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Abstract Aims Tafamidis improves clinical outcomes in transthyretin amyloid cardiomyopathy (ATTR‐CM), yet how tafamidis affects cardiac structure and function remains poorly described. This study prospectively analysed the effect of tafamidis on 12‐month longitudinal changes in cardiac structure and function by cardiac magnetic resonance (CMR) compared with the natural course of disease in an untreated historic control cohort. Methods and results ATTR‐CM patients underwent CMR at tafamidis initiation and at 12 months. Untreated patients with serial CMRs served as reference to compare biventricular function, global longitudinal strain (GLS), LV mass and extracellular volume fraction (ECV). Thirty‐six tafamidis‐treated (n = 35; 97.1% male) and 15 untreated patients (n = 14; 93.3% male) with a mean age of 78.3 ± 6.5 and 76.9 ± 6.5, respectively, and comparable baseline characteristics were included. Tafamidis was associated with preserving biventricular function (LVEF (%): 50.5 ± 12 to 50.7 ± 11.5, P = 0.87; RVEF (%): 48.2 ± 10.4 to 48.2 ± 9.4, P = 0.99) and LV‐GLS (−9.6 ± 3.2 to −9.9 ± 2.4%; P = 0.595) at 12 months, while a significantly reduced RV‐function (50.8 ± 7.3 to 44.2 ± 11.6%, P = 0.028; P (change over time between groups) = 0.032) and numerically worsening LVGLS (−10.9 ± 3.3 to −9.1 ± 2.9%, P = 0.097; P (change over time between groups) = 0.048) was observed without treatment. LV mass significantly declined with tafamidis (184.7 ± 47.7 to 176.5 ± 44.3 g; P = 0.011), yet remained unchanged in untreated patients (163.8 ± 47.5 to 171.2 ± 39.7 g P = 0.356, P (change over time between groups) = 0.027). Irrespective of tafamidis, ECV and native T1‐mapping did not change significantly from baseline to 12‐month follow‐up (P > 0.05). Conclusions Compared with untreated ATTR‐CM patients, initiation of tafamidis preserved CMR‐measured biventricular function and reduced LV mass at 12 months. ECV and native T1‐mapping did not change significantly comparable to baseline in both groups.

Abstract Background We assessed the prognostic value of serological humoral markers measured one month after the last dose of the primary COVID-19 vaccine course for predicting the risk of severe acute respiratory syndrome coronavirus 2 SARS-CoV-2 infection over the following six months in specific populations. Methods ANRS0001SCOV-POPART is a French nationwide multicenter prospective observational cohort study assessing the immune response to Covid-19 vaccines routinely administered to 11 subgroups of patients with chronic disease and a control group. Participants from the ANRS0001S COV-POPART were included if they received at least two doses of Covid-19 vaccine for the primary vaccine course, had measurements of anti-Spike, anti-receptor binding domain (RBD) IgG-specific or neutralizing antibodies one month after the end of the primary vaccine course, without being infected by SARS-CoV-2 before the measurement. SARS-CoV-2 infections defined by a positive PCR/antigenic test or seroconversion to detectable anti nucleocapsid antibodies were evaluated until the first COVID-19 booster injection. Cox proportional hazards models taking into account interval-censored data were implemented to estimate the association between each antibody level and the risk of SARS-CoV-2 infection. Predictive performances were evaluated by the area under the receiving operating characteristic curve (AUROC). Results Two thousand five hundred seventy adults from a specific population and 1,123 from the control group were included. The cumulative probabilities of SARS-CoV-2 infections at five months after serological measurement were 6.0% 95% confidence interval: [5.0; 7.9] and 10.1% 95% confidence interval: [8.3; 11.9], respectively. Higher levels of anti-Spike IgG antibody were associated with a lower risk of SARS-CoV-2 infections in the control group, but not in the specific populations. Among the specific populations, AUROC were 74.5%, 74.9%, and 72.4% for anti-Spike IgG, anti-RBD IgG, and neutralizing antibodies, respectively. AUROC were superior in the specific populations, 82.0%, 81.2%, and 81.4% for anti-Spike IgG, anti-RBD IgG, and neutralizing antibodies, respectively. Conclusions Vaccine-induced antibody response after the primary course of Covid-19 infection only moderately discriminated between participants developing a SARS-CoV-2 infection during the Omicron wave. Trial registration NCT04824651 (first posted: 2021-04-01).

Abstract Background Toxoplasma gondii is a zoonotic protozoan parasite with a heteroxenus life cycle that involves felids as the definitive hosts and any warm-blooded animal, including humans, as intermediate hosts. Cats are key players in parasite transmission as they are capable of shedding high numbers of oocysts in their feces that contaminate the environment. Methods The study was performed on 31 domestic cats (31.23 ± 27.18 months old) originating from rural and urban areas (5.17:1) in the center and north-west Romania. Feces (n = 31), blood (n = 28), and heart samples (n = 27) were collected. Fecal samples were analyzed by flotation technique, and PCR (529 bp repetitive element). Fecal samples with T. gondii oocysts were bioassayed in mice. Serum samples were analyzed by modified agglutination test and ImmunoComb for the detection of specific anti-T. gondii IgG antibodies. Heart samples were bioassayed in mice, and analyzed by PCR. Toxoplasma gondii positive samples were genotyped by nPCR-RFLP targeting eleven genetic loci (SAG1, SAG2, alt-SAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1, and Apico). Results Toxoplasma gondii oocysts were found in 2 out of 31 fecal samples collected from a 3-months old stray kitten, and a 4-years old female. In total, 17 out of 27 sera were positive for T. gondii IgG antibodies. The antibody titers in MAT ranged from 1:6 to 1:384. Toxoplasma gondii DNA was detected in 7 out of 27 heart samples, and four of them were positive also by bioassay. Six T. gondii DNA samples from bioassayed mice could be assigned to ToxoDB PCR-RFLP genotype #1 or #3 (Type II) and one T. gondii DNA from heart digest to genotype #2 (Type III). Both of these genotypes are common in Europe. Conclusions Our results revealed that the infection with T. gondii is still high in cats from Romania. The oocysts shedded by these cats represent an important source of infection for intermediate hosts, including humans. Further studies on a wider range of cases are necessary for a more exhaustive definition of the T. gondii genotypes circulating in Romania.

