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Background: Women with higher body mass index report low rates of and face unique barriers to exercise. Increasing exercise participation can improve mental and physical health independent of weight loss; however, most exercise programs targeting this population focus predominately on losing weight. This paper aims to describe the development of Fit&Fab, a community-based exercise intervention focused on increasing exercise participation and enjoyment for women with obesity. Methods: In partnership with the YMCA, we recruited women ages 35–64 years (body mass index ≥ 30) to participate in 4 focus groups to understand exercise preferences. Formative work was used to identify theory constructs and associated intervention components. Women from the focus groups were recruited for a community advisory board that finalized the intervention design, recruitment, and evaluation plan. Results: Focus groups participants (N = 29) preferred to exercise without men and wanted a cohort-style class that included women of similar exercise levels and body types, incorporated social support, fun activities, and broke exercise into smaller bouts. They wanted a supportive instructor who was fit but understood weight-related challenges. The community advisory board and research team used focus group findings to inform design of the final intervention including group exercise classes, psychosocial support sessions, personalized training, exercise tracking, outcome monitoring, and rewards. Conclusions: Our findings emphasize the need to focus on exercise enjoyment and benefits other than losing weight to improve exercise participation among women with higher body mass index. In addition to having outcomes other than weight loss, exercise interventions with this population should also consider group composition, instructor, and class format. [ABSTRACT FROM AUTHOR]

Purpose: There have been significant advances in the treatment of metastatic breast cancer (BC) over the past years, and long-term outcomes after a diagnosis of brain metastases are lacking. We aimed to identify predictors of brain metastases at initial breast cancer diagnosis, describe overall survival (OS) in the past decade, and identify factors associated with OS after brain metastases diagnosis. Methods: We evaluated patients with de novo stage IV BC using the Surveillance, Epidemiology and End Results database from 2010 to 2019. Multivariate logistic regression was conducted to assess predictors of brain metastases at initial breast cancer diagnosis. OS was estimated using the Kaplan-Meier method and log rank test was used to compare differences between groups. Cox regression was used to assess associations between several variables and OS. Results: 1,939 patients with brain metastases at initial breast cancer diagnosis were included. Factors associated with this presentation were grade III/IV tumors, ductal histology, hormone receptor (HR)-negative/human epidermal growth factor receptor 2 (HER2)-positive subtype, and extracranial metastases. Patients with HR-positive/HER2-positive disease had the longest OS (median 18 months) and 12.2% were alive at 8 years. Factors associated with shorter OS included older age, lower income, triple-negative subtype, higher grade, and visceral metastases. Conclusion: Over the last decade, the median OS of patients with brain metastases at initial breast cancer diagnosis remained poor; however, a substantial minority survive 5 or more years, with rates higher in patients with HER2-positive tumors. In addition to tumor subtype, OS varied according to age, extracranial metastases, and sociodemographic factors. [ABSTRACT FROM AUTHOR]

Background: Clinical and preclinical studies have shown that extra virgin olive oil (EVOO), a major component of the Mediterranean diet, has beneficial effects on brain aging and cognition. Individuals with Down syndrome develop age-dependent cognitive decline and synaptic dysfunction. However, whether EVOO intake is beneficial in Down syndrome is not known. Objective: In this study, by implementing a mouse model of Down syndrome, we aimed to investigate the effect that chronic administration of EVOO has on memory, synaptic function, and neuroinflammation. Methods: Starting at 4 months of age Ts65dn mice were randomized to receive EVOO for 5 months in their diet, after which they were tested for learning and memory impairment. After euthanasia, synaptic function was measured in freshly obtained hippocampal slices, whereas brain tissues were assessed for inflammatory biomarkers. Results: Compared with controls, mice receiving EVOO had a significant improvement in learning and spatial memory. Additionally, field potential recordings showed that treated mice had an improvement in synaptic function. Finally, array analysis showed that EVOO modulated the expression levels of several inflammatory biomarkers. Conclusions: Chronic administration of EVOO to a mouse model of Down syndrome has beneficial effects on memory impairments, synaptic function deficits and neuroinflammation. Our findings provide additional support for the potential therapeutic effects of EVOO also in individuals with Down syndrome. [ABSTRACT FROM AUTHOR]

Introduction: According to the Institute of Medicine patient-centered medicine is one of the six crucial dimensions of health care quality. Although the patient-centered care model is widely recognized for its ethical underpinnings and effectiveness, its practical implementation still raises challenges, especially in end-of-treatment situations. This discussion paper offers an overview of the challenges facing the physician-patient relationship in end-of-treatment situations. Methods: We developed three clinical vignettes and made some theoretical considerations about ethical issues related to the decision-making process leading to the end of treatment. Results: We identified two main challenges that end-of-treatment situations pose to patient-centered care: (1) when the patient's autonomy challenges the best clinical treatment; and (2) when the proposed treatment (discontinuation of treatment) challenges the patient's preferences. Discussions: Patient-centered care supports personalized decision-making, in which the physician's approach varies according to the patient's situation and individuality. The idea of beneficence may change during care, because of acceptance of the patient's principles or a change in the primary goal of care. [ABSTRACT FROM AUTHOR]

Introduction: Chemoradiotherapy in head and neck cancer patients has a curative intent but often deteriorates nutritional status leading to sarcopenia and cachexia. Methods: In this observational and single-centered study, a prospective evaluation of several biochemical and anthropometrical parameters, weight loss, handgrip strength, visual analogue scale of appetite, questionnaires associated with malnutrition & quality of life and body composition (obtained by Bioelectrical Impedance Vector Analysis) was performed before and after high-dose cisplatin chemotherapy combined with radiotherapy in 60 patients affected by head and neck cancer. Oral nutritional supplements were used to reach the correct number of daily calories and proteins. Results and discussion: All patients completed radiotherapy as planned and the 96,4% of them did not interrupt chemotherapy for toxicity, reaching a total dose of at least 200mg/m2. Despite a rapid deterioration of body composition during treatment, nutritional support helped patients to maintain (or in some cases improve) anthropometric parameters from the end of chemoradiotherapy to the following 3 months. Low prealbumin and albumin pre-treatment led to higher risk of toxicities with consequent reduction of cisplatin dose intensity, whereas weight at the end of the treatment seems to be an interesting predicting factor for disease free and overall survival (p=0.007; p=0.015). [ABSTRACT FROM AUTHOR]

Background: Birth asphyxia remains one of the leading causes of neonatal deaths worldwide with a higher incidence in resource limited countries such as Malawi. At Balaka district hospital, Birth asphyxia is the primary cause of neonatal mortality accounting for 37.3% of the district's neonatal deaths. Although various quality improvement initiatives on birth asphyxia such as Helping Babies Breathe have been documented in Malawi, there is limited information on use of criterion-based audit (CBA) to enhance the care of neonates with birth asphyxia. Criterion-based audit is a systematic and critical analysis that seeks to improve quality of care by reviewing cases against an explicit criterion and using findings to modify practice as necessary. This study aimed to evaluate the effectiveness of CBA in improving the quality of neonatal birth asphyxia care at Balaka district hospital in Malawi. Methods: A CBA on the care of asphyxiated neonates was conducted at Balaka district hospital in Malawi. The care practices were assessed through a retrospective review of 110 cases notes which were selected by systematic random sampling technique. The care practices were compared with locally established standards, by a multidisciplinary team, based on the Malawi guidelines on care of the infant and newborn and World Health Organization documents. The gaps in the current practice were identified, reasons discussed, and recommendations were made and implemented. A re-audit was conducted on 110 case notes, six months after the initial audit. Results: The re-audit showed significant improvements in most of the set criteria for quality care: Checking of vital signs (80% vs. 98.2%; p = 0.000), laboratory investigations done (0.9% vs. 74%; p = 0.000), thermal support (82.7% vs. 91.8%; p = 0.041), correct diagnosis (60% vs. 81%; p = 0.001), correct treatment (18.7% vs. 81%; p = 0.000), correct feeding (12.7% vs. 56.4%; p = 0.000), Clinical officers conducting ward rounds (0% vs. 72%; p = 0.000), and daily weight check (49.1% vs. 93%; p = 0.000). Additionally, neonatal death decreased from 11% in the initial audit to 5% in the re-audit. Conclusion: Criterion-based audit is a low-cost tool that can significantly improve the care of neonates with birth asphyxia in resource-limited countries. [ABSTRACT FROM AUTHOR]

