent in situ hybridization to assess chromosomal rearrangements in 40 cases with available material. Seventy percent of the cases showed localized stages. BCL6 rearrangements were detected in 36% of cases, and no concomitant BCL2 and MYC rearrangements were found. TLBCL had fewer copy number alterations (p

Extraoral bitter taste receptors offer intriguing potential for modulating metabolism and the gut-brain axis through dietary interventions. Our understanding of these receptors is limited, and data on their effects on ageing are scarce. The complexity conveyed by their high diversity, low expression levels and species-dependent variability challenges our comprehension. We used real-time PCR to examine the relative abundance of multiple TAS2R across different segments of gastrointestinal mucosa in four human cohorts and related them to enteroendocrine secretions at the colon site. TAS2R14 exhibited the highest expression levels in all analyzed tissues. In contrast, TAS2R39, -38 and -42 consistently exhibited lower expression levels. Ageing was found to upregulate TAS2R4, -5, -13, -20 and GLP-1 mRNA in the descending colon. Stimulating TAS2R14 in Hutu-80 cells induced GLP-1 secretion, while stimulating TAS2R5 modulated GLP-1 and PYY secretion. Given the modifications TAS2R agonists may undergo along the GIT, as well as the distinctive expression patterns and possible functional roles of TAS2R receptors along the intestinal tract, our findings suggest the viability of a targeted strategy aimed at enhancing specific functions to improve health outcomes. This study offers valuable insights into the intricate interplay between bitter taste receptors, gut physiology and potential dietary interventions.

Summary: Background: The identification of patients with an elevated risk of developing Alzheimer's disease (AD) dementia and eligible for the disease-modifying treatments (DMTs) in the earliest stages is one of the greatest challenges in the clinical practice. Plasma biomarkers has the potential to predict these issues, but further research is still needed to translate them to clinical practice. Here we evaluated the clinical applicability of plasma pTau181 as a predictive marker of AD pathology in a large real-world cohort of a memory clinic. Methods: Three independent cohorts (modelling [n = 991, 59.7% female], testing [n = 642, 56.2% female] and validation [n = 441, 55.1% female]) of real-world patients with subjective cognitive decline (SCD), mild cognitive impairment (MCI), AD dementia, and other dementias were included. Paired cerebrospinal fluid (CSF) and plasma samples were used to measure AT(N) CSF biomarkers and plasma pTau181. Findings: CSF and plasma pTau181 showed correlation in all phenotypes except in SCD and other dementias. Age significantly influenced the biomarker's performance. The general Aβ(+) vs Aβ(−) ROC curve showed an AUC = 0.77 [0.74–0.80], whereas the specific ROC curve of MCI due to AD vs non-AD MCI showed an AUC = 0.89 [0.85–0.93]. A cut-off value of 1.30 pg/ml of plasma pTau181 exhibited a sensitivity of 93.57% [88.72–96.52], specificity of 72.38% [62.51–79.01], VPP of 77.85% [70.61–83.54], and 8.30% false negatives in the subjects with MCI of the testing cohort. The HR of cox regression showed that patients with MCI up to this cut-off value exhibited a HR = 1.84 [1.05–3.22] higher risk to convert to AD dementia than patients with MCI below the cut-off value. Interpretation: Plasma pTau181 has the potential to be used in the memory clinics as a screening biomarker of AD pathology in subjects with MCI, presenting a valuable prognostic utility in predicting the MCI conversion to AD dementia. In the context of a real-world population, a confirmatory test employing gold-standard procedures is still advisable. Funding: This study has been mainly funded by Ace Alzheimer Center Barcelona, Instituto de Salud Carlos III (ISCIII), Biomedical Research Networking Centre in Neurodegenerative Diseases (CIBERNED), Spanish Ministry of Science and Innovation, Fundación ADEY, Fundación Echevarne and Grífols S.A.