Abstract Background The C-terminal-binding protein 1/brefeldin A ADP-ribosylation substrate (CtBP1/BARS) acts both as an oncogenic transcriptional co-repressor and as a fission inducing protein required for membrane trafficking and Golgi complex partitioning during mitosis, hence for mitotic entry. CtBP1/BARS overexpression, in multiple cancers, has pro-tumorigenic functions regulating gene networks associated with “cancer hallmarks” and malignant behavior including: increased cell survival, proliferation, migration/invasion, epithelial-mesenchymal transition (EMT). Structurally, CtBP1/BARS belongs to the hydroxyacid-dehydrogenase family and possesses a NAD(H)-binding Rossmann fold, which, depending on ligands bound, controls the oligomerization of CtBP1/BARS and, in turn, its cellular functions. Here, we proposed to target the CtBP1/BARS Rossmann fold with small molecules as selective inhibitors of mitotic entry and pro-tumoral transcriptional activities. Methods Structured-based screening of drug databases at different development stages was applied to discover novel ligands targeting the Rossmann fold. Among these identified ligands, N-(3,4-dichlorophenyl)-4-{[(4-nitrophenyl)carbamoyl]amino}benzenesulfonamide, called Comp.11, was selected for further analysis. Fluorescence spectroscopy, isothermal calorimetry, computational modelling and site-directed mutagenesis were employed to define the binding of Comp.11 to the Rossmann fold. Effects of Comp.11 on the oligomerization state, protein partners binding and pro-tumoral activities were evaluated by size-exclusion chromatography, pull-down, membrane transport and mitotic entry assays, Flow cytometry, quantitative real-time PCR, motility/invasion, and colony assays in A375MM and B16F10 melanoma cell lines. Effects of Comp.11 on tumor growth in vivo were analyzed in mouse tumor model. Results We identify Comp.11 as a new, potent and selective inhibitor of CtBP1/BARS (but not CtBP2). Comp.11 directly binds to the CtBP1/BARS Rossmann fold affecting the oligomerization state of the protein (unlike other known CtBPs inhibitors), which, in turn, hinders interactions with relevant partners, resulting in the inhibition of both CtBP1/BARS cellular functions: i) membrane fission, with block of mitotic entry and cellular secretion; and ii) transcriptional pro-tumoral effects with significantly hampered proliferation, EMT, migration/invasion, and colony-forming capabilities. The combination of these effects impairs melanoma tumor growth in mouse models. Conclusions This study identifies a potent and selective inhibitor of CtBP1/BARS active in cellular and melanoma animal models revealing new opportunities to study the role of CtBP1/BARS in tumor biology and to develop novel melanoma treatments.

Background Immune checkpoint inhibitors (ICIs) have been a major advance in cancer management. However, we still lack prospective real-world data regarding their usage in people with HIV infection (PWH).Methods The ANRS CO24 OncoVIHAC study (NCT03354936) is an ongoing prospective observational cohort study in France of PWH with cancer treated with ICI. We assessed the incidence of grade ≥3 immune-related adverse events (irAEs). All grade ≥3 irAEs were reviewed by an event review.Results Between January 17, 2018, and December 05, 2023, 150 participants were recruited from 33 sites and 140 were included in this analysis. At the data cut-off date of December 05, 2023, the median follow-up was 9.2 months (IQR: 3.9–18.3), with a total of 126.2 person-years.Median age was 59 years (IQR: 54–64) and 111 (79.3%) were men. Median time since HIV diagnosis was 25 years (12–31), the median duration on antiretroviral (ARV) was 19.5 years (7.7–25.4), and the CD4 nadir was 117/µL (51–240). ICI regimens comprised anti-programmed cell death protein-1 (PD-1) for 111 (79.3%) participants, anti-programmed death-ligand 1 for 25 (17.9%), a combination of anti-PD-1 and anti-cytotoxic T-lymphocyte associated protein 4 for 3 (2.1%), and anti-PD-1 along with anti-vascular endothelial growth factor receptor for 1 (0.7%). The most frequent cancers were lung (n=65), head/neck (n=15), melanoma (n=12), liver (n=11) and Hodgkin’s lymphoma (n=9).During follow-up, a total of 34 grade ≥3 irAEs occurred in 20 participants, leading to an incidence rate of 26.9 per 100 person-years. The Kaplan-Meier estimates of the proportion of participants with at least one episode of grade ≥3 irAEs were 13.8% at 6 months, 15.0% at 12 months and 18.7% at 18 months. One treatment-related death due to myocarditis was reported (0.7%). Multivariable analysis of cumulative incidence showed that participants with time since HIV diagnosis >17 years (incidence rate ratio (IRR)=4.66, p=0.002), with CD4

Significant changes in the quality and metabolic profile of fresh turkey sperm as a result of both cryopreservation and reproductive age have already been individually confirmed in our previous studies. This new dataset adds a relevant piece to the tangled puzzle of changes in metabolite levels affecting cryopreserved turkey sperm quality, taking into consideration two different reproductive period ages. Fresh semen samples were collected at 44 and 56 weeks of age and exposed to the cryopreservation process. All fresh and frozen-thawed samples were subjected to analysis of mobility, viability and osmotic tolerance as parameters for evaluating the sperm quality, while NMR spectroscopy was used to assess the quantitative changes in water and lipid-soluble metabolites. Our results showed that the cryopreservation process significantly affected all of the measured qualitative parameters both at 44 and 56 weeks. Concerning the metabolic profile, a greater number of quantitative changes for both water and lipid-soluble components were found in frozen semen at 56 weeks than at 44 weeks of age. These data could contribute to identifying new strategies aimed at improving freezing procedures even as reproductive age increases.

Abstract Risk behaviours are common in adolescent and persist into adulthood, people who engage in more risk behaviours are more likely to have lower educational attainment. We applied genetic causal inference methods to explore the causal relationship between adolescent risk behaviours and educational achievement. Risk behaviours were phenotypically associated with educational achievement at age 16 after adjusting for confounders (−0.11, 95%CI: −0.11, −0.09). Genomic-based restricted maximum likelihood (GREML) results indicated that both traits were heritable and have a shared genetic architecture (Risk $${{{{{{\boldsymbol{h}}}}}}}^{{{{{{\boldsymbol{2}}}}}}}$$ h 2 = 0.18, 95% CI: −0.11,0.47; education $${{{{{{\boldsymbol{h}}}}}}}^{{{{{{\boldsymbol{2}}}}}}}$$ h 2 = 0.60, 95%CI: 0.50,0.70). Consistent with the phenotypic results, genetic variation associated with risk behaviour was negatively associated with education ( $${{{{{{\boldsymbol{r}}}}}}}_{{{{{{\boldsymbol{g}}}}}}}$$ r g = −0.51, 95%CI: −1.04,0.02). Lastly, the bidirectional MR results indicate that educational achievement or a closely related trait is likely to affect risk behaviours PGI (β=−1.04, 95% CI: −1.41, −0.67), but we found little evidence that the genetic variation associated with risk behaviours affected educational achievement (β=0.00, 95% CI: −0.24,0.24). The results suggest engagement in risk behaviour may be partly driven by educational achievement or a closely related trait.

Abstract CELSR3 codes for a planar cell polarity protein. We describe twelve affected individuals from eleven independent families with bi-allelic variants in CELSR3. Affected individuals presented with an overlapping phenotypic spectrum comprising central nervous system (CNS) anomalies (7/12), combined CNS anomalies and congenital anomalies of the kidneys and urinary tract (CAKUT) (3/12) and CAKUT only (2/12). Computational simulation of the 3D protein structure suggests the position of the identified variants to be implicated in penetrance and phenotype expression. CELSR3 immunolocalization in human embryonic urinary tract and transient suppression and rescue experiments of Celsr3 in fluorescent zebrafish reporter lines further support an embryonic role of CELSR3 in CNS and urinary tract formation.