Introduction: Urothelial carcinoma is a common malignancy affecting the urinary system, with the spectrum of disease encompassing non-muscle invasive, muscle-invasive and metastatic disease. On a background of almost half a century of immunogenic management with BCG, various immune checkpoint inhibitors, including durvalumab, have now demonstrated clinical efficacy in the treatment of urothelial carcinoma. Areas covered: This article reviews the available literature on durvalumab in the treatment of urothelial carcinoma for all stages of the disease including mechanisms of action, pharmacokinetics, efficacy and safety and covers a broad portfolio of reported and ongoing trials. Expert opinion: The management of UC is rapidly evolving, which is reflected in the diverse range of upcoming pivotal trials incorporating durvalumab with additional immunomodulatory agents and therapeutics targeting key oncogenic pathways, each with the potential to change the standard of care. As the complexity of UC management increases, future efforts should be directed at identifying better predictive biomarkers and selecting rational synergistic combinations from the novel treatments available. This will allow the addressing of existing gaps, facilitate the exploitation of new techniques of treatment delivery and ultimately deliver more personalized and efficacious care to the individual patient. [ABSTRACT FROM AUTHOR]

Introduction Concerns about safety and effectiveness of tobacco treatments reduce their use. We explored integrating the nicotine metabolite ratio (NMR), and messaging about its potential for improving safety and effectiveness, as a strategy to increase the use of tobacco treatments within primary care. Aims and Methods Through a prospective cohort design, we explored the effects of integrating NMR testing within primary care on the provision of tobacco treatment; 65 patients completed assessments including NMR before a clinic visit. At the clinic visit, patients' clinicians received an electronic health record (EHR) alert about the patient's NMR and personalized treatment recommendations to improve effectiveness and safety. Being asked about smoking and advised to quit, and a referral for tobacco treatment or medication prescription, were assessed within 30 days of the appointment and were compared to a usual care cohort (N  = 85). Results The NMR and usual care cohorts reported similar rates of being asked about smoking (92.3% vs. 92.9%, p  = 1.0), being advised to quit (72.3% vs. 74.1%, p  = .85), being referred for tobacco treatment (23.1% vs. 36.5%, p  = .11), and receiving tobacco use medications (20% vs. 27.1%, p  = .34). In the NMR cohort, fast versus slow metabolizers were more likely to receive medication (26% vs. 0%, p  = .003) and all patients who received varenicline (n  = 8) were fast metabolizers. Conclusions NMR results and treatment recommendations did not increase tobacco treatment rates in primary care, although it may increase treatment rates and the use of varenicline for fast metabolizers. Future studies could test ways to use the NMR to increase tobacco treatment rates in clinical settings. Implications This study generated a novel implementation strategy, namely an EHR alert about patients' NMR and personalized treatment recommendations, in an effort to increase tobacco treatment rates in primary care. While the strategy did not increase tobacco treatment rates, it may have boosted the rate of varenicline prescription for patients who metabolize nicotine faster, aligning with evidence-based practice. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess the need for tube feeding in a cohort of treated infants with type I SMA and to identify predictive factors. All patients were classified at baseline, when treatment started, and at follow-up according to their functional level and the need for tube feeding. Fisher's exact test was used to examine the associations between the outcome at the last follow-up and SMA type, SMN2 copy number, and baseline nutritional status. ANOVA was performed to compare CHOP INTEND scores and age at treatment initiation with outcomes. The cohort includes 75 type I SMA infants treated between 0.1 and 5 years of age. At the last follow-up, 34 had no need for tube feeding, 9 had tube feeding but were also able to be fed by mouth, and 32 had tube feeding and were unable to be fed by mouth. Thirty of the 41 infants with tube feeding at follow-up already had feeding difficulties when treatment was started. The need for tube feeding at follow-up was associated with the level of feeding involvement at baseline and with CHOP INTEND scores [p < 0.001] but not with SMN2 copy number, SMA type 1 subtypes or age at treatment. The results of this study suggest that the need for tube feeding is not frequent in treated infants with type I SMA and, when occurring, can be predicted by the level of feeding involvement and low CHOP INTEND scores at baseline. What is Known: • The advent of disease-modifying therapies is increasingly changing the approach to swallowing and nutritional management in type I SMA. • Clinical trials and real-world data using all three disease-modifying therapies report a rather wide variability of feeding outcome and need for tube feeding that is often related to different cohorts that makes comparison between studies very difficult. What is New: • The real-world findings of this study, including all the children treated since treatments became available, confirmed that the need for tube feeding is not an invariable finding. • The level of feeding involvement at baseline appears to be a reliable prognostic indicator of bulbar outcome. • The results highlight the need for interventional studies with structured Speech and Language Therapist protocols that will help to better understand the extent to which bulbar function can be maintained or regained even in children requiring tube feeding. [ABSTRACT FROM AUTHOR]

Multisystem inflammatory syndrome is a severe complication of SARS-CoV-2 infection in children (MIS-C). To date, data on long-term sequelae mainly concern cardiac outcomes. All ≤ 18 year olds consecutively admitted to the Buzzi Children's Hospital with a diagnosis of MIS-C between October 1, 2020, and May 31, 2022, were followed up for up to 12 months by a dedicated multidisciplinary team. They underwent laboratory tests, multi-organ clinical and instrumental assessments, and psychosocial evaluation. 56/62 patients, 40 M, mean age 8.7 years (95% CI 7.7, 9.7), completed the follow-up. Cardiological, gastroenterological, pneumological, and neurological evaluations, including IQ and EEG, were normal. Alterations of HOMA-IR index and/or TyG index, observed in almost all patients during hospitalisation, persisted in about a third of the population at 12 months. At 6 and 12 months respectively, impairment of adaptive functions was observed in 38/56 patients (67.9%) and 25/56 (44.6%), emotional and behavioural problems in 10/56 (17.9%) and 9/56 (16.1%), and decline in QoL in 14/56 (25.0%) and 9/56 (16.1%). Psychosocial well-being impairment was significantly more frequent in the subgroup with persistent glycometabolic dysfunction at 12 months (75% vs. 40.9% p < 0.001). Conlusion: The mechanisms that might explain the long-term persistence of both metabolic alterations and neuro-behavioural outcomes and their possible relationship are far from being clarified. Our study points out to the potential long-term effects of pandemics and to the importance of a multidisciplinary follow-up to detect potential negative sequelae in different areas of health, both physical and psychosocial. What is known: • Multisystem inflammatory syndrome in children (MIS-C) is a severe complication of SARS-CoV-2 infection. • Few data exist on the medium- and long-term outcomes of MIS-C, mostly focused on cardiac involvement. Emerging evidence shows neurological and psychological sequelae at mid- and long-term follow-up. What is new: • This study reveals that MIS-C may lead to long-term glycometabolic dysfunctions joined to impairment in the realm of general well-being and decline in quality of life, in a subgroup of children. • This study highlights the importance of a long-term multidisciplinary follow-up of children hospitalised with MIS-C, in order to detect the potential long-term sequelae in different areas of health, both physical and psychosocial well-being. [ABSTRACT FROM AUTHOR]

