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Abstract Objectives to evaluate over a 48-month follow-up period the: 1) long-term effectiveness and safety; 2) drug retention rate (DRR); 3) impact of comorbidities and bDMARDs line on MDA and DAPSA remission/low disease activity (LDA) of secukinumab in a multicenter Italian cohort of PsA patients. Methods Consecutive PsA patients receiving secukinumab were followed prospectively in Italian centers between 2016 and 2023. Disease characteristics, previous/ongoing treatments, comorbidities and follow-up duration were recorded. Treatment response was evaluated at 6 and 12 months after initiation, and every year up to 48 months (T48). DRR was assessed according to clinical and demographic features, comorbidities and bDMARDs line. Adverse events (AE) were recorded. Results Six hundred eighty-five patients [42.5% male] were enrolled; 32.9% naïve received secukinumab; 74.2% had ≥ 1 comorbidity. Overall, secukinumab yielded improved outcomes at T48: naïve maintained lower disease activity vs. non-naïve [DAPSA 4.0 (1.4–8.1) vs. 6.0 (2.2–10.4);p = 0.04]; 76.9% naïve and 66.2% non-naïve achieved MDA; MDA no comorbidities vs. 1–3 comorbidities 78.8% vs. 73.3% (p 3 comorbidities 78.8% vs. 48.7% (p 3 comorbidities. Treatment was discontinued in 233 patients due to loss of effectiveness, and in 41 due to AE. The overall DRR at T48 was 66%, with differences according to bDMARDs line (p

Abstract Obesity-related disability-adjusted life years (DALYs) are expected to increase by approximately 40% from 2020 to 2030. DALYs and mortality related to obesity are the consequence of multiple comorbidities such as cardiovascular (i.e., heart failure) and metabolic diseases (i.e. type 2 diabetes [T2D], metabolic dysfunction-associated steatotic liver disease [MASLD]). Lifestyle interventions represent the foundation of obesity treatment, yet an escalation to pharmacological and/or surgical interventions is often needed. Liraglutide, semaglutide and tirzepatide are incretin-based therapies currently approved by FDA for the management of obesity, while triple GIPR/GCGR/GLP-1R agonist retatrutide (LY3437943), the cagrilintide/semaglutide (CagriSema) 2.4 mg combination, high-dose oral semaglutide, and oral orforglipron are in advanced stages of development. Incretin-based therapies have been associated with a body weight (BW) reduction of ≥5% in at least half of patients in most randomized controlled trials (RCT) and real-world studies (RWS). Semaglutide and tirzepatide have also displayed a mean 60–69% 10-years relative risk reduction of T2D development. In line with evidence accrued in patients with T2D, incretin-based therapies produced a favorable effect on traditional cardiovascular risk factors, such as lipids and blood pressure, and even reduced the risk of major cardiovascular events and heart failure-related events in individuals with obesity, as recently demonstrated for the first time in the SELECT trial with semaglutide 2.4 mg once-weekly. Moreover, incretin-based therapies have also been proven beneficial on obesity-related comorbidities, such as knee osteoarthritis (KOA), obstructive sleep apnea (OSA) syndrome, and MASLD. Further research is needed to improve our understanding of their effects on obesity-related comorbidities and the underlying mechanism, whether involving direct effects on target tissues or mediated by improvement in BW, glucose levels and other CV risk factors.

Abstract The Irpinia Fault, also known as the Monte Marzano Fault System, located in the Southern Apennines (Italy), is one of the most seismically active structures in the Mediterranean. It is the source of the 1980, Ms 6.9, multi-segment rupture earthquake that caused significant damage and nearly 3,000 casualties. Paleoseismological surveys indicate that this structure has generated at least four Mw ~ 7 surface-rupturing earthquakes in the past 2 ka. This paper presents a comprehensive, high-resolution geophysical investigation focused on the southernmost fault segment of the Monte Marzano Fault System, i.e., the Pantano-Ripa Rossa Fault, outcropping within the Pantano di San Gregorio Magno intramontane basin. The project, named TEst Site IRpinia fAult (TESIRA), was supported by the University of Napoli Federico II to study the near-surface structure of this intra-basin fault splay that repeatedly ruptured co-seismically in the past thousands of years. Our imaging approach included 2D and 3D electrical and seismic surveys, gravimetry, 3D FullWaver electrical tomography, drone-borne GPR and magnetic surveys, and CO2 soil flux assessment across the surface rupture. This multidisciplinary investigation improved our understanding of the basin shallow structure, providing an image of a rather complex subsurface fault and basin geometry. Seismic data suggest that fault activity at the Pantano segment of MMFS is characterized by a near-surface cumulative displacement greater than previous estimations, calling into question earlier assumptions about the timing of its activation. Despite some challenges with our drone-mounted survey equipment, the integrated dataset provides a comprehensive and reliable image of the subsurface structure. This work demonstrates the utility of developing an integrated approach at high-resolution geophysical imaging and interpretation of fault zones with weak morphological expressions.

Abstract Our previous manuscript showed that thrombocytopenia predicts all-cause mortality in Chinese hemodialysis (HD) patients. Based on the role of platelets in coagulation, clot formation, and systemic inflammation, we speculate that high platelets increase risk of thrombo-embolic events, hence the mortality. However, research evidence is currently lacking. Therefore, we utilized data from a very large international cohort study to explore the association of platelet counts with mortality and cardiovascular (CV) death in hemodialysis (HD) patients. International data from 396 facilities enrolled in the Dialysis Outcomes and Practice Patterns Study (DOPPS) phase 5 (2012–2015) were analyzed. Participants were divided into 3 groups according to their platelet counts (low: 300*109). Associations between platelet counts and all-cause and CV mortality were analyzed using Cox regression, adjusted for confounders. There were 13,631 patients with median age of 65 years old. Males accounted for 61.2%. Mean platelet count was 205*109/L overall and ranged from 173 *109/L in China to 227 *109/L in Sweden. Overall, 2,348 (17.2%) patients died and 1017 (7.5%) died from CV disease. Both low (HR:1.48, 95% CI 1.21–1.80, p

Abstract Background Hepatitis virus infection remains a serious public health concern worldwide. Percutaneous, mucosal, or non-intact skin exposure to infectious blood, semen, and other body fluids are the major routes of infection in endemic areas, including Ethiopia, where little is known about the community’s knowledge, attitudes, and practice toward hepatitis infection. Thus, this study aimed to determine the knowledge, attitude, and practices towards hepatitis infection among adults in Gondar town. Methods A community-based cross-sectional study was conducted from July to August 2021 on a total of 390 participants. Proportional sample allocation was used in 3 randomly selected sub-cities. Then, study participants from randomly selected households were recruited by using a systematic random sampling technique. Socio-demographic data and questions regarding KAP were collected via a self-administered and interviewer-administered questionnaire. Statistical analysis was performed using SPSS version 20. Logistic regression analyses were used to identify the associated factors and a p-value

Abstract Multi-modal image analysis using deep learning (DL) lays the foundation for neoadjuvant treatment (NAT) response monitoring. However, existing methods prioritize extracting multi-modal features to enhance predictive performance, with limited consideration on real-world clinical applicability, particularly in longitudinal NAT scenarios with multi-modal data. Here, we propose the Multi-modal Response Prediction (MRP) system, designed to mimic real-world physician assessments of NAT responses in breast cancer. To enhance feasibility, MRP integrates cross-modal knowledge mining and temporal information embedding strategy to handle missing modalities and remain less affected by different NAT settings. We validated MRP through multi-center studies and multinational reader studies. MRP exhibited comparable robustness to breast radiologists, outperforming humans in predicting pathological complete response in the Pre-NAT phase (ΔAUROC 14% and 10% on in-house and external datasets, respectively). Furthermore, we assessed MRP’s clinical utility impact on treatment decision-making. MRP may have profound implications for enrolment into NAT trials and determining surgery extensiveness.