Summary: Despite extensive global research into genetic predisposition for severe COVID-19, knowledge on the role of rare host genetic variants and their relation to other risk factors remains limited. Here, 52 genes with prior etiological evidence were sequenced in 1,772 severe COVID-19 cases and 5,347 population-based controls from Spain/Italy. Rare deleterious TLR7 variants were present in 2.4% of young (

A sequential common-pool resource game with variable elastic marginal profit is studied in this work both analytically and through numerical simulation. The game is studied in both classic and quantum approaches considering symmetric and asymmetric costs. In the classic approach, it is shown how the increase in the level of inelasticity in the model boosts the leader advantage in the perfect equilibrium solution as well as contributes to the depletion of the resource. The quantum approach enables the emergence of the symmetric Pareto optimal solution when the entanglement increases. Furthermore, for high values of the factor of entanglement, the Pareto solution is reached regardless of the level of elasticity of the game. These results are applicable to the model with symmetric and asymmetric costs.

Background: Physicians manage multiple obligations, providing best-practice treatment and patient- centred care in the standard treatment pathway while contributing to clinical trials simultaneously. These multifaceted responsibilities may introduce barriers and dilemmas to clinical trial execution, potentially impacting the clinical trial decision- making process. This study explores physicians’ barriers and dilemmas in executing clinical trials and the impact on clinical trial decision-making. Method: Qualitative semi-structured interviews were conducted with experienced oncologists. Moreover, participant observations were performed during clinical encounters involving discussions about clinical trials. The analysis followed a structured approach: (1) transcription of data, (2) inductive text coding, (3) exploration of patterns, and (4) interpretation, leading to the results. The results were discussed and validated by the study participants. Results: The results comprise (1) a description of the clinical practice, which presents the setting of clinical trial execution; (2) results regarding physicians’ barriers and dilemmas in executing clinical trials, leading to (3) the impact on clinical trial decision- making. The results involve barriers to time constraints for clinical trial tasks, dilemmas emerging from trial requirements or deviations from standard guidelines, and challenges with providing sufficient trial communication and adequate decision-making support, balancing between a paternalistic approach and respecting patient autonomy. Conclusion: The demanding obligations of clinical practice constitute a complex setting for executing clinical trials, resulting in numerous barriers and dilemmas that impact the decision-making process in clinical trials. The study emphasises the need for tailored clinical trial decision-making interventions to facilitate supportive, informed, and non-directive clinical trial decision-making.

Background and purpose: As preparation for a national randomized study comparing proton radiotherapy to photon radiotherapy, DAHANCA 35, we performed a non-randomized pilot study to investigate patient selection, logistics, planning, and treatment delivery. With the present study, as a comprehensive safety analysis, we want to compare toxicity during and up to two months after therapy to a historically matched group of patients treated with photon radiotherapy. Materials and methods: 62 patients treated with protons were matched to 124 patients who received photon treatment outside a protocol. Available data were retrieved from the DAHANCA database. Patients were matched on treatment centre, concurrent chemotherapy, tumour site, stage, p16 status for oropharynx cancers. Selection of patients for proton therapy was based on comparative treatment plans with a NTCP reduction for dysphagia and xerostomia at six months. Results: Baseline characteristics between groups were well balanced, except for the type of drug used concurrently; more photon patients received Carboplatin (21.2 % vs 5.8 %, p = 0.01). Proton therapy was associated with significantly less weight loss at the end of treatment, mean weight loss of 3 % for protons and 5 % for photons (p

Esta investigación tuvo como objetivo determinar la relación existente entre la calidad de servicio y la satisfacción del cliente en las redes de subtransmisión de la provincia de Santiago de Cuba en el año 2023; la investigación toma importancia y se hace necesaria dado que permite conocer los aspectos concernientes a la calidad de servicio y la satisfacción del contribuyente en las redes analizadas. El estudio es descriptivo, correlacional, con enfoque cuantitativo, el diseño fue no experimental, transversal, por medio de encuesta; la población estudiada estuvo constituida por un aproximado de 362,749 contribuyentes y una muestra aleatoria de 1,486 clientes, de acuerdo con los resultados se ha encontrado evidencia acerca de la existencia de una relación significativa y directa entre la calidad de servicio y la satisfacción del cliente, a pesar de que no ocurre lo mismo en los clientes más alejados o con menor umbral de calidad.