Echocardiography represents an essential tool for imagers and clinical cardiologists in the management of patients with heart failure. Advanced heart failure (AdHF) is a more severe and, typically, later stage of HF that exposes patients to a high risk of adverse outcomes, with a 1-year mortality rate of around 50%. Currently, several therapies are available to improve the outcomes of these patients, reduce their mortality rate, and, possibly, delay the need for advanced therapies such as heart transplant and long-term mechanical circulatory support. When accurately performed and interpreted, echocardiography provides crucial information to properly tailor medical and device therapy of patients with AdHF and to identify those at even higher risk. In this review, we present the state of the art of echocardiography applications in the clinical management of patients with AdHF. We will discuss the role of echocardiography chronologically, beginning with the prediction of AdHF, proceeding through diagnosis, and detailing how echocardiography informs clinical decision-making, before concluding with indications for advanced therapies. The role of echocardiography in the management of patients with advanced heart failure. Echocardiography is a useful method for predicting the occurrence of AdHF during follow-up of patients with HF (top line). The diagnosis of AdHF requires an echocardiographic criterion for AdHF (middle line). In patients with AdHF, echocardiography is useful to identify patients who will benefit most from medical therapy adjustment, device therapy, and LVAD implantation. HF, heart failure; LA, left atrium; RV, right ventricle; LVEF, left ventricular ejection fraction. HF, heart failure; LA, left atrium; LVEF, left ventricular ejection fraction; RV, right ventricle [ABSTRACT FROM AUTHOR]

We present the case of a 7-year-old Ecuadorian mestizo girl with multiple orofacial malformations. The patient is the product of a first-degree relationship (father–daughter). A cytogenetic study revealed a normal karyotype. The genetic mapping array study identified 0.73 Gb of alterations, 727,087,295 bp involved in regions of homozygosity (ROH) in all chromosomes (25.2% of the genome) and 764,028 bp in gains in chromosomes 9 and 14. Genes from the TGFB, BMP, FGF, SHH and WNT families, among others, were identified in the ROH. They are related to craniofacial development and their protein products showed a strong association in the interactome analysis. [ABSTRACT FROM AUTHOR]

Suicide is a significant leading cause of death among young people, particularly those struggling with mental disorders. The present study utilised data from 230 young people (aged 16–18 years) undergoing a transitional care process from Child and Adolescent Mental Health Services to Adult Mental Health Services within the MILESTONE European project (2014–2019), a longitudinal cluster randomised controlled trial. The objectives of this study were to monitor temporal patterns of general health and social functioning over two years, to detect sex differences, and to identify factors associated with Suicidal Thoughts and Behaviours (STB) at the first and last time points. The results demonstrate a decrease in STB over the two-year follow-up period among all participants. Females exhibited a higher prevalence of STB across all time points, whereas males only exhibited STB at the nine-month follow-up. The most influential factors associated with STB were previous suicide attempts and mood disorders at baseline, and mood disorders and relational problems at the end of follow-up. These findings emphasise the importance of monitoring STB and informing young people undergoing a transitional care period about its key risk factors. Moreover, sex differences in STB suggest the need for different preventive strategies for males and females. [ABSTRACT FROM AUTHOR]

Background: Although insect-based foods (IBFs) have been recently proposed as a way to face climate crisis and starvation, they encounter aversion from Western countries, which express fear, disgust, and high risk. The contribution of psychology research to food choices highlights how decisions are made, not only through reasoned attitudes and goal-directed behavior, but also through more automatic associations (dual-system models). Methods: In this paper, we investigated people's dispositions towards IBFs by combining (a) explicit attitudes (as assessed via self-report scales), (b) automatic associations (as measured via indirect measures), and (c) intention to taste, and comparing different profiles based on (d) psychological factors, including decision-making style, food neophobia, and trust in science and scientist. A pilot sample of 175 Italian university students participated in the study. Results: The analyses of the general sample highlighted rather negative attitudes. The cluster analysis identified 4 decision-making profiles: 'the gut feeling', 'the suspicious', 'the vicarious', and 'the mind'. It revealed more favorable opinions in 'the mind' profile, characterized by a rational decision-making style and high trust in science, and very aversive reactions from 'the suspicious' profile, characterized by high food neophobia and low trust in science. Conclusions: The results underline the importance of psychological factors in interpreting people's reactions to IBF and changes in dietary habits based on the decision-making process. They suggest possible strategies to promote eco-friendly diets. [ABSTRACT FROM AUTHOR]

Background : Current treatments for mental disorders, like pharmacotherapy or psychological approaches, do not lead to full remission in all individuals. Physical activity (PA) is effective at improving psycho-physical health in major depressive and anxiety disorders. However, the efficacy of PA as an adjunctive treatment for borderline personality disorder (BPD) has not been studied. To date, there are no approved pharmacological treatments for this severe condition and limited accessibility to effective psychotherapeutic interventions. This study tests the efficacy of a structured PA programme as an additional treatment for BPD outpatients. Methods: The PABORD is a randomised controlled trial for female outpatients (18–40 years) with a BPD diagnosis. The intervention group (n = 32) will participate in a 12-week structured PA programme supervised by a sport medicine physician and preceded by three psychoeducation sessions on healthy eating habits. The control group (n = 32) will receive a 12-week psychoeducation programme on PA, diet, and health risks of a sedentary lifestyle for a total of 8 sessions. The study aims to determine if the PA intervention is superior to the control in reducing BPD symptoms. Secondary aims include improving PA levels and physical and psychological health. Assessments will be conducted at baseline, post-intervention, and 3 months post-intervention. Discussion: The structured PA programme is expected to outperform the control group in terms of health and PA outcomes at the end of the intervention. Repeated assessments will also help to identify psychosocial factors that influence PA maintenance. Findings will support the potential widespread implementation of PA programmes for BPD treatment. Trial registration: ClinicalTrials.gov NCT06461104. Registered on 6 June 2024 {2a}. [ABSTRACT FROM AUTHOR]

Estimating and understanding the ratio between effective population size (Ne) and census population size (Nc) are pivotal in the conservation of large marine pelagic fish species, including bony fish such as tunas and cartilaginous fish such as sharks, given the challenges associated with obtaining accurate estimates of their abundance. The difficulties inherent in capturing and monitoring these species in vast and dynamic marine environments often make direct estimation of their population size challenging. By focusing on Ne, it is conceivable in certain cases to approximate census size once the Ne/Nc ratio is known, although this ratio can vary and does not always increase linearly, as it is influenced by various ecological and evolutionary factors. Thus, this ratio presents challenges and complexities in the context of pelagic species conservation. To delve deeper into these challenges, firstly, we recall the diverse types of effective population sizes, including contemporary and historical sizes, and their implications in conservation biology. Secondly, we outline current knowledge about the influence of life history traits on the Ne/Nc ratio in the light of examples drawn from large and abundant pelagic fish species. Despite efforts to document an increasing number of marine species using recent technologies and statistical methods, establishing general rules to predict Ne/Nc remains elusive, necessitating further research and investment. Finally, we recall statistical challenges in relating Ne and Nc emphasizing the necessity of aligning temporal and spatial scales. This last part discusses the roles of generation and reproductive cycle effective population sizes to predict genetic erosion and guiding management strategies. Collectively, these sections underscore the multifaceted nature of effective population size estimation, crucial for preserving genetic diversity and ensuring the long‐term viability of populations. By navigating statistical and theoretical complexities, and addressing methodological challenges, scientists should be able to advance our understanding of the Ne/Nc ratio. [ABSTRACT FROM AUTHOR]