Every year, numerous major events with thousands of participants take place around the world, for which extensive safety measures are taken to ensure the well-being and safety of visitors. Nevertheless, incidents that lead to injuries and deaths occur time and again. This year, Germany is looking forward to the UEFA EURO 2024, an international football championship for which the host country, Germany, has made extensive preparations on several levels. One component of this is the Medical Task Force (MTF) of the Federal Office of Civil Protection and Disaster Assistance (BBK), which has trained a possible medical service deployment in the event of a mass casualty incident with a specially coordinated series of exercises. The extent to which current remote sensing data can make a useful contribution and be meaningfully integrated was analyzed during the large-scale EUROMED exercise with the help of an airborne camera system on board a helicopter. The system provided up-to-date aerial images of the exercise site, but was also used to record the traffic situation during the transfer of the vehicle convoys to the exercise site. In addition, state-of-the-art AI-based image analysis methods were tested on site and the results were provided and evaluated. An important operational exercise to bring science and practice together step by step in order to be better prepared for an emergency.

Background: 177-LuDOTATE is an effective but expensive treatment for neuroendocrine tumors (NETs). Reducing treatment-related costs, such as the number of images, could improve access to 177-LuDOTATE. We evaluated early radiological tumor progression and prognostic factors in patients with NETs treated with 177-LuDOTATE. Methods: We retrospectively included all patients with NETs who received at least one cycle of 177-LuDOTATE. The primary endpoint was the rate of early radiological progression between cycles 2 and 3 (in 10–16 weeks). Secondary endpoints were progression-free survival (PFS) and overall survival (OS) according to prognostic factors (tumor grade, primary site, functioning syndrome, 177-LuDOTATE treatment line) in Cox proportional hazards models. Results: The median number of 177-LuDOTATE cycles was 3 (range 1–6) among 59 patients included. Ten (17%) patients had early progression. Among 14 patients who received ≤2 cycles of 177-LuDOTATE, ten (72%) stopped treatment due to disease progression, with five patients having a G2 (ki67: 5–25%) and 4, a G3 (ki67: 25–90%) NET. In the Cox multivariable analysis, higher grade (G2 or G3 vs G1) were significantly associated with inferior PFS and OS. The median PFS of G1, G2 and G3 NET patients were: 34.1, 11.7 and 6.1 months (P = 0.015), respectively. Conclusions: It is feasible to perform imaging tests after 177-LuDOTATE completion for patients with indolent NETs with the intent to avoid futile assessments. For patients with more aggressive diseases, such as G3 NETs and G2 tumors with high tumor burden, we advise to perform more frequent images during 177-LuDOTATE therapy.

We used cross-sectional data from 226 patients with monkeypox virus to investigate the association between anatomic exposure site and lesion development. Penile, anorectal, and oral exposures predicted lesion presence at correlating anatomic sites. Exposure site also predicted the first lesion site of the penis and anus.

La problématique de la rémunération des agents par les entreprises chinoises n’a pas que fait couler beaucoup d’encre et de salive dans le continent africain, en général; la République Démocratique du Congo, en particulier, en a aussi payé les frais. En effet, les investissements chinois, qui sont devenus depuis une certaine année importants dans le continent, se révèlent être une aubaine pour les Etats Africains dans la création de nouveaux emplois pour leurs populations. Cependant, les entrepreneurs chinois, surtout ceux du secteur minier, se sont illustrés par une politique salariale, qui rémunère moins bien leurs agents et n’intègre pas tous les éléments de la rémunération, tels qu’édictés par les normes de l’Organisation Internationale du Travail (OIT) et par la Loi n°015/2002 du 16 octobre 2002 portant Code du Travail telle que modifiée et complétée à ces jours par la Loi n° 16/010 du 15 juillet 2016 de la RDC. Cet article retrace les grandes lignes de la problématique ainsi soulevée après un constat fait en Afrique, en général et en RDC, particulièrement; en détermine les causes avant d’en proposer quelques pistes de solutions.

Cervical septic arthritis can lead to complications such as epidural abscess, which may result in respiratory failure. We present a case of a 78-year-old male with cervical septic arthritis complicated by epidural abscess, leading to severe diaphragm dysfunction. Ultrasound evaluation revealed dysfunction of the left hemidiaphragm and compensatory activation of accessory respiratory muscles. Treatment included antibiotic therapy and corticosteroids, alongside respiratory support. After 21 days, improvements were observed in diaphragmatic function and respiratory muscle activation. Our findings highlight the importance of assessing both diaphragm and accessory respiratory muscles in cases of cervical septic arthritis with respiratory complications.

California is the primary US producer of processing tomatoes. After decades-long excellent protection against the common tropical Meloidogyne spp. M. incognita, M. javanica, and M. arenaria (root-knot nematode: RKN) by Mi-resistant tomato cultivars, resistance-breaking RKN populations are spreading throughout the San Joaquin Valley. For some time, nematicidal crop management tools have diminished under CA State regulatory pressure. In recent years, new non-volatile compounds have been developed with novel modes of action. In this project with susceptible processing tomato grown on an M. incognita-infested site, the efficacy of three fluorinated nematicides was evaluated in 10 field trials from 2011 to 2021. Seven trials included fluensulfone, six included fluazaindolizine, and five included fluopyram. On average, tomato root-galling (0 – 10 scale) at harvest was reduced by 3.2, 2.3, and 2.5 by fluazaindolizine, fluensulfone, and fluopyram, respectively, compared to the untreated control. These reductions in root-galling corresponded with estimated yield gains of approximately 21%, 14%, and 15%, respectively, over the untreated control. The reproduction of RKN during the tomato crop was not affected by the nematicides. The tested compounds have a very low acute mammalian toxicity and are more target-specific than previous generations of nematicides. However, there is considerable concern about the persistence of synthetic per- and polyfluoroalkyl substances (PFAS) in the environment, including pharmaceuticals and pesticides containing fluorine with the C-F3 functional group.

Abstract We investigated the relationship between the degree of alveolarization and ultrasound-assessed lung aeration in a validated preterm rabbit model of experimental bronchopulmonary dysplasia (BPD). Lung ultrasound findings were heterogeneously abnormal and consisted of zones with interstitial, interstitial-alveolar or consolidated patterns. The median radial alveolar count was 10.1 [8.4–11.5], 7.8 [6.1–9] and 7.3 [1.8–10.1] in rabbits with interstitial, interstitial-alveolar or consolidated ultrasound pattern, respectively (overall p = 0.036). Alveolar count and lung ultrasound score were significantly correlated (ρ = − 0.044 (95%CI: − 1; − 0.143), p = 0.009; τ-b = − 0.362 (95%CI: − 0.6; − 0.1), p = 0.017).

Abstract Observed North Atlantic sea-surface temperatures are modulated by a recurrent alternation of anomalously warm and cold interdecadal phases known as Atlantic Multidecadal Variability. Here we use observations and a multi-model ensemble of climate simulations to demonstrate an ongoing acceleration of North Atlantic surface warming, which implies a smaller contribution of the Atlantic Multidecadal Variability to 21st century North Atlantic sea-surface temperature anomalies than previously thought. Future projections of the Atlantic Multidecadal Variability from realistic climate simulations are poorly constrained, yet a relaxation to a neutral phase by the mid-21st century emerges as the most probable evolution of the Atlantic Multidecadal Variability. In the simulations, the mitigating effects of a less likely upcoming cold phase of the Atlantic Multidecadal Variability are overwhelmed by fast North Atlantic surface warming, which is robustly projected to persist in upcoming decades independent of emission scenarios. Sustained North Atlantic surface warming is therefore expected to continue in the near future.