Cuando se emplean transformadores monofásicos con derivación central en las redes de distribución, para dar servicio a cargas no lineales, estos suelen estar cargados de forma desigual entre los extremos del devanado secundario, haciendo que circule una corriente por el neutro con un contenido armónico elevado y, que las corrientes que circulan por ambas mitades del devanado secundario, sean distintas en amplitud y forma de onda. Para determinar con mayor precisión la influencia de la distorsión armónica en las pérdidas, se propone un modelo a partir del empleo de factores de pérdidas de distorsión promedio. Este modelo, fue validado mediante un esquema que combina cargas lineales y no lineales, para distintos valores de cargabilidad del transformador, obteniéndose que la diferencia entre las pérdidas calculadas y las medidas en el laboratorio no exceden el 5 % en ninguna de las pruebas realizadas, arrojando un error absoluto medio de 2,04 W.

Abstract The emergence of new structures can often be linked to the evolution of novel cell types that follows the rewiring of developmental gene regulatory subnetworks. Vertebrates are characterized by a complex body plan compared to the other chordate clades and the question remains of whether and how the emergence of vertebrate morphological innovations can be related to the appearance of new embryonic cell populations. We previously proposed, by studying mesoderm development in the cephalochordate amphioxus, a scenario for the evolution of the vertebrate head mesoderm. To further test this scenario at the cell population level, we used scRNA-seq to construct a cell atlas of the amphioxus neurula, stage at which the main mesodermal compartments are specified. Our data allowed us to validate the presence of a prechordal-plate like territory in amphioxus. Additionally, the transcriptomic profile of somite cell populations supports the homology between specific territories of amphioxus somites and vertebrate cranial/pharyngeal and lateral plate mesoderm. Finally, our work provides evidence that the appearance of the specific mesodermal structures of the vertebrate head was associated to both segregation of pre-existing cell populations, and co-option of new genes for the control of myogenesis.

Abstract Substance use disorder (SUD) is a global health problem with a significant impact on individuals and society. The presentation of SUD is diverse, involving various substances, ages at onset, comorbid conditions, and disease trajectories. Current treatments for SUD struggle to address this heterogeneity, resulting in high relapse rates. SUD often co-occurs with other psychiatric and mental health-related conditions that contribute to the heterogeneity of the disorder and predispose to adverse disease trajectories. Family and genetic studies highlight the role of genetic and environmental factors in the course of SUD, and point to a shared genetic liability between SUDs and comorbid psychopathology. In this study, we aimed to disentangle SUD heterogeneity using a deeply phenotyped SUD cohort and polygenic scores (PGSs) for psychiatric disorders and related traits. We explored associations between PGSs and various SUD-related phenotypes, as well as PGS-environment interactions using information on lifetime emotional, physical, and/or sexual abuse. Our results identify clusters of individuals who exhibit differences in their phenotypic profile and reveal different patterns of associations between SUD-related phenotypes and the genetic liability for mental health-related traits, which may help explain part of the heterogeneity observed in SUD. In our SUD sample, we found associations linking the genetic liability for attention-deficit hyperactivity disorder (ADHD) with lower educational attainment, the genetic liability for post-traumatic stress disorder (PTSD) with higher rates of unemployment, the genetic liability for educational attainment with lower rates of criminal records and unemployment, and the genetic liability for well-being with lower rates of outpatient treatments and fewer problems related to family and social relationships. We also found evidence of PGS-environment interactions showing that genetic liability for suicide attempts worsened the psychiatric status in SUD individuals with a history of emotional physical and/or sexual abuse. Collectively, these data contribute to a better understanding of the role of genetic liability for mental health-related conditions and adverse life experiences in SUD heterogeneity.