Aims: Research on probiotics for constipation management is still growing, and plays a crucial role in the definition of a management strategy for bowel wellbeing, constipation, and related outcomes. The present systematic review and meta-analysis of the beneficial effects of the SYNBIO® blend, to consolidate the data from various clinical trials, was conducted. Methods: A literature search using PubMed, Web of Science, and Google Scholar databases was conducted. The search was limited to clinical trials that used the SYNBIO® blend, either as dietary supplements or probiotic-enriched foods. Independently, two reviewers evaluated the trial's quality and extracted all data. A 95% confidence interval (CI) of a weighted mean difference (MD) was used to pool continuous data. For the analysis, Review Manager version 5.4 was used. Results: Seven clinical trials involving a total of 1095 subjects were included in the analysis. Overall, the SYNBIO® blend significantly improved constipation relief by 0.75 (95% CI: 0.31 to 1.19; p = 0.0008) in 52% of the subjects, and significantly increased intestinal regularity by 1.90 compared to the placebo (95% CI: 1.02 to 2.78; p < 0.0001) in more than 60% of individuals. No adverse events were reported. Conclusions: The SYNBIO® blend was found to significantly improve overall constipation, intestinal regularity, abdominal pain, and intestinal cramping. This suggests that people with these specific symptoms could benefit from this probiotic combination. [ABSTRACT FROM AUTHOR]

Background/Objectives: Urinary tract infections (UTIs) are infections that involve the urethra, bladder, and, in much more severe cases, even kidneys. These infections represent one of the most common diseases worldwide. Various pathogens are responsible for this condition, the most common being Escherichia coli (E. coli). Bromelain is a proteolytic complex obtained from the stem and stalk of Ananas comosus (L.) Merr. showing several beneficial activities. In addition to bromelain, N-acetylcysteine (NAC) has also been used. Methods: The purpose of this experiment was to evaluate the antibacterial, anti-motility, and anti-biofilm effects of a new polyenzymatic complex (DIF17BRO®) in combination with NAC (the Formulation) on various strains of E. coli isolated from patients with UTIs. Subsequently, the anti-inflammatory and antioxidant effects of the Formulation were studied in an ex vivo model of cystitis, using bladder samples from mice exposed to E. coli lipopolysaccharide (LPS). Results: Our results showed that the Formulation significantly affects the capability of bacteria to form biofilm and reduces the bacteria amount in the mature biofilm. Moreover, it combines the interesting properties of NAC and a polyenzyme plant complex based on bromelain in a right dose to affect the E. coli adhesion capability. Finally, the Formulation exhibited protective effects, as confirmed by the inhibitory activities on multiple inflammatory and oxidative stress-related pathways on bladder specimens exposed to LPS. Conclusions: This blend of active compounds could represent a promising and versatile approach to use to overcome the limitations associated with conventional therapies. [ABSTRACT FROM AUTHOR]

New environmentally friendly methods for extracting vegetable oils are in development, with a focus on pressurized liquid extraction (PLE) in an intermittent process. Ethanol, a renewable and generally recognized as safe (GRAS) solvent, is gaining prominence in this process. It is crucial for these methods to maintain the physicochemical characteristics of the extracted oils and be economically viable on a large scale. Using SuperPro Design software v 8.5, a simulation of PLE scaled up to industrial levels was conducted. Measurements of oils extracted with pressurized hexane and ethanol showed minimal density variations, with slightly higher viscosity for ethanol-extracted oil. Accelerated oxidative degradation revealed a longer induction period for hexane-extracted oil, indicating that ethanol-extracted oil degrades more easily. The antioxidant activity of the oil extracted with hexane was lower than that with ethanol. In the differential scanning calorimetry analysis, the oils extracted with hexane and ethanol presented onset melting point temperatures of −43.2 and −36.1 °C, respectively. The economic assessment considered 16 scenarios, showing a return on investment ranging from 9.0 to 133.5% in the first year and payback times from 0.7 to 11.1 years. Scenario 8, involving two 5000 L extractors, ethanol recycling, and an annual production of 3,325,300 L of soybean oil at USD 1.25/L, demonstrated the best return on investment (133.5%) in less than one year. Overall, this study suggests that industrial-scale soybean oil extraction via PLE in an intermittent process can be more cost-effective than conventional methods, making implementation feasible. [ABSTRACT FROM AUTHOR]

Excessive daytime sleepiness (EDS) and insomnia (IN) complaints represent the most common sleep/wake disorders. Currently, the specific needs of these patients and their relatives, as well as the overall socio-economic burden of IN and EDS remains widely unexplored. This pilot study to be carried out in Switzerland is a retro- and prospective, national, one-center cohort observational study for the systematic evaluation of the burden of EDS and IN and its evolution 12 months after the first assessment. Patient recruitment will be organized through 7–8 primary care providers (primary/general care practitioners and pharmacies). Primary outcomes are the prevalence of EDS/IN in the primary care setting and the association between EDS/IN with health-related quality of life (QOL) as assessed with the established instruments. Secondary outcomes are the association between EDS/IN with the presence of comorbidities, number of injuries/accidents, and number of sick/leave days for the subgroup of working subjects. Calculation of direct per-patient costs will be undertaken to analyze the economic implications of sleep/wake disorders, providing valuable insights into the financial burden experienced by affected individuals within the healthcare system. This research will provide information on the feasibility of such a study and inform on aspects of the QOL most associated with EDS/IN. Based on this pilot project, a European multicenter study on the burden of sleep/wake disorders will be conducted by the European Academy of Neurology. [ABSTRACT FROM AUTHOR]

Type 1 diabetes mellitus (T1DM) is a chronic condition primarily managed with insulin replacement, leading to significant treatment costs. Complications include vasculopathy, cardiovascular diseases, nephropathy, neuropathy, and reticulopathy. Pancreatic islet transplantation is an option but its success does not depend solely on adequate vascularization. The main limitations to clinical islet transplantation are the scarcity of human pancreas, the need for immunosuppression, and the inadequacy of the islet isolation process. Despite extensive research, T1DM remains a major global health issue. In 2015, diabetes affected approximately 415 million people, with projected expenditures of USD 1.7 trillion by 2030. Pancreas transplantation faces challenges due to limited organ availability and complex vascularization. T1DM is caused by the autoimmune destruction of insulin-producing pancreatic cells. Advances in biomaterials, particularly the extracellular matrix (ECM), show promise in tissue reconstruction and transplantation, offering structural and regulatory functions critical for cell migration, differentiation, and adhesion. Tissue engineering aims to create bioartificial pancreases integrating insulin-producing cells and suitable frameworks. This involves decellularization and recellularization techniques to develop biological scaffolds. The challenges include replicating the pancreas's intricate architecture and maintaining cell viability and functionality. Emerging technologies, such as 3D printing and advanced biomaterials, have shown potential in constructing bioartificial organs. ECM components, including collagens and glycoproteins, play essential roles in cell adhesion, migration, and differentiation. Clinical applications focus on developing functional scaffolds for transplantation, with ongoing research addressing immunological responses and long-term efficacy. Pancreatic bioengineering represents a promising avenue for T1DM treatment, requiring further research to ensure successful implementation. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this research is to examine the roles of trust and electronic word-of-mouth (e-WOM) in crowdfunding (CF) participation for equity CF by taking into account the following antecedents of trust and e-WOM: intrinsic motivation (IM), extrinsic motivation (EM), deterrents, venture quality (VQ), third-party seal (TPS), value congruence (VC) and perceived accreditation (PA). Design/methodology/approach: In this research, a survey among 408 active and potential funders in Iran was conducted. The statistical analysis used partial least squares structural equation modeling (PLS-SEM). Findings: The results of this research revealed a significant influence of trust and e-WOM on participation in CF for equity CF. Extrinsic motivation had the greatest impact on trust and VC had the greatest impact on e-WOM. Originality/value: This research extends the equity CF research area to CF success and considers the effects of some parameters on CF participation. This research provides many theoretical and practical implications. [ABSTRACT FROM AUTHOR]