Abstract The high penetration of renewable energy sources (RES) results in a low‐inertia, weak power grid. To mitigate this and restore system inertia, it has been widely proposed to operate the inverters of RES units to mimic synchronous generators; this technology is known as a virtual synchronous generator (VSG). In weak grids there is, however, strong coupling between active power (P) and reactive power (Q), and any VSG technique therefore requires PQ decoupling in order to operate effectively. This article proposes a new PQ decoupling technique based on the transformation of the PQ power circle of a VSG connected to a weak grid: first, the power circle is translated from its designed position to that of a conventional synchronous generator (SG) connected to a strong grid, achieving partial PQ decoupling. Then, to achieve full PQ decoupling, the authors propose further to modulate the radius of the translated PQ power circle; this is achieved using a series resistance‐capacitance–inductance (RCL) circuit which is virtually implemented in the VSG controller. The efficacy of the proposed scheme is validated using a modified synchronverter connected to the weak grid in representative loading scenarios. It is demonstrated that the technique achieves a decoupled PQ control for the synchronverter connected in a weak grid. Moreover, the modified synchronverter is capable of supporting frequency and voltage regulation in the grid without inducing large transient grid currents during mild frequency and voltage variations.

INTRODUCTION: The oldest old adults, aged 80 years and above, is the fastest growing age group in the world. In this section of the population, functional disability (FD) is more prevalent compared to other age groups. OBJECTIVE: To characterize functional capacity and analyze potential associations in the oldest old from a Brazilian capital city, based on a decision model. METHODS: Cross-sectional study of 100 non-institutionalized oldest old participants assisted at the Family Health Strategy of Recife, in the Brazilian northeastern state of Pernambuco, selected by probabilistic sample. Sociodemographic, economic, and clinical data were collected by means of home interviews, anthropometric measurements, and medical records. For bivariate analysis, Pearson's chi-square test was used, establishing significance at p, < 0.05. For the multivariate analysis, a decision tree was built from the Exhaustive CHAID algorithm. RESULTS: The prevalence of FD in the sample corresponded to 67.0%. In the bivariate analysis, the following data contributed to this outcome: income (p = 0.032), social security status (p < 0.01), nutritional status (p = 0.010), neurological diseases (p < 0.01), neoplasms (p < 0.01), self-perceived health (p = 0.025) and social support network (p = 0.032), remaining in the multivariate analysis: income (p = 0.003), social support network (p = 0.032), and nutritional status (p = 0.040). The decision tree allowed the identification of the variables most strongly associated with the outcome, being able to adequately predict moderate dependence, with 72.1% assertiveness. CONCLUSION: The decision model proved to be a timely tool in deducing the most relevant determinants of FD. Its use potentially contributes to increase the accuracy of the diagnosis and to identify populations at risk.

Abstract Background GP registrars (specialist vocational trainees in general practice) are interested in teaching, and there are considerable benefits to teaching during training. There are, however, significant barriers for registrars as teachers, including inadequate funding, time pressures, and limited teacher training. Current evidence does not include medical educator (ME) perspectives or compare teaching settings (e.g. university vs. in-practice). Further evidence is needed to inform programs supporting registrar teaching roles. This project aimed to explore the experiences of Australian GP registrars as teachers in different contexts and from multiple stakeholder perspectives. Methods A qualitative study with GP registrars, GP supervisors, MEs, and medical students was conducted. Participants were registrars and new (within 12 months) Fellows with teaching experience during training, supervisors who supervised a registrar in the preceding 12 months, Royal Australian College of General Practitioner MEs, and medical students with experiences of being taught by registrars. Recruitment was open to participants nationwide and sampling was purposive, aiming for a maximum variation sample. Data collection was performed via videoconference and analysed using reflexive thematic analysis. Findings Interviews were conducted with 15 registrars, 10 supervisors, and one ME. Two focus groups involved four MEs and five medical students respectively. Registrar participants taught in a variety of settings, including in-practice, universities, hospitals, and at educational workshop days. Three had experience in GP academic posts and one as a registrar ME. There were four major themes. 1) Near-peer teaching by registrars is valuable - both for medical students and registrars. 2) Teaching makes you a better GP - participants noted the transferability of teaching skills to clinical practice. 3) The importance of the teaching context – this was identified as an important determinant for registrars in teaching roles. 4) Registrar teaching strengthens the GP workforce – participants noted that teaching could elevate general practice as a specialty and increase interest in GP training. Conclusions Study participants saw teaching as a core skill for GPs, with transferability to their clinical practice. Registrar participants wanted greater promotion and support for teaching opportunities that counted towards attainment of Fellowship. These findings have implications for teaching practices, MEs, universities, and training providers.

Abstract Background Autologous haematopoietic stem cell transplantation (AHSCT) is more effective than conventional immunosuppressive therapies (CIT) in improving the outcome of patients with rapidly progressive diffuse cutaneous systemic sclerosis (dcSSc). So far, there is still a paucity of data comparing AHSCT with rituximab (RTX). Aim of the study is to retrospectively compare, in patients with dcSSc, the effectiveness of AHSCT with that of RTX and CIT. Methods Thirty-five dcSSc AHSCT-treated patients were compared with 29 and 36 matched cases treated with RTX and CIT, respectively. The patients were followed up for 5 years by assessing selected outcome measures every year. Overall survival, modified Rodnan skin score (mRSS), lung function tests (FVC and DLCO), and the revised EUSTAR Activity Index (REAI) were the outcome measures chosen to evaluate the therapy efficacy. Results AHSCT was significantly more effective than RTX and CIT in prolonging survival, inducing a rapid reduction of the mRSS and REAI and maintaining the baseline level of lung function tests for a longer time. RTX therapy was also superior to CIT in reducing REAI, mRSS and in saving lung function. Conclusion AHSCT is more effective than both RTX and CIT in prolonging survival and inducing prolonged remission in patients with rapidly progressive dcSSc.

The Italian sporting event ‘XIV Convittiadi’ involving students at boarding schools took place in Molise region, central Italy, in April 2022. The study describes the public health protocol with specific countermeasures developed for the event, including testing, isolation, and contact tracing during the COVID-19 pandemic, and reports the main related findings. There were 590 Italian white participants, with 514 athletes (mean age 13.6 ± 1.6 years) and 76 accompanying teachers/guardians (50 ± 8.7 years) of 21 boarding schools from different Italian regions. During the event, 1281 antigenic swabs were performed, and twelve COVID-19 cases were promptly identified due to active screening, involving ten (83.3%) athletes and two (16.7%) accompanying teachers. Among the infected athletes, 83.3% complained mild symptoms, either before or after the ascertained positivity, and 40% had received primary cycle vaccination and booster, or only completed the primary course. The enhanced surveillance and contact tracing activities allowed identifying 34 participants as close contacts who were subjected to a daily follow-up that revealed only four (11.8%) as infected. Since in mass gathering events public health risk is not clear and could not be available through the traditional surveillance systems, increased monitoring activities are necessary. The practical approach implemented for this event was valuable for SARS-CoV-2 control and case management either among participants, or the host country population, suggesting its application to other airborne communicable diseases.

Abstract Background The Subglottic Cysts (SGCs) are a rare cause of respiratory distress in infants. Typical risk factors include male gender, extreme prematurity, gastro-oesophageal reflux and invasive ventilation, the latter being associated with mucosal damage and blockage of the subglottic cysts’ ducts. We describe a case of acquired subglottic cysts in a premature infants presented with respiratory distress. Case presentation A premature male infant was born at 25 weeks + 2 days with a history of monochorionic diamniotic twin pregnancy with twin-to-twin transfusion syndrome. During hospitalization, invasive mechanical ventilation was necessary for a total of 18 days; the patient was discharged at postmenstrual age of 40 weeks + 1 day in good condition. At 43 weeks post-menstrual age, he presented to our department with mixed stridor and worsening of respiratory dynamics. A laryngotracheoscopy evaluation was performed. The exam showed the presence of multiple SGCs causing an almost complete obstruction of the airway. Because of the significant reduction of the airway’s patency, the child underwent a tracheotomy and thereafter cysts’ removal using cold steel microinstruments. A better airway patency was restored although a slight glottic edema persisted. The histopathology confirmed the benign nature of the lesions. Successive controls showed a completely patent airway and absence of SGCs. Conclusion In conclusion, SGCs should be considered in preterm infants with respiratory distress previously intubated, which cannot be explained by the most common causes. Early diagnosis and treatment are fundamental to reducing the morbidity and mortality associated with this disease.

