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The Ionian Sea is a crucial intersection for various water masses in the Mediterranean. Its hydrography and dynamics play a significant role in the seawater budgets and biogeochemistry of the neighboring sub-basins. Multiple theories have been formulated to gain a better understanding of the Ionian dynamics. These theories primarily attribute the variability of the near-surface Ionian circulation to internal processes. Here, we utilize horizontal currents and temperature–salinity profiles from the Copernicus reanalysis to examine the contribution of baroclinic modes to the variability of the basin horizontal circulation. Our findings demonstrate that, although the basin vertical structure is characterized by three layers, the primary patterns of the Ionian circulation can be attributed to the first baroclinic mode. This mode, along with the barotropic mode, accounts for over 85% of the overall variability in the Ionian circulation, suggesting that only one of the three interfaces separating the different water masses in the basin is dynamically active. We estimate the depth of this interface to be about 490 m. Additionally, our analysis shows that more than 90% of the kinetic energy over the water column is localized above this interface, indicating that the deep layer of the Ionian is dynamically nearly inert.

Early support should help autistic children lead flourishing lives. We sought to understand parents' experiences of their children's involvement in early intervention and associated research, through focus groups with 23 parents (of 22 children) enrolled in a university-affiliated service. Reflexive thematic analysis revealed four themes. Parents conveyed a strong sense of gratitude (Theme 1) arising from their perceptions of the importance of early intervention and feelings of having 'hit the jackpot' to secure access to the service from which they perceived their children 'gained so much'. They valued the service and staff expertise which made them feel secure (Theme 2). University affiliation and the associated research also contributed to parents' sense of safety, from perceived 'accountability' and 'integrity'. Parents conveyed deep commitment to the service (Theme 3) but shared often-negative experiences as their child's enrolment came to an end (Theme 4) and they expressed feelings of abandonment and disempowerment, being confronted with the reality of needing to secure next-stage support for their children and of perceived critical need for 'conversion of research into practice'. These parents' accounts offer insights into the benefits and ongoing challenges of achieving truly effective supports for autistic preschoolers and their families.

Nevins W Todd,1,2 Rachel G Scheraga,1,3 Jeffrey R Galvin,1,4 Aldo T Iacono,1 E James Britt,1 Irina G Luzina,1,2 Allen P Burke,5,* Sergei P Atamas1,2,* 1Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA; 2Baltimore VA Medical Center, Baltimore, MD, USA; 3Critical Care Medicine Department, National Institutes of Health, Bethesda, MD, USA; 4Department of Diagnostic Radiology, University of Maryland School of Medicine, Baltimore, MD, USA; 5Department of Pathology, University of Maryland School of Medicine, Baltimore, MD, USA *These authors contributed equally to this work Background: Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease with no known effective therapy. It is often assumed, but has not been objectively evaluated, that pulmonary inflammation subsides as IPF progresses. The goal of this work was to assess changes in the degree of inflammatory cell infiltration, particularly lymphocytic infiltration, over the duration of illness in IPF. Methods: Sixteen patients with confirmed IPF were identified in patients whom surgical lung biopsy (SLB) was performed in early disease, and in patients whom lung transplantation was subsequently performed in end stage disease. A numerical scoring system was used to histologically quantify the amount of fibrosis, honeycomb change, fibroblastic foci, and lymphocyte aggregates in each SLB and lung explant tissue sample. Analyses of quantitative scores were performed by comparing paired, matched samples of SLB to lung explant tissue. Results: Median time [1st, 3rd quartiles] from SLB to lung transplantation was 24 [15, 29] months. Histologic fibrosis and honeycomb change were more pronounced in the explant samples compared with SLB (P < 0.001 and P < 0.01, respectively), and most notably, higher numbers of lymphocyte aggregates were observed in the explant samples compared to SLB (P = 0.013). Immunohistochemical analyses revealed abundant CD3+ (T lymphocyte) and CD20+ (B lymphocyte) cells, but not CD68+ (macrophage) cells, within the aggregates. Conclusion: Contrary to the frequent assumption, lymphocyte aggregates were present in greater numbers in advanced disease (explant tissue) compared to early disease (surgical lung biopsy). This finding suggests that active cellular inflammation continues in IPF even in severe end stage disease. Keywords: idiopathic pulmonary fibrosis, inflammation, lymphocyte aggregates