Introduction: This study sought to examine the relationship between adverse childhood experiences (ACEs) and mental health issues among transgender individuals in Kenya. Methods: Descriptive and correlational design was utilized with a sample size of 55 transgender people. Self-report online questionnaire was used to collect data. Results: Respondents showed high exposure to ACEs, high levels of psychological distress, significant risk of suicide and moderate perceived social support. A significant relationship was found between ACEs and psychological distress, ACEs and suicidal ideation, and ACEs and perceived social support. Conclusion: ACEs strongly influence mental health of transgender people in adulthood. [ABSTRACT FROM AUTHOR]

PROTEIN ARGININE METHYLTRANSFERASES (PRMTs) catalyze arginine (R) methylation that is critical for transcriptional and post-transcriptional gene regulation. In Arabidopsis, PRMT5 that catalyzes symmetric R dimethylation is best characterized. PRMT5 mutants are late-flowering and show altered responses to environmental stress. Among PRMT5 targets are Arabidopsis thaliana GLYCINE RICH RNA BINDING PROTEIN 7 (AtGRP7) and AtGRP8 that promote the transition to flowering. AtGRP7 R141 has been shown to be modified by PRMT5. Here, we tested whether this symmetric dimethylation of R141 is important for AtGRP7's physiological role in flowering time control. We constructed AtGRP7 mutant variants with non-methylable R141 (R141A, R141K). Genomic clones containing these variants complemented the late-flowering phenotype of the grp7-1 mutant to the same extent as wild-type AtGRP7. Furthermore, overexpression of AtGRP7 R141A or R141K promoted flowering similar to overexpression of the wild-type protein. Thus, flowering time does not depend on R141 and its modification. However, germination experiments showed that R141 contributes to the activity of AtGRP7 in response to abiotic stress reactions mediated by abscisic acid during early development. Immunoprecipitation of AtGRP7-GFP in the prmt5 background revealed that antibodies against dimethylated arginine still recognized AtGRP7, suggesting that additional methyltransferases may be responsible for modification of AtGRP7. [ABSTRACT FROM AUTHOR]

Urban green infrastructure (UGI) is a network composed of natural and semi-natural areas, such as greenspaces, open areas, and water bodies, designed to enhance the provision of ecosystem services and to meet the needs and expectations of local communities. UGIs should be accessible and should improve the well-being and health of their users, protect and enhance biodiversity, and allow for the enjoyment of natural resources. The study proposes a methodological approach to defining a UGI, conceived as a network of areas connected by urban ecological corridors and suitable for providing climate regulation, flood risk mitigation, outdoor recreation, and biodiversity and habitat quality enhancement. The methodology is applied to the functional urban area (FUA) of the City of Cagliari, Italy. The analysis results show that areas with high values of climate regulation, carbon storage and sequestration, and habitat quality enhancement are particularly suitable to be part of a UGI. Although values for outdoor recreation appear to be less significant, the provision of this service is particularly relevant within the Cagliari FUA. However, areas characterized by high values of flood risk mitigation show a different behavior, which highlights how the presence of impermeable surface within urban areas is associated with a loss of patch connectivity. [ABSTRACT FROM AUTHOR]

In recent decades, the scientific community has increasingly focused on extreme events linked to climate change, which are leading to more intense and frequent natural disasters. The Mediterranean can be considered a hotspot where the effects of these changes are expected to be more intense compared to other regions of the planet. Italy is not exempt; in fact, with its extensive shoreline, it is particularly vulnerable, especially to high sea levels and coastal erosions. In this framework, from late October to early November 2023, six storm surges occurred in the Gulf of Trieste (NE Italy). These events, characterized by winds from 190°N to 220°N and the significant wave height, which reached up to 1.81 m nearshore—an uncommon meteorological condition in the northern Adriatic Sea—caused the occurrence of eight coastal sinkholes and substantial damages to man-made structures. Thanks to Unmanned Aerial Vehicles (UAVs) and their derived products (high-resolution orthomosaics, Digital Elevation Models—DEMs, and point clouds), it was possible to study these features over time, enabling long-term coastal dynamics monitoring, which can be crucial for timely and effective response and restoration efforts. [ABSTRACT FROM AUTHOR]

The Sam (Sterile alpha motif) domain of the lipid phosphatase Ship2 (Ship2-Sam) is engaged by the Sam domain of the receptor tyrosine kinase EphA2 (EphA2-Sam) and, this interaction is principally linked to procancer effects. Peptides able to hinder the formation of the EphA2-Sam/Ship2-Sam complex could possess therapeutic potential. Herein, by employing the FoldX software suite, we set up an in silico approach to improve the peptide targeting of the so-called Mid Loop interface of Ship2-Sam, representing the EphA2-Sam binding site. Starting from a formerly identified peptide antagonist of the EphA2-Sam/Ship2-Sam association, first, the most stabilizing mutations that could be inserted in each peptide position were predicted. Then, they were combined, producing a list of potentially enhanced Ship2-Sam ligands. A few of the in silico generated peptides were experimentally evaluated. Interaction assays with Ship2-Sam were performed using NMR and BLI (BioLayer Interferometry). In vitro assays were conducted as well to check for cytotoxic effects against both cancerous and healthy cells, and also to assess the capacity to regulate EphA2 degradation. This study undoubtedly enlarges our knowledge on how to properly target EphA2-Sam/Ship2-Sam associations with peptide-based tools and provides a promising strategy that can be used to target any protein–protein interaction. [ABSTRACT FROM AUTHOR]

In the last three decades, high-relaxivity Magnetic Resonance Imaging (MRI) contrast agents (CAs) have been intensively sought, aiming at a reduction in the clinically injected dose while maintaining the safety of the CA and obtaining the same pathological information. Thus, four new Gd(III) complexes based on modified 10-(2-hydroxypropyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid (HP-DO3A) macrocyclic structure were designed and synthesized by introducing further polar and protic functional groups (amides, phosphonates, and diols) adjacent to the metal-coordinated hydroxyl group. A detailed 1H NMR relaxometric analysis allowed us to investigate the effect of these functional groups on the relaxivity, which showed a 20–60% increase (at 0.5 T, 298 K, and pH 7.4) with respect to that of clinically approved CAs. The contribution of the water molecules H-bonded to these peripheral functional groups on the relaxivity was evaluated in terms of the second sphere effect or prototropic exchange of labile protons. [ABSTRACT FROM AUTHOR]

