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Abstract We explore the decay of bound neutrons in the JUNO liquid scintillator detector into invisible particles (e.g., $$n\rightarrow 3 \nu $$ n → 3 ν or $$nn \rightarrow 2 \nu $$ n n → 2 ν ), which do not produce an observable signal. The invisible decay includes two decay modes: $$ n \rightarrow { inv} $$ n → inv and $$ nn \rightarrow { inv} $$ n n → inv . The invisible decays of s-shell neutrons in $$^{12}\textrm{C}$$ 12 C will leave a highly excited residual nucleus. Subsequently, some de-excitation modes of the excited residual nuclei can produce a time- and space-correlated triple coincidence signal in the JUNO detector. Based on a full Monte Carlo simulation informed with the latest available data, we estimate all backgrounds, including inverse beta decay events of the reactor antineutrino $${\bar{\nu }}_e$$ ν ¯ e , natural radioactivity, cosmogenic isotopes and neutral current interactions of atmospheric neutrinos. Pulse shape discrimination and multivariate analysis techniques are employed to further suppress backgrounds. With two years of exposure, JUNO is expected to give an order of magnitude improvement compared to the current best limits. After 10 years of data taking, the JUNO expected sensitivities at a 90% confidence level are $$\tau /B( n \rightarrow { inv} ) > 5.0 \times 10^{31} \, \textrm{years}$$ τ / B ( n → inv ) > 5.0 × 10 31 years and $$\tau /B( nn \rightarrow { inv} ) > 1.4 \times 10^{32} \, \textrm{years}$$ τ / B ( n n → inv ) > 1.4 × 10 32 years .

Alcohol consumption has been consistently linked to an increased risk of several cancers, including breast and ovarian cancer. Despite substantial evidence supporting this association, the precise mechanisms underlying alcohol’s contribution to cancer pathogenesis remain incompletely understood. This narrative review focuses on the key current literature on the biological pathways through which alcohol may influence the development of breast and ovarian cancer. Key mechanisms discussed include the modulation of estrogen levels, the generation of reactive oxygen species, the production of acetaldehyde, the promotion of chronic inflammation, and the induction of epigenetic changes. Alcohol’s impact on estrogenic signaling, particularly in the regulation of estrogen and progesterone, is explored in the context of hormone-dependent cancers. Additionally, the role of alcohol-induced DNA damage, mutagenesis, and immune system modulation in tumor initiation and progression is examined. Overall, this review emphasizes the importance of alcohol as a modifiable risk factor for breast and ovarian cancer and highlights the need for further research to clarify its role in cancer biology.

The aim of this study was to investigate aggression-related work accidents in an inpatient psychiatric unit before and after implementing a no-restraint policy in Italy. Results revealed that, over the study period (2007–2022), 113 accidents occurred, mostly related to physical aggression (81.4%), with healthcare assistants and psychiatric nurses being the most affected and more accidents occurring during the morning shift (49.6%). A transitory peak of accidents occurred during the policy transition (χ22 = 16.0, p < 0.001; V = 1.000), falling rapidly in the subsequent years. In conclusion, adopting a no-restraint policy is not associated with increased aggression toward staff in psychiatric healthcare in the longer term, although greater support is needed during the transition phase to minimize risks.

Abstract Uterine corpus endometrial carcinoma (EC) is one of the most common malignancies in the female reproductive system, characterized by tumor heterogeneity at both radiological and pathological scales. Both radiomics and pathomics have the potential to assess this heterogeneity and support EC diagnosis. This study examines the correlation between radiomics features from Apparent Diffusion Coefficient (ADC) maps and post-contrast T1 (T1C) images with pathomic features from pathology images in 32 patients from the CPTAC-UCEC database. 91 radiomics features were extracted from ADC maps and T1C images, and 566 pathomic features from cell detections and cell density maps at four different resolutions. Spearman’s correlation and Bayes Factor analysis were used to evaluate radio-pathomic correlations. Significant cross-scale correlations were found, with strengths ranging from 0.57 to 0.89 in absolute value (9.47 × 104

Abstract Background While immune checkpoint inhibitors (ICIs) are increasingly reshaping the therapeutic landscape of non‐small‐cell lung cancer (NSCLC), only a limited proportion of patients achieve a relevant and long‐lasting benefit with these treatments, calling for the identification of clinical and, ideally modifiable, predictors of efficacy. Body composition phenotypes may reflect aspects of patients' immunology and thereby their ability to respond to ICIs. This study aims to explore the possible association between pre‐treatment body composition phenotypes, tumour response, and clinical outcomes in patients receiving first‐line pembrolizumab monotherapy for advanced NSCLC. Methods A retrospective review of consecutive patients with treatment‐naïve NSCLC and PD‐L1 expression ≥50% undergoing pembrolizumab at three academic institutions was performed. Pre‐treatment body composition parameters were measured at the third lumbar vertebra level by computed tomography, defined using pre‐established cut‐offs. Primary endpoint was objective response rate (ORR), secondary endpoints progression‐free survival and overall survival (PFS and OS), compared through the log‐rank test and the Cox proportional hazards model. Results Data from 134 patients (93 males [69.4%] and 41 females [30.6%]) were collected. Median age was 69 years (range 36–85), with a median follow‐up of 12 months (range 1–131). The median body mass index (BMI) was 24.5 (IQR 21.5; 26.1) kg/m2. Overall, 59.0% and 51.5% of patients met established radiographic criteria for evidence of sarcopenia and myosteatosis, respectively, which occur across the BMI spectrum. Multivariate regression analysis, adjusted for co‐morbidities, revealed that sarcopenia (aOR 5.56, 95% CI. 2.46–12.6, P

Abstract Background To investigate Feeding and Eating Disorders (FED) heterogeneity based on the co-occurrence of FED symptoms and personality psychopathology, on the hypothesis that empirical profiles would not confirm current FED categories but identify unique phenotypes carrying different levels of clinical complexity. Methods Latent Profile Analysis profiled FED patients based on the assessment of both FED symptoms, through the Eating Disorders Inventory, third version (EDI-3), and personality characteristics, through the Minnesota Multiphasic Personality Inventory-2. Then, profiles were compared across socio-demographic and clinical characteristics. Results Among 109 eligible patients, three FED profiles were identified: (i) FED simplex (low eating symptoms, absence of dysfunctional personality); (ii) FED simplex-severe (high eating symptoms only); and (iii) FED complex-severe (high eating symptoms and dysfunctional personality). Despite an uneven distribution (χ2(6) = 15.20, adjusted-p = 0.029), FED profiles did not unequivocally confirm clinical diagnoses (e.g., Anorexia Nervosa). A difference in Body Mass Index (BMI) was observed (K(2) = 15.06, adjusted-p = 0.001), but lower BMI did not identify the most severe group. Profiles differed in EDI-3 overall scores (e.g., Eating Disorder Risk Composite: K(2) = 43.08, adjusted-p