Abstract Bipolar disorder (BD) has been associated with premature cellular aging with shortened telomere length (TL) as compared to the general population. We recently identified a subgroup of young individuals with prematurely shortened TL. The aims of the present study were to replicate this observation in a larger sample and analyze the expression levels of genes associated with age or TL in a subsample of these individuals. TL was measured on peripheral blood DNA using quantitative polymerase chain reaction in a sample of 542 individuals with BD and clustering analyses were performed. Gene expression level of 29 genes, associated with aging or with telomere maintenance, was analyzed in RNA samples from a subsample of 129 individuals. Clustering analyses identified a group of young individuals (mean age 29.64 years), with shorter TL. None of the tested clinical variables were significantly associated with this subgroup. Gene expression level analyses showed significant downregulation of MYC, POT1, and CD27 in the prematurely aged young individuals compared to the young individuals with longer TL. After adjustment only POT1 remained significantly differentially expressed between the two groups of young individuals. This study confirms the existence of a subgroup of young individuals with BD with shortened TL. The observed decrease of POT1 expression level suggests a newly described cellular mechanism in individuals with BD, that may contribute to telomere shortening.

Abstract Glioblastoma (GBM) remains a deadly tumor. Treatment with chemo-radiotherapy and corticosteroids is known to impair the functionality of lymphocytes, potentially compromising the development of autologous CAR T cell therapies. We here generated pre-clinical investigations of autologous anti-GD2 CAR T cells tested against 2D and 3D models of GBM primary cells. We detected a robust antitumor effect, highlighting the feasibility of developing an autologous anti-GD2 CAR T cell-based therapy for GBM patients.

During the sampling of a stratigraphic section along the shore of the Fiastra Lake (Carg Project - Sheet 313 “Camerino” of the Geological Map of Italy at 1:50 000 scale), a small rock boulder with partially exposed bony material was discovered at the base of a small cliff at the northern termination of the Sibillini Mts. In this area, the classical facies of Umbria-Marche stratigraphic succession are well exposed. The Oligocene-Miocene portion of the succession is represented by the ~200 m-thick Scaglia Cinerea Formation, passing upwards to the ~100 m-thick Bisciaro Formation. The microfossil assemblage has allowed the specimen to be constrained to the lower Burdigalian. The skeletal remains were examined using a CT-SCAN, a non-invasive method that has proven to be highly performing. The analysis revealed some articulated vertebrae, deformed by lithostatic compaction, which are attributed to a shark of the Order Lamniformes. Subsequently, the vertebrae were digitally isolated, extracted from the surrounding matrix, and rendered into three-dimensional prints. Through digital retro-deformation, the body length of the lamniform shark was estimated to be approximately 4 metres. Further considerations on the vertebrae allowed us to infer that the studied shark had similarities to either Isurus oxyrinchus Rafinesque, 1810 or Carcharodon carcharias Linnaeus, 1758. The development of a dead-fall microbial community likely facilitated the preservation of the vertebrae. The studied specimen represents the first occurrence of a lamniform shark in the Lower Miocene of the Umbria-Marche Domain and represents one of the very rare recorded occurrences of lamniforms from the Lower Miocene of Italy.

Non-Hodgkin lymphomas (NHL) commonly occur in immune-deficient (ID) patients, both HIV-infected and transplanted, and are often EBV-driven with cerebral localization, raising the question of tumor immunogenicity, a critical issue for treatment responses. We investigated the immunogenomics of 68 lymphoproliferative disorders from 51 ID (34 posttransplant, 17 HIV+) and 17 immunocompetent patients. Overall, 72% were Large B Cells Lymphoma (LBCL) and 25% were primary central-nervous-system lymphoma (PCNSL) while 40% were EBV-positive. Tumor whole-exome and RNA sequencing, along with a bioinformatics pipeline allowed analysis of tumor mutational burden (TMB), tumor landscape and microenvironment (TME) and prediction of tumor neoepitopes. Both TMB (2.2 vs 3.4/Mb, p=0.001) and neoepitopes numbers (40 vs 200, p=0.00019) were lower in EBVpositive than in EBV-negative NHL, regardless of the immune status. In contrast both EBV and the immune status influenced the tumor mutational profile, with HNRNPF and STAT3 mutations exclusively observed in EBV-positive and ID NHL, respectively. Peripheral blood T-cell responses against tumor neoepitopes were detected in all EBV-negative cases but in only half EBV-positive ones, including responses against IgH-derived MHC-class-II restricted neoepitopes. The TME analysis showed higher CD8 T cell infiltrates in EBVpositive vs EBV-negative NHL, together with a more tolerogenic profile composed of Tregs, type-M2 macrophages and an increased expression of negative immune-regulators. Our results highlight that the immunogenomics of NHL in patients with immunodeficiency primarily relies on the tumor EBV status, while T cell recognition of tumor- and IgH-specific neoepitopes is conserved in EBV-negative patients, offering potential opportunities for future T cell-based immune therapies.

Hardware implementations represent the major challenges when digital signal processors for ultra-wideband (UWB) signals must be developed. Due to the limitation of the maximum clock rate in digital devices, systems with high sampling rates (above GHz) cannot easily be implemented. In the literature, several works propose parallel architectures for the implementation of UWB. They are implemented on Field-Programmable Gate Arrays (FPGAs) and Application-Specific Integrated Circuits (ASICs) and try to overcome the limitation on the maximum clock frequency. In this work, a novel parallel architecture for digital UWB equalizer and an optimized version of the Least Mean Square Block (LMS) based on the Fast FIR Algorithms (FFA) are presented. Circuit simulations show that the proposed equalizer can process a UWB signal with a bandwidth reaching several GHz, using the typical clock frequencies available in FPGAs. The proposed version of the Block LMS is compared with the Fast Block LMS in terms of computational complexity. It exhibits better results and greater hardware design flexibility. Finally, the hardware implementation based on a Xilinx Kintex Ultrascale to process a UWB signal sampled at 1.6 GHz is described.

This paper proposes a Design Space Exploration for Edge machine learning through the utilization of the novel MathWorks FPGA Deep Learning Processor IP, featured in the HDL Deep Learning toolbox. With the ever-increasing demand for real-time machine learning applications, there is a critical need for efficient and low-latency hardware solutions that can operate at the edge of the network, in close proximity to the data source. The HDL Deep Learning toolbox provides a flexible and customizable platform for deploying deep learning models on FPGAs, enabling effective inference acceleration for embedded IoT applications. In this study, our primary focus lies in investigating the impact of parallel processing elements on the performance and resource utilization of the FPGA-based processor. By analyzing the trade-offs between accuracy, speed, energy efficiency, and hardware resource utilization, we aim to gain valuable insights into making optimal design choices for FPGA-based implementations. Our evaluation is conducted on the AMD-Xilinx ZC706 development board, which serves as the target device for our experiments. We consider all the compatible Convolutional Neural Networks available within the HDL Deep Learning toolbox to comprehensively assess the performances.

Kingdon’s Multiple Streams Approach (MSA) and Jones and Baumgartner’s Punctuated Equilibrium Theory (PET) are public policy frameworks that have existed for many years. Given their long-term popularity, it is important for readers to have a strong working knowledge on how said frameworks function, and be able to compare and contrast them. It has also been put forth that PET only serves as an updated version of MSA, but this paper argues that said assertion is inaccurate, as PET is a useful framework in its own right. By inspecting this paper, readers will learn about MSA, PET, how they are similar and different, how they can be operationalized or used in real life circumstances, how they have been tested, and it is ultimately concluded that PET is not just a reworking of MSA.

