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Objective: The submental flap is a fasciocutaneous flap used in head and neck reconstruction. The aim of this study was to share the indications and outcomes of submental flap reconstruction based on our experience. Methods: A retrospective descriptive study was conducted on a group of 14 patients who underwent reconstructive surgery of the orofacial region with the submental flap. All reconstructions were performed following oncologic resections. Results: The submental flap was employed for the reconstruction of mobile tongue in 5 cases, maxilla and hard palate in 4 cases, cheek in 2 cases, floor of the mouth in 1 case, retromolar trigone in 1 case and oropharyngeal defects in 1 case. Satisfactory oral cavity opening was achieved in all cases. No transfer of metastatic lymph nodes to the recipient area was detected in this study. Conclusions: The submental flap significantly shortens the surgical time compared to microvascular flaps. In our experience, the necessity for neck lymph node surgery does not preclude the use of the submental flap. Meticulous dissection of the flap greatly reduces the risk of potential transfer of tumours through the flap to the recipient area.

Species richness is not homogeneous in space and it normally presents differences when comparing among different sites. These differences often respond to gradients in one or several factors which create biodiversity patterns in space and are scale-dependent. At a local scale, diversity patterns depend on the habitat size (species-area relationship), the productivity, the environmental harshness, the frequency and intensity of disturbance, or the regional species pool. Regional diversity may be influenced by environmental heterogeneity (increasing dissimilarity), although it could act also at smaller or larger spatial scales, and the connectivity among habitats. Finally, at a global scale, diversity patterns are found with the latitude, the altitude or the depth, although these factors are surrogates for one or several environmental variables (productivity, area, isolation, or harshness).

Undernutrition during pregnancy has been associated to increased vulnerability to develop metabolic and behavior alterations later in life. The endocannabinoid system might play an important role in these processes. Therefore, we investigated the effects of a moderate maternal calorie-restricted diet on the levels of the endocannabinoid 2-arachidonoyl glycerol (2-AG), arachidonic acid (AA) and the N-acylethanolamines (NAEs) anandamide (AEA), oleoylethanolamide (OEA) and palmitoylethanolamide (PEA) in the brain of newborn rat offspring. We focused on brain structures involved in metabolism, feeding behavior, as well as emotional and cognitive responses. Female Wistar rats were assigned during the entire pregnancy to either control diet (C) or restriction diet (R), consisting of a 20% calorie-restricted diet. Weight gain and caloric intake of rat dams were monitored and birth outcomes were assessed. 2-AG, AA and NAE levels were measured in hypothalamus, hippocampus and olfactory bulb of the offspring. R dams displayed lower gain weight from the middle pregnancy and consumed less calories during the entire pregnancy. Offspring from R dams were underweight at birth, but litter size was unaffected. In hypothalamus, R male offspring displayed decreased levels of AA and OEA, with no change in the levels of the endocannabinoids 2-AG and AEA. R female exhibited decreased 2-AG and PEA levels. The opposite was found in the hippocampus, where R male displayed increased 2-AG and AA levels, and R female exhibited elevated levels of AEA, AA and PEA. In the olfactory bulb, only R female presented decreased levels of AEA, AA and PEA. Therefore, a moderate diet restriction during the entire pregnancy alters differentially the endocannabinoids and/or endocannabinoid-related lipids in hypothalamus and hippocampus of the underweight offspring, similarly in both sexes, whereas sex-specific alterations occur in the olfactory bulb. Consequently, endocannabinoid and endocannabinoid-related lipid signaling alterations might be involved in the long-term and sexual dimorphism effects commonly observed after undernutrition and low birth weight.

El objetivo del artículo es estudiar las transformaciones de la Cornisa de Madrid desde su nombramiento como capital. El fuerte simbolismo que ha venido transmitiendo como fachada icónica de la ciudad se ha visto recientemente desdibujado con las últimas intervenciones en su entorno. Sin embargo, la sección de la vega del río, de algún modo, ha revivido. Si las representaciones tradicionales de la Cornisa eran planas y estáticas, y tenían como fin exaltar la ciudad; en su nueva comprensión prima el recorrido y una lectura tridimensional y dinámica del lugar.

Abstract Background This study aimed to identify profiles of patients with cardiovascular disease (CVD) risk factors, based on their sociodemographic and clinical characteristics, and to analyse how their complexity is related to their frequency of visits in Primary Care. Methods Observational longitudinal study conducted in the Spanish CArdiovascular Risk factors for HEalth Services research (CARhES) cohort. Individuals older than 15 with hypertension, type 2 diabetes mellitus (DM) and/or dyslipidaemia in 2017 were selected and followed until 2021. Cluster analyses were performed to identify patients’ profiles according to age, sex and morbidity burden. Characteristics and annual visits in Primary Care in the different profiles were described. Panel data models were applied to study the variability of the frequency of visits to both physicians and nurses in Primary Care in the profiles across different time points. Results In this population-based cohort of 446,998 individuals, different profiles were identified among those with hypertension, type 2 DM and/or dyslipidaemia. Profiles comprising the elderly showed the highest morbidity burden. Among the profiles of individuals under 80, those that included women had a higher burden than profiles with men. This higher complexity was associated with higher frequency of Primary Care visits, regardless of the patient’s socioeconomic level and depopulation level of his/her Basic Health Area. Conclusions Women and the elderly comprised the profiles with the highest morbidity burden and Primary Care attendance. Tailoring care and resources according to the complexity profile is essential to ensure that patients receive the best possible care based on their needs.