Abstract There is increasing interest in the pathophysiological role of arginine metabolism in schizophrenia, particularly in relation to the modulation of the endogenous messenger nitric oxide (NO). The assessment of specific arginine metabolites that, unlike NO, are stable can provide useful insights into NO regulatory enzymes such as isoform 1 of dimethylarginine dimethylaminohydrolase (DDAH1) and arginase. We investigated the role of arginine metabolomics in schizophrenia by conducting a systematic review and meta-analysis of the circulating concentrations of arginine metabolites associated with DDAH1, arginase, and NO synthesis [arginine, citrulline, asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), dimethylamine, and ornithine] in this patient group. We searched PubMed, Scopus, and Web of Science from inception to the 31st of May 2023 for studies investigating arginine metabolites in patients with schizophrenia and healthy controls. The JBI Critical Appraisal Checklist for analytical studies and GRADE were used to assess the risk of bias and the certainty of evidence, respectively (PROSPERO registration number: CRD42023433000). Twenty-one studies were identified for analysis. There were no significant between-group differences in arginine, citrulline, and SDMA. By contrast, patients with schizophrenia had significantly higher ADMA (DDAH1 substrate, standard mean difference, SMD = 1.23, 95% CI 0.86–1.61, p

Abstract Background Trabectedin (Tbt) is an alkylating agent prescribed for soft tissue sarcomas after treatment failure of first line agents. While cardiomyopathy can occur with Tbt treatment after anthracycline exposure, Tbt-induced fulminant myocardial cytotoxic injury in the setting of other systemic cytotoxicity associated with Tbt has not been reported. Case presentation 51-year-old female with hypertension, hyperlipidemia, metastatic leiomyosarcoma with progression of disease despite several lines of chemotherapy including doxorubicin-based therapy was started on Trabectedin (Tbt) 5 days prior to presentation with symptoms of fever, myalgias, arthralgias, and palpitations. She was admitted for management of rhabdomyolysis, acute kidney and liver injuries which were reportedly known to be associated with Tbt treatment. A baseline electrocardiogram (ECG) revealed sinus tachycardia with non-specific T-wave changes, and a transthoracic echocardiogram (TTE) was unremarkable. However, on day 3 of hospitalization, an episode of asymptomatic sustained monomorphic ventricular tachycardia with a heart rate of 150 beats per minute was captured on telemetry. A 12-lead ECG revealed new septal T-wave inversions. Labs revealed rising hs-TnI levels (peak at 37,933ng/L) and serum markers suggested multi-organ failure. Steroids were initiated given its role in treating multi-organ Tbt-induced toxicity. A cardiac MRI to rule out myocarditis and left heart catheterization to rule out obstructive coronary artery disease were forgone due to acute renal failure. A right heart catheterization with an endomyocardial biopsy was performed revealing normal cardiac filling pressures and indices. Pathology showed cytoplasmic vacuoles indicating drug-induced myocardial cytotoxicity. Serial echocardiograms revealed preserved biventricular function. The patient’s clinical condition deteriorated with multi-organ failure despite maximal supportive care in the intensive care unit. She ultimately passed away, and an autopsy was declined. Conclusion This is the first reported case of fulminant myocardial injury after initiation of Tbt with histologic evidence of drug-induced myocardial cytotoxicity. While it is unclear if anthracyclines potentiate Tbt cytotoxic injury as in this case, it is plausible; and that Tbt-induced cardiotoxicity ranges from subclinical to fulminant. Given increasing use of Tbt in refractory high-grade sarcomas, raising awareness of its toxicity profile will improve early detection and outcomes.

Abstract MP0250 is a designed ankyrin repeat protein that specifically inhibits both vascular endothelial growth factor A (VEGF‐A) and hepatocyte growth factor (HGF), aiming at potentiating cancer therapy by disrupting the tumour microenvironment. Encouraging results from a phase 1 trial of MP0250 in patients with solid tumours prompted further investigation in multiple myeloma (MM) as both MP0250 targets are reported to be drivers of MM pathogenesis. In this open‐label, single‐arm phase 1b/2 study (NCT03136653) in patients with proteasome inhibitor‐ and/or immunomodulatory drug‐relapsed or refractory MM, MP0250 was administered every 3 weeks with standard bortezomib/dexamethasone regimen. Thirty‐three patients received at least one dose of MP0250. The most frequent treatment‐related adverse events were arterial hypertension (58.1%), thrombocytopenia (32.3%), proteinuria (29.0%) and peripheral oedema (19.4%). Of the 28 patients evaluable for response (median age: 60 [range 44–75]), nine achieved at least partial response, corresponding to an overall response rate of 32.1% (95% confidence interval [CI]: 17.9%, 50.7%), with a median duration of response of 8 months (95% CI 5–NR). An additional three patients achieved minimal response and nine stable diseases as the best overall response. Overall median progression‐free survival was 4.2 months (95% CI 1.9–7.1). These findings are in line with the results of recent trials testing new agents on comparable patient cohorts and provide initial evidence of clinical benefit for patients with refractory/relapsed MM treated with MP0250 in combination with bortezomib/dexamethasone. Further clinical evaluation in the emerging MM treatment landscape would be required to confirm the clinical potential of MP0250.

Abstract The seismic‐electromagnetic phenomenon entails the generation of transient electromagnetic signals, which can be observed both simultaneously (co‐seismic) and preceding (pre‐seismic) a seismic wave arrival. Following the most accredited hypothesis, these signals are mainly due to electrokinetic effects, generated on microscopic scale in porous media containing electrolytic fluids. Thus, the seismic‐electromagnetic signals are expected to be suitable for the detection and tracking of crustal fluids. Despite the growing interest in this phenomenon, there is a lack of freely available observational database of earthquake‐related electromagnetic signals recorded at co‐located seismic and magnetotelluric stations. To fill this gap, we set up two multicomponent monitoring stations in two seismically active areas of Southern Italy: the Gargano Promontory and the High Agri Valley. This work is both aimed to systematically analyse earthquake‐generated seismic‐electromagnetic recordings and to make the collected database accessible to the scientific community.

Abstract While the life expectancy of older people has increased significantly, this is often related to more long-term care in healthcare residences and nursing homes. Staying in these facilities can lead to a reduction in the sense of connection with others and the world around, as well as in vigor, with significant psychophysical repercussions in the long term. Although previous studies have shown that the virtual nature can benefit both, there are no significant studies that have tested its effect in generating these positive outcomes in the older population. Therefore, our study sought to investigate, in a sample of 53 older people in care at a nursing home or healthcare residence, the indirect effect of a 3D built virtual arctic environment (vs. a 3D built virtual urban environment) exposure in virtual reality on vigor through connectedness. Both the virtual scenarios were designed with a first-person view, with no translation around the environment and only in-situ rotation. Results highlighted that exposure to the 3D built virtual arctic environment leads to higher connectedness than the 3D built virtual urban environment, and this, in turn, leads to an increase in vigor. Findings were discussed based on the potential of adopting virtual nature in facilities to improve older people’s sense of connectedness and, in turn, improve their well-being.