Abstract Background The practice of self-medication is common but not without risk, especially for vulnerable populations such as the pediatric population. Community pharmacists have an important role of vigilance in dispensing drugs available without a medical prescription, with the possibility of carrying out a Pharmaceutical Intervention (PI) if necessary. The aim of our study was to characterize the Pediatric Pharmaceutical Interventions (PPIs) in self-medication carried out during a spontaneous request for a drug at the community pharmacy. Methods We conducted a descriptive study in 139 pharmacies in the Auvergne-Rhône-Alpes region (France). Data were collected from students under the supervision of internship masters in the pharmacy, using the validated GIPAMED (GrId for PhArmaceutical Self-MEDication interventions) notification grid, the first week of each month, from February to May for five years (2017 to 2021). Collected data were entered on a secure university platform. Results Of the 3,552 PIs collected, 8,3% (n = 286) were PPIs. Of these PPIs, 35% (n = 100) was generated by requests for optional prescription drugs contraindicated by the pathophysiological condition, 28.3% for drugs requiring a prescription and 20.6% for over the counter drugs not indicated by the symptomatology. Finally, 10% of requests required a referral for a medical consultation. Four Anatomical Therapeutic Chemical (ATC) classes accounted for more than 90% of the requests: respiratory system (39.5%), alimentary tract and metabolism (19.2%), nervous system (11.5%), and musculoskeletal system (10.8%). The most common drugs generating PPIs were: ibuprofen, oxomemazine and combination camphor/essential oils, mainly due to age-related or weight-related contraindication. Paracetamol also generated PPIs frequently, mainly due to problems with drug compliance and more precise infra-therapeutic doses. When these PPIs were dispensed, the pharmacist’s proposed solutions were accepted in 94.8% (n = 271) of the cases. Conclusions The community pharmacist has an important role in providing information about medicines and their correct use to patients. Our research shows that this attention benefits vulnerable populations, such as children, even for drugs that are widely used (e.g. paracetamol and non-steroidal anti-inflammatory drugs) or active substances for which there are age-related or weight-related contraindications (e.g. antitussives, camphor combinations).

Neurodegenerative disorders are the main cause of cognitive and physical disabilities, affect millions of people worldwide, and their incidence is on the rise. Emerging evidence pinpoints a disturbance of the communication of the gut–brain axis, and in particular to gut microbial dysbiosis, as one of the contributors to the pathogenesis of these diseases. In fact, dysbiosis has been associated with neuro-inflammatory processes, hyperactivation of the neuronal immune system, impaired cognitive functions, aging, depression, sleeping disorders, and anxiety. With the rapid advance in metagenomics, metabolomics, and big data analysis, together with a multidisciplinary approach, a new horizon has just emerged in the fields of translational neurodegenerative disease. In fact, recent studies focusing on taxonomic profiling and leaky gut in the pathogenesis of neurodegenerative disorders are not only shedding light on an overlooked field but are also creating opportunities for biomarker discovery and development of new therapeutic and adjuvant strategies to treat these disorders. Lactiplantibacillus plantarum (LBP) strains are emerging as promising psychobiotics for the treatment of these diseases. In fact, LBP strains are able to promote eubiosis, increase the enrichment of bacteria producing beneficial metabolites such as short-chain fatty acids, boost the production of neurotransmitters, and support the homeostasis of the gut–brain axis. In this review, we summarize the current knowledge on the role of the gut microbiota in the pathogenesis of neurodegenerative disorders with a particular focus on the benefits of LBP strains in Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, autism, anxiety, and depression.

Purpose: This study assesses the efficacy and safety of self-expandable (SE) versus balloon-expandable (BE) stent grafts for managing visceral artery aneurysms (VAAs), focusing on procedural success and complication rates. Materials and Methods: We conducted a retrospective analysis of VAA patients treated at our institution from April 2006 to September 2021. The study reviewed patient demographics, aneurysm characteristics, treatment details, and outcomes, including endoleaks. Results: Among the 23 patients analyzed, splenic artery aneurysms represented 44% of cases. Fifteen patients were treated with balloon-expandable stent grafts (BE SGs), and eight patients were treated with self-expandable stent grafts (SE SGs). For saccular aneurysms, the average neck size was 10.10 ± 8.70 mm in the BE group versus 18.50 ± 3.40 mm in the SE group (p = 0.23), with an average sac size of 20.10 ± 18.9 mm in the BE group versus 15.60 ± 12.7 mm in the SE group (p = 0.16). The average sac-to-neck ratio was 1.69 ± 2.23 in the BE group versus 1.38 ± 0.33 in the SE group (p = 0.63). The BE group exhibited a significantly higher endoleak rate (60%) compared to the SE group (12.5%; p = 0.03). Conclusions: While further investigation is needed to fully assess the outcomes of stent graft treatment for VAAs, initial data show a significantly higher endoleak rate with BE SGs compared to SE SGs. The SE SGs may offer better outcomes due to their superior ability to conform to tortuous and mobile visceral arteries.

Introduction A 10-15 years decrease in life expectancy has been observed in individuals with bipolar disorder (BD) and has been associated with premature cellular aging, but mechanisms involved remain unclear. Our team recently identified a subgroup of young individuals with prematurely shortened telomere length (TL). Objectives The aims of the present study were to replicate this observation in a larger sample and to analyze the expression levels of genes associated with age or TL in a subsample of these individuals. Methods TL was measured by qPCR using peripheral blood DNA from 542 individuals with BD. Clustering analyzes were performed with age and TL as classification variables to identify similar groups. Gene expression of 29 genes, including 20 associated with age and 9 with TL, was analyzed by RT-qPCR using peripheral blood RNA in a subgroup of 129 individuals. Gene expressions were compared between groups obtained from the previous clustering analyzes by Kruskal-Wallis and Mann-Whitney tests. Results Clustering analyzes identified 3 subgroups and replicated the clustering previously described: a subgroup of aged individuals with a low TL (mean age : 51.73 years ; mean TL : 2), a subgroup of young individuals with a high TL (mean age : 29.02 years ; mean TL : 4.36) and a subgroup of young individuals but with a low TL (mean age : 29.64 years ; mean TL : 1.96). None of the tested clinical variables were significantly associated with this subgroup. Furthermore, gene expression level analyzes showed that only POT1 expression was different between the two subgroups of young individuals, with a downregulation of POT1 expression in the subgroup with a lower TL level. POT1 is a protein involved in the maintenance of TL. POT1 binds to another protein TPP1 allowing the recruitment of telomerase, the enzyme which extends TL. Our hypothesis is that in the subgroup presenting a lower POT1 expression, the POT1-TPP1 complex cannot form and thus prevents telomerase recruitment and TL elongation. Conclusions This study confirms, on a larger sample, the existence of a subgroup of young individuals with BD presenting accelerated cellular aging. The observed decrease of POT1 expression level suggests a newly described cellular mechanism in individuals with BD, that may contribute to telomere shortening. Disclosure of Interest None Declared

The thought of P.A. Florensky is a peculiar expression of Russian philosophy and, more generally, of Russian cultural identity. At the same time, it can nevertheless be regarded as a legitimate heir to the cultural tradition which from its powerful Ionian roots unfolds through the peaks and abysses of Western philosophy stricto sensu, up to the ultimate crises of contemporary thought...