Abstract This study investigates how environmental, social, and governance (ESG) factors affect the financial performance of fintech companies in Jordan, with a focus on sustainable fintech practices. The study employed a survey methodology, distributing questionnaires to employees in the Jordanian fintech sector to gather primary data. The data were analyzed using partial least squares structural equation modeling (PLS-SEM), ensuring methodological rigor through a robust sample size. The findings reveal that ESG factors have a significant positive impact on fintech performance, which is further enhanced by the adoption of sustainable practices. This underscores the critical role of sustainability in fintech operations and provides actionable insights for industry professionals and policymakers aiming to promote responsible growth. The study contributes to the literature by advancing understanding of ESG integration within fintech and laying the groundwork for future research. It highlights the importance of sustainable practices in enhancing financial performance and provides a foundation for exploring how these practices influence fintech operations. Future research should consider the evolving regulatory environment and its impact on ESG integration in fintech. Longitudinal studies could investigate the sustainability-performance relationship over time, revealing trends and obstacles as fintech firms expand. Additionally, comparative studies across different regions or sectors could offer insights into how various factors shape ESG adoption and its effects on financial outcomes. These future directions will improve our understanding of sustainable fintech and support the global development of responsible financial innovations.

Abstract Background Local recurrence of rectal cancer (LRRC) previously treated with radiotherapy is associated with a poor prognosis. Historically, the integration of radiotherapy (RT) with surgery has improved the likelihood of complete resections (R0) and, consequently, enhanced survival. Unfortunately, many LRRC cases are not amenable to surgical intervention. The inclusion of chemotherapy (CHT) alongside advanced RT techniques including proton and carbon ion RT (CIRT) and stereotactic body radiation therapy (SBRT), has generated new treatment options. Therefore, there is a need for improved stratification of LRRC patients to enhance treatment outcomes. The RETRY is an integrated trial with the primary aim to explore if combining CHT with RT in all available modalities can enhance local control (LC) in LRRC patients, consequently improving survival. Methods Experts from Italian centers specializing in rectal cancer and LRRC management collaborated to design a prospective multicenter observational study within the AIRO group for gastrointestinal malignancies. Eligible participants are adult LRRC patients who previously had pelvic RT, meet specific criteria, and are affiliated with the participating Italian centers. Specific criteria must be met for CIRT referral. A total of 88 patients will be enrolled over three years. The primary objective is to determine the 3-year LC rate. Secondary outcomes include assessing survival, quality of life, and R0 resection rates in surgery cases. A minimum dose of 40 Gy, conventional fractionation with concomitant fluoropyrimidine—with/without oxaliplatin-based CHT (CRT) is prescribed in neoadjuvant setting. Alternatively, the dose will vary from 35 to 40 Gy in 5 fractions based on clinical judgment, by SBRT. Both proton and photon therapies will be evaluated in these approaches. Surgery will be considered if deemed operable. In inoperable cases, CIRT with a dose of 40–60 Gy relative biological effectiveness (RBE) will be administered with a daily dose fraction ranging between 3 and 4.8 Gy RBE. Discussion The RETRY trial aims to investigate the combined effects of RT and CHT and when feasible the addition of surgery, to determine whether this comprehensive approach can result in improved survival and quality of life for LRRC patients. Trial registration number ClinicalTrials.gov (No. NCT05984576).

Introduction: Colorectal cancer screening programs are effective in reducing incidence and mortality. In Europe, every FIT+ patient is referred to colonoscopy. The available data show that ~75.0% of these patients are negative. It is desirable to select patients at a greater risk of having a positive colonoscopy. Materials and Methods: 711 subjects, aged 50–74, attending the screening program of ASL-NA-3-SUD (Naples, Italy), were enrolled in a cross-sectional study to evaluate the performance of the QuantiDNA™ test and the non-inferiority of an alternative approach (AAP). This evaluation is based on FIT+ and QuantiDNA™+ patients referred to colonoscopy, compared to Standard of Care (SOC) colonoscopy following a FIT+ test alone. A non-inferiority margin (NIM) for colorectal neoplasia (CN) and advanced adenomas (AA) was set at −10% and at −3.8% for CRC. Results: The odds ratio was 1.76 (p-value = 0.009). The detection rate of AAP was 15.9% for colorectal neoplasia, 13.0% for advanced adenoma, and 3.0% for CRC. The risk difference between AAP and SOC was −5.07% (95% C.I. −9.23, −0.90) for colorectal neoplasia, −4.02% (95% C.I. −7.89, −0.16) for advanced adenomas, and −1.04% (95% C.I. −3.16, 1.07) for CRC. This data suggests that AAP is non-inferior to SOC for detecting CN, AA, and CRC. The expected decrease in colonoscopies is 33.4%. Conclusions: The QuantiDNA™ test is straightforward, non-invasive, and well-tolerated. Data from this study indicate that it is effective in the reduction of the need for colonoscopy examinations (−33.4%) and is non-inferior to SOC in the detection of significant colorectal lesions.

The implementation of e-government undoubtedly offers considerable benefits, but it can also widen social inequalities. From this perspective, this study addresses administrative digitalization and its impact on citizenship. It is noted how state and regional regulations that develop the right of option to interact electronically with the Administration blur the formal and material boundaries of the provision contained in Article 14 of Law 39/2015. The changing jurisprudence of the Supreme Court on this matter is examined, and the effectiveness of regulatory measures aimed at alleviating this situation is questioned.