Abstract Lynch syndrome is rarely associated with rectal cancer (RC) and thus, metachronous RC has been scarcely investigated. This study aimed to analyze the mucosal immune microenvironment in sporadic and metachronous RC. We analyzed the mucosal immune microenvironment in the 25 metachronous RCs present in the IMMUNOREACT 1 and 2 multicentre observational studies (624 patients). A panel of immune markers was retrospectively investigated at immunohistochemistry: CD3, CD4, CD8, CD8b, Tbet, FoxP3, PD-L1, MSH6, and PMS2 and CD80. Single-cell suspensions were subjected to flow-cytometry to determine the proportion of epithelial cells (pan-cytokeratin) acting as antigen-presenting cells (expressing CD80, CD86, HLA-ABC) and the proportion of activated CD8 + T cells (CD8 + positive for CD28, CD38), inhibitory T cells (CD3 + CTLA-4+) of activated CD4 + T helper cells (CD4 + CD25+) and activated T regulatory cells (CD4 + CD25 + FoxP3+). No mismatch repair gene deficiencies were observed in the patients. The previous history of colorectal adenoma was significantly more frequent in metachronous RC. In healthy epithelial cells, HLA-ABC expression was significantly higher in patients with metachronous RC. In therapy-naïve metachronous RC patients, a significantly lower level of circulating lymphocytes and CD3 + T-cell infiltration in the healthy mucosa surrounding the RC was observed compared to patients with non-metachronous cancer. Our study supports the hypothesis that metachronous RC can occur in a cancerization field in patients with weak systemic and local immune systems. The peculiar site of RC makes the mismatch-repair genes deficiency in metachronous cancer onset less relevant.

Aim: The aim of this study was to explore Italian nurses’ publications from 1980 to 2020. Background/Objectives: Several studies have been conducted internationally to assess nursing research output. In Italy, there are some older studies, but a comprehensive analysis of the Italian nursing scientific production after 2010 is needed. Methods: A bibliometric analysis was conducted through a retrospective descriptive study. All articles (n = 3423) published by Italian nurses (n = 2170) and indexed in Scopus were included, in accordance with the PRISMA guidelines. Results: Publication trends show a steady growth, with an increase in publications in journals with higher IFs. Most publications were focused on clinical research and used quantitative methods (n = 2473 articles (86.71%)). The most frequently conducted quantitative studies were observational studies (52.91%), followed by experimental studies (12.5%), instrumental studies (6.72%), and other methodologies (0.15%). Qualitative studies accounted for n = 318 articles (11.15%), and mixed-method studies accounted for n = 61 articles (2.14%). Conclusions: The overall improvement in Italian nursing research is due to the increase in the number of nurses with PhDs and academics in the country. More funding and nursing research positions are needed to further improve research.

Abstract Background Exercise-induced bronchoconstriction (EIB) is common in children with asthma but can be present also in children without asthma, especially athletes. Differential diagnosis includes several conditions such as exercise-induced laryngeal obstruction (EILO), cardiac disease, or physical deconditioning. Detailed medical history, clinical examination and specific tests are mandatory to exclude alternative diagnoses. Given the high prevalence of EIB in children and its potential impact on health, sport performance, and daily levels of physical activity, health care professionals should be aware of this condition and able to provide a specific work-up for its identification. The aims of the present study were: (a) to assess the agreement among hospital pediatricians and primary care pediatricians of Emilia-Romagna Region (Italy) about the management of EIB in children and (b) formulate statements in a consensus document to help clinicians in daily clinical practice. Methods According to Delphi method, a panel of specialists scored 40 statements that were then revised and discussed during online meetings to reach full consensus. Statements were then formulated. Results To obtain full consensus, the questionnaire was administered in two rounds after full discussion of the uncertain topics on the basis of the latest evidence on EIB published over the last 10 years. Despite an overall agreement on EIB management, some gaps emerged in the sections dedicated to diagnosis and treatment. Nine summary statements on definition, pathogenesis, diagnostic work-up, treatment, and follow-up were eventually formulated. Conclusions This study describes the knowledge of EIB in a group of pediatricians and highlights gaps and uncertainties in diagnosis and treatment. The creation of statements shared by the specialists of the same area may improve the management of EIB in children. However, more research and evidence are needed to better clarify the best treatment and to standardize the best diagnostic protocol limiting useless examinations but at the same time assuring the best management.

Abstract The heparan sulfate (HS)-rich extracellular matrix (ECM) serves as an initial interaction site for the homotrimeric spike (S) protein of SARS-CoV-2 to facilitate subsequent docking to angiotensin-converting enzyme 2 (ACE2) receptors and cellular infection. More recent variants, notably Omicron, have evolved by swapping several amino acids to positively charged residues to enhance the interaction of the S-protein trimer with the negatively charged HS. However, these enhanced interactions may reduce Omicron’s ability to move through the HS-rich ECM to effectively find ACE2 receptors and infect cells, raising the question of how to mechanistically explain HS-associated viral movement. In this work, we show that Omicron S proteins have evolved to balance HS interaction stability and dynamics, resulting in enhanced mobility on an HS-functionalized artificial matrix. This property is achieved by the ability of Omicron S-proteins to cross-link at least two HS chains, allowing direct S-protein switching between chains as a prerequisite for cell surface mobility. Optimized HS interactions can be targeted pharmaceutically, as an HS mimetic significantly suppressed surface binding and cellular infection specifically of the Omicron variant. These findings suggest a robust way to interfere with SARS-CoV-2 Omicron infection and potentially future variants.

In this paper, we present the significant results from the Covid Radiographic imaging System based on AI (Co.R.S.A.) project, which took place in Italy. This project aims to develop a state-of-the-art AI-based system for diagnosing Covid-19 pneumonia from Chest X-ray (CXR) images. The contributions of this work are manifold: the release of the public CORDA dataset, a deep learning pipeline for Covid-19 detection and prioritization, the clinical validation of the developed solution by expert radiologists, and an in-depth analysis of possible biases embedded in the data and in the models, in order to build more trust in our AI-based pipeline. The proposed detection model is based on a two-step approach that provides reliable results based on objective radiological findings. Our prioritization scheme ensures the ordering of the patients so that severe cases are presented first. We showcase the impact of our pipeline on radiologists' workflow with a clinical study, allowing us to assess the real benefits in terms of accuracy and time efficiency. Project homepage: https://corsa.di.unito.it/.

Abstract Background In patients with atrial fibrillation (AF), the impact of peripheral artery disease (PAD) on oral anticoagulant (OAC) therapy use and the risk of outcomes remains unclear. Objective To analyse the epidemiology of PAD in a large cohort of European and Asian AF patients, and the impact on treatment patterns and risks of adverse outcomes. Methods We analysed AF patients from two large prospective observational registries. OAC prescription and risk of outcomes were analysed according to the presence of PAD, using adjusted Logistic and Cox regression analyses. The primary outcome was the composite of all-cause death and major adverse cardiovascular events (MACE). Interaction analyses were also performed. Results Fifteen-thousand-four-hundred-ninety-seven patients with AF (mean age 68.9, SD 11.6 years; 38.6% female, 30% from Asia) were included in the analysis. PAD was found in 941 patients (6.1%), with a higher prevalence among European individuals compared to Asian (8.1% vs 1.2%, p

Krabbe disease is a sphingolipidosis characterized by the genetic deficiency of the acid hydrolase β-galactosylceramidase (GALC). Most of the studies concerning the biological role of GALC performed on Krabbe patients and Galc-deficient twitcher mice (an authentic animal model of the disease) indicate that the pathogenesis of this disorder is the consequence of the accumulation of the neurotoxic GALC substrate β-galactosylsphingosine (psychosine), ignoring the possibility that this enzyme may exert a wider biological impact. Indeed, limited information is available about the effect of GALC downregulation on the cell lipidome in adult and developing organisms. The teleost zebrafish (Danio rerio) has emerged as a useful platform to model human genetic diseases, including sphingolipidoses, and two GALC co-orthologs have been identified in zebrafish (galca and galcb). Here, we investigated the effect of the competitive and irreversible GALC inhibitor β-galactose-cyclophellitol (GCP) on the lipid profile of zebrafish embryos. Molecular modelling indicates that GCP can be sequestered in the catalytic site of the enzyme and covalently binds human GALC, and the zebrafish Galca and Galcb proteins in a similar manner. Accordingly, GCP inhibits the β-galactosylceramide hydrolase activity of zebrafish in vitro and in vivo, leading to significant alterations of the lipidome of zebrafish embryos. These results indicate that the lack of GALC activity deeply affects the lipidome during the early stages of embryonic development, and thereby provide insights into the pathogenesis of Krabbe disease.