Summary: Thyroid carcinoma represents the first malignancy among the endocrine organs. Investigating the cellular hierarchy and the mechanisms underlying the initiation of thyroid carcinoma is crucial in thyroid cancer research. Here, we present a protocol for deriving thyroid cell lineage from human embryonic stem cells. We also describe steps for engineering thyroid progenitor cells utilizing CRISPR-Cas9 technology, which can be used to perform in vivo studies, thus facilitating the development of representative thyroid tumorigenesis models.For complete details on the use and execution of this protocol, please refer to Veschi et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Background: Medical students are at high risk for mental disorders, and the COVID-19 pandemic might have exacerbated psychological distress. However, no data are available for the southern part of Italy. The SMS-ME (Sicilian Medical Students’ MEntal health) project aimed to estimate the prevalence of and predictors of depression, anxiety, stress, and suicidal ideation in a sample of Sicilian medical students. Methods: A web-based cross-sectional survey was carried out from September 2022 to December 2022. The study protocol investigated sociodemographic factors and clinical data including Depression, Anxiety, Stress Scale-21 (DASS-21), and a specific question addressing suicidal ideation frequency over the last six months. Multivariate regression models were assessed to examine the association between symptoms and relevant predictors and then regressed their residuals with suicidal thought frequency. Result: We collected 1,866 records (age=22.5, SD=3.4; 65.2 % females). One out of four students presented highly severe depression (25 %) and referred to the presence of some suicidal ideation in the six months preceding the interview (26.1 %). DASS-21 scores, especially depression (F(5, 1,828)=58.8, p = 6.59–57), increasingly predicted the frequency of suicidal thoughts when above the sample's mean. Limitations: The cross-sectional study design does not allow inferences on temporal relationships and the self-report strategy could be intrinsically biased by the person's feelings at the time of the interview. Conclusions: High prevalence of anxiety and depressive symptoms and suicidal thoughts were observed among Sicilian medical students. The DASS-21 was a good predictor for suicidal ideation that Universities could use as a simple tool to assess the need for psychological healthcare in this population.

BackgroundThe use of Non-Pharmaceutical Interventions (NPIs) during the COVID-19 pandemic is debated. Understanding the consequences these measures may have on vulnerable populations including children and adolescents is important.MethodsThis is a multicenter, quasi-experimental before-after study involving 12 hospitals of the North Italian Emilia-Romagna Region, with NPI implementation as the intervention event. The 3 years preceding NPI implementation (in March 2020) constituted the pre-pandemic phase. The subsequent 2 years were further subdivided into a school closure phase (SC) and a subsequent mitigation measures phase (MM) with milder restrictions. Interrupted Time Series (ITS) regression analysis was used to calculate PED Standardized Incidence Rate Ratios (SIRR) on the diagnostic categories exhibiting the greatest frequency and/or variation.ResultsIn the 60 months of the study there were 765,215 PED visits. Compared to the pre-pandemic rate, overall PED presentations dropped by 58 and 39% during SC and MM, respectively. “Symptoms, signs and Ill-defined conditions,” “Injury and poisoning” and “Diseases of the Respiratory System” accounted for 74% of the reduction. A different pattern was instead seen for “Mental Disorders,” which exhibited the smallest decrease during SC, and is the only category which rose already at the end of SC. ITS analysis confirmed the strong decrease during SC (level change, IRR 0.17, 95%CI 0.12–0.27) and a significant increase in MM (slope change, IRR 1.23, 95%CI 1.13–1.33), with the sharpest decline (−94%) and rise (+36%) observed in the “Diseases of the Respiratory System” category. Mental Disorders showed a significant increasing trend of 1% monthly over the whole study period exceeding pre-pandemic levels at the end of MM. Females and adolescents showed higher increasing rates both in SC and MM.ConclusionNPIs appear to have influenced PED attendance in different ways according to diagnostic categories, mirroring different mechanisms of action. These effects are beneficial in some cases and harmful in others, and establishing a clear balance between pros and cons is a difficult task for public health decision makers. The role of NPIs on PED use appropriateness deserves investigation. The rise in pediatric mental disorders independent of the pandemic makes interventions addressing these issues urgent.