Il pensiero di P.A. Florenskij è peculiare espressione della filosofia e dell’identità culturale russa; nel contempo, esso è viva e autentica eredità di una tradizione culturale che dalla potente radice ionica si dispiega attraverso le vette e gli abissi della filosofia stricto sensu occidentale, fino alle crisi ultime del pensiero contemporaneo...

Summary: Background: Immune-checkpoint inhibitors (ICI) have revolutionized cancer treatment by harnessing the immune system but ICI can induce life-threatening immune-related adverse events (irAE) affecting every organ. Methods: We extracted irAE from VigiBase, the international pharmacovigilance database, first reported in 2008 until 01/2023 to characterize irAE reporting trends, clinical features, risk factors and outcomes. Findings: We distinguished 25 types of irAE (n = 50,347cases, single irAE/case in 84.9%). Cases mainly involved anti-PD1 (programmed-death-1) monotherapy (62.4%) in male (61.7%) aged 64.3 ± 12.6 years. After 2020 vs. prior to 2016, proportion of anti-CTLA4 (Cytotoxic-T-Lymphocyte-Antigen-4) monotherapy prescription almost vanished (1.6% vs. 47%, respectively) contrasting with increased use of anti-PDL1 (PD1-ligand) monotherapy (18% vs. 0.9%) and anti-CTLA4+anti-PD(L)1 combination (20% vs. 8.9%). Anti-LAG3 (Lymphocyte-Activation-Gene-3) prescription was limited (5) were presence of thymic cancer for ICI-myotoxicities or hepatitis; presence of melanoma for vitiligo, uveitis or sarcoidosis; specific types of ICI regimen (anti-LAG3 for meningitis, anti-CTLA4 for hypophysitis); and specific reporting regions (eastern Asia for cholangitis). Median time-to-onset ranged from 31 to 273 days, being shortest for myotoxicities and most delayed for skin-bullous auto-immune reactions. Overall fatality was highest for myocarditis = 27.6%, myasthenia = 23.1%, severe cutaneous adverse reactions (SCAR) = 22.1%, myositis = 21.9%, pneumonitis = 21%, and encephalomyelitis = 18%; generally decreasing after 2020, except for myasthenia and SCAR. When reported, irAE recurrence rate after rechallenge was 28.9% (n = 275/951). Interpretation: This up-to-date comprehensive worldwide pharmacovigilance study defines the spectrum, characteristics, and evolution of irAE reporting summarizing over a decade of use. Multiple risk factors and clinical peculiarities for specific irAE have been identified as signals to guide clinical practice and future research. Funding: Paul Gougis was supported by the academic program: “Contrats ED: Programme blanc Institut Curie PSL” for the conduct of his PhD. Baptiste Abbar was supported by “the Fondation ARC Pour le Rechercher Sur le Cancer”. The RT2L research group (Institut Curie) was supported by the academic program “SHS INCa”, Sanofi iTech award, and by Monoprix∗.

Evapotranspiration (ET) is a crucial component of the soil–plant-atmosphere system. In semi-arid Mediterranean regions, most land water loss occurs through ET, encompassing both evaporation from the earth's surface and plant transpiration. A comprehensive understanding of the actual ET spatiotemporal dynamics is critically important for hydrological modelling and effective water resource management. This significance is further pronounced considering the growing stress on water resources and the potential influence of climate change on water fluxes. Remote sensing (RS) provides long-term, high-resolution data that can contribute to the monitoring and management of natural ecosystems. Surface energy balance (SEB) methods relying on satellite remote sensing have proven effective in measuring actual evapotranspiration (ETa eb) across different scales. However, their applicability may be constrained by interruptions in image acquisition caused by cloud cover and/or the spatio-temporal resolution limitations of satellites. In this research, a model-based methodology is suggested for simulating the dynamics of the soil–plant-atmosphere system and for estimating the daily actual evapotranspiration (ETp act) of a Mediterranean Maquis ecosystem in northwest Sardinia. The model integrates ETa eb estimates obtained from the SEBAL model utilizing Landsat-8 data, satellite-derived vegetation indices, on-site measurements of potential evapotranspiration, and the mono-dimensional transient flow Richards equation for simulating soil moisture within the root zone. By combining these elements, the proposed model provides a more comprehensive and accurate estimate of the ETp act between Landsat acquisitions. The SEBAL model showed satisfactory performance in estimating actual evapotranspiration (ETa eb) on satellite acquisition days, with an average error of 17 % compared to Eddy Covariance measurements. In addition, the integrated modelling approach yielded an ETp act average estimation error of ± 37 % in the whole studied period. The soil moisture simulation by the model had a notable accuracy with an average error of 7.1 %. Temporal analysis showed that the model effectively simulated ETp act and soil moisture under both dry and wet conditions, exhibiting similar monthly and daily variations as observed data. Furthermore, a sensitivity analysis revealed that the stress index significantly improved the model's accuracy, while vegetation dynamics had a lower impact. Overall, the proposed model is a valuable tool for estimating ETp act in semi-arid Mediterranean regions, providing important information for water resource management and conservation efforts. Further application and validation of the model are recommended as new data becomes accessible, especially in areas characterized by cropped and irrigated agriculture. In future work, we aim to spatialize the Richards equation and integrate a multi-dimensional water balance hydrologic model.

Hemp (Cannabis sativa L.) is known to tolerate high concentrations of soil contaminants which however can limit its biomass yield. On the other hand, organic-based amendments such as biochar can immobilize soil contaminants and assist hemp growth in soils contaminated by potentially toxic elements (PTEs), allowing for environmental recovery and income generation, e.g. due to green energy production from plant biomass. The aim of this study was therefore to evaluate the suitability of a softwood-derived biochar to enhance hemp growth and promote the assisted phytoremediation of a PTE-contaminated soil (i.e., Sb 2175 mg kg−1; Zn 3149 mg kg−1; Pb 403 mg kg−1; and Cd 12 mg kg−1). Adding 3% (w/w) biochar to soil favoured the reduction of soluble and exchangeable PTEs, decreased soil dehydrogenase activity (by ∼2.08-fold), and increased alkaline phosphomonoesterase and urease activities, basal respiration and soil microbial carbon (by ∼1.18-, 1.22-, 1.22-, and 1.66-fold, respectively). Biochar increased the abundance of selected soil culturable microorganisms, while amplicon sequencing analysis showed a positive biochar impact on α-diversity and the induction of structural changes on soil bacterial community structure. Biochar did not affect root growth of hemp but significantly increased its aboveground biomass by ∼1.67-fold for shoots, and by ∼2-fold for both seed number and weight. Biochar increased the PTEs phytostabilisation potential of hemp with respect to Cd, Pb and Zn, and also stimulated hemp phytoextracting capacity with respect to Sb. Overall, the results showed that biochar can boost hemp yield and its phytoremediation effectiveness in soils contaminated by PTEs providing valuable biomass that can generate profit in economic, environmental and sustainability terms.