La Amazonía peruana ha sido imaginada como una despensa, desintegrada de la historia nacional, y utilizada, únicamente, para fines extractivos. En esa línea, sus habitantes han sido obliterados; no obstante, existe un corpus de jóvenes poetas indígenas amazónicos que complejizan la presencia indígena amazónica en la historia nacional y lo hacen en poemas que dan a conocer en medios tradicionales como revistas literarias y libros. El presente artículo analiza la mención y el desarrollo de las categorías políticas como ciudadanía, pueblo y patria en las poéticas de dos jóvenes poetas indígenas amazónicos peruanos: Bikut Sanchium y Tony Ramirez Nunta, llamado Inin Rono en el idioma shipibo-konibo. El objetivo es mostrar las maneras en que se construye un ciudadano amazónico a partir de la conciencia de la pertenencia y de la denuncia hacia diversos tipos de violencia dentro del ámbito poético. Este análisis es una propuesta ética y académica que espera contribuir a una mejor comprensión de las producciones y de las subjetividades amazónicas usualmente subestimadas en la literatura peruana y latinoamericana, para mostrar sus complejas formas de resiliencia a partir de su escritura.

The intensity of the backscattered signal collected by active radars over wet, seasonal snowpacks depends on numerous variables related to the snowpack, which are often difficult to determine accurately. In recent years, thanks to the increased availability of spaceborne synthetic aperture radars (SARs), a temporal relationship between wet-snow metamorphism and microwave backscattering has been demonstrated. However, a precise quantitative description of this phenomenon has yet to be fully determined. In this article, we propose a new mixed analytical-numerical model to describe the effect of the physical parameters related to the wet snowpack metamorphism on the intensity of the backscattering at L, C, and X bands, with a focus on high alpine snowpacks. Particular attention was paid to integrate the effects of the snow superficial roughness and the snow scattering. The model is first applied to several simulated snowpacks and then validated against a real multitemporal SAR signature acquired by Sentinel-1 over the snow station of Malga Fadner (South Tyrol, Italy) and of Torgnon (Aosta Valley, Italy). The comparison between the model outcomes and the satellite data were in good agreement, leading to the possibility of using such method for operational identification of the run-off phase from remote locations.

This paper analyses electromagnetic (EM) wave propagation within a metasurface-cladded waveguide filled with magnetized plasma. First, an analytical model is developed to understand the governing dynamics of the system. Second, a realistic numerical design is presented to assess the feasibility of the proposed concept. This technology targets microwave-driven plasma production, with the cladding metasurface enabling control over the cut-off frequency of the waveguide. Results suggest that EM propagation can be triggered regardless of the value of the static magnetic induction field. This represents a significant advance over standard implementations, promoting system miniaturization and facilitating the integration of waveguides with plasma sources.

Abstract Background Treadmill-based gait training is part of rehabilitation programs focused on walking abilities. The use of handrails embedded in treadmill systems is debated, and current literature only explores the issue from a behavioral perspective. Methods We examined the cortical correlates of treadmill walking in healthy participants using functional near-infrared spectroscopy. We investigated whether the utilization of treadmill handrails at varying walking speeds could affect cortical activation associated with the task, and we evaluated potential differences in task-based functional connectivity across the various walking conditions. Results Significant differences in cortical activation were found between the two walking speeds (3 and 5 km/h) in the unsupported condition; these differences were reduced when using the handrails. Specifically, cortical activation was significantly higher when the participants swung their arms freely while walking at a speed of 5 compared to 3 km/h in several Brodmann’s Areas (BA): left BA10, BA3 and BA39, and right BA10, BA9, BA8, BA3, and BA40. No significant differences were found when participants were holding onto the handrails. A significant difference was found in the left BA40 between the two speeds, regardless of whether the participants were holding onto the handrails. Furthermore, at the higher speed and without the use of handrails, a wider pattern of task-based functional connectivity was observed, with significantly stronger connectivity between the left BA10 and BA40. Conclusions We suggest that speed and handrails use play a role in walking cortical activity patterns, therefore they are key ingredients to take into account when planning a rehabilitation program.

Abstract Prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) has improved localization of prostate cancer (PC) lesions in biochemical recurrence (BCR) for salvage radiotherapy (SRT). We conducted a retrospective review of patients undergoing 18F-rhPSMA-7 or 18F-flotufolastat (18F-rhPSMA-7.3)-PET-guided SRT compared with conventional-SRT (C-SRT) without PET. We evaluated biochemical failure-free survival (bFS) and overall rates of bFS in 110 evaluable patients with recurrent PC after radical prostatectomy who received SRT. 82 patients received 18F-rhPSMA-7/18F-flotufolastat-PET-guided SRT and 28 received C-SRT. Median bFS for patients with 18F-rhPSMA-7/18F-flotufolastat-PET-guided SRT was not reached while median bFS was 45.6 months for patients with C-SRT (p = 0.101). %bFS were 95% (52/55) vs 87% (20/23), 90% (27/30) vs 75% (15/20), 89% (16/18) vs 68% (13/19) and 100% (3/3) vs 57% (8/14) for PET-guided vs C-SRT at 12, 24, 36, and 48 months, respectively. Among patients treated in the prostate bed only, median bFS was not reached for PSMA-PET-guided SRT (n = 52) vs 55.1 months in the C-SRT group (n = 25; p = 0.063). %bFS was greater for PSMA-PET-guided SRT than C-SRT at all evaluated timepoints. 18F-rhPSMA-7/18F-flotufolastat-guided SRT yielded favorable disease outcomes. Although statistical significance was not reached, likely due to the limited sample size in this preliminary analysis, our data illustrate potential for 18F-flotufolastat-PET-guided SRT.

Abstract Bioelectrical Impedance Vector Analysis (BIVA) is a valuable tool for evaluating hydration and body composition, but its application in subacute post-stroke patients remains unexplored. This study aimed to fill this gap by analyzing BIVA in a cohort of 87 subacute post-stroke patients (42 women, mean age 69 ± 12) undergoing rehabilitation. At admission (T0), diagnosis of malnutrition with GLIM criteria and of sarcopenia with EWGSOP2 was done, and patients were analyzed with BIVA. The change in modified Barthel Index (mBIT1-mBIT0) was assessed to evaluate the improvement in functional recovery. BIVA revealed that both adult patients (

Abstract Data scarcity in medical images makes transfer learning a common approach in computer-aided diagnosis. Some disease classification tasks can rely on large homogeneous public datasets to train the transferred model, while others cannot, i.e., endoscopic laryngeal cancer image identification. Distinguished from most current works, this work pioneers exploring a two-step heterogeneous transfer learning (THTL) framework for laryngeal cancer identification and summarizing the fundamental principles for the intermediate domain selection. For heterogeneity and clear vascular representation, diabetic retinopathy images were chosen as THTL’s intermediate domain. The experiment results reveal two vital principles in intermediate domain selection for future studies: 1) the size of the intermediate domain is not a sufficient condition to improve the transfer learning performance; 2) even distinct vascular features in the intermediate domain do not guarantee improved performance in the target domain. We observe that radial vascular patterns benefit benign classification, whereas twisted and tangled patterns align more with malignant classification. Additionally, to compensate for the absence of twisted patterns in the intermediate domains, we propose the Step-Wise Fine-Tuning (SWFT) technique, guided by the Layer Class Activate Map (LayerCAM) visualization result, getting 20.4% accuracy increases compared to accuracy from THTL’s, even higher than fine-tune all layers.