Abstract Background Resilience is an essential psychological trait that empowers individuals to adapt and thrive in the face of challenges. Although it is acknowledged that health professionals need to possess high levels of resilience, there has been limited research comparing how different groups of health students, particularly school leaver undergraduates and mature age graduate entry students, develop resilience in their coursework. Methods This study combines both objective (academic grades with validated survey results) and subjective data (interviews) to compare how resilience is related to academic coursework performance for two groups of pharmacy students: the mature age graduate entry (GE, N = 64) learners and school leaver undergraduate (UG, N = 208) learners. We employed a sequential explanatory mixed methods design using surveys, academic performance data and semi-structured interviews. The survey tapped constructs related to resilience (burnout, stressors and coping methods) while the interviews elicited a more nuanced understanding of individual and environmental factors. Results Although there was no statistical difference in burnout experience between the two groups, GE students exhibited more positive resilience attitudes than UG when selecting resilience statements on the survey. Both cohorts indicated in the survey that engaging in distraction activities (physical exercise, sleeping, listening to music, anything other than the stressor) was their most preferred method of relieving stress. Within UG student survey responses, those who indicated support from partners, friends and family had better academic performance, while those who did not report coping methods did worse academically. The three key environmental factors we identified that contributed to both undergraduate and graduate entry resilience were workload, feedback provision and psychosocial support. Conclusions Currently, there is still a need for resilience programs geared at academic success to be implemented in higher education. This study provides objective evidence of academic success coupled with exploration into the nuances of resilience amongst different student groups. It not only highlights the differing resilience development strategies and burnout coping mechanisms in emerging health professionals, but showcases the juxtaposition of two different learner groups (UG and GE students) within a discipline. The cross-cohort facilitation of learning as in the discipline-specific strategies identified can help both groups develop resilience and inform future innovations. By comparing mature-age graduate students and younger-in-age undergraduate students, we identified a wider range of strategies and more positive attitudes to burnout in mature-age students. Health and clinical educators in university health degrees, clinical placements and clinical workplaces can develop effective training materials based on findings from this study to 1) assist undergraduate younger-age health students with developing resilience and 2) further refine mature-age health students’ and practicing health professionals’ resilience in today’s fast-paced clinical workplaces.

Abstract Background Nutrient content and degree of processing are complementary but distinct concepts, and a growing body of evidence shows that ultra-processed foods (UPFs) can have detrimental health effects independently from nutrient content. 10 + countries currently mandate front-of-package labels (FOPL) to inform consumers when products are high in added sugars, saturated fat, and/or sodium. Public health advocates have been calling for the addition of ultra-processed warning labels to these FOPLs, but the extent to which consumers would understand and be influenced by such labels remains unknown. We examined whether the addition of ultra-processed warning labels to existing nutrient warning labels could influence consumers’ product perceptions and purchase intentions. Methods In 2023, a sample of adults in Brazil (n = 1,004) answered an open-ended question about the meaning of the term “ultra-processed,” followed by an online experiment where they saw four ultra-processed products carrying warning labels. Participants were randomly assigned to view either only nutrient warning labels or nutrient plus ultra-processed warning labels. Participants then answered questions about their intentions to purchase the products, product perceptions, and perceived label effectiveness. Results Most participants (69%) exhibited a moderate understanding of the term “ultra-processed” prior to the experiment. The addition of an ultra-processed warning label led to a higher share of participants who correctly identified the products as UPFs compared to nutrient warning labels alone (Cohen’s d = 0.16, p = 0.02). However, the addition of the ultra-processed warning label did not significantly influence purchase intentions, product healthfulness perceptions, or perceived label effectiveness compared to nutrient warning labels alone (all p > 0.05). In exploratory analyses, demographic characteristics and prior understanding of the concept of UPF did not moderate the effect of ultra-processed warning labels. Conclusions Ultra-processed warning labels may help consumers better identify UPFs, although they do not seem to influence behavioral intentions and product perceptions beyond the influence already exerted by nutrient warning labels. Future research should examine how ultra-processed warning labels would work for products that do and do not require nutrient warnings, as well as examine the benefits of labeling approaches that signal the health effects of UPFs. Trial registration ClinicalTrials.gov, NCT05842460. Prospectively registered March 15th, 2023.

Abstract Objective Epileptic seizures occurring in late adulthood often remain of unknown origin. Sporadic cerebral amyloid angiopathy (CAA) is a cerebral small vessel disease characterized by intracerebral hemorrhage, microhemorrhage and superficial siderosis, occurring mostly in elderly. This observational case–control study aimed to assess the occurrence of CAA in patients experiencing their first seizure in late adulthood. Methods We enrolled consecutive patients aged ≥55 years presenting with late‐onset seizures (LOS) to the emergency departments or outpatient clinics of two Italian centers, from April 2021 to October 2022. Two age‐matched control subjects with neurological symptoms other than epileptic seizure were recruited for each enrolled case. All participants underwent brain MRI (1.5 Tesla) including blood‐sensitive sequences and were assessed for probable CAA diagnosis according to Boston criteria 2.0. Chi‐squared test was performed to evaluate group differences. Univariate logistic regression analysis tested the association between clinical variables and CAA. Results We included 65 patients with LOS (27 females; mean age 72.2 ± 8.9 years) and 130 controls (49 females; mean age 70.3 ± 8.9 years). Diagnosis of probable CAA was achieved in 10.8% (7/65) of LOS patients and 2.3% (3/130) controls, with a statistically significant difference (p = 0.011). The OR for CAA in the LOS group was 5.2 as compared to the control group (95% CI = 1.3–20.6, p = 0.02). Significance The frequency of CAA is significatively higher in patients with LOS as compared to other neurological diseases, suggesting that a portion of LOS of unknown or vascular origin are associated with CAA. Plain Language Summary Late‐onset seizures (LOS) are very frequent in the elderly and often have no clear cause. Cerebral amyloid angiopathy (CAA) is a condition where amyloid proteins build up in the blood vessels of the brain, causing them to become weak and prone to bleeding. In this study, we explored the occurrence of CAA in people with LOS. We found that people with LOS were more likely to have a diagnosis of CAA than controls (i.e., people with other neurological diseases).

Abstract Background The EAT-Lancet diet is a diet aimed at promoting population and planetary health from the perspective of sustainable diets in terms of environmental and health aspects. This study aimed to assess the association between adherence to the EAT-Lancet diet and cardiometabolic risk factors among adults and elderly individuals in a capital city in the northeastern region of Brazil. Methods This is an analytical cross-sectional observational study from a population-based sample conducted between 2019 and 2020, involving 398 non-institutionalized adults and elderly people, of both sexes from “Brazilian Usual Consumption Assessment” study (Brazuca-Natal). There was a 38% response rate due to the suspension of data collection due to the covid-19 pandemic, but According to the comparative analysis of socioeconomic and demographic variables between the surveyed and non-surveyed sectors, losses were found to be random (p = 0.135, Little’s MCAR test). Socioeconomic and lifestyle data, anthropometric measurements, and dietary consumption were collected. We used the Planetary Health Diet Index (PHDI) and the Cardiovascular Health Diet Index (CHDI) for cardiovascular health to assess adherence to the diet’s sustainability. The evaluated cardiometabolic parameters included fasting blood glucose, triglycerides, total cholesterol, HDL-C, LDL-C, and systolic and diastolic blood pressure measurements. We also assessed the presence of type 2 diabetes mellitus, arterial hypertension, and dyslipidemia. For the data analyses, sample weights and the effect of the study design were taken into account. Pearson’s chi-square test was used to evaluate the statistical significance of frequencies. Multiple linear regression models assessed the associations between PHDI and CHDI and its components and the cardiometabolic parameters. Results The mean PHDI was 29.4 (95% CI 28.04:30.81), on a total score ranging from 0 to 150 points and the mean CHDI was 32.63 (95% CI 31.50:33.78), on a total score ranging from 0 to 110 points. PHDI showed a significant positive association with the final CHDI score and components of fruits, vegetables, and legumes, and a negative association with Ultra-processed Food (UPF) (p

Abstract Wetland ecosystems are vital for both biodiversity and communities that depend on them. The Ligawasan Marsh in the southern part of the Philippines is one of the most threatened wetlands in the country. Apart from increasing anthropogenic development, wetlands have faced warfare-driven threats that have hindered research and conservation efforts in the area for many decades. Our study is the first to investigate the patterns of physicochemical parameters, patterns of land use cover, and the relationship between land use change and marshland environmental status. We also developed the Marshland Impact Area (MARia) index to assess the potential impact contributions of the surrounding towns. We found a strong negative correlation between dissolved oxygen (DO) and indicators of pollution such as biochemical oxygen demand (BOD), chemical oxygen demand (COD), and heavy metals. Interestingly, we observed elevated levels of phosphate and mercury at all sampling sites in the Ligawasan Marsh. Our landscape-level modelling showed that these elevated levels are associated with expanding croplands and urbanisation surrounding the marsh. We found that the potential impact contribution of cropland and urbanisation from surrounding towns of the Ligawasan Marsh varied significantly, suggesting the importance of implementing local policies to reduce land use change impacts. With the current yet remaims limited knowledge and beyond safe pollution levels in the Ligawasan Marsh, it is crucial to implement collaborative and science-based governance to integrate conservation initiatives with the priorities of global targets, such as the Kunming-Montreal Global Biodiversity Framework, for a comprehensive and sustainable approach to Ligawasan Marsh conservation.