IntroductionUrbanization processes are constantly increasing, and most of the European population currently live in urban areas. Nevertheless, evidence is consistent in highlighting the positive association between nature exposure and human wellbeing, although individual differences might affect this association.MethodsThe present study aimed to investigate the association among nature connectedness, conceptualized as Love and Care for Nature, place identity, and physical wellbeing, via restorativeness and positive and negative affect. A total of 312 visitors of an urban green area (i.e., Milan’s Parco Nord) participated in the study. They completed an anonymous questionnaire.ResultsFindings showed that nature connectedness and place identity positively affect physical wellbeing, via restorativeness and positive affect, but not through the negative ones.DiscussionResults highlight the importance of the joint role of exposure to nature and individual differences in promoting wellbeing. This study offers implications for interventions aimed at enhancing individuals’ health through exposure to nature. Limitations of the study and future research developments are discussed.

Objective: Patients with lung cancer patients report a worse quality of life than other cancer patients. Telenursing interventions should represent effective solutions in their clinical pathways. The study aims to provide an overview of telenursing interventions in lung cancer patients on chemotherapy. Materials and Methods: A systematic review following the PRISMA Statement was performed. The following databases were consulted: PubMed, EMBASE, Cochrane Library, and CINAHL. The quality of the studies includ- ed was assessed through the GRADE method. Primary quantitative, qualitative, and mixed-method studies on telenursing intervention in lung cancer patients ≥ 18 years old, on chemotherapy, and in home-setting care were included (International Prospective Registry of Systematic Reviews Protocol ID: CRD42022332779). Results: From the 801 studies retrieved, three were finally included in the review and resumed in a narrative synthesis. Conclusions: Despite the increase in telenursing interventions during the pandemic, limited evidence was found in lung cancer patients on chemotherapy. The little evidence identified does not allow for drawing conclusive con- clusions regarding effectiveness, usability, and satisfaction with the care provided, either in addition to or as an alternative to usual care. Telenursing interventions and the perceived satisfaction of patients with lung cancer are potentially consistent and should improve access and quality of care, healthcare costs and resources.

Abstract Background Neoplastic subpopulations can include polyploid cells that can be involved in tumor evolution and recurrence. Their origin can be traced back to the tumor microenvironment or chemotherapeutic treatment, which can alter cell division or favor cell fusion, generating multinucleated cells. Their progeny, frequently genetically unstable, can result in new aggressive and more resistant to chemotherapy subpopulations. In our work, we used NIHs cells, previously derived from the NIH/3T3 line after serum deprivation, that induced a polyploidization increase with the appearance of cells with DNA content ranging from 4 to 24c. This study aimed to analyze the cellular dynamics of NIHs culture subpopulations before and after treatment with the fusogenic agent polyethylene glycol (PEG), which allowed us to obtain new giant polyploid cells. Successively, PEG-untreated and PEG-treated cultures were incubated with the antimicrotubular poison vinblastine. The dynamics of appearance, decrease and loss of cell subpopulations were evaluated by correlating cell DNA content to mono-multinuclearity resulting from cell fusion and division process alteration and to the peculiarities of cell death events. Results DNA microfluorimetry and morphological techniques (phase contrast, fluorescence and TEM microscopies) indicated that PEG treatment induced a 4–24c cell increase and the appearance of new giant elements (64–140c DNA content). Ultrastructural analysis and autophagosomal–lysosomal compartment fluorochromization, which allowed us to correlate cytoplasmic changes to death events, indicated that cell depletion occurred through distinct mechanisms: apoptotic death involved 2c, 4c and 8c cells, while autophagic-like death involved intermediate 12–24c cells, showing nuclear (lobulation/micronucleation) and autophagic cytoplasm alterations. Death, spontaneously occurring, especially in intermediate-sized cells, was increased after vinblastine treatment. No evident cell loss by death events was detected in the 64–140c range. Conclusions PEG-treated NIHs cultures can represent a model of heterogeneous subpopulations originating from cell fusion and division process anomalies. Altogether, our results suggest that the different cell dynamics of NIHs subpopulations can affect the variability of responses to stimuli able to induce cell degeneration and death. Apoptptic, autophagic or hybrid forms of cell death can also depend on the DNA content and ability to progress through the cell cycle, which may influence the persistence and fate of polyploid cell descendants, also concerning chemotherapeutic agent action.

Abstract Modern livestock farm technologies allow operators to have access to a multitude of data thanks to the high number of mobile and fixed sensors available on both the livestock farming machinery and the animals. These data can be consulted via PC, tablet, and smartphone, which must be handheld by the operators, leading to an increase in the time needed for on-field activities. In this scenario, the use of augmented reality smart glasses could allow the visualization of data directly in the field, providing for a hands-free environment for the operator to work. Nevertheless, to visualize specific animal information, a connection between the augmented reality smart glasses and electronic animal identification is needed. Therefore, the main objective of this study was to develop and test a wearable framework, called SmartGlove that is able to link RFID animal tags and augmented reality smart glasses via a Bluetooth connection, allowing the visualization of specific animal data directly in the field. Moreover, another objective of the study was to compare different levels of augmented reality technologies (assisted reality vs. mixed reality) to assess the most suitable solution for livestock management scenarios. For this reason, the developed framework and the related augmented reality smart glasses applications were tested in the laboratory and in the field. Furthermore, the stakeholders’ point of view was analyzed using two standard questionnaires, the NASA-Task Load Index and the IBM-Post Study System Usability Questionnaire. The outcomes of the laboratory tests underlined promising results regarding the operating performances of the developed framework, showing no significant differences if compared to a commercial RFID reader. During the on-field trial, all the tested systems were capable of performing the task in a short time frame. Furthermore, the operators underlined the advantages of using the SmartGlove system coupled with the augmented reality smart glasses for the direct on-field visualization of animal data.

Abstract The beneficial effect of exposure to nature and immersion in natural environments on perceived well-being is well established. Nevertheless, we acknowledge an emerging need to disentangle the role of specific environmental features from individual factors that encourage a positive person-environment interaction. This study aimed at evaluating the associations between four buffer distances of greenness and dimensions of perceived restorativeness, with connectedness towards nature (CTN) as a confounder variable, in a sample of 312 visitors to a large urban park. Variables investigating ecosystem services (ES, e.g., thermal comfort) were included as covariates. Results revealed differentiated effects of greenness level, sunlight intensity, and connectedness to nature in the pathways towards dimensions of restorativeness. Greenness level at 300 m was associated with Fascination, Scope, and Being Away, while at 500 m was associated with Coherence, Scope, and Being Away. ES was found to be associated with Coherence, while CTN with the other three dimensions of restorativeness. The moderating effect of sunlight level in the relationship between NDVI buffer distances and the total score of perceived restorativeness was also confirmed. The present work is intended to offer insights on the interplay between environmental features and individual differences for implications in several contexts, including the opportunity to develop tailor-made planning for urban forestry.