Abstract Background Inclusion Body Myositis is an acquired muscle disease. Its pathogenesis is unclear due to the co-existence of inflammation, muscle degeneration and mitochondrial dysfunction. We aimed to provide a more advanced understanding of the disease by combining multi-omics analysis with prior knowledge. We applied molecular subnetwork identification to find highly interconnected subnetworks with a high degree of change in Inclusion Body Myositis. These could be used as hypotheses for potential pathomechanisms and biomarkers that are implicated in this disease. Results Our multi-omics analysis resulted in five subnetworks that exhibit changes in multiple omics layers. These subnetworks are related to antigen processing and presentation, chemokine-mediated signaling, immune response-signal transduction, rRNA processing, and mRNA splicing. An interesting finding is that the antigen processing and presentation subnetwork links the underexpressed miR-16-5p to overexpressed HLA genes by negative expression correlation. In addition, the rRNA processing subnetwork contains the RPS18 gene, which is not differentially expressed, but has significant variant association. The RPS18 gene could potentially play a role in the underexpression of the genes involved in 18 S ribosomal RNA processing, which it is highly connected to. Conclusions Our analysis highlights the importance of interrogating multiple omics to enhance knowledge discovery in rare diseases. We report five subnetworks that can provide additional insights into the molecular pathogenesis of Inclusion Body Myositis. Our analytical workflow can be reused as a method to study disease mechanisms involved in other diseases when multiple omics datasets are available.

Purpose – The purpose of this article is to investigate factors related to the time students spent on remote activities during the coronavirus (COVID-19) pandemic in 2020. Specifically, it analyzes whether the school’s relationship with the family and the guardians’ support are associated with longer study times for children and youth. Design/methodology/approach – This was performed using an ordered logit model on data from two waves of the survey Remote Education in the Perspective of Students and Their Families (PENP) with a nationally and regionally representative sample of Brazilian public school students. Findings – Results show the importance of contact between the school and the family and, to a greater extent, the direct support of parents or guardians. The odds of learners spending more hours studying increase 36% when schools provide guidance for parents and guardians; in turn, when they provide support for students during activities, these odds increase 144%. Originality/value – Moreover, students spend more time doing school activities in the later years of elementary school, high school and when they attend a state school.

Background and objective: Bladder cancer (BC) represents a significant health care challenge and is frequently detected during evaluations for haematuria in emergency departments (EDs). Our aim was to evaluate the clinical performance and economic implications of the Xpert BC Detection (BCD) test for patients presenting to the ED with haematuria to address the pressing need for more efficient and accurate diagnostic tools in this setting. Methods: We conducted a prospective single-centre observational study in the ED of a tertiary university hospital. Patients presenting with gross haematuria as the primary reason for their visit were enrolled. Urine samples collected in the ED were analysed using the Xpert BCD test. The primary outcomes were sensitivity, specificity, and a cost analysis for the Xpert BCD test in comparison to standard diagnostic methods such as urine cytology (UC) and white-light cystoscopy (WLC). Key findings and limitations: The Xpert BCD test exhibited superior sensitivity to UC, particularly in identifying high-grade tumours. Importantly, Xpert BCD implementation has the potential to significantly reduce the number of unnecessary WLC procedures and streamline diagnostic pathways. The cost analysis also highlighted potential cost savings for Xpert BCD adoption in the ED setting. Conclusions and clinical implications: Our findings underscore the promise of Xpert BCD for revolutionising the diagnostic approach to BC in the ED for patients with gross haematuria. Its greater sensitivity and efficiency mean that Xpert BCD has the potential to improve patient care, optimise resource use, and alleviate the economic burden associated with unnecessary procedures. Patient summary: Xpert Bladder Cancer Detection is a simple urine test that detects the presence of five genes associated with bladder cancer. We found that for patients visiting the emergency department because of blood in their urine, use of this test could save time and money over urine cell analysis (UCA) for ruling out or diagnosing bladder cancer. The test was also more sensitive in detecting higher-grade cancers. More research is needed to confirm our results.

Objective The objective of this study was to evaluate the use of condensed tannin from black acacia (Acacia mearnsii) as a substitute additive for zinc oxide and growth-promoting antibiotics on the performance, digestibility, and intestinal health of piglets in the nursery phase. Methods A total of 200 PIC piglets that were 22 days old and weighed 6.0±0.9 kg were subjected to four treatments in the nursery phase (22 to 64 days of age): CONTR (control diet); ENR+ZnO (control diet + 10 mg/kg of enramycin + 2,500 mg/kg of zinc oxide during the first 21 days); BUT (control diet + 900 mg/kg of sodium butyrate) and TAN (control diet + 2,000 mg/kg of condensed tannin). The experimental design was a randomized block with 4 treatments and 10 replicates, with a pen of five animals each as the experimental unit. The zootechnical performance, diarrhea index score, dietary digestibility and metagenomics of the deep rectum microbiota were evaluated. Results The TAN had greater weight gain in the nursery phase and final weight (p

Purpose: Despite the significant role of varicocele in the pathogenesis of male infertility, its association with anti-sperm antibodies (ASA) remains controversial. This systematic review and meta-analysis (SRMA) aims to investigate the frequency of ASA positivity in men with varicocele. Materials and Methods: This SRMA is conducted in accordance with the Meta-analysis of Observational Studies in Epidemiology guidelines. We investigated the frequency of ASA positivity in ejaculates or serum of men with varicocele as compared to men without varicocele (controls). A literature search was performed using the Scopus and PubMed databases following the Population Exposure Comparison Outcome, Study Design model. Data extracted from eligible studies were meta-analyzed and expressed as odds ratios (ORs) and confidence intervals (CIs). Results: Out of 151 abstracts identified during the initial screening, 6 articles met the inclusion criteria and were included in the meta-analysis. Using mixed antiglobulin reaction (MAR) assay, 61 out of the 153 (39.8%) patients with varicocele tested positive for ASA in their ejaculates as compared to 22 out of the 129 control subjects (17%, OR=4.34 [95% CI: 1.09–17.28]; p=0.04). Using direct or indirect immunobead test, 30 out of 60 cases diagnosed with varicocele (50%) had shown ASA positivity in their ejaculates as compared to 16 out of 104 controls (15.4%, OR=3.57 [95% CI: 0.81–15.68]; p=0.09). Using enzyme-linked immunosorbent assay (ELISA), out of 89 varicocele patients, 33 (37.1%) tested positive for serum ASA as compared to 9 out of 57 participants in the control group (15.8%, OR=7.87 [95% CI: 2.39–25.89]; p