Abstract We describe the geographical variation in tree species composition across Amazonian forests and show how environmental conditions are associated with species turnover. Our analyses are based on 2023 forest inventory plots (1 ha) that provide abundance data for a total of 5188 tree species. Within-plot species composition reflected both local environmental conditions (especially soil nutrients and hydrology) and geographical regions. A broader-scale view of species turnover was obtained by interpolating the relative tree species abundances over Amazonia into 47,441 0.1-degree grid cells. Two main dimensions of spatial change in tree species composition were identified. The first was a gradient between western Amazonia at the Andean forelands (with young geology and relatively nutrient-rich soils) and central–eastern Amazonia associated with the Guiana and Brazilian Shields (with more ancient geology and poor soils). The second gradient was between the wet forests of the northwest and the drier forests in southern Amazonia. Isolines linking cells of similar composition crossed major Amazonian rivers, suggesting that tree species distributions are not limited by rivers. Even though some areas of relatively sharp species turnover were identified, mostly the tree species composition changed gradually over large extents, which does not support delimiting clear discrete biogeographic regions within Amazonia.

Abstract Background Substantial variability in response to lifestyle interventions has been recognized for many years, and researchers have begun to disentangle sources of error from inherent differences in individual responsiveness. The objective of this secondary analysis of an intensive lifestyle intervention (diet and exercise) for metabolic syndrome (MetS) was to identify potentially important differences among study completers grouped by treatment response as measured by change in a continuous metabolic syndrome score (Gurka/MetS). Methods All study completers from a 12-month primary care study were categorized into one of five groups according to change in the Gurka/MetS score. A change of 0.4 in z-score defined clinically relevant change in line with results of previous studies. Repeated measures analysis of variance was used to examine cardiovascular disease risk and individual clinical indicators of MetS over 12 months, looking for differences in response over time by the five groups. Results Of 176 participants, 50% (n = 88) had stable scores, 10% (n = 18) had relevant change scores in the first 3 months only and reverted toward baseline, 20% (n = 35) achieved meaningful change over the whole study, 11% (n = 20) had a delayed response at 3–12 months, and 9% (n = 15) demonstrated worsening scores. Significant differential patterns were noted for groups over the duration of the intervention (p

Purpose: Non-obstructive azoospermia (NOA) represents the persistent absence of sperm in ejaculate without obstruction, stemming from diverse disease processes. This survey explores global practices in NOA diagnosis, comparing them with guidelines and offering expert recommendations. Materials and Methods:Materials and Methods: A 56-item questionnaire survey on NOA diagnosis and management was conducted globally from July to September 2022. This paper focuses on part 1, evaluating NOA diagnosis. Data from 367 participants across 49 coun-tries were analyzed descriptively, with a Delphi process used for expert recommendations. Results:Results: Of 336 eligible responses, most participants were experienced attending physicians (70.93%). To diagnose azoosper-mia definitively, 81.7% requested two semen samples. Commonly ordered hormone tests included serum follicle-stimulating hormone (FSH) (97.0%), total testosterone (92.9%), and luteinizing hormone (86.9%). Genetic testing was requested by 66.6%, with karyotype analysis (86.2%) and Y chromosome microdeletions (88.3%) prevalent. Diagnostic testicular biopsy, distinguishing obstructive azoospermia (OA) from NOA, was not performed by 45.1%, while 34.6% did it selectively. Differ-entiation relied on physical examination (76.1%), serum hormone profiles (69.6%), and semen tests (68.1%). Expectations of finding sperm surgically were higher in men with normal FSH, larger testes, and a history of sperm in ejaculate. Conclusions:Conclusions: This expert survey, encompassing 367 participants from 49 countries, unveils congruence with recommended guidelines in NOA diagnosis. However, noteworthy disparities in practices suggest a need for evidence-based, international consensus guidelines to standardize NOA evaluation, addressing existing gaps in professional recommendations.

Abstract Aims The use of loop diuretics in pulmonary arterial hypertension (PAH) is less frequent compared with heart failure. The clinical and prognostic characteristics of PAH patients according to loop diuretic use remain unexplored. In this study, we retrospectively analysed the characteristics and survival of PAH patients requiring different doses of loop diuretics. Methods and results Patients diagnosed with PAH between 2001 and 2022 at seven European centres for the management of PAH. According to the median equivalent dose of furosemide in the overall cohort, patients were divided into two subgroups: no/low‐dose loop diuretic and high‐dose loop diuretic. Primary outcome was 5 year all‐cause mortality. Among the 397 patients included, 227 (57%) were treated with loop diuretics. Median daily furosemide equivalent dose was 25 mg, and accordingly patients were divided in no/low dose (i.e. ≤25 mg, n = 257, 65%) vs. high dose (i.e. >25 mg, n = 140, 35%). Patients in the high‐dose group were older, more likely to have comorbidities, and had a more severe disease according to the ESC/ERS risk category. Crude 5 year survival was significantly shorter in patients in the high‐dose group, but after adjustment for age, sex, and risk category, high loop diuretic dose was not significantly associated with the primary outcome. Conclusions Use of high dose of loop diuretics in PAH is associated with a higher burden of comorbidities, more severe disease, and worse survival. However, in PAH, the need of high loop diuretic dose is a marker of disease severity and not an independent prognostic factor.

Abstract Aims Technological advances and the current shortage of donor organs have contributed to an increase in the number of left ventricular assist device (LVAD) implantations in patients with end‐stage heart failure. Demographic change and medical progress might raise the number of these patients, resulting in a further increase in the number of LVAD implantations. The aim of this study was to evaluate the long‐term costs of LVAD therapy and identify diagnoses resulting in expensive stays. Methods and results In this retrospective analysis of prospectively collected data, all patients after implantation of a second‐ or third‐generation LVAD by 31 March 2022 were included. In addition to demographic and survival data, revenues and case mix points were determined for each patient. Of the 163 patients included, 75.5% were male. The mean age at LVAD implantation was 52 ± 14 years. The mean survival was 1458 ± 127 days. During follow‐up, the total inpatient treatment time per patient was 70 ± 87 days. The average duration of outpatient treatment was 55.1%, based on the total duration of support. The average revenue per patient for the implant stay was $193 192.35 ± $111 801.29, for inpatient readmissions $52 068.96 ± $116 630.00, and for outpatient care $53 195.94 ± $62 363.53. Conclusions LVAD implantation in patients with end‐stage heart failure leads to improved survival but a significant increase in treatment costs. Further multi‐centre studies are necessary in order to be able to assess the effects of long‐term LVAD treatment on the healthcare system.

Osteopoikilosis, a sclerosing bone dysplasia, is an asymptomatic incidental finding characterised by multiple bone islands. Although it requires no treatment there can be diagnostic uncertainty as appearances can be similar to osteoblastic metastases or metabolic disorders such as Paget disease. We present a case of osteopoikilosis in a patient with familial adenopolyposis and discuss the clinical presentation, image findings and key considerations in diagnosis of this benign entity.