The mutual relationship between peptides and metal ions enables metalloproteins to have crucial roles in biological systems, including structural, sensing, electron transport, and catalytic functions. The effort to reproduce or/and enhance these roles, or even to create unprecedented functions, is the focus of protein design, the first step toward the comprehension of the complex machinery of nature. Nowadays, protein design allows the building of sophisticated scaffolds, with novel functions and exceptional stability. Recent progress in metalloprotein design has led to the building of peptides/proteins capable of orchestrating the desired functions of different metal cofactors. The structural diversity of peptides allows proper selection of first‐ and second‐shell ligands, as well as long‐range electrostatic and hydrophobic interactions, which represent precious tools for tuning metal properties. The scope of this review is to discuss the construction of metal sites in de novo designed and miniaturized scaffolds. Selected examples of mono‐, di‐, and multi‐nuclear binding sites, from the last 20 years will be described in an effort to highlight key artificial models of catalytic or electron‐transfer metalloproteins. The authors' goal is to make readers feel like guests at the marriage between peptides and metal ions while offering sources of inspiration for future architects of innovative, artificial metalloproteins. [ABSTRACT FROM AUTHOR]

Background: Intravenous thrombolysis (IVT) and/or endovascular therapy (EVT) are currently considered best practices in acute stroke patients. Data regarding the efficacy and safety of reperfusion therapies in patients with atrial fibrillation (AF) are conflicting as regards haemorrhagic transformation, mortality, and functional outcome. This study sought to investigate for any differences, in terms of safety and effectiveness, between AF patients with acute ischaemic stroke (AIS) treated and untreated with reperfusion therapies. Methods: Data from two multicenter cohort studies (RAF and RAF-NOACs) on consecutive patients with AF and AIS were analyzed to compare patients treated and not treated with reperfusion therapies (IVT and/or EVT). Multivariable logistic regression analysis was performed to identify independent predictors for outcome events: 90-day good functional outcome and mortality. A propensity score matching (PSM) analysis compared treated and untreated patients. Results: Overall, 441 (25.4%) were included in the reperfusion-treated group and 1,295 (74.6%) in the untreated group. The multivariable model suggested that reperfusion therapies were significantly associated with good functional outcome. Rates of mortality and disability were higher in patients not treated, especially in the case of higher NIHSS scores. In the PSM comparison, 173/250 patients (69.2%) who had received reperfusion therapies had good functional outcome at 90 days, compared to 146/250 (58.4%) untreated patients (p = 0.009, OR: 1.60, 95% CI:1.11–2.31). Conclusions: Patients with AF and AIS treated with reperfusion therapies had a significantly higher rate of good functional outcome and lower rates of mortality compared to those patients with AF and AIS who had undergone conservative treatment. [ABSTRACT FROM AUTHOR]

Purpose: To analyze the learning curve for thoracic endovascular aortic repair (TEVAR) in a single center over a period of 25 years. Materials and Methods: In total, 390 consecutive standard TEVAR procedures undertaken between 1996 and 2021 were included in a retrospective, observational, single-center study. Cumulative sum charts were elaborated for the entire center experience (primary outcome) as well as for the first and second implanting physicians. Data on procedural variables (contrast volume, operative and fluoroscopy time), 30-day major adverse events (MAEs) and clinical success, and endoleak and reintervention rates were secondary outcomes and subdivided into 4 quartiles of experience (Q1–Q4) or presented as first 2 versus latest 2 quartiles (Q1–Q2 vs Q3–Q4). Results: The mean follow-up was 4.3±4.0 years. The center's learning curve was achieved after 75 procedures, and it was similar for the first implanting physician. The surgeon coming thereafter had a significantly shorter curve (10 TEVARs). Comparing Q1–Q2 with Q3–Q4, 30-day MAEs (16.1 vs 11.3%, p=0.164), 30-day mortality (11.4% vs 3.6%, p=0.003), and intraoperative additional maneuvers (21.5% vs 13.3%, p=0.033) were reduced along with an improvement in clinical success (85.9% vs 90.3%, p=0.190). From Q1 to Q4, operative time (139.8±65.5 to 76.7±43.7 min, p=0.001), fluoroscopy time (15.1±8.8 to 7.1±5.1 min, p<0.001), and contrast volume (244.0±112.1 to 104.3±46.1 mL, p<0.001) showed a considerable reduction. Late endoleak and aortic-related mortality declined significantly from Q1–Q2 to Q3–Q4 (24.1% to 15.5%, p=0.033 and 18.6% vs 8.2%, p=0.006, respectively). Operative time (p=0.021), contrast volume (p=0.016), and fluoroscopy time (p=0.004) were independent risk factors for endoleak, causing a 1.3-fold risk increase for both each 60 minutes of additional operative time (p=0.021) and every 100 mL of additional contrast medium (p=0.016). Each 10-minute increase in fluoroscopy time determined a 1.4-fold risk increment (p=0.004). Conclusion: The learning curve shortened significantly over time with non-negligible clinical outcome improvements, suggesting that specific endovascular training is mandatory to become an effective TEVAR performer. Clinical Impact: For the first time in literature, the standard TEVAR's learning curve has been evaluated at a single vascular surgery center over a period of 25 years. The learning curve for the center and the first physician historically undertaking TEVAR was achieved at the 75th treated patient. The learning curve of the surgeons coming thereafter was significantly shorter (10 cases). This quarter-century demonstrated that intraoperative learning-related variables were associated with long-term clinical outcomes and all have improved over time. Centers approaching TEVAR for the first time and training program providers could use these data to aim to offer better clinical outcomes. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the outcomes of preserving the internal iliac artery (IIA) with iliac branched devices (IBDs) during acute endovascular repair of ruptured aortoiliac aneurysms. Material and Methods: This is a multicenter retrospective review of all consecutive patients undergoing acute endovascular repair of ruptured aortoiliac aneurysm with an IBD at 8 aortic centers between December 2012 and June 2020. A control group was used where the IIA was intentionally occluded from the same study period. The main outcome measures were 30-day mortality, major adverse events, technical success, and clinical success. Secondary outcomes were buttock claudication, primary patency, primary-assisted and secondary patency of the IBD, occurrence of endoleak types I/III, and reintervention. Values are presented as numbers and percentages or interquartile range in parenthesis. Results: Forty-eight patients were included in the study: 24 with IBD and 24 with IIA occlusion. There was no difference in demographics, cardiovascular risk factors, and aneurysm extent. Twenty (83%) of them were hemodynamically stable during the procedure as opposed to 14 (58%, p=.23) with the IIA occlusion. Technical success was achieved in all cases with a procedure time of 180 (133–254) minutes, 45 (23–65) of which were from IBD. There were 2 (8%) deaths during the first 30 days and 2 (8%) major complications unrelated to the IBD, whereas in the IIA occlusion, the figures were 10 (42%) and 7 (29%), respectively. No patient in the IBD group developed buttock claudication compared to 8 (57%, p<.0001) in the IIA occlusion group; 1 (4%) patient developed bowel ischemia on both groups, with 1 in the IIA occlusion group needing resection. The median follow-up duration was 17 months (interquartile range 2–39) for the IBD group, with a primary patency of 60±14% at 3 years that went up to 92±8% with reinterventions (8 reinterventions in 6 patients). When the first 90 days were disregarded, there were no differences in survival between the groups. Conclusion: IBD is a valid alternative for maintaining the pelvic circulation for endovascular aortic aneurysm repair of ruptured aortoiliac aneurysms. The technical success and midterm outcomes are very satisfactory but require patient selection particularly regarding hemodynamic stability. The reintervention rate is considerable, mandating continuous follow-up. Clinical Impact: This multicenter study demonstrates that ruptured aortoiliac aneurysms do not necessarily require mandatory occlusion of hypogastric arteries. Iliac branch devices are shown to be a valid alternative in highly selected cases, with good midterm results, even if reinterventions are required in a significant proportion of patients. [ABSTRACT FROM AUTHOR]