Abstract Primary ciliary dyskinesia (PCD) is a genetic disorder associated with recurrent and chronic respiratory infections due to functional defects of motile cilia. In this study, we aimed to elucidate inflammatory and proliferative responses in PCD respiratory epithelium and evaluate the effect of Azithromycin (AZT) on these responses. Airway basal cells (BCs) were isolated from nasal samples of Wild-type (WT) epitope of healthy donors and PCD donors with bi-allelic mutations in DNAH5, DNAH11 and CCDC39. Cells were expanded in vitro and stimulated with either Lipopolysaccharide (LPS) or vehicle control. Post stimulation, cells were treated with either Azithromycin (AZT) or vehicle control. Cell proliferation was imaged in real-time. Separately, BCs from the same donors were expanded and grown at an air–liquid interface (ALI) to generate a multi-ciliated epithelium (MCE). Once fully mature, cells were stimulated with LPS, AZT, LPS + AZT or vehicle control. Inflammatory profiling was performed on collected media by cytokine Luminex assay. At baseline, there was a significantly higher mean production of pro-inflammatory cytokines by CCDC39 BCs and MCEs when compared to WT, DNAH11 and DNAH5 cells. AZT inhibited production of cytokines induced by LPS in PCD cells. Differences in cell proliferation were noted in PCD and this was also corrected with AZT treatment.

Background and Objectives: Vision significantly contributes to postural control, balance, coordination, and body kinematics, thus deeply influencing everyday functionality. Sight-impaired subjects often show upper body anatomofunctional and kinetic chain alterations negatively impacting daily living efficiency and autonomy. The present study aimed to investigate and train, for the first time, upper body sensorimotor control in an Italian blind baseball team to boost global and segmental functionality while contemporarily prevent injuries. Materials and Methods: The whole team underwent a validated test battery using both quantitative traditional tools, such as goniometric active range of motion and muscular/functional tests, and an innovative biofeedback-based device, a Libra proprioceptive board. Consequently, a 6-week adapted training protocol was designed and leaded to improve sensorimotor control and, hence, counteract disability-related deficits and sport-specific overuse syndromes. Results: Statistically significant improvements were observed in all the investigated parameters. Noteworthy, an overall boost of global and segmental stability was detected through an orthostatic dynamic balance enhancement during the Y Balance test (p = 0.01) and trunk multiplanar control improvement on the Libra board (p = 0.01). Concurrently, the comparison of baseline vs. post-intervention outcomes revealed a consistent increase in upper body mobility (p < 0.05 for all the assessed districts), core recruitment (p = 0.01 for all the administered functional tests), and proprioceptive postural control (p = 0.01 for the Libra board validated test). Conclusions: Our findings suggest that a tailored sensorimotor training, conceived and led by an adapted physical activity kinesiologist, may effectively improve upper body functional prerequisites and global proprioceptive control, thus potentially promoting autonomy, quality of life, and physical activity/sport practice adherence in visually impaired individuals.

Tenebrio molitor larvae represent a sustainable protein source for food and feed. The aim of this study was to evaluate the supplementation of chestnut shell, a by-product of the agro-industrial chain, in growth substrates for T. molitor larvae rearing. Seven-week-old larvae were reared on three different growth substrates: the control group (CTRL) was fed wheat bran, treatment group one was fed wheat bran supplemented with 12.5% w/w chestnut shell (TRT1), and treatment group two was fed wheat bran supplemented with 25% w/w chestnut shell (TRT2). Larval weight, substrate consumption, and mortality were recorded weekly. After 14 days, insect meals were produced for bromatological and colorimetric analysis, and bacterial inhibition activity assay using a microdilution method. The amino acid profile of insects was determined using quantitative nuclear magnetic resonance spectroscopy. Our results showed a lower feed conversion ratio and higher larval survival rate % in TRT2 compared to CTRL (p < 0.05). Proteins and lipids of TRT2 were higher than other groups (p < 0.05). Important differences were observed in the amino acid profile of TRT1 and TRT2 compared to CTRL (p < 0.05). TRT1 and TRT2 showed higher E. coli inhibitory activity than CTRL (p < 0.05). In conclusion, chestnut shell supplementation improved the survival and functional characteristics of larvae and likely impacted the insects’ metabolism.

Officinal plants are a source of metabolites whose chemical composition depends on pedoclimatic conditions. In this study, the NMR-based approach was applied to investigate the impacts of different altitudes and agronomical practices (Land, Mountain Spontaneous, and Organically Grown Ecotypes, namely LSE, MSE, and OE, respectively) on the metabolite profiles of Burdock root, Dandelion root and aerial part, and Lemon balm aerial part. Sugars, amino acids, organic acids, polyphenols, fatty acids, and other metabolites were identified and quantified in all samples. Some metabolites turned out to be tissue-specific markers. Arginine was found in roots, whereas myo-inositol, galactose, glyceroyldigalactose moiety, pheophytin, and chlorophyll were identified in aerial parts. Caftaric and chicoric acids, 3,5 di-caffeoylquinic acid, and chlorogenic and rosmarinic acids were detected in Dandelion, Burdock and Lemon balm, respectively. The metabolite amount changed significantly according to crop, tissue type, and ecotype. All ecotypes of Burdock had the highest contents of amino acids and the lowest contents of organic acids, whereas an opposite trend was observed in Lemon balm. Dandelion parts contained high levels of carbohydrates, except for the MSE aerial part, which showed the highest content of organic acids. The results provided insights into the chemistry of officinal plants, thus supporting nutraceutical–phytopharmaceutical research.

Conducting polymers are used in a wide range of applications, especially in the design and development of electrochemical sensors. Their main advantage, in this context, is their ability to efficiently modify an electrode surface using the direct polymerization of a suitable monomer in an electrochemical cell, or by physical coating. Additionally, the conducting polymers can be mixed with further materials (metal nanoparticles, carbonaceous materials) to enhance conductivity and analytical features (linear range, limit of detection, sensitivity, and selectivity). Due to their characteristics, conducting polymer-based amperometric sensors are applied to the determination of different organic and inorganic analytes. A view of recent advances in this field focusing on pyrrole, thiophene, and 3,4-ethylenedioxythiophene as starting materials is reported.

Institutional and Chaos Theory are frameworks in organizational behavior that have existed for many years. Given their long-term popularity in said field, it is important to have a strong working knowledge of each theory and be able to compare and contrast them. Both theories are wholly applicable to current world happenings, such as the COVID-19 pandemic and the Black Lives Matter movement. By inspecting this paper, readers will learn about Institutional and Chaos Theory, be able to identify how they relate to timely world occurrences, discover their implications in regard to public policy and public administrations, and reflect upon how they can be useful in respect to other organizational and global matters.