Spontaneous osteonecrosis of the knee (SONK) is a poorly understood but debilitating disease, that is a common cause of unilateral acute knee pain and swelling. The term “SONK” has been replaced by the term “subchondral insufficiency fracture” in the latest pathology and imaging literature. Few studies investigated the pathogenesis of SONK by examining the histological changes of the tissues. Very recently, the development of SONK was associated with a meniscal root tear. In terms of the preferred imaging, plain radiographs can confirm the diagnosis in late stages; however, magnetic resonance imaging (MRI) scan is often required. Regarding the treatment, conservative management is usually the treatment of choice in early stages, including a period of non-weightbearing or the use of medications, such as nonsteroidal anti-inflammatory drug (NSAIDS) or bisphosphonates. However, when SONK progresses, often a surgical intervention is required, such as knee replacement, but also minimally invasive techniques, such as arthroscopic intervention, have been described. We present a case of early SONK and discuss the possible pathogenesis of SONK, the clinical presentation, the radiological findings, and we focus on the importance of early diagnosis and early off-load period that is required to prevent further progression of the disease.

Abstract Psoriasis is a chronic, immune-mediated, inflammatory skin disease, associated with multiple comorbidities and psychological and psychiatric disorders. The quality of life of patients with this disease is severely compromised, especially in moderate-to-severe plaque psoriasis. Secukinumab, a fully humanized monoclonal antibody, was the first anti-interleukin (IL)-17 biologic approved for treating psoriasis. Secukinumab demonstrated long-lasting efficacy and a good safety profile in individuals with plaque psoriasis, and it is associated with an improvement in health-related quality of life. While there is evidence that early treatment with systemic therapy can affect disease progression and improve long-term outcomes in other autoimmune diseases, evidence is limited in psoriasis, especially in real-world settings. This review provides an overview of studies describing the effectiveness of secukinumab in the treatment of psoriasis summarizing the literature and focusing on real-world evidence and early intervention.

Embodiment (the sensation that arises when the properties of an external instrument are processed as if they are the attributes of one's own biological body) and (tele)presence (the sensation of being fully engaged and immersed in a location other than the physical space occupied by one's body) sustain the perception of the physical self and potentially improve performance in teleoperations (a system that enables human intelligence to control robots and requires implementing an effective human-machine interface). Embodiment and presence may be interdependent and influenced by right temporo-parietal junction (rTPJ) activity. We investigated the interplay between embodiment, (tele)presence, and performance in teleoperation, focusing on the role of the rTPJ. Participants underwent a virtual reality task with transcranial direct current stimulation (tDCS) twice, receiving either active or sham stimulation. Behavioral measures (driving inaccuracy, elapsed time in the lap, time spent in attentional lapses, short-term self-similarity, and long-term self-similarity), perceived workload (mental demand, physical demand, temporal demand, own performance, effort, and frustration), embodiment's components (ownership, agency, tactile sensations, location, and external appearance), and presence's components (realism, possibility to act, quality of interface, possibility to examine, self-evaluation of performance, haptic, and sounds) were assessed. The results showed that rTPJ stimulation decreased perceived ownership but enhanced presence with changes in the complexity of visuomotor adjustments (long and short-term self-similarity indices). Structural equation modeling revealed that embodiment increased visuomotor inaccuracy (a composite variable of overall performance, including deviations from the optimal trajectory and the time taken to complete the task), presence reduced workload, and workload increased inaccuracy. These results suggested a dissociation between embodiment and presence, with embodiment hindering performance. Prioritizing virtual integration may lower human performance, while reduced workload from presence could aid engagement. These findings emphasize the intricate interplay between rTPJ, subjective experiences, and performance in teleoperation.

Introduction. Determination of strength and deformation characteristics of soils composing the soil mass is the key process of calculation and design of structures of all types. High accuracy in determining mechanical characteristics plays a huge role at every stage of project development. Triaxial compression units are one of the most popular and widely used devices for laboratory research, as this type of testing allows you to reproduce the stress-strain state of the soil mass and determine its mechanical characteristics most accurately.Materials and methods. Experimental studies were performed on clay soil specimens (sandy loam, loam, clay) in a triaxial compression device in a consolidated-drained mode in order to study the effect of the coefficient of non-uniformity of expansion of the soil specimen on its mechanical properties.Results. Analyzing the data of experimental studies, it was found that the coefficient of non-uniformity of expansion of specimen b has a significant effect on the obtained values of the mechanical characteristics of clay soil, namely: the values of the angle of internal friction in the medium increased by 5 %; the values of specific adhesion increased by 4.4 % on average. However, it should be noted that despite the increase in the strength characteristics of the tested soil specimens, the exclusion of the coefficient b from the treatment process led to a decrease in the values of the secant deformation modulus at 50 % strength E50 by an average of 4.5 %.Conclusions. The obtained overestimated values of strength characteristics φ, c and underestimated values of deformation characteristics E50 are not critical, however, to increase the accuracy of calculations performed based on the results obtained as a result of in-house processing of laboratory test specimens, the coefficient of uneven expansion b of the specimen should be taken into account.

In this study, Batem Pınarı, Interdonato, Meyer, and Ak Limon lemon cultivars were studied. Lemon peel's essential oils were obtained by two different methods (hydrodistillation and cold pressing) during four different harvest periods for each cultivar. Essential oil content, density, refractive index, optical activity, and composition were evaluated. The highest essential oil amount was found in the Interdonato cultivar (2.54%) and the lowest in Ak Limon (1.37%). The highest density value was 0.8471 g/mL (Ak Limon) and the lowest was 0.8423 g/mL (Meyer). Essential oil densities obtained by cold pressing were higher than those obtained by hydrodistillation. The highest refractive index values were determined for Batem Pınarı and Meyer (1.4747), and the lowest were determined for Ak Limon (1.4740). The refractive index values obtained by cold pressing were higher than those obtained by hydrodistillation. Optical activity values were found to be highest in Ak Limon and lowest in Batem Pınarı, and higher following hydrodistillation than cold pressing. The essential oil compositions of the samples showed significant differences depending on the cultivar and isolation method. Limonene, the highest component proportionally, composed 76.0%–89.0% of samples. The highest limonene content was determined for Ak Limon (88.7%), and the lowest for Batem Pınarı (76.7%). Limonene content did not change significantly between hydrodistillation (82.2%) and cold press (82.2%) isolation methods. Findings show that there is significant variation in quality parameters of lemon peel essential oils.

Hyaluronic acid (HA) is a major component of the extracellular matrix, providing essential mechanical scaffolding for cells and, at the same time, mediating essential biochemical signals required for tissue homeostasis. Many solid tumors are characterized by dysregulated HA metabolism, resulting in increased HA levels in cancer tissues. HA interacts with several cell surface receptors, such as cluster of differentiation 44 and receptor for hyaluronan‐mediated motility, thus co‐regulating important signaling pathways in cancer development and progression. In this review, we describe the enzymes controlling HA metabolism and its intracellular effectors emphasizing their impact on cancer chemotherapy resistance. We will also explore the current and future prospects of HA‐based therapy, highlighting the opportunities and challenges in the field.

Abstract People with type 2 diabetes mellitus (T2DM) show a high prevalence of steatotic liver disease (SLD), and especially metabolic dysfunction-associated steatotic liver disease (MASLD), with liver fibrosis. Their health-related quality of life (HRQL) is affected by multiple in part overlapping factors and aggravated by metabolic and liver-related comorbidities, including liver fibrosis stage. The aim of this study was to investigate the effect size of advanced fibrosis (AF) on the HRQL in people with T2DM. A total of 149 individuals with T2DM treated at a primary care provider within the German disease management program (DMP) were included in the final analysis. Vibration-controlled transient elastography (VCTE) was used to non-invasively detect steatosis and AF. The EQ-5D-3L questionnaire was used to assess the HRQL. Uni- and multivariable linear regression models were used to identify independent predictors of impaired HRQL. The majority was male (63.1%), and the median age was 67 years (IQR 59; 71). In the entire cohort, the prevalence of MASLD and AF was 70.7% and 19.5%, respectively. People with T2DM and AF had an overall lower HRQL in comparison to those without AF (p

Abstract Medication poisoning, resulting from the ingestion of cardiotoxic drugs, presents a significant health issue. The mortality rate remains high for patients with myocardial dysfunction refractory to conventional treatments. Venoarterial Extracorporeal Membrane Oxygenation (V-A ECMO) provides temporary support, potentially enhancing patient outcomes. This study aims to assess the efficacy of V-A ECMO in treating cardiovascular failure induced by cardiovascular medication poisoning. We utilized inpatient data from all hospitalisations in Germany from 2007 to 2022 due to cardiovascular medication poisoning treated with V-A ECMO. Patient characteristics, comorbidities, complications and application of ECMO were described descriptively and analysed for statistical significance between survivors and non-survivors. Overall, 49 patients received V-A ECMO for cardiovascular medication poisoning, with a survival rate of 63.6%. The most ingested medications were calcium-channel blockers (38.8%) and beta-adrenoceptor antagonists (34.7%). Half of non-survivors received in-hospital CPR, compared to 12.9% of survivors. Early ECMO implantation (within 24 h of admission) was common (83.7%) but did not significantly impact survival rates. A substantial number of patients presented with multiple substances ingested. V-A ECMO represents a viable option for patients experiencing cardiac failure due to medication poisoning. A structured implementation of V-A ECMO for cardiovascular medication poisoning could lead to higher survival rates.