Abstract The immune effector mechanisms involved in protecting against severe COVID-19 infection in elderly nursing home residents following vaccination or natural infection are not well understood. Here, we measured SARS-CoV-2 Spike (S)-directed functional antibody responses, including neutralizing antibodies (NtAb) and antibody Fc-mediated NK cell activity (degranulation and IFNγ production), against the Wuhan-Hu-1, BA.4/5 (for NtAb), and Omicron XBB.1.5 variants in elderly nursing home residents (n = 39; median age, 91 years) before and following a third (pre- and post-3D) and a fourth (pre- and post-4D) mRNA COVID-19 vaccine dose. Both 3D and 4D boosted NtAb levels against both (sub)variants. Likewise, 3D and 4D increased the ability of sera to trigger both LAMP1- and IFNγ-producing NK cells, in particular against XBB.1.5. In contrast to NtAb titres, the frequencies of LAMP1- and IFNγ-producing NK cells activated by antibodies binding to Wuhan-Hu-1 and Omicron XBB.1.5 S were comparable at all testing times. Stronger functional antibody responses were observed in vaccine-experienced participants compared to vaccine-naïve at some testing times. These findings can contribute to identifying a reliable correlate of protection in elderly nursing home residents against severe COVID-19 and inform future vaccine strategies in this population group.

(1) Background: Because life events when there is a family member with a disability can affect the overall family wellbeing, contributing to enhance family quality of life (FQoL) in the field of early childhood intervention has become a priority. However, it is a distal outcome that needs other short-term outcomes to be addressed, some of them under the potential impact of support services. This study examines the relationships between caregiver burden, family confidence, and FQoL, as well as the influence of child and family variables. (2) Method: A total of 58 families with children in early intervention from four Spanish communities participated. Hierarchical regression was conducted to assess the relevance of each predictor. Also, a mediation was performed to investigate the mediating role of family confidence. (3) Results: The family income impacted FQoL scores, and when burden and confidence were added, it was no longer relevant. Mothers with higher levels of confidence predicted a higher FQoL. Finally, we found a complete mediation of family confidence in the relations between severity and caregiver burden on FQoL. (4) Conclusions: Caregiver burden and family confidence affect FQoL. Building families’ confidence contributes to attenuating the impact of burden on FQoL.

Abstract We study the O(3) critical model and the free theory of a scalar triplet in the presence of a magnetic impurity. We use analytic bootstrap techniques to extract results in the ε-expansion. First, we extend by one order in perturbation theory the computation of the beta function for the defect coupling in the free theory. Then, we analyze in detail the low-lying spectrum of defect operators, focusing on their perturbative realization when the defect is constructed as a path-ordered exponential. After this, we consider two different bulk two-point functions and we compute them using the defect dispersion relation. For a free bulk theory, we are able to fix the form of the correlator at all orders in ε. In particular, taking ε → 1, we can show that in d = 3 one does not have a consistent and non-trivial defect CFT. For an interacting bulk, we compute the correlator up to second order in ε. Expanding these results in the bulk and defect block expansions, we are able to extract an infinite set of defect CFT data. We discuss low-spin ambiguities that affect every result computed through the dispersion relation and we use a combination of consistency conditions and explicit diagrammatic calculations to fix this ambiguity.

Abstract Follicular lymphoma (FL), the most common indolent non-Hodgkin lymphoma, constitutes a paradigm of immune tumor microenvironment (TME) contribution to disease onset, progression, and heterogenous clinical outcome. Here we present the first FL-Patient Derived Lymphoma Spheroid (FL-PDLS), including fundamental immune actors and features of TME in FL lymph nodes (LNs). FL-PDLS is organized in disc-shaped 3D structures composed of proliferating B and T cells, together with macrophages with an intermediate M1/M2 phenotype. FL-PDLS recapitulates the most relevant B-cell transcriptional pathways present in FL-LN (proliferation, epigenetic regulation, mTOR, adaptive immune system, among others). The T cell compartment in the FL-PDLS preserves CD4 subsets (follicular helper, regulatory, and follicular regulatory), also encompassing the spectrum of activation/exhaustion phenotypes in CD4 and CD8 populations. Moreover, this system is suitable for chemo and immunotherapy testing, recapitulating results obtained in the clinic. FL-PDLS allowed uncovering that soluble galectin-9 limits rituximab, rituximab, plus nivolumab/TIM-3 antitumoral activities. Blocking galectin-9 improves rituximab efficacy, highlighting galectin-9 as a novel immunotherapeutic target in FL. In conclusion, FL-PDLS maintains the crosstalk between malignant B cells and the immune LN-TME and constitutes a robust and multiplexed pre-clinical tool to perform drug screening in a patient-derived system, advancing toward personalized therapeutic approaches.