Abstract Introduction Hand grip strength (HGS) is an important measure in a physiotherapy assessment and for this purpose it is necessary to have valid and reliable instruments to measure it. In this study we aimed at investigating the reliability, validity, and agreement of the new hand-held dynamometer NOD (OT-Bioelettronica, To-Italy) compared to Jamar® hydraulic dynamometer (JD), the gold standard. Methods Fifty healthy subjects were selected; 9 trials for the dominant hand and 9 trials for the non-dominant hand were administrated to each of them: 3 trials of HGS with the JD in rung #3, 3 trials with the JD-adapted-grip (like the NOD one), and 3 trials with NOD. To verify the reliability of NOD, the Intraclass Correlation Coefficient (ICC 3,1) was calculated with a mixed effects model with the addition of adjustment variables (age, gender, dominant / non-dominant limb, trials). The model used single HGS measurements to estimate variance components, so reflecting both degree of correspondence and agreement among devices. To assess concurrent validity NOD was compared to the “gold standard” JD, in terms of ICCs and through Pearson correlation. The agreement between the methods of measurement was calculated with the Limits of Agreement (LoA) and the plots of Bland–Altman. Results All ICCs show high inter-reliability; the results are very similar for both dynamometers. The value of the adjusted ICC of NOD was 0.90. For validity, Pearson correlations of NOD towards JD and JD-adapted-grip were high (r = 0.87 and 0.88). However, the LoA and the plots of Bland–Altman demonstrated that there is no agreement between NOD and JD and between NOD and JD-adapted-grip, with NOD showing lower mean scores than JD. Conclusions NOD is a reliable and valid instrument for HGS. However, even if it cannot be considered interchangeable with JD because there is no agreement between them in free-living adults, NOD is easier to carry than other dynamometers, it has a Bluetooth® connection with a free App and it is a multi-purpose tool that should be considered both in daily practice and in clinical settings.

Abstract In this paper we study the bounds that can be inferred on New Physics couplings to heavy sterile neutrinos N from the recent measurements performed by the Belle collaboration of the angular analysis of B → D ∗ ℓ ν ¯ ℓ $$ B\to {D}^{\ast}\ell {\overline{\nu}}_{\ell } $$ decays, with ℓ = e, μ. Indeed, a sterile neutrino N may lead to competing B → D ∗ ℓ N ¯ $$ B\to {D}^{\ast}\ell \overline{N} $$ decays and Belle might have measured an incoherent sum of these two independent channels. After reviewing the theoretical formalism required to describe this phenomenon in full generality, we first perform a bump hunt in the M miss 2 $$ {M}_{\textrm{miss}}^2 $$ Belle distribution to search for evidences of an additional massive neutrino. We found in such a way a small hint at M miss 2 $$ {M}_{\textrm{miss}}^2 $$ ∼ (354 MeV)2. However, the Belle angular analysis is sensitive to N masses up to O $$ \mathcal{O} $$ (50 MeV), preventing us to further inspect this hint. Nevertheless, we study the potential impact of this additional channel in the allowed mass range on the measured angular distributions and extract model-independent bounds on the new-physics couplings which could mediate such an interaction. In particular, in the mass window here inspected, we obtain the most stringent bounds for vector and left-handed scalar operators to date.

Abstract Background Photon-counting detector (PCD) technology has the potential to reduce noise in computed tomography (CT). This study aimed to carry out a voxelwise noise characterization for a clinical PCD-CT scanner with a model-based iterative reconstruction algorithm (QIR). Methods Forty repeated axial acquisitions (tube voltage 120 kV, tube load 200 mAs, slice thickness 0.4 mm) of a homogeneous water phantom and CTP404 module (Catphan-504) were performed. Water phantom acquisitions were also performed on a conventional energy-integrating detector (EID) scanner with a sinogram/image-based iterative reconstruction algorithm, using similar acquisition/reconstruction parameters. For smooth/sharp kernels, filtered back projection (FBP)- and iterative-reconstructed images were obtained. Noise maps, non-uniformity index (NUI) of noise maps, image noise histograms, and noise power spectrum (NPS) curves were computed. Results For FBP-reconstructed images of water phantom, mean noise was (smooth/sharp kernel) 11.7 HU/51.1 HU and 18.3 HU/80.1 HU for PCD-scanner and EID-scanner, respectively, with NUI values for PCD-scanner less than half those for EID-scanner. Percentage noise reduction increased with increasing iterative power, up to (smooth/sharp kernel) 57.7%/72.5% and 56.3%/70.1% for PCD-scanner and EID-scanner, respectively. For PCD-scanner, FBP- and QIR-reconstructed images featured an almost Gaussian distribution of noise values, whose shape did not appreciably vary with iterative power. Noise maps of CTP404 module showed increased NUI values with increasing iterative power, up to (smooth/sharp kernel) 15.7%/9.2%. QIR-reconstructed images showed limited low-frequency shift of NPS peak frequency. Conclusion PCD-CT allowed appreciably reducing image noise while improving its spatial uniformity. QIR algorithm decreases image noise without modifying its histogram distribution shape, and partly preserving noise texture. Relevance statement This phantom study corroborates the capability of photon-counting detector technology in appreciably reducing CT imaging noise and improving spatial uniformity of noise values, yielding a potential reduction of radiation exposure, though this needs to be assessed in more detail. Key Points First voxelwise characterization of noise for a clinical CT scanner with photon-counting detector technology. Photon-counting detector technology has the capability to appreciably reduce CT imaging noise and improve spatial uniformity of noise values. In photon-counting CT, a model-based iterative reconstruction algorithm (QIR) allows decreasing effectively image noise. This is done without modifying noise histogram distribution shape, while limiting the low-frequency shift of noise power spectrum peak frequency. Graphical Abstract

Abstract Hibernating brown bears, due to a drastic reduction in metabolic rate, show only moderate muscle wasting. Here, we evaluate if ATPase activity of resting skeletal muscle myosin can contribute to this energy sparing. By analyzing single muscle fibers taken from the same bears, either during hibernation or in summer, we find that fibers from hibernating bears have a mild decline in force production and a significant reduction in ATPase activity. Single fiber proteomics, western blotting, and immunohistochemical analyses reveal major remodeling of the mitochondrial proteome during hibernation. Furthermore, using bioinformatical approaches and western blotting we find that phosphorylated myosin light chain, a known stimulator of basal myosin ATPase activity, is decreased in hibernating and disused muscles. These results suggest that skeletal muscle limits energy loss by reducing myosin ATPase activity, indicating a possible role for myosin ATPase activity modulation in multiple muscle wasting conditions.

Abstract Background In-person interaction offers invaluable benefits to people. To guarantee safe in-person activities during a COVID-19 outbreak, effective identification of infectious individuals is essential. In this study, we aim to analyze the impact of screening with antigen tests in schools and workplaces on identifying COVID-19 infections. Methods We assess the effectiveness of various screening test strategies with antigen tests in schools and workplaces through quantitative simulations. The primary outcome of our analyses is the proportion of infected individuals identified. The transmission process at the population level is modeled using a deterministic compartmental model. Infected individuals are identified through screening tests or symptom development. The time-varying sensitivity of antigen tests and infectiousness is determined by a viral dynamics model. Screening test strategies are characterized by the screening schedule, sensitivity of antigen tests, screening duration, timing of screening initiation, and available tests per person. Results Here, we show that early and frequent screening is the key to maximizing the effectiveness of the screening program. For example, 44.5% (95% CI: 40.8–47.5) of infected individuals are identified by daily testing, whereas it is only 33.7% (95% CI: 30.5–37.3) when testing is performed at the end of the program duration. If high sensitivity antigen tests (Detection limit: $$6.3\times {10}^{4}$$ 6.3 × 10 4 copies/mL) are deployed, it reaches 69.3% (95% CI: 66.5–72.5). Conclusions High sensitivity antigen tests, high frequency screening tests, and immediate initiation of screening tests are important to safely restart educational and economic activities in-person. Our computational framework is useful for assessing screening programs by incorporating situation-specific factors.