Background and purpose: This study investigated the effects of deep abdominal breathing on cardiovascular parameters and symptoms in patients with postural orthostatic tachycardia syndrome (POTS) during head‐up tilt‐table (HUT) challenge. Methods: Thirty POTS patients completed two consecutive rounds of 10‐min HUT in a crossover design. One round was HUT without intervention, and one round combined the HUT with deep breathing at a rate of 6 breaths/min. Cardiovascular parameters, including mean blood pressure and maximum and mean heart rate (HR), were measured supine and standing. Symptoms were assessed using the Vanderbilt Orthostatic Symptom Score (VOSS). Results: During the breathing technique, the mean HR increase was −7.35 bpm (95% confidence interval [CI] = −11.71 to −2.98), and the maximum HR increase was −6.27 bpm (95% CI = −11.85 to −0.68, p = 0.041), significantly lower compared to normal breathing. Additionally, improvements were observed in all absolute cardiovascular parameters during standing, with VOSS symptoms simultaneously and significantly decreasing by −5.38 (95% CI = −10.43 to −0.36). Conclusions: Slow deep abdominal breathing can act as a simple technique to reduce the standing HR increase upon HUT in patients with POTS. This suggests that modulation of the cardiopulmonary neurocircuits and the respiratory pump may reduce HR increase and symptoms in patients with POTS. The findings of this study highlight the use of a safe, zero‐cost, and simple behavioral tool to suggest to POTS patients for symptom relief apart from standard treatment. The observed improvements in cardiovascular parameters and symptoms offer a promising therapeutic approach for patients in times of inadequate treatment options. [ABSTRACT FROM AUTHOR]

Purpose: With the increasing demand for intensified processes in biopharmaceutical manufacturing, there is a growing requirement for a rapid and precise analytical method to measure product yield. Aligning with FDA guidelines, this requirement aims to enhance process monitoring and control. Currently, the monitoring of monoclonal antibody (mAb) titer during manufacturing heavily relies on offline testing conducted in quality control laboratories. However, the lengthy turnaround time for analytical results, often taking hours or even days, undermines their usefulness for process control and decision-making. Methods: This manuscript presents a case study on HaLCon® protein analyzer, a compact Liquid Chromatography (LC) system equipped with a Protein A affinity column. HaLCon® is specifically designed for at-line/on-line titer measurement directly at the biopharmaceutical manufacturing site, enabling the rapid acquisition of product yield information. The study investigates the capabilities, performance, and potential applications of HaLCon® at the laboratory scale. Results and Conclusion: The results obtained demonstrate the effectiveness and reliability of HaLCon® as an analytical instrument for at-line titer measurement, offering valuable insights into its potential application within the biopharmaceutical manufacturing industry. [ABSTRACT FROM AUTHOR]

The production of açaí seed waste from the commercial and extractive exploitation of the Euterpe oleraceae palm tree is a serious problem that contributes to environmental contamination and production of greenhouse gases, a fact that suggests the need for an environmentally correct destination for this waste produced on a large scale. To this end, this study was conducted to evaluate the potential of acaí seed biochar (BCA) in mitigating the toxic effects of copper in Brazilian mahogany plants, analyzing biometrics and gas exchange. The experimental design was in randomized blocks, with five blocks, in a 4 × 3 factorial scheme, corresponding to the control (without Cu) and three concentration of Cu (200, 400, and 600 mg Cu kg−1) and three levels of BCA (0%, 5% and 10%) proportional to the amount of soil in the pots, totaling sixty experimental units. The use of 5% BCA in soils contaminated with up to 200 mg kg−1 Cu promoted biometric increase (height, diameter, number of leaves), maintaining gas exchange (photosynthesis, stomatal conductance, transpiration, internal carbon and internal/external carbon), and consequently, maintaining water use efficiency in plants under abiotic stress, resulting in plant growth. The findings of this study allow us to indicate the use of biochar in remediating and improving the growth of plants grown in copper-contaminated soils. The production of biochar from açaí seeds is an ecologically sustainable alternative, because it reduces its accumulation on public roads and contributes to reducing soil pollution. In the context of public policies, biochar production could be a source of income in the context of the bioeconomy and circular economy practiced in the Amazon, because it is produced in large quantities. [ABSTRACT FROM AUTHOR]

We propose a novel approach for determining the orbital inclination of low-mass X-ray binary systems by modelling the Hα and Hβ line profiles emitted by the accretion disc, with a Newtonian (i.e. non-relativistic) version of DISKLINE. We applied the model to two sample sources, Swift J1357.2–0933 and MAXI J1305–704, which are both transient black hole systems, and analyse two observations that were collected during a quiescent state and one observation of an outburst. The line profile is well described by the DISKLINE model, although we had to add a Gaussian line to describe the deep inner core of the double-peaked profile, which the DISKLINE model was unable to reproduce. The Hβ emission lines in the spectrum of Swift 1357.2–0933 and the Hα emission lines in that of MAXI J1305–704 during the quiescent state are consistent with a scenario in which these lines originate from a disc ring between (9.6 − 57)×103 Rg and (1.94 − 20)×104 Rg, respectively. We estimate an inclination angle of 81 ± 5 degrees for Swift J1357.2−0933 and an angle of 73 ± 4 degrees for MAXI J1305−704. This is entirely consistent with the values reported in the literature. In agreement with the recent literature, our analysis of the outburst spectrum of MAXI J1305−704 revealed that the radius of the emission region deviates from expected values. It is larger than the orbital separation of the system. This outcome implies several potential scenarios, including line profile contamination, an alternative disc configuration that deviates from the Keplerian model, or even the possibility of a circumbinary disc. We caution that these results were derived from a simplistic model that may not fully describe the complicated physics of accretion discs. Despite these limitations, our results for the inclination angles are remarkably consistent with recent complementary studies, and the proposed description of the emitting region remains entirely plausible. [ABSTRACT FROM AUTHOR]

Background: Although crackles on chest auscultation represent a fundamental component of the diagnostic suspect for fibrotic interstitial lung disease (ILD), their reliability has not been properly studied. We assessed the agreement among respiratory physicians on the presence and changes over time of audible crackles collected in a prospective longitudinal cohort of patients with fibrotic ILD. Methods: Lung sounds were digitally recorded at baseline and after 12 months at eight anatomical sites. Nine respiratory physicians blindly assessed randomized couples of recordings obtained from the same anatomical site at different timepoints. The physicians indicated the presence of crackles in individual recordings and which recording from each couple eventually had more intense crackles. Fleiss' kappa coefficient was used to measure inter- and intra-rater agreement. Results: Fifty-two patients, mostly with a diagnosis of IPF (n = 40, 76.9%) were prospectively enrolled between October 2019 and May 2021. The final acoustic dataset included 702 single recordings, corresponding to 351 couples of recordings from baseline and 12-months timepoints. Kappa coefficient was 0.57 (95% CI 0.55–0.58) for the presence of crackles and 0.42 (95% CI 0.41–0.43) for acoustic change. Intra-rater agreement, measured for three respiratory physicians on three repeated assessments, ranged from good to excellent for the presence of crackles (κ = 0.87, κ = 0.86, κ = 0.79), and from moderate to good for acoustic change (κ = 0.75, κ = 0.76, κ = 0.57). Conclusions: Agreement between respiratory physicians for the presence of crackles and acoustic change was acceptable, suggesting that crackles represent a reliable acoustic finding in patients with fibrotic ILD. Their role as a lung-derived indicator of disease progression merits further studies. [ABSTRACT FROM AUTHOR]