Abstract Background Despite the recognized advantages of Peer-Assisted Learning (PAL) in academic settings, there is a notable absence of research analyzing its effects on students' Academic Burnout. This study aims to cover this gap by assessing the underlying effectiveness of Informal Peer-Assisted Learning (IPAL) as a cooperative learning method, focusing on its potential to mitigate academic burnout among medical students. Methods In 2022, a cross-sectional study was conducted at the School of Medicine, Universidad Central del Caribe, in Puerto Rico. The research team gathered data from 151 participants, 49.19% of 307 total student body. This cohort included 76 female students, 71 male students, and 4 individuals saying other. The School Burnout Inventory questionnaire (SBI-9) was employed to assess Academic Burnout, along with an added query about self-reported IPAL. The SBI-9 underwent validation processes to ascertain its reliability and validity, incorporating the Exploratory Factor Analysis and Confirmatory Factor Analysis. Following this, the investigators conducted an analysis to determine the correlation between academic burnout levels and involvement in IPAL. Results The validation process of the questionnaire affirmed its alignment with an eight-item inventory, encapsulating two principal factors that elucidate academic burnout. The first factor pertains to exhaustion, while the second encompasses the combined subscales of cynicism and inadequacy. The questionnaire shows high reliability (Cronbach's alpha = 0.829) and good fit indices (Comparative Fit Index = 0.934; Tucker-Lewis Index = 0.902; Standardized Root Mean Squared Residual = 0.0495; Root Mean Squared Error of Approximation = 0.09791; p-value

Abstract Background Monitoring elite athletes’ body composition (BC) is vital for health and optimizing performance in sports emphasizing leanness, such as athletics. This study aims to investigate and compare sex- and event-specific off-to in-season BC changes in endurance and power event athletics competitors. Methods Elite male and female endurance athletes (> 800 m runners; n = 21) and power event athletes (sprinters, jumpers; n = 32) underwent dual-energy X-ray absorptiometry (DXA) scans for whole and regional lean mass (LM), fat mass (FM), bone mineral content (BMC), and density (BMD) during off-season (September-October) and in-season (April-May). Linear mixed models tested between-group off-season differences in BC, within-group off-season to in-season changes, and between-group differences in change. To assess meaningful or least significant changes (LSC) in BC, DXA precision errors were determined from two consecutive total body scans in a subsample of athletes (n = 30). Results Male athletes (n = 26) gained significantly (p

Abstract This study aims at identifying risk-related patterns of left ventricular contraction dynamics via novel volume transient characterization. A multicenter cohort of AMI survivors (n = 1021) who underwent Cardiac Magnetic Resonance (CMR) after infarction was considered for the study. The clinical endpoint was the 12-month rate of major adverse cardiac events (MACE, n = 73), consisting of all-cause death, reinfarction, and new congestive heart failure. Cardiac function was characterized from CMR in 3 potential directions: by (1) volume temporal transients (i.e. contraction dynamics); (2) feature tracking strain analysis (i.e. bulk tissue peak contraction); and (3) 3D shape analysis (i.e. 3D contraction morphology). A fully automated pipeline was developed to extract conventional and novel artificial-intelligence-derived metrics of cardiac contraction, and their relationship with MACE was investigated. Any of the 3 proposed directions demonstrated its additional prognostic value on top of established CMR indexes, myocardial injury markers, basic characteristics, and cardiovascular risk factors (P