Purpose: Non-obstructive azoospermia (NOA) is a common, but complex problem, with multiple therapeutic options and a lack of clear guidelines. Hence, there is considerable controversy and marked variation in the management of NOA. This survey evaluates contemporary global practices related to medical and surgical management for patients with NOA. Materials and Methods: A 56-question online survey covering various aspects of the evaluation and management of NOA was sent to specialists around the globe. This paper analyzes the results of the second half of the survey dealing with the management of NOA. Results have been compared to current guidelines, and expert recommendations have been provided using a Delphi process. Results: Participants from 49 countries submitted 336 valid responses. Hormonal therapy for 3 to 6 months was suggested before surgical sperm retrieval (SSR) by 29.6% and 23.6% of participants for normogonadotropic hypogonadism and hypergonadotropic hypogonadism respectively. The SSR rate was reported as 50.0% by 26.0% to 50.0% of participants. Interestingly, 46.0% reported successful SSR in

Static Analysis (SA) and Dynamic Analysis (DA) are complementary techniques for searching web application vulnerabilities. Typically, SA detects more vulnerabilities but reports a higher number of false positives, whereas DA finds less but with better precision. In this paper, we blend SA and DA to simultaneously improve the detection and decrease the false alarms. Our approach starts with SA to identify an initial set of potential vulnerabilities. Then, the target application is executed to obtain specific runtime information. These data are used to automatically configure the DA, improving its ability to confirm if the vulnerabilities reported by the SA are indeed exploitable. We evaluated the proposed approach using 49 WordPress plugins with more than 450 SQLi vulnerabilities. Our approach was able to confirm either as a vulnerability or a false alarm 76.7% of the results reported by the SA, decreasing tremendously the usual need for manual work, which is a huge improvement for security practitioners.

La mise en abyme, definida como relación especular entre la obra entera y un fragmento que refleja características importantes de ésta, se basa en un desdoblamiento (o una multiplicación) interno de una parte del texto, una repetición que puede ser figurada o literal. Mientras que la mise en abyme por sustitución metonímica y metafórica ha sido objeto de numerosos estudios, la autocita en cuanto reiteración de pasajes idénticos en la misma obra no ha atraído mucho la atención crítica y su carácter de mise en abyme resulta dudoso en muchos casos. En este artículo se examinan tres textos en que se repiten, con funciones y significados variados y en contextos diferentes, frases o incluso páginas enteras: 1. las variaciones de una conversación telefónica en la pieza teatral Cartas de amor a Stalin de Juan Mayorga; 2. la recreación de ficciones y recuerdos en la novela Remake de Bruno Galindo; 3. la autocita anticipadora del final en El Maestro y Margarita de Mijaíl Bulgákov. El análisis de estas obras permite afirmar que la repetición textual, y no sólo en su forma de autocita con cambio del nivel de enunciación, puede ser una especie de fractal especular que comparte algunas características y funciones con la mise en abyme.

The mitogen‐activated protein kinase (MAPK) extracellular signal‐regulated kinase 5 (ERK5) is emerging as a promising target in cancer. Indeed, alterations of the MEK5/ERK5 pathway are present in many types of cancer, including melanoma. One of the key events in MAPK signalling is MAPK nuclear translocation and its subsequent regulation of gene expression. Likewise, the effects of ERK5 in supporting cancer cell proliferation have been linked to its nuclear localization. Despite many processes regulating ERK5 nuclear translocation having been determined, the nuclear transporters involved have not yet been identified. Here, we investigated the role of importin subunit alpha (α importin) and importin subunit beta‐1 (importin β1) in ERK5 nuclear shuttling to identify additional targets for cancer treatment. Either importin β1 knockdown or the α/β1 importin inhibitor ivermectin reduced the nuclear amount of overexpressed and endogenous ERK5 in HEK293T and A375 melanoma cells, respectively. These results were confirmed in single‐molecule microscopy in HeLa cells. Moreover, immunofluorescence analysis showed that ivermectin impairs epidermal growth factor (EGF)‐induced ERK5 nuclear shuttling in HeLa cells. Both co‐immunoprecipitation experiments and proximity ligation assay provided evidence that ERK5 and importin β1 interact and that this interaction is further induced by EGF administration and prevented by ivermectin treatment. The combination of ivermectin and the ERK5 inhibitor AX15836 synergistically reduced cell viability and colony formation ability in A375 and HeLa cells and was more effective than single treatments in preventing the growth of A375 and HeLa spheroids. The increased reduction of cell viability upon the same combination was also observed in patient‐derived metastatic melanoma cells. The combination of ivermectin and ERK5 inhibitors other than AX15836 provided similar effects on cell viability. The identification of importin β1 as the nuclear transporter of ERK5 may be exploited for additional ERK5‐inhibiting strategies for cancer therapy.

Networked sensing refers to the capability of multiple wireless terminals to cooperate with the aim of enhancing specific figures of merit, e.g., positioning accuracy or imaging resolution. Regarding radio-based sensing, it is essential to understand when and how sensing terminals should cooperate, namely the best strategy that trades between performance and cost (e.g., energy consumption, communication overhead, and complexity). This tutorial paper revises networked sensing from a wavefield interaction perspective, aiming to provide a general theoretical benchmark to evaluate its imaging performance bounds and to guide the sensing cooperation accordingly. Diffraction tomography theory (DTT) is the method to quantify the imaging resolution of any radio sensing experiment from inspection of its spectral (or wavenumber) content. In networked sensing, the image formation is based on the back-projection integral, valid for any network topology and physical configuration of the terminals. The wavefield networked sensing is a framework in which multiple sensing terminals cooperate during the acquisition process to maximize the imaging quality (resolution and sidelobes suppression) by pursuing the wavenumber tessellation principle. We discuss all the coherent data fusion possibilities between sensing terminals and possible killer applications. Remarkably, we show the possibility that the proposed method allows obtaining high-quality images of the environment in limited bandwidth conditions, leveraging the coherent combination of multiple multi-static low-resolution images.

Biting midges (Culicoides spp.) are important vectors of several insect borne arboviruses but are underrepresented in terms of availability of high-resolution genomic resources. We assembled and annotated complete mitochondrial genomes for two Culicoides species, namely C. brevitarsis and C. imicola which are proven vectors for Bluetongue Virus (BTV). We used both long read and short read sequencing technologies to assemble the circular genomes. The genome sizes are 17,100 bp and 17,031 bp, respectively, all comprising 37 genes, including 13 protein, 22 tRNA, two rRNA coding genes, and one non-coding AT rich control region. The gene organizations and orientations are comparable to other available Culicoides mitogenomes, except for a translocation of ND2 and six tRNA genes in both C. brevitarsis and C. imicola. Eleven protein-coding genes encode a full TAA stop codon, while two (ND5, COX3) are completed by mRNA polyadenylation. Phylogenetic analysis of the mitogenomes showed C. brevitarsis and C. imicola form a monophyletic group. The sequences of these mitogenomes contribute to a baseline of molecular tools for diagnostics and surveillance for use by World Organisation for Animal Health (WOAH) reference laboratories for monitoring vectors of emerging diseases.