Abstract Background/Aim Current approaches for locally advanced rectal cancer (LARC) typically recommend neoadjuvant chemoradiotherapy (nCRT) with 5-fluorouracil (5FU) or its oral analogs followed by surgery as the standard of care. However, the question of whether intensifying concurrent chemotherapy by adding oxaliplatin to the 5FU-based backbone can yield better outcomes remains unresolved. This study aimed to investigate the benefits of incorporating oxaliplatin into fluoropyrimidine-based chemoradiotherapy (CRT) to increase locoregional control and survival. Methods Among 290 patients with LARC admitted to the Iran Cancer Institute’s radiation oncology department between January 2008 and December 2019, 29 received CAPEOX (capecitabine 625 mg/m²/bid on RT days and weekly oxaliplatin 50 mg/m²), whereas 293 received capecitabine (825 mg/m² twice daily or rarely 5FU in the first 4 days and last week of radiotherapy (RT)). Variables potentially affecting treatment outcomes were used for propensity score matching. Kaplan‒Meier and log-rank tests were employed for overall survival (OS) and disease-free survival (DFS) analyses and were adjusted with propensity score matching. Results Data from 29 patients who received CAPEOX and 216 patients who received capecitabine were analyzed after propensity score matching without replacement. After propensity score matching, in the multivariate analysis, CAPEOX significantly increased the likelihood of achieving a pathologic complete response (pCR) by 4.38 times (CI: 1.90–10.08, p value

Abstract Introduction Self‐expanding Y‐metal stents (SEMS) are best suited lesions with involvement of the carina and proximal main bronchi; however, Y‐stents can be difficult to place. These difficulties guided us to develop a modification of the classic technique that addresses some of the challenges during positioning. We present the Y reverse technique for Y stent insertion using a combination of rigid and flexible bronchoscopy. Materials and Methods This retrospective study included 15 consecutive patients, suffering from tracheal‐carina‐lower main bronchi complex, hospitalized at the Thoracic Surgery Unit of the Vanvitelli University of Naples between October 2021 and October 2023. Inclusion criteria: patients in which the length of the stenosis of the right bronchi was greater than that of the left bronchi, advanced oncological conditions, severe respiratory failure; exclusion criteria: Karnofsky scale with

Podolian cattle is an autochthonous breed well adapted to the harsh semi-arid environments of the Southern Italy regions; the extensive rearing system used for these indigenous animals is based on grazing on spontaneous pastures, such as grasslands or wood pastures These grazing systems respect animal welfare and enrich animal products with characteristics closely related to the feeding system and the farming environment. The aim of the present study was to characterize the nutritional value of a forage crop and a wood-pasture and to evaluate the effects of grazing by Podolian young bulls on the performances and meat quality in relation to the age at slaughter (14 or 18 months) and to the ageing time of meat (3, 9 or 14 days). The metabolizable energy and the gas production were greater in April and June for both pasture systems. Young bulls raised on the grassland showed greater slaughter weights (p

Abstract Background Postoperative intracranial neurosurgical infections (PINI) complicate

Abstract Introduction There are grounds for the hypothesis that poor sleep quality, regardless of the pre-gestational nutritional status, is a risk factor for inadequate gestational weight gain. Objective To investigate the association between sleep quality and insufficient or excessive gestational weight gain in Brazilian pregnant women without gestational complications and monitored in public prenatal care units. Methods This is a cross-sectional study nested within a cohort study that reviewed pregnant women’s mental health, sleep, and nutritional outcome. Data collection was carried out from May 2018 to June 2019 through face-to-face and telephone interviews and consultation of pregnant women’s medical records. Sleep quality was assessed using the Mini-sleep Questionnaire. The pregnancy weight gain was measured based on the Institute of Medicine’s recommendations. Univariate and multivariate Poisson regression analysis was used for the two outcomes: insufficient or excessive weight gain, using pregnant women with adequate weight gain as the reference category. Associations were considered significant when p

Abstract Background Violence against health professionals is a growing problem that affects the quality of care provided and the well-being of workers. In the Alentejo region (Southern Portugal), the Regional Health Administration has been developing strategies to prevent and combat this phenomenon, namely, through the implementation of the Action Plan for the Prevention of Violence in the Health Sector. Violence in the health sector includes all situations in which a worker in the Ministry of Health's health institutions is exposed to any type of violence related to their work, putting their safety, well-being or health at risk, or that of others. The aim of this study was to analyze the perceptions and practices of local focal points (e.g.,departments, services, offices or functional units) on violence against health professionals in the Alentejo region. Methods Semi-structured interviews were carried out local focal points in the Alentejo region. The sampling was selected for convenience from different health units. The interviews were recorded, transcribed and analyzed according to the analysis protocol of the IRaMuTeQ software (Interface de R pour les Analyses Multidimensionnelles de Textes et de Questionnaires) version 0.7 alpha 2. Results In total, 43 interviews were conducted between February and April 2024. Interviews revealed that local focal points face various challenges in combating violence against health workers. The lack of specific training, the scarcity of security resources and the culture of underreporting were some of the obstacles identified. However, participants also stressed the importance of teamwork, effective communication and institutional support in dealing with this problem. Conclusions Violence against health professionals is a worrying reality that requires effective measures to prevent and combat it, requiring a coordinated and multifaceted response. Local focal points play a key role in this process, but they need adequate training, resources and institutional support. Comprehensive and regular training programs on violence, interpersonal communication and conflict management, and investment in security resources, including physical and technological measures, should be implemented in health facilities. Clear protocols should be created for dealing with situations of violence and a culture of reporting situations of violence to health professionals should be promoted, as well as the monitoring of victims by the authorities involved in cases of violence. Ongoing training and the simulation of real-life scenarios are crucial for preparing professionals to effectively manage situations of violence.

Background: The aim of this study was to evaluate the impact of trabecular attenuation of the L1 vertebral body in low-dose CT in adult patients with multiple myeloma (MM), smoldering multiple myeloma (SMM), and monoclonal gammopathy of undetermined significance (MGUS). Materials and Methods: The study population consisted of 22 patients with MGUS and 51 consecutive patients with newly diagnosed MM (SMM, n = 21; symptomatic MM, n = 36). CT scans were conducted using a 128-slice CT scanner (Somatom go.Top, Siemens, Munich, Germany). Low-dose whole-body CT scans were performed at a single time point for each patient. Trabecular bone density values were obtained by defining regions of interest on non-contrast images at the level of L1 vertebra. A threshold of p = 0.05 was applied to determine statistical significance. Results: The median Hounsfield unit (HU) value in patients with MGUS, SMM, and MM was 148 HU (range 81–190), 130 HU (range 93–193), and 92 HU (range 26–190), respectively, with a statistically significant difference between the groups (p = 0.0015). Patients with HU values ≤ 92 had lower progression-free survival with statistically significant differences compared to the group with HU values > 92 (p < 0.0499). Conclusions: This is the earliest evidence of the importance of evaluating L1 attenuation values in low-dose CT images in patients with MGUS, SMM, and MM. Further prospective studies could contribute to reinforcing these results and exploring the clinical applicability and generalization of L1 attenuation values in low-dose whole-body CT scans in routine clinical practice.