Abstract Non‐native species can affect ecosystems by influencing native predator‐prey dynamics. Therefore, management interventions designed to remove non‐natives may inadvertently lead to increased predation on native species. Feral horses are widely distributed throughout the arid parts of western North America. A growing body of research indicates that horses can be an important prey species to mountain lions in ecosystems where they overlap. In December 2020, the Bureau of Land Management removed 455 horses from the Delamar Mountains, Nevada, USA. We leveraged this management intervention to implement a before–after–control–impact study to test hypotheses about predation on horses and native ungulates. We predicted (1) that horses would comprise an important part of the diet in this mixed‐prey community, (2) following removal, the proportion of horses in the diet would decrease and native ungulates would increase, and (3) mountain lion home ranges overlapping the treatment areas would increase in response to decreased prey availability. From 2018 to 2022, we investigated 1360 clusters from 29 GPS‐collared lions and identified 1056 prey items. To model the probability of a predation event (a kill), we fit a mixed‐effects logistic regression model for ungulate prey as a function of lion sex, treatment area (in/out), and treatment period (pre‐/post‐removal). We used a log‐linear regression model to evaluate changes in home range size. The most common prey were mule deer (55%), feral horses (32%), and coyotes (4%). Twenty‐two of 29 lions consumed horses, although the rate of horse consumption was highly variable across individuals. Horses of both sexes and all age classes were predated. In contrast to predictions, our models detected no effect of removals on diet composition (βinteraction = 0.30 ± 1.1), nor did the removal influence home range size (βinteraction = 0.02 ± 0.02). Despite a 46% reduction in horse abundance, we found no evidence for prey‐switching following the horse removal treatment. Removal magnitude, rapid horse immigration, and/or behavioral specialization of individual mountain lions may help explain these results. Our findings have important implications for mountain lion and feral horse management in arid environments characterized by high prey diversity, but low prey abundance.

Purpose: To examine the sex differences in performance and perceived fatigue during resistance training prescribed using traditional (TRA) and autoregulation rest-redistribution training (ARRT) approaches. Methods: Twelve resistance-trained men and 12 women completed 2 sessions including the bench-press exercise matched for load (75% of 1-repetition maximum), volume (24 repetitions), and total rest (240 s). Sessions were performed in a counterbalanced randomized design with TRA consisting of 3 sets of 8 repetitions with 120-second interset rest and ARRT employing a personalized combination of clusters, repetitions per cluster, and between-clusters rest regulated with a 20% velocity-loss threshold. The effects of TRA and ARRT on velocity loss, unilateral isometric peak force, and rating of fatigue (ROF) were compared between sexes. Results: The velocity loss was generally lower during ARRT compared with TRA (−0.47% [0.11%]), with velocity loss being mitigated by ARRT to a greater extent among males compared with females (−0.37% [0.15%]). A smaller unilateral isometric peak force decline was observed after ARRT than TRA among males compared with females (−38.4 [8.4] N). Lower ROF after ARRT than TRA was found among males compared to females (−1.97 [0.55] AU). Additionally, males reported greater ROF than females across both conditions (1.92 [0.53] AU), and ARRT resulted in lower ROF than TRA overall (−0.83 [0.39] AU). Conclusions: The ARRT approach resulted in decreased velocity loss, peak force impairment, and ROF compared with TRA in both sexes. However, male subjects exhibited more pronounced acute within-session benefits from the ARRT method. [ABSTRACT FROM AUTHOR]