Aluminum scandium nitride barrier layers increase the available sheet charge carrier density in gallium nitride‐based high‐electron‐mobility transistors and boost the output power of high‐frequency amplifiers and high voltage switches. Growth of AlScN by metal‐organic chemical vapor deposition is challenging due to the low vapor pressure of the conventional Sc precursor Cp3Sc, which induces low growth rates of AlScN and leads to thermally‐induced AlScN/GaN‐interface degradation. In this work, novel Sc precursors are employed to reduce the thermal budget by increasing the growth rate of the AlScN layer. The AlScN/GaN interfaces are investigated by high‐resolution X‐ray diffraction, high‐resolution transmission electron microscopy, time‐of‐flight secondary ion mass spectrometry, capacitance–voltage, current–voltage and temperature‐dependent Hall measurements. Linearly graded interlayers with strain‐induced stacking faults, edge, and screw dislocations form at the AlScN/GaN interface at growth rates of 0.015 nms−1. Growth rates of 0.034 nms−1 and higher allow for abrupt interfaces, but a compositional grading in the barrier remains. Homogeneous barrier layers can be achieved at growth rates of 0.067 nms−1 or by growing an AlN interlayer. The electrical properties of the heterostructures are sensitive to Sc accumulations at the cap/barrier interface, residual impurities from precursor synthesis, and surface roughness. This study paves the way for high‐performing devices. [ABSTRACT FROM AUTHOR]

Background: Metastatic pancreatic ductal adenocarcinoma (mPDAC) patients have very poor prognosis highlighting the urgent need of novel treatments. In this regard, repurposing non-oncology already-approved drugs might be an attractive strategy to offer more-effective treatment easily tested in clinical trials. Accumulating evidence suggests that epigenetic deregulation is a hallmark of cancer contributing to treatment resistance in several solid tumors, including PDAC. Histone deacetylase inhibitors (HDACi) are epigenetic drugs we have investigated preclinically and clinically as anticancer agents. Valproic acid (VPA) is a generic low-cost anticonvulsant and mood stabilizer with HDAC inhibitory activity, and anticancer properties also demonstrated in PDAC models. Statins use was reported to be associated with lower mortality risk in patients with pancreatic cancer and statins have been shown to have a direct antitumor effect when used alone or in combination therapy. We recently showed capability of VPA/Simvastatin (SIM) combination to potentiate the antitumor activity of gemcitabine/nab-paclitaxel in vitro and in vivo PDAC preclinical models. Methods/Design: VESPA is a patient-centric open label randomized multicenter phase-II investigator-initiated trial, evaluating the feasibility, safety, and efficacy of VPA/SIM plus first line gemcitabine/nab-paclitaxel-based regimens (AG or PAXG) (experimental arm) versus chemotherapy alone (standard arm) in mPDAC patients. The study involves Italian and Spanish oncology centers and includes an initial 6-patients safety run-in-phase. A sample size of 240 patients (120 for each arm) was calculated under the hypothesis that the addition of VPA/SIM to gemcitabine and nab-paclitaxel-based regimens may extend progression free survival from 6 to 9 months in the experimental arm. Secondary endpoints are overall survival, response rate, disease control rate, duration of response, CA 19.9 reduction, toxicity, and quality of life. The study includes a patient engagement plan and complementary biomarkers studies on tumor and blood samples. Conclusions: VESPA is the first trial evaluating efficacy and safety of two repurposed drugs in oncology such as VPA and SIM, in combination with standard chemotherapy, with the aim of improving mPDAC survival. The study is ongoing. Enrollment started in June 2023 and a total of 63 patients have been enrolled as of June 2024. Trial registration: EudraCT number: 2022-004154-63; ClinicalTrials.gov identifier NCT05821556, posted 2023/04/20. [ABSTRACT FROM AUTHOR]

Introduction: Many stroke survivors do not receive optimal levels of personalised therapy to support their recovery. Use of technology for stroke rehabilitation has increased in recent years to help minimise gaps in service provision. Markerless motion capture technology is currently being used for musculoskeletal and occupational health screening and could offer a means to provide personalised guidance to stroke survivors struggling to access rehabilitation. Aims: This study considered context, stakeholders, and key uncertainties surrounding the use of markerless motion capture technology in community stroke rehabilitation from the perspectives of stroke survivors and physiotherapists with a view to adapting an existing intervention in a new context. Methods: Three focus groups were conducted with eight stroke survivors and five therapists. Data were analysed using reflexive thematic analysis. Results: Five themes were identified: limited access to community care; personal motivation; pandemic changed rehabilitation practice; perceptions of technology; and role of markerless technology for providing feedback. Conclusions: Participants identified problems associated with the access of community stroke rehabilitation, exacerbated by Covid-19 restrictions. Participants were positive about the potential for the use of markerless motion capture technology to support personalised, effective stroke rehabilitation in the future, providing it is developed to meet stroke survivor specific needs. [ABSTRACT FROM AUTHOR]

Background: Despite the worldwide increasing incidence of Group A Streptococcus (GAS) infections reported since December 2022, data on noninvasive GAS (nGAS) infections in the post COVID-19 era are limited. By a self-reported survey performed in an outpatient setting, we investigated the number and clinical features of GAS infections, the diagnostic work-up and the type of treatment utilized. In addition, the rate of influenza vaccination was evaluated. Methods: In June 2023 family pediatricians involved in the study sent the survey to parents of patients aged 0–16 years. The survey included questions on GAS infections that occurred from January 1 to May 31, 2023. Results: Among 3580 children, 20.3% had a GAS infection (0,8% < 1 year, 16,4% 1–3 years, 42,3% 3–6 years, 26,5% 6–9 years, 11,4%, 9–12 years, and 2,6% 12–16 years). Symptoms reported were sore throat (76.9%), fever (75.2%), tonsillar exudate (25.2%), lymphadenopathy (21.8%), and scarlet fever (14.7%). A single patient was hospitalized due to GAS meningitis. Twenty four percent of children had more than one GAS infection. In this group, frequencies of symptoms reported in the first and in the following infection were similar, except for fever and scarlet fever which were less frequent during relapses. GAS was identified by rapid antigen detection test in 81.0% of children. Eighty-nine per cent of children were treated with antibiotics, mostly amoxicillin/clavulanate (40.4%) and amoxicillin (39.4%). Thirty four percent of children received influenza vaccine. No difference was observed among immunized and not immunized regarding the number and characteristics of GAS infection. Conclusions: We reported a certain prevalence of nGAS infections in children, mainly those aged 3–6 years age, who were mostly characterized by a low score of symptoms, and in most of the cases diagnosed and treated using a microbiological test as confirmatory tool. In this new clinical setting, a national study would be useful to reach more significant data for the definition of a correct diagnosis and clinical management of nGAS infections in children. Moreover, it is important to improve flu vaccination campaign and coverage to protect children from coinfections that could worsen the disease and misdiagnose the etiology of pharyngitis. [ABSTRACT FROM AUTHOR]