Dental students are frequently exposed to percutaneous injuries (PCIs) due to the nature of their clinical work, which involves sharp instruments and close patient contact. The COVID-19 pandemic further emphasized the need for stringent biosafety measures and the use of personal protective equipment (PPE). Despite these precautions, injuries remain prevalent, highlighting the need for comprehensive education and training in biosafety and infection control. This study investigates the incidence and causes of injuries among undergraduate dental students during clinical sessions. This study was conducted at the Department of Dentistry, National and Kapodistrian University of Athens, focusing on injuries reported from 2021 to 2024. Data were collected through self-reported clinical records. The primary variables assessed included the type of injury, the instrument involved, the clinical procedure performed, and the immediate actions taken post-injury. Serological testing was conducted on students and patients to assess the risk of the transmission of bloodborne pathogens. The findings reveal a high prevalence of injuries, with needles being the most common cause (51.4%), followed by other tools such as dental probes (25.7%) and burs (8.6%). The most frequent injury type is piercing (74.2%), primarily affecting the fingers (88.6%). Periodontal treatments, restorative procedures, and endodontic treatments are the main activities leading to injuries, with 17.1% of injuries being caused by each. No statistically significant results are recorded. Despite regular medical records for most patients treated by injured students, serological testing shows significant positivity rates for HCV and HBV. Notably, most injured students demonstrate their commitment to safety by adhering to recommended post-exposure protocols, including wound cleaning, disinfecting, and serological testing. Furthermore, the impact of COVID-19 heightened the importance of personal protective equipment (PPE) and reinforced occupational health standards. Our study highlights the critical need for enhanced biosafety awareness and training among undergraduate dental students to reduce injury risks.

Background: In the transition to a professional learning environment, healthcare professionals in their first year of specialized postgraduate clinical training (known as residents in Spain) are suddenly required to handle confidential information with little or no prior training in the safe and appropriate use of digital media with respect to confidentiality issues. The aims of this study were: (1) to explore the usefulness of an advanced clinical simulation program for educating residents from different healthcare disciplines about confidentiality and the dissemination of clinical data or patient images; (2) to explore the use of social networks in healthcare settings; and (3) to explore participants’ knowledge and attitudes on current regulations regarding confidentiality, image dissemination, and the use of social networks; Methods: This was a cross-sectional study. Data were collected from all 49 first-year residents of different health professions at a Spanish hospital between June and August 2022. High-fidelity clinical simulation sessions designed to address confidentiality and health information dissemination issues in hospital settings, including the use of social networks, were developed and implemented. Data were assessed using a 12-item ad hoc questionnaire on confidentiality and the use of social media in the healthcare setting. Descriptive of general data and chi-square test or Fisher’s exact test were performed using the SPSS 25.0 software; Results: All the participants reported using the messaging application WhatsApp regularly during their working day. A total of 20.4% of the participants stated that they had taken photos of clinical data (radiographs, analyses, etc.) without permission, with 40.8% claiming that they were unaware of the legal consequences of improper access to clinical records. After the course, the participants reported intending to modify their behavior when sharing patient data without their consent and with respect to how patients are informed; Conclusions: The use of advanced simulation in the training of interprofessional teams of residents is as an effective tool for initiating attitudinal change and increasing knowledge related to patient privacy and confidentiality. Further follow-up studies are needed to see how these attitudes are incorporated into clinical practice.

Background: Violence against health professionals is a global and growing problem, with significant impacts on the quality of care and the mental health of workers. Objectives: To analyze the level of knowledge, reporting practices and consequences of violence against health professionals in the Alentejo region (southern Portugal). Methods: This was an observational, cross-sectional study involving 440 health professionals (doctors and nurses). Data were collected using an online platform and a structured questionnaire created specifically for this study. In the statistical analysis, the data were described as counts and proportions and the X2 test was used considering a significance level of 0.05. Results: This study reveals that violence against health professionals in the southern region of Portugal is a frequent problem (40%), with a higher incidence among nurses (80%). Despite awareness of the existence and functioning of reporting channels, reporting is low (52%). The main causes are related to the health system, professionals and users. The consequences include mental health problems and a reduction in the quality of care provided. Suggested measures to combat violence include improving security, training and punishing aggressors. Conclusions: This study reveals that violence against health professionals in the southern region of Portugal is a frequent, under-reported problem with serious consequences for professionals and the quality of care.