The standardisation and correction of taxonomic names in large biodiversity databases remain persistent challenges for researchers, as errors in species names can compromise ecological analyses, land-use planning and conservation efforts, particularly when inaccurate data are shared on global biodiversity portals.We present pytaxon, a Python software designed to resolve and correct taxonomic names in biodiversity data by leveraging the Global Names Verifier (GNV) API and employing fuzzy matching techniques to suggest corrections for discrepancies and nomenclatural inconsistencies. The pytaxon offers both a Command Line Interface (CLI) and a Graphical User Interface (GUI), ensuring accessibility to users with different levels of computing expertise. Tests on spreadsheets derived from datasets published in the Global Biodiversity Information Facility (GBIF) demonstrated its effectiveness in identifying and resolving taxonomic errors. By mitigating the propagation of inaccuracies from researchers' datasets to global biodiversity databases, pytaxon supports more reliable conservation decisions and robust scientific investigations. Its contributions enhance data integrity and promote informed biodiversity management in a rapidly evolving global environment.

Non-invasive mechanical ventilation (NIMV) has emerged as a pivotal intervention for the care of individuals with lung cancer. NIMV offers substantial advantages in enhancing oxygenation, optimizing respiratory function, elevating pulmonary capacities, and facilitating patient comfort. NIMV’s utility extends to enhancing clinical conditions that range from chronic obstructive pulmonary disease and emphysematous lung ailments to aiding patients with lung cancer facing acute respiratory failure. Furthermore, NIVM includes perioperative pulmonary rehabilitation. This approach is particularly relevant for individuals with limited lung capacity. Since both non-invasive positive pressure ventilation modes, including BiLevel positive airway pressure and continuous positive airway pressure, address the underlying pathophysiological mechanisms that contribute to postoperative respiratory failure, the proactive and early integration of NIMV has the potential to significantly enhance gas exchange and overall respiratory performance in meticulously chosen patients within the perioperative phase. Although non-intubated video-assisted thoracic surgery represents an interesting field of application for NIMV strategies, further studies are needed to optimize operative modalities. Lastly, NIMV has a pivotal role in the settings of intensive care and palliative care units, thereby cementing its versatile utility across various medical contexts.

The increasing complexity and unpredictability of many ICT scenarios let us envision that future systems will have to dynamically learn how to act and adapt to face evolving situations with little or no a priori knowledge, both at the level of individual components and at the collective level. In other words, such systems should become able to autonomously (i.e., self-) develop mental models of themselves and of their environment. Autonomous mental development includes: learning models of own capabilities; learning how to act purposefully towards the achievement of specific goals; and learning how to act in the presence of others, i.e., at the collective level. In this paper, we introduce a conceptual framework for autonomous mental development in ICT systems – at both the individual and collective levels – by framing its key concepts and illustrating suitable application domains. Then, we overview the many research areas that are contributing or can potentially contribute to the realization of the framework, and identify some key research challenges.

Among the converters currently employed for ac–dc conversion, diode rectifiers (DRs) and voltage source rectifiers are the most prevalent due to their accessibility, cost-effectiveness, and efficiency. However, current source rectifiers (CSRs) present several advantages, such as short-circuit protection, step-down capabilities, minimal output current ripple, and the elimination of dc bus capacitors. These features can lead to a reduction in overall size and an enhancement in power quality, although CSRs are often associated with higher conversion losses. Recent advancements in applications that can leverage the benefits of CSRs, along with the development of new devices to improve their efficiency, have produced renewed interest in this configuration. This article aims to review the design parameters of CSR components, modulation schemes, and control strategies, while also conducting a loss analysis using both established literature methods and innovative approaches developed by the authors. In addition, a comparison with other topologies is presented, illustrating that in certain applications and conditions, CSRs can be a compelling choice. Thus, rather than focusing on a specific aspect of CSRs, this article provides a comprehensive overview of the topic, offering practical insights for engineers.

Abstract Background Digital interventions (DIs) have emerged as promising tools for promoting mental health in the workplace. However, evidence on if, how, and under what circumstances they affect positive outcomes requires elucidation. This systematic realist review aimed to synthesize current knowledge on contexts, mechanisms, and outcomes of workplace DIs to enhance mental health at work. Methods The review integrates elements of both systematic and realist review methodologies. Forty-four workplace mental health DIs studies were gathered through a systematic electronic search using PsycNet, Scopus, Web of Science, and PubPsych. Results Results showed that demographics, previous mental health, and personal skills were the main individual context factors influencing the success of DIs. Key mechanisms were DIs usage, frequency, adherence, and relevance of content triggering positive perceptual shifts. Results showed improvements in psychological resources, wellbeing, and affect. Reduced ill-health symptoms were also evidenced. Five propositions were developed on the contexts and mechanisms under which digital interventions yield positive outcomes for mental health at work. Conclusions This study highlights several areas where future research can expand our understanding of DIs in the workplace by examining interactions between mechanisms and cultural aspects influencing implementation.

Abstract Rapid urbanization and migration in Latin America have intensified exposure to insect-borne diseases. Malaria, Chagas disease, yellow fever, and leishmaniasis have historically afflicted the region, while dengue, chikungunya, and Zika have been described and expanded more recently. The increased presence of synanthropic vector species and spread into previously unaffected areas due to urbanization and climate warming have intensified pathogen transmission risks. This review examines recent outbreaks and reemergence of insect-borne diseases through five case studies: (i) malaria transmission linked to political instability and large-scale migration through the Amazon jungle; (ii) the expansion of triatomine bug habitats into overcrowded, substandard urban settlements, increasing Chagas disease incidence; (iii) the influence of movement and ecotourism in the Amazonia on yellow fever transmission in peri-urban areas; (iv) the spread of visceral leishmaniasis driven by deforestation and human–canine movement; and (v) dengue outbreaks in rural Amazon regions, spurred by urbanization and rural development. The findings underscore the complex interactions among vectors, pathogens, and shifting environmental and social conditions, complicating predictability and control. Addressing the social, economic, and political determinants of health is crucial to reducing disease transmission. Key measures include scaling vaccine coverage, especially for dengue and yellow fever; developing vaccines and treatments for neglected diseases; improving housing and sanitation; strengthening vector surveillance and control; fostering community engagement; enhancing data-driven interventions. Graphical Abstract