Abstract Neuroblastoma (NB) is the most common pediatric tumor and is currently treated by several types of therapies including chemotherapies, such as bortezomib treatment. However, resistance to bortezomib is frequently observed by mechanisms that remain to be deciphered. Bortezomib treatment leads to caspase activation and aggresome formation. Using models of patients-derived NB cell lines with different levels of sensitivity to bortezomib, we show that the activated form of caspase 3 accumulates within aggresomes of NB resistant cells leading to an impairment of bortezomib-induced apoptosis and increased cell survival. Our findings unveil a new mechanism of resistance to chemotherapy based on an altered subcellular distribution of the executioner caspase 3. This mechanism could explain the resistance developed in NB patients treated with bortezomib, emphasizing the potential of drugs targeting aggresomes.

Push notifications are widely used in Android apps to show users timely and potentially sensitive information outside the apps’ regular user interface. Google’s default service for sending push notifications, Firebase Cloud Messaging (FCM), provides only transport layer security and does not offer app developers message protection schemes to prevent access or detect modifications by the push notification service provider or other intermediate systems. We present and discuss an in-depth mixed-methods study of push notification message security and privacy in Android apps. We statically analyze a representative set of 100,000 up-to-date and popular Android apps from Google Play to get an overview of push notification usage in the wild. In an in-depth follow-up analysis of 60 apps, we gain detailed insights into the leaked content and what some developers do to protect the messages. We find that (a) about half of the analyzed apps use push notifications, (b) about half of the in-depth analyzed messaging apps do not protect their push notifications, allowing access to sensitive data that jeopardizes users’ security and privacy and (c) the means of protection lack a standardized approach, manifesting in various developer-defined encryption schemes, custom protocols, or out-of-band communication methods. Our research highlights gaps in developer-centric security regarding appropriate technologies and supporting measures that researchers and platform providers should address.

“Comunicazione Digitale XR” is a project that exploits the EON-XR platform to enrich Information Technology education by incorporating interactive 360-degree visuals and 3D models to complement traditional teaching methods. This study probes the efficacy of Extended Reality (XR) technologies in augmenting educational experiences through the integration of gamification techniques within the curriculum. The evaluation, involving twenty-six students, delved into factors such as engagement levels, comprehension of material, and the contributory role of XR in exam readiness. Data collection was conducted using electronic log files, which provided detailed quantitative metrics on student interactions, and a post-intervention survey that assessed changes in comprehension and engagement. Additionally, qualitative data was gathered through semi-structured interviews. Quantitative data from surveys and log files were analyzed using descriptive statistics, while qualitative data from interviews were subjected to thematic analysis. This investigation has demonstrated substantial enhancements in student comprehension and engagement with the educational content facilitated by XR technologies. These findings underscore the potential of XR to augment the educational paradigm and improve students’ preparedness for academic evaluations.

ABSTRACTWe present maps of geohazard features identified across north-western Sicily and Pantelleria in the framework of the Magic project (MArine Geohazard along Italian Coasts), which involved Italian marine geological researchers in 2007-2013. These seafloor features were recognized using high-resolution bathymetry data and rely on the morphological expression of the seafloor and shallow sub-surface processes. The north-western Sicily is a complex continental margin, affected by morphodynamic, depositional, and tectonic processes. The Egadi offshore is controlled by fault escarpments and alternating retreating and progradational processes. Ustica and Pantelleria submerged edifices show the effect of volcanic activity. The Ustica seafloor is interested in volcanic, tectonic, and gravitational instability processes, while the Pantelleria offshore underwent erosive-depositional processes and the effect of bottom currents. Two levels of interpretation are represented: the physiographic domain at a scale of 1:250.000 and the morphological units and morpho-bathymetric elements at a 1:100.000 scale.