Abstract Background Understanding the timing of food introduction in infants is essential for promoting optimal complementary feeding practices. However, existing studies often rely on cross-sectional data, limiting the ability to capture age-specific patterns. We aimed to describe food introduction during the first year of life by identifying patterns related to age at food introduction and associated factors in a cohort of Brazilian infants. Methods Data were collected through standardized questionnaires administered to mothers via face-to-face interviews during the infant’s first month of life and at 3, 6, 9, and 12 months of age. Additionally, two telephone interviews were conducted at 2 and 4 months of age. Information regarding food intake was assessed using a list of 48 foods, with two key aspects recorded: whether the food was introduced (yes/no) and the age at introduction. To define food introduction patterns, we employed k-means cluster analysis. Hierarchical Poisson multiple regression was employed to examine the associations between sociodemographic, biological, and healthcare factors and patterns of food introduction. Results Three distinct patterns were identified and named according to their main characteristics: Pattern 1 – “Low Infant Formula and Timely CF Introduction”; Pattern 2 – “High Infant Formula and Early CF Introduction”; and Pattern 3 – “High Infant Formula and Later Ultra-processed Food Introduction”. Breastfeeding at six months showed a positive association with Pattern 1 (PR = 1.40; 95% CI = 1.10–1.80), while bottle use at four months was negatively associated with Pattern 1 (PR = 0.68; 95% CI = 0.53–0.87). No variables studied exhibited an association with Pattern 2. For Pattern 3, higher prevalences were observed among children whose mothers were aged 34 years (PR = 1.42; 95% CI = 1.04–1.93). Not receiving guidance on the recommended duration of breastfeeding and complementary feeding during prenatal care was associated with a higher prevalence of children in this pattern (PR = 1.35; 95% CI = 1.01–1.80). Conclusions We identified three distinct patterns of age at food introduction in the study population, although none perfectly aligned with Brazilian or WHO dietary recommendations. These findings underscore the need for targeted interventions to promote timely and healthy complementary feeding practices in Brazilian infants.

Abstract Background Cormus domestica (L.) is a monophyletic wild fruit tree belonging to the Rosaceae family, with well-documented use in the Mediterranean region. Traditionally, these fruits are harvested and stored for at least 2 weeks before consumption. During this period, the fruit reaches its well-known and peculiar organoleptic and texture characteristics. However, the spread of more profitable fruit tree species, resulted in its progressive erosion. In this work we performed proteomic and metabolomic fruit analyses at three times after harvesting, to characterise postharvest physiological and molecular changes, it related to nutritional and organoleptic properties at consumption. Results Proteomics and metabolomics analysis were performed on fruits harvested at different time points: freshly harvested fruit (T0), fruit two weeks after harvest (T1) and fruit four weeks after harvest (T2). Proteomic analysis (Shotgun Proteomic in LC-MS/MS) resulted in 643 proteins identified. Most of the differentially abundant proteins between the three phases observed were involved in the softening process, carbohydrate metabolism and stress responses. Enzymes, such as xyloglucan endotransglucosylase/hydrolase, pectin acetylesterase, beta-galactosidase and pectinesterase, accumulated during fruit ripening and could explain the pulp breakdown observed in C. domestica. At the same time, enzymes abundant in the early stages (T0), such as sucrose synthase and malic enzyme, explain the accumulation of sugars and the lowering of acidity during the process. The metabolites extraction from C. domestica fruits enabled the identification of 606 statistically significant differentially abundant metabolites. Some compounds such as piptamine and resorcinol, well-known for their antimicrobial and antifungal properties, and several bioactive compounds such as endocannabinoids, usually described in the leaves, accumulate in C. domestica fruit during the post-harvest process. Conclusions The metabolomic and proteomic profiling of the C. domestica fruit during the postharvest process, evaluated in the study, provides a considerable contribution to filling the existing information gap, enabling the molecular and phytochemical characterisation of this erosion-endangered fruit. Data show biochemical changes that transform the harvested fruit into palatable consumable product.

Abstract Background Pediatric residency in Italy has undergone significant changes in recent years, with a notable increase in the number of pediatric residents. Exploring the implications of this increase, highlighting disparities in training opportunities, and discussing the broader socio-economic impacts on pediatric healthcare, represent a crucial consideration for the healthcare system in the future. Main Body The Italian National Association of Pediatric Residents (“Osservatorio Nazionale Specializzandi in Pediatria”, ONSP) conducted an extensive survey among pediatric residents to assess the current state of pediatric residency. Key findings indicate that 50% of respondents believe the number of residents is excessive for the available training opportunities, leading to concerns about the quality of education and hands-on experience. Despite the increased number of residents, the workload has increased, but up to one-third of residents feel that the autonomy provided by their programs is insufficient. Significant disparities in training quality were found across different regions, with notable shortages in neonatology and pediatric emergency departments. Research opportunities are also limited, with only 17% of residents finding the time allocated to research satisfactory, especially in central and southern Italy. Conclusion The increase in pediatric residents presents both challenges and opportunities. Addressing these challenges through strategic reforms, such as implementing standardized national curricula, investing in training resources and mobility programs, and enhancing research opportunities, is crucial for the future of pediatric residency in Italy. Ensuring high-quality training for all residents is an ethical and practical obligation that will significantly impact pediatric healthcare.

Abstract In multicentric studies, data sharing between institutions might negatively impact patient privacy or data security. An alternative is federated analysis by secure multiparty computation. This pilot study demonstrates an architecture and implementation addressing both technical challenges and legal difficulties in the particularly demanding setting of clinical research on cancer patients within the strict European regulation on patient privacy and data protection: 24 patients from LMU University Hospital in Munich, Germany, and 24 patients from Policlinico Universitario Fondazione Agostino Gemelli, Rome, Italy, were treated for adrenal gland metastasis with typically 40 Gy in 3 or 5 fractions of online-adaptive radiotherapy guided by real-time MR. High local control (21% complete remission, 27% partial remission, 40% stable disease) and low toxicity (73% reporting no toxicity) were observed. Median overall survival was 19 months. Federated analysis was found to improve clinical science through privacy-friendly evaluation of patient data in the European health data space.