Abstract In their natural habitats, microbes rarely exist in isolation; instead, they thrive in consortia, where various interactions occur. In this study, a defined synthetic co-culture of the cyanobacterium S. elongatus cscB, which supplies sucrose to the heterotrophic P. putida cscRABY, is investigated to identify potential interactions. Initial experiments reveal a remarkable growth-promoting effect of the heterotrophic partner on the cyanobacterium, resulting in an up to 80% increase in the growth rate and enhanced photosynthetic capacity. Vice versa, the presence of the cyanobacterium has a neutral effect on P. putida cscRABY, highlighting the resilience of pseudomonads against stress and their potential as co-culture partners. Next, a suitable reference process reinforcing the growth-promoting effect is established in a parallel photobioreactor system, which sets the basis for the analysis of the co-culture at the transcriptome, proteome, and metabolome levels. In addition to several moderate changes, including alterations in the metabolism and stress response in both microbes, this comprehensive multi-OMICs approach strongly hints towards the exchange of further molecules beyond the unidirectional feeding with sucrose. Taken together, these findings provide valuable insights into the complex dynamics between both co-culture partners, indicating multi-level interactions, which can be employed for further streamlining of the co-cultivation system.

Abstract Background Most patients suffering from Leber hereditary optic neuropathy carry one of the three classic pathologic mutations, but not all individuals with these genetic alterations develop the disease. There are different risk factors that modify the penetrance of these mutations. The remaining patients carry one of a set of very rare genetic variants and, it appears that, some of the risk factors that modify the penetrance of the classical pathologic mutations may also affect the phenotype of these other rare mutations. Results We describe a large family including 95 maternally related individuals, showing 30 patients with Leber hereditary optic neuropathy. The mutation responsible for the phenotype is a novel transition, m.3734A > G, in the mitochondrial gene encoding the ND1 subunit of respiratory complex I. Molecular-genetic, biochemical and cellular studies corroborate the pathogenicity of this genetic change. Conclusions With the study of this family, we confirm that, also for this very rare mutation, sex and age are important factors modifying penetrance. Moreover, this pedigree offers an excellent opportunity to search for other genetic or environmental factors that additionally contribute to modify penetrance.

Objective: The present study aims to provide norms and age-, education-, and sex-adjusted data for the Wisconsin Card Sorting Test (WCST), the Modified Taylor Complex Figure (MTCF), and the Ruff-Light Trail Learning Test (RULIT) as part of the NEURONORMA-Plus project. Methods: We recruited 308 cognitively healthy individuals aged between 18 and 92 years. Tables are provided to convert raw scores to age-adjusted scaled scores, as well as adjustments for education and sex after applying independent regression models in 2 age groups (< 50 and ≥ 50 years). Results: Older age had a negative effect on performance in both age groups. We observed a positive effect of education on WCST performance in the younger group (< 50 years), and on all MTCF measures (with the exception of the recognition task) in the older group (≥ 50 years). Education had no impact on performance in the RULIT, although sex did, with a small but significant effect whereby young men showed higher performance for one variable. Conclusion: The normative data provided can contribute to the clinical interpretation of performance in these tests in the Spanish population. Resumen: Objetivo: el presente estudio tiene como objetivo proporcionar normas y ajustes para edad, educación y el género para el Wisconsin Card Sorting Test (WCST), la Figura Compleja Modificada de Taylor (FCMT) y el Ruff-Light Trail Learning Test (RULIT) como parte del proyecto NEURONORMA-Plus. Método: la muestra consiste en 308 individuos cognitivamente sanos de entre 18 y 92 años. Se proporcionan tablas para convertir las puntuaciones brutas en puntuaciones escalares ajustadas por edad y ajustes por educación y género tras aplicar modelos de regresión independientes en dos grupos de edad (

Resumen: Objetivo: El presente estudio tiene como objetivo proporcionar normas y ajustes para edad, educación y género para el Wisconsin Card Sorting Test (WCST), la Figura Compleja Modificada de Taylor (FCMT) y el Ruff-Light Trail Learning Test (RULIT) como parte del proyecto NEURONORMA-Plus. Método: La muestra consiste en 308 individuos cognitivamente sanos de entre 18 y 92 años. Se proporcionan tablas para convertir las puntuaciones brutas en puntuaciones escalares ajustadas por edad y ajustes por educación y género tras aplicar modelos de regresión independientes en 2 grupos de edad (