Abstract Background Systematic reviews (SRs) are time-consuming and labor-intensive to perform. With the growing number of scientific publications, the SR development process becomes even more laborious. This is problematic because timely SR evidence is essential for decision-making in evidence-based healthcare and policymaking. Numerous methods and tools that accelerate SR development have recently emerged. To date, no scoping review has been conducted to provide a comprehensive summary of methods and ready-to-use tools to improve efficiency in SR production. Objective To present an overview of primary studies that evaluated the use of ready-to-use applications of tools or review methods to improve efficiency in the review process. Methods We conducted a scoping review. An information specialist performed a systematic literature search in four databases, supplemented with citation-based and grey literature searching. We included studies reporting the performance of methods and ready-to-use tools for improving efficiency when producing or updating a SR in the health field. We performed dual, independent title and abstract screening, full-text selection, and data extraction. The results were analyzed descriptively and presented narratively. Results We included 103 studies: 51 studies reported on methods, 54 studies on tools, and 2 studies reported on both methods and tools to make SR production more efficient. A total of 72 studies evaluated the validity (n = 69) or usability (n = 3) of one method (n = 33) or tool (n = 39), and 31 studies performed comparative analyses of different methods (n = 15) or tools (n = 16). 20 studies conducted prospective evaluations in real-time workflows. Most studies evaluated methods or tools that aimed at screening titles and abstracts (n = 42) and literature searching (n = 24), while for other steps of the SR process, only a few studies were found. Regarding the outcomes included, most studies reported on validity outcomes (n = 84), while outcomes such as impact on results (n = 23), time-saving (n = 24), usability (n = 13), and cost-saving (n = 3) were less often evaluated. Conclusion For title and abstract screening and literature searching, various evaluated methods and tools are available that aim at improving the efficiency of SR production. However, only few studies have addressed the influence of these methods and tools in real-world workflows. Few studies exist that evaluate methods or tools supporting the remaining tasks. Additionally, while validity outcomes are frequently reported, there is a lack of evaluation regarding other outcomes.

Introduction: Caring for the dying can generate anxiety and emotional distress, particularly in nursing students, and perceived competence could play a crucial role in enabling nurses to perform their duties with greater confidence. Unfortunately, few studies describe the relationship between students’ nursing attitudes and perceived self-efficacy in palliative care (PC). To overcome this gap, this survey aimed to assess the attitudes towards dying patients and the perceived competence of nursing students in palliative care at different universities in the south of Italy. Methods: A cross-sectional study was conducted from September 2022 to March 2023 involving nursing students from the three major Sicilian universities (Italy). The study included a survey investigating socio-demographic characteristics, palliative care training, knowledge about pain management, and previous experience with dying. Moreover, the Professional Competence of the Core Curriculum in Palliative Care Nursing (CCPCN) questionnaire and the Frommelt Attitudes Toward Care of the Dying—B Italian version (FATCOD-B-I) assessed competencies and emotional attitudes. Results: A total of 1913 nursing students were recruited, of which 71.3% were females, and 53.9% were in the age range of 18 to 21 years. In the multivariable analysis, practical PC training was a substantial factor in enhancing competencies (Adj-OR 2.78 [95% CI = 2.12–3.65]). Male students had higher competence odds (Adj-OR 1.38 [95% CI = 1.14–1.66]), and perceived knowledge strongly correlated with self-assessed competence. Advancement in academic years also positively influenced competence self-assessment (Adj-OR 1.98 [95% CI = 1.75–2.24]). Regarding emotional attitudes, a per-quartile increase in competence score was found to improve the attitude score (Adj-OR 1.24 [95% CI = 1.13–1.35]). Conclusions: Nursing students gain valuable experience during clinical experience. PC training and perceived knowledge of PC significantly increase nurses’ competencies, and the latter seem to be strongly associated with attitudes. Thus, introducing palliative care education into nurses’ core curricula could be a way to reduce anxiety and emotional distress in young students.

Abstract Single-cell omics technologies that profile genes (genomic and epigenomic) and determine the abundance of mRNA (transcriptomic), protein (proteomic and secretomic), lipids (lipidomic), and extracellular matrix (matrisomic) support the dissection of adipose tissue heterogeneity at unprecedented resolution in a temporally and spatially defined manner. In particular, cell omics technologies may provide innovative biomarkers for the identification of rare specific progenitor cell subpopulations, assess transcriptional and proteomic changes affecting cell proliferation and immunomodulatory potential, and accurately define the lineage hierarchy and differentiation status of progenitor cells. Unraveling adipose tissue complexity may also provide for the precise assessment of a dysfunctional state, which has been associated with cancer, as cancer-associated adipocytes play an important role in shaping the tumor microenvironment supporting tumor progression and metastasis, obesity, metabolic syndrome, and type 2 diabetes mellitus. The information collected by single-cell omics has relevant implications for regenerative medicine because adipose tissue is an accessible source of multipotent cells; alternative cell-free approaches, including the use of adipose tissue stromal cell-conditioned medium, extracellular vesicles, or decellularized extracellular matrix, are clinically valid options. Subcutaneous white adipose tissue, which is generally harvested via liposuction, is highly heterogeneous because of intrinsic biological variability and extrinsic inconsistencies in the harvesting and processing procedures. The current limited understanding of adipose tissue heterogeneity impinges on the definition of quality standards appropriate for clinical translation, which requires consistency and uniformity of the administered product. We review the methods used for dissecting adipose tissue heterogeneity and provide an overview of advances in omics technology that may contribute to the exploration of heterogeneity and dynamics of adipose tissue at the single-cell level.

Abstract Vitamin D deficiency is an emerging public health problem globally, with devastating health consequences. Some studies suggest that exogenous sex hormones, found in hormonal contraceptives, may enhance vitamin D levels. However, the reasons for this association are not fully understood, as women using hormonal contraception may have different lifestyle habits affecting their vitamin D status. Therefore, this study seeks to explore the relationship between hormonal contraceptive use and vitamin D levels. A Facility based comparative cross-sectional study was conducted in Gondar town from February to April 2023, involving a total of 162 women using three types of hormonal contraceptives (Norplant, DMPA, and COC) and 162 age and BMI-matched non-users as controls in a 1:1 ratio. Participants were selected using systematic random sampling. A semi-structured questionnaire was used to collected data regarding the socio-demographic, economic, obstetric, lifestyle, and clinical information. 5 milliliters of blood samples were collected from each participant for Laboratory analysis of serum vitamin D, calcium, and alkaline phosphates using a Beckman Coulter chemistry analyzer. Independent t-tests, ANOVA with post hoc Bonferroni test was used to compare statistics between the two groups, and logistic regression models to identify factors associated with Vitamin D deficiency. The mean serum Vitamin D levels of Norplant, DMPA, and COC users were 24.08 (± 5.17), 24.83 (± 5.52), and 31.90 (± 6.94) respectively; whereas control group has mean Vitamin D level of 22.00 (± 7.97). On the current study the prevalence of Vitamin D deficiency (