Coeliac disease is a common condition for which the only current treatment is a gluten-free diet. Adherence to this diet is not always easy and is associated with a reduction in quality of life for the patient and their family. Non-adherence is associated with complications of varying severity. The lack of control at the outpatient care level in a high percentage of these patients evinces the need to improve follow-up protocols and the approach to care delivery with coordination of paediatric gastroenterology units (PGU) and primary care paediatricians. With this aim in mind, the present document was developed by consensus to offer a set of recommendations adapted to our region, based on the recent recommendations published by the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN), and with participation of the pertinent scientific societies, including those concerning the adult population, for the management and follow-up of adolescents and the transition to adult care. Resumen: La enfermedad celíaca es una patología frecuente y cuyo único tratamiento en el momento actual es la dieta sin gluten. El seguimiento de esta dieta no siempre es fácil e implica limitaciones en la calidad de vida del paciente y su familia. La no adherencia se asociaría a complicaciones de distinta gravedad. La falta de control de estos pacientes en consultas en un alto porcentaje de casos plantea la necesidad de mejorar los protocolos de seguimiento y de abordarlos de forma coordinada entre las Unidades de Gastroenterología Pediátrica (UGP) y los pediatras de Atención Primaria. Con ese objetivo se han consensuado en este documento, basándose en las recomendaciones recientemente publicadas por la Sociedad Europea de Gastroenterología, Hepatología y Nutrición Pediátrica (ESPGHAN), un conjunto de recomendaciones adaptadas a nuestro entorno y contando con la participación de las Sociedades Científicas implicadas, incluyendo a las Sociedades de adultos para el abordaje del seguimiento del adolescente y de la transición de cuidados a los profesionales de adultos.

Since 2014, the provision of the aquatic ecosystem services has been gradually affected due to the biological invasion of Callinectes sapidus (Rathbun, 1896, Crustacea, Decapoda, Portunidae), commonly known as Atlantic blue crab, across several lagoon-like locations in Italy. In addition, this serious aquatic invasive species, native of North American coasts, has already inflicted economic damage of about EUR 100 million to the Italian fishing and farming communities over the past year. To counter their severe and rapid spread, the Italian Government has encouraged the fishing communities to catch as many as possible and commercially exploit them for human consumption in an attempt to manage their expansion. Since there is an ongoing promotion for the consumption of blue crab by forging novel food businesses in Italy, this paper aims to predict the public preferences and their willingness to pay (WTP) towards this biological invader. For this purpose, a discrete choice experiment approach is used, by means of a multinomial logit model (MNL) and latent class model (LCM). The social field survey involves a representative sample of 440 valid respondents in Apulia Region, southern Italy. The descriptive statistics results reveal that 67.50% of the local citizens interviewed know about the blue crab invasion, while 29.09% of them have already consumed this seafood species. In addition, the MNL results show that the most appreciated attributes of the blue crabs by respondents are freshness and large size. Further, the LCM findings reveal two representative classes of Apulian consumers; the first group of citizens (70.9% of total respondents) expresses positive appreciation for consuming blue crabs, while the second group (29.1% of total respondents) is not willing to pay a premium price regarding this potential commercial activity. Furthermore, the econometric results show that the average value that Apulian’s (i.e. those belonging to Class/Group I of respondents) WTP for blue crabs’ consumption is about EUR 18 per kilogram. In this regard, this research has public and private implications and may reasonably promote the commercial exploitation of blue crabs, enhancing the reduction of its population density through human consumption as a promised management control strategy and forging a novel profitable business mainly for local small-scale artisanal fisheries.

Abstract Background Facioscapulohumeral dystrophy (FSHD) is a myopathy characterized by the loss of repressive epigenetic features affecting the D4Z4 locus (4q35). The assessment of DNA methylation at two regions (DUX4-PAS and DR1) of D4Z4 locus proved to be an effective method to detect epigenetic signatures compatible with FSHD. The present study aims at validating the employment of this method into clinical practice and improving the protocol by refining the classification thresholds of 4qA/4qA patients. To this purpose, 218 subjects with clinical suspicion of FSHD collected in 2022–2023 were analyzed. Each participant underwent in parallel the traditional FSHD molecular testing (D4Z4 sizing) and the proposed methylation assay. The results provided by both analyses were compared to evaluate the concordance and calculate the performance metrics of the methylation test. Results Among the 218 subjects, the 4q variant type distribution was 54% 4qA/4qA, 43% 4qA/4qB and 3% 4qB/4qB. The methylation analysis was performed only on carriers of at least one 4qA allele. After refining the classification threshold, the test reached the following performance metrics: sensitivity = 0.90, specificity = 1.00 and accuracy = 0.93. These results confirmed the effectiveness of the methylation assay in identifying patients with genetic signature compatible with FSHD1 and FSHD2 based on their DUX4-PAS and DR1 profile, respectively. The methylation data were also evaluated with respect to the clinical information. Conclusions The study confirmed the ability of the method to accurately identify methylation profiles compatible with FSHD genetic signatures considering the 4q genotype. Moreover, the test allows the detection of hypomethylated profiles in asymptomatic patients, suggesting its potential application in identifying preclinical conditions in patients with positive family history and FSHD genetic signatures. Furthermore, the present work emphasizes the importance of interpreting methylation profiles considering the patients’ clinical data.

Abstract Controlling crystal growth alignment in low-dimensional perovskites (LDPs) for solar cells has been a persistent challenge, especially for low-n LDPs (n 1.7 eV) impeding charge flow. Here we overcome such transport limits by inducing vertical crystal growth through the addition of chlorine to the precursor solution. In contrast to 3D halide perovskites (APbX3), we find that Cl substitutes I in the equatorial position of the unit cell, inducing a vertical strain in the perovskite octahedra, and is critical for initiating vertical growth. Atomistic modelling demonstrates the thermodynamic stability and miscibility of Cl/I structures indicating the preferential arrangement for Cl-incorporation at I-sites. Vertical alignment persists at the solar cell level, giving rise to a record 9.4% power conversion efficiency with a 1.4 V open circuit voltage, the highest reported for a 2 eV wide band gap device. This study demonstrates an atomic-level understanding of crystal tunability in low-n LDPs and unlocks new device possibilities for smart solar facades and indoor energy generation.