Abstract Background Spent coffee grounds (SCG) are the most abundant waste byproducts generated from coffee beverage production worldwide. Typically, these grounds are seen as waste and end up in landfills. However, SCG contain valuable compounds that can be valorized and used in different applications. Notably, they are rich in carbohydrates, primarily galactomannan, arabinogalactan type II, and cellulose. Within the framework of a circular bioeconomy, the targeted degradation of these polysaccharides via a tailored cocktail of carbohydrate-active enzymes offers a promising strategy for producing high-value saccharides from coffee waste. Results In this study, various mild pretreatments were evaluated to increase the enzyme accessibility of SCG-derived biomass, reduce lignin content, and minimize hemicellulose loss. Thermostable enzymes were selected to construct an enzymatic cocktail specifically targeting cellulose and hemicelluloses in pretreated SCGs. The approach used achieved a conversion of 52% of the polysaccharide content to oligo- and monosaccharides, producing 17.4 mg of reducing sugars and 5.1 mg of monosaccharides from 50 mg of SCG. Additionally, microwave pretreatment followed by the application of a thermostable endo β-mannanase resulted in the production of 62.3 mg of mannooligosaccharides from 500 mg of SCG. In vitro experiments demonstrated that the produced mannooligosaccharides exhibited prebiotic activity, promoting the growth and biofilm formation of five probiotic bacterial strains. Conclusions This study highlights an effective strategy for the valorization of SCG polysaccharides through mild pretreatment and customized enzymatic cocktails in a circular bioeconomic context. The production of both monosaccharides and oligosaccharides with prebiotic activity illustrates the versatility and commercial potential of SCG as a substrate for high-value saccharides. Furthermore, the use of mild pretreatment methods and thermostable enzymes minimizes chemical inputs and energy demands, aligning with sustainable processing practices. The ability to selectively target and degrade specific polysaccharides within SCG not only enhances the yield of desirable products, but also preserves key structural components, reducing waste and promoting resource efficiency.

Abstract The compositional heterogeneity of clinopyroxene in products of the 1888-90 eruption at La Fossa of Vulcano has been used to constrain times of the plumbing system reactivation before the eruption. We have also investigated the temporal trend of the SO2 flux at La Fossa crater since 1978 to gather information about the origin, depths and quantity of magma involved in the recent degassing crises. Petrological data emphasizes migration of deep-seated magmas and their emplacement in the shallow system, clearly supporting the involvement of three distinct phases of mafic replenishments occurred respectively 85–140, 16–35 and 2–7 years before the 1888-90 eruption. These results reconcile with the dynamics of magma emplacement and degassing inferred for the recent periods of unrest. SO2 data for the period January 1978 – September 2024 imply a volume of intrusive magma of ~ 26–86 × 106 m3, which is comparable to the order of magnitude of magma volumes erupted during the 1888-90 cycle. Our petrological and geochemical data suggest that shallow reservoirs have been already largely pressurized by multiple mafic injections occurred over the last century.

Abstract The study aimed to assess the feasibility and potential efficacy of a non-motor intervention utilizing motor imagery (MI) and transcranial direct current stimulation (tDCS) to enhance motor function. The research involved a double-blind, randomized, controlled trial with three groups: MIActive, MISham, and Control. Participants engaged in a cognitively demanding obstacle course, with time and prefrontal activation (ΔO2Hb and ΔHHb) measured across three-time points (Baseline, Post-test, 1-week follow-up). Following a pretest, active or sham tDCS was administered during an MI session, while the Control group did not receive this intervention. The MIActive group showed significant improvements in time-to-completion immediately after the intervention and one week later. Additionally, ΔO2Hb levels were lower in the MIActive group than in the other groups. These findings suggest that the combination of MI and tDCS could lead to motor improvements. The study outcomes support the feasibility and initial effectiveness of using MI and tDCS as a non-motor intervention to enhance motor outcomes in short and medium terms. Further research is recommended to explore the impact of this intervention in individuals with existing motor impairments. This study contributes to the growing body of evidence on the potential of non-motor interventions to induce neuroplastic changes that improve motor function. Clinical trial registration: ClinicalTrials.gov, identifier NCT06414213 16/05/2024.

Abstract Acute stroke management is time-sensitive, making time data crucial for both research and quality management. However, these time data are often not reliably captured in routine clinical practice. In this proof-of-concept study we analysed image-based time data automatically captured in the DICOM format. We enrolled data from two separate stroke centers (n = 3136 and n = 2089). Data from the first center was additionally separated into groups with large-vessel-occlusion (LVO, n = 1.092), medium-vessel-occlusions (MVO, n = 416), and no occlusion (NVO, n = 1630). The DICOM-tag StudyTime was used to analyze the distribution of scan times throughout the day. Additionally, manually documented onset- and admission were extracted from the patients’ records in a subset of cases (n = 347). Timestamps were compared across centers and occlusion groups, and a probabilistic model was developed to illustrate and compare stroke occurrence patterns throughout the day. The temporal distribution of the scan times at both centers was exceptionally consistent with a peak around noon and a nighttime low. The groups with vessel occlusions showed an earlier peak compared to those without (p

Abstract Rare diseases may affect the quality of life of patients and be life-threatening. Therapeutic opportunities are often limited, in part because of the lack of understanding of the molecular mechanisms underlying these diseases. This can be ascribed to the low prevalence of rare diseases and therefore the lower sample sizes available for research. A way to overcome this is to integrate experimental rare disease data with prior knowledge using network-based methods. Taking this one step further, we hypothesized that combining and analyzing the results from multiple network-based methods could provide data-driven hypotheses of pathogenic mechanisms from multiple perspectives. We analyzed a Huntington’s disease transcriptomics dataset using six network-based methods in a collaborative way. These methods either inherently reported enriched annotation terms or their results were fed into enrichment analyses. The resulting significantly enriched Reactome pathways were then summarized using the ontological hierarchy which allowed the integration and interpretation of outputs from multiple methods. Among the resulting enriched pathways, there are pathways that have been shown previously to be involved in Huntington’s disease and pathways whose direct contribution to disease pathogenesis remains unclear and requires further investigation. In summary, our study shows that collaborative network analysis approaches are well-suited to study rare diseases, as they provide hypotheses for pathogenic mechanisms from multiple perspectives. Applying different methods to the same case study can uncover different disease mechanisms that would not be apparent with the application of a single method.

Abstract Inefficient targeting of muscle stem cells (MuSCs), also called satellite cells, represents a major bottleneck of current therapeutic strategies for muscular dystrophies, as it precludes the possibility of promoting compensatory regeneration. Here we describe a muscle-targeting delivery platform, based on gold nanoparticles, that enables the release of therapeutic oligonucleotides into MuSCs. We demonstrate that AuNPs conjugation to an aptamer against α7/β1 integrin dimers directs either local or systemic delivery of microRNA-206 to MuSCs, thereby promoting muscle regeneration and improving muscle functionality, in a mouse model of Duchenne Muscular Dystrophy. We show here that this platform is biocompatible, non-toxic, and non-immunogenic, and it can be easily adapted for the release of a wide range of therapeutic oligonucleotides into diseased muscles.

Abstract Although sex determination is a fundamental process in vertebrate development, it is very plastic. Diverse genes became major sex determinants in teleost fishes. Deciphering how individual sex-determining genes orchestrate sex determination can reveal new actors in sexual development. Here, we demonstrate that the Y-chromosomal copy of the TGF-β family member gdf6 (gdf6Y) in Nothobranchius furzeri, an emerging model organism in aging research, gained the function of the male sex determinant through allelic diversification while retaining the skeletal developmental function shared with the X-chromosomal gdf6 allele (gdf6X). Concerning sex determination, gdf6Y is expressed by somatic supporting cells of the developing testes. There it induces the male sex in a germ cell-independent manner in contrast to sex determination in zebrafish and the medaka. Looking for downstream effectors of Gdf6Y, we identified besides TGF-β signaling modulators, especially the inhibitor of DNA binding genes id1/2/3, the mRNA decay activator zfp36l2 as a new GDF6 signaling target.