Abstract Background Checkpoint immunotherapy unleashes tumor control by T cells, but it is undermined in non-immunogenic tumors, e.g. with low MHC class I expression and low neoantigen burden, such as neuroblastoma (NB). Endoplasmic reticulum aminopeptidase 1 (ERAP1) is an enzyme that trims peptides before loading on MHC class I molecules. Inhibition of ERAP1 results in the generation of new antigens able of inducing potent anti-tumor immune responses. Here, we identify a novel non-toxic combinatorial strategy based on genetic inhibition of ERAP1 and administration of the HDAC inhibitor (HDACi) entinostat that increase the immunogenicity of NB, making it responsive to PD-1 therapy. Methods CRISPR/Cas9-mediated gene editing was used to knockout (KO) the ERAP1 gene in 9464D NB cells derived from spontaneous tumors of TH-MYCN transgenic mice. The expression of MHC class I and PD-L1 was evaluated by flow cytometry (FC). The immunopeptidome of these cells was studied by mass spectrometry. Cocultures of splenocytes derived from 9464D bearing mice and tumor cells allowed the assessment of the effect of ERAP1 inhibition on the secretion of inflammatory cytokines and activation and migration of immune cells towards ERAP1 KO cells by FC. Tumor cell killing was evaluated by Caspase 3/7 assay and flow cytometry analysis. The effect of ERAP1 inhibition on the immune content of tumors was analyzed by FC, immunohistochemistry and multiple immunofluorescence. Results We found that inhibition of ERAP1 makes 9464D cells more susceptible to immune cell-mediated killing by increasing both the recall and activation of CD4+ and CD8+ T cells and NK cells. Treatment with entinostat induces the expression of MHC class I and PD-L1 molecules in 9464D both in vitro and in vivo. This results in pronounced changes in the immunopeptidome induced by ERAP1 inhibition, but also restrains the growth of ERAP1 KO tumors in vivo by remodelling the tumor-infiltrating T-cell compartment. Interestingly, the absence of ERAP1 in combination with entinostat and PD-1 blockade overcomes resistance to PD-1 immunotherapy and increases host survival. Conclusions These findings demonstrate that ERAP1 inhibition combined with HDACi entinostat treatment and PD-1 blockade remodels the immune landscape of a non-immunogenic tumor such as NB, making it responsive to checkpoint immunotherapy.

Abstract Bradykinesia is defined as a “complex” of motor alterations including decreased movement amplitude and/or speed and tendency to reduce them with movement repetition (sequence effect). This study aimed at investigating the neural and kinematic correlates of bradykinesia during hand-tapping in people with Parkinson’s disease (pwPD) relative to healthy controls. Twenty-five pwPD and 25 age- and sex-matched healthy controls underwent brain functional MRI (fMRI) during a hand-tapping task: subjects alternatively opened and closed their right hand as fully and quickly as possible. Hand-tapping kinematic parameters were objectively measured during the fMRI task using an optical fibre glove. During the fMRI task, pwPD showed reduced hand-tapping amplitude (hypokinesia) and a greater sequence effect. PwPD relative to healthy controls showed a reduced activity of fronto-parietal areas, middle cingulum/supplementary motor area (SMA), parahippocampus, pallidum/thalamus and motor cerebellar areas. Moreover, pwPD showed an increased activity of brain cognitive areas such as superior temporal gyrus, posterior cingulum, and cerebellum crus I. The decreased activity of cerebellum IV–V–VI, vermis IV–V, inferior frontal gyrus, and cingulum/SMA correlated with hypokinesia and with the sequence effect. Interestingly, a reduced activity of areas involved in motor planning and timing correlated both with hypokinesia and with the sequence effect in pwPD. This study has the major strength of collecting objective motor parameters and brain activity simultaneously, providing a unique opportunity to investigate the neural correlates of the “bradykinesia complex”.

Abstract Objectives Thrombocytosis is a clinical condition generally associated with poor prognosis in patients with cancer. Thrombocytosis may be present after lung cancer resection, but the clinical significance of thrombocytosis remains unclear. Herein, we evaluated whether postoperative thrombocytosis was a negative prognostic factor in patients undergoing thoracoscopic lobectomy for lung cancer. Methods It was a retrospective monocentric study including consecutive patients undergoing thoracoscopic lobectomy for lung cancer from January 2020 to January 2023. The outcome of patients with postoperative thrombocytosis (defined as platelet count ≥ 450 × 10^9/L at 24 h after the surgery and confirmed at postoperative day 7) was compared with a control group. Postoperative morbidity, mortality, and survival were compared between the two groups to define whether thrombocytosis negatively affected outcomes. Results Our study population included 183 patients; of these, 22 (12%) presented postoperative thrombocytosis: 9 (5%) mild thrombocytosis (451–700 × 10^9/L), 10 (5%) moderate thrombocytosis (701–900 × 10^9/L), and 3 (2%) severe thrombocytosis (901–1000 × 10^9/L). No significant differences were found regarding postoperative morbidity (p = 0.92), mortality (p = 0.53), overall survival (p = 0.45), and disease-free survival (p = 0.60) between the two study groups. Thrombocytosis was associated with higher rate of atelectasis (36% vs. 6%, p

Background: Biopuncture is a described technique that consists in subcutaneous injection of antihomotoxic drugs (homeopathic compounds) mixed with other substances such as local anesthetics or dextrose; This has been proposed as a treatment option to reduce musculoskeletal pain in various locations, including knee osteoarthritis.Objectives: The objective of this manuscript was to carry out a comprehensive review of the published information on the use of Biopuncture in patients with knee osteoarthritis.Methods: A scientific search was performed using online databases following the terms (Biopuncture) and (Knee Osteoarthritis) to identify scientific manuscripts that were related to the use of Biopuncture in the treatment of individuals with knee osteoarthritis.Results: With the information found, a theoretical framework was integrated that describes the components of Biopuncture, its mechanism of action and practical topics for the application of the technique.Conclusion: Biopuncture appears to be a potential, simple and low-risk therapeutic strategy in the treatment of knee osteoarthritis, which is applied through periarticular subcutaneous injections, with multitarget mechanisms of action at various physiopathological levels such as the modulation of the inflammatory process, decreased peripheral sensitization, and stimulation of antidegenerative and trophic mechanisms. Perhaps it can be part of the integrative treatments for knee osteoarthritis.

Historically, several classification systems have been used for brachytherapy, and they were based on the type of clinical purpose, type of implant and timing of the implant, dose-rate, and type of loading for treatment delivery. However, over the last decades, there have been some major technological advancements, including the introduction of image-guidance and possibility to modulate the dose delivered, which have led several authors (in order to highlight the differences between old technique and new approach) to label it in a different way by replacing “brachytherapy” with “interventional radiotherapy”. Modern interventional procedures involve several key aspects, which contribute to the complexity of implant phase, such as implant type, imaging used during the procedure, and role of multi-disciplinary team in operating room. By assigning scores to these procedural elements, it is possible to classify the procedure’s complexity using a COMIRI classification (COMplexity Index of interventional Radiotherapy Implants). The aim of the COMIRI classification system is to appropriately highlight the need for suitable resources based on the complexity level of different procedures in terms of personnel expertise, equipment availability, and multi-disciplinary teamwork.

Abstract We report the case of a 36‐year‐old woman who presented to the emergency department complaining of palpitations and asthenia. Investigations showed frequent ventricular ectopy and severe left ventricular ejection fraction impairment. She was diagnosed with a peculiar condition defined multifocal ectopic premature Purkinje‐related contractions syndrome, which in some cases can be associated with a dilated cardiomyopathy phenotype. Genetic testing showed a novel mutation in the SCN5A gene (c.673C > G). In the context of acute left ventricular dysfunction in a young patient, we discuss the clinical presentation of this rare condition and its clinical management, as well as its genetic substrate.

Abstract Air pollution stands as an environmental risk to child mental health, with proven relationships hitherto observed only in urban areas. Understanding the impact of pollution in rural settings is equally crucial. The novelty of this article lies in the study of the relationship between air pollution and behavioural and developmental disorders, attention deficit hyperactivity disorder (ADHD), anxiety, and eating disorders in children below 15 living in a rural area. The methodology combines spatio-temporal models, Bayesian inference and Compositional Data (CoDa), that make it possible to study areas with few pollution monitoring stations. Exposure to nitrogen dioxide (NO2), ozone (O3), and sulphur dioxide (SO2) is related to behavioural and development disorders, anxiety is related to particulate matter (PM10), O3 and SO2, and overall pollution is associated to ADHD and eating disorders. To sum up, like their urban counterparts, rural children are also subject to mental health risks related to air pollution, and the combination of spatio-temporal models, Bayesian inference and CoDa make it possible to relate mental health problems to pollutant concentrations in rural settings with few monitoring stations. Certain limitations persist related to misclassification of exposure to air pollutants and to the covariables available in the data sources used.

Las exportaciones de un país son clave para su economía. El objetivo de esta investigación es indagar sobre la contribución de las exportaciones no tradicionales al crecimiento económico del Paraguay a través del caso del sector alimenticio, durante el periodo 2011-2020. Para tal efecto, se planteó un diseño metodológico bibliográfico-documental, en el que se recurrió a un modelo econométrico que vinculaba el Producto Interno Bruto con las exportaciones tradicionales y no tradicionales del sector alimenticio junto con otras variables, para verificar sus efectos. Entre los principales resultados cabe señalar el efecto positivo de las exportaciones no tradicionales en el crecimiento de la economía y su potencial para diversificar la canasta exportadora del país.

The educational environment is important for the development of life skills of nursing students in late- and post-adolescence. Strengthening their mental resilience, enhancing their individual confidence, and controlling stress are necessary conditions in this direction, which will help them cope with the future challenges of their chosen profession. We aimed to study the resilience profiles of nursing students by investigating their mental resilience and its association with their individual characteristics and lifestyle factors. The Connor-Davidson Resilience Scale (CD–RISC–25) scale for resilience, the Perceived Stress Scale (PSS–14) scale for perceived stress, and the Personal Trust and Connection (PerTC) scale for trust and connections were used. The lifestyle determinants were also assessed. An e-survey that targeted 250 nursing students was conducted from November 22 to April 23. Descriptive and advanced statistical analyses were performed. 146 students participated in the study via an on-line questionnaire; the students were predominantly female (82.2%) with mean age of 22 years (SD = 6.8). Two out of ten students smoked (20.5%), 66.4% consumed at least one drink during a usual week, and 48.0% participated in sports during the last year. The mean hours spent on the Internet daily was 4.2 (SD = 1.8) and on social media was 2.7 (SD = 1.6) hours/day. The students scored highly on the 1-to-10 life-satisfaction item (Mean = 6.3, SD = 1.9), where the perceived stress was assessed as moderate/high with a mean of 33 (SD = 4.4) and trust and connections had a mean of 6.2 (SD = 1.1). In the multivariate analysis, the factors found to significantly associate with resilience (CD–RISC–25; Mean = 64.2, SD = 11.8) were age (β = 0.4; 95% CI: 0.1, 0.7), sports participation (β = 5.7; 95% CI: 2.3, 9.1), hours per day spent on social media (β = -1.3; 95% CI: -2.3, -0.3), and the number of friends (β = 0.3; 95% CI: 0.05, 0.5). Finally, resilience was positively associated with life satisfaction and the trust and connections scale (β = 1.8; 95% CI: 0.9, 2.7 and β = 1.8; 95% CI: 0.2, 3.4, respectively).