Summary: Toxoplasma gondii causes morbidity, mortality, and disseminates widely via cat sexual stages. Here, we find T. gondii ornithine aminotransferase (OAT) is conserved across phyla. We solve TgO/GABA-AT structures with bound inactivators at 1.55 Å and identify an inactivator selective for TgO/GABA-AT over human OAT and GABA-AT. However, abrogating TgO/GABA-AT genetically does not diminish replication, virulence, cyst-formation, or eliminate cat’s oocyst shedding. Increased sporozoite/merozoite TgO/GABA-AT expression led to our study of a mutagenized clone with oocyst formation blocked, arresting after forming male and female gametes, with “Rosetta stone”-like mutations in genes expressed in merozoites. Mutations are similar to those in organisms from plants to mammals, causing defects in conception and zygote formation, affecting merozoite capacitation, pH/ionicity/sodium-GABA concentrations, drawing attention to cyclic AMP/PKA, and genes enhancing energy or substrate formation in TgO/GABA-AT-related-pathways. These candidates potentially influence merozoite’s capacity to make gametes that fuse to become zygotes, thereby contaminating environments and causing disease.

Background & Aims: There is concern about the burden of liver injury in patients with cancer exposed to immune checkpoints inhibitors (ICIs). Methods: In a retrospective cohort study, we evaluated the likelihood of grade 3/4 liver injury, of grade 3/4 cholestatic liver injury, and of liver failure, as per the Common Terminology Criteria for Adverse Events (CTCAE) version 5, following treatment with ICIs. We compared these occurrences with a group of cancer patients who were propensity-matched and treated with conventional chemotherapy. For all ICI patients experiencing grade 3/4 liver injury, we conducted a causality assessment using the RUCAM method and examined patient outcomes. Results: Among 952 patients (median [IQR] age 66 [57–73] years, 64% males) who were treated with ICI between January 1, 2015, and December 31, 2019, a total of 86 (9%) progressed to grade 3/4 liver injury, and liver failure was not observed. Anti-PD-(L)1/anti-CTLA-4 antibodies combinations (adjusted hazard ratio 3.36 [95% CI: 1.67–6.79]; p

Background: Evidence available on the associations between urban greenness and mental health is mainly based on cross-sectional studies and has relied on 2D indicators of greenness. This longitudinal study aimed at investigating the association between 2D and 3D indicators of green and grey spaces and incident mental health-related outcomes in a large population-based cohort. Methods: Our study used data from 593,894 Italian adults (≥30 years) from the Rome Longitudinal Study. Mental health outcomes were defined using either drug prescriptions (antidepressants, antipsychotics, lithium and other mood stabilisers, and anxiolytics, hypnotics and sedatives), or hospitalisation records (for schizophrenia spectrum disorder, depression, anxiety, stress-related and somatoform, or substance use disorders). We obtained 2D and 3D indicators of green and grey exposures including Normalized Difference Vegetation Index (NDVI), green volume, grey volume, number of trees, and Normalized Difference Green-Grey Volume Index around participants’ homes. Cox proportional hazards regression models were developed to estimate the association of green and grey space exposure and psychiatric conditions and medicine use, adjusted for relevant covariates. Results: We found beneficial associations of NDVI and the number of trees with antipsychotic and lithium and other mood stabiliser drugs. We also observed detrimental associations between grey volume and lithium and other mood stabilisers and anxiolytic, hypnotic and sedative drugs. Finally, we found a protective association of the NDGG with lithium and other mood stabilisers (HR: 0.977; 95% CI: 0.965–0.990) and anxiolytic, hypnotic and sedative drugs (HR: 0.851; 95% CI: 0.762–0.950). The associations for hospitalisation for psychiatric conditions were less consistent and generally not statistically significant. Conclusions: Findings suggested that higher greenness areas around residential addresses are associated with reduced use of drugs for psychiatric conditions, while the opposite is true for higher grey space exposure. The study highlights the importance of accurately characterising green and grey spaces, using novel exposure indicators.

Toxoplasma gondii is a zoonotic parasite infecting all warm-blooded animals, including humans. The contribution of environmental contamination by T. gondii oocysts to infections is understudied. The aim of the current work was to explore T. gondii serology as a means of attributing the source of infection using a robust stepwise approach. We identified in silico thirty-two promising oocyst-specific antigens from T. gondii ´omics data, recombinantly expressed and purified them and validated whether serology based on these proteins could discriminate oocyst- from tissue cyst-driven experimental infections. For this, three well-characterized serum panels, sampled from 0 to 6 weeks post-infection, from pigs and sheep experimentally infected with T. gondii oocysts or tissue cysts, were used. Candidate proteins were initially screened by Western blot with sera from pigs or sheep, infected for different times, either with oocysts or tissue cysts, as well as non-infected animals. Only the recombinant proteins TgCCp5A and TgSR1 provoked seroconversion upon infection and appeared to discriminate between oocyst- and tissue cyst-driven infections with pig sera. They were subsequently used to develop an enzyme-linked immunosorbent assay test for pigs. Based on this assay and Western blot analyses, a lack of stage specificity and low antigenicity was observed with all pig sera. The same was true for proteins TgERP, TgSporoSAG, TgOWP1 and TgOWP8, previously described as source-attributing antigens, when analyzed using the whole panels of sera. We conclude that there is currently no antigen that allows the discrimination of T. gondii infections acquired from either oocysts or tissue cysts by serological tests. This work provides robust new knowledge that can inform further research and development toward source-attributing T. gondii serology.

Abstract People who make habitual use of an emotion regulation strategy such as cognitive reappraisal may be more sensitive to the emotion cues coming from a surrounding natural environment and, thus, get more benefits from virtual nature exposure such as enhanced subjective vitality. However, no previous study investigated the moderating role of cognitive reappraisal in the relationship between exposure to different types of natural environments (a national park, a lacustrine environment, and an arctic environment vs. an urban environment) and subjective vitality. We designed a between-subject design (four conditions, one per type of environment) with a sample of 187 university students (Mage = 21.17, SD = 2.55). Participants were exposed to four 360° panoramic photos of the environment for one minute each with a virtual reality head-mounted display. The results of a multicategorical moderation analysis attested that there were two significant interactions, respectively between lacustrine and arctic environments and cognitive reappraisal. More specifically, for participants with low levels of habitual use of cognitive reappraisal, the effects of virtual nature (vs. urban) exposure on subjective vitality were not significant, while for participants with high levels, the effects were significant and positive. Findings show how the potential of virtual nature may be boosted with training aimed at increasing the general use of cognitive reappraisal, supports enhancing the applications of virtual nature, and demonstrates the need to take individual differences into account when determining the benefits of these applications.

Background: Reducing a child’s level of anxiety before magnetic resonance imaging (MRI) procedures allows for better behavioral outcomes. The aim of this retrospective study was to evaluate anxiolytic efficacy of Midazolam/γ-cyclodextrin oral formulation. Methods: We retrospectively reviewed 100 medical charts of children who, between 1 February and 31 July 2022, underwent MRI under general anesthesia with or without premedication with midazolam/γ-cyclodextrin. Primary outcome was comparison of behavior to facemask positioning, while secondary endpoints were degree of drugs acceptance, anxiolytic effect evaluation, child’s behavior on separation, and sevoflurane need. Results: Facemask positioning was accepted by 58% of the midazolam/γ-cyclodextrin group compared to 22% of children in the control group. The rate of acceptance was >90%. At the moment of separation from parent, none of the premedicated children needed to be restrained compared to 18% in the control group. A lower percentage of sevoflurane was needed for eye-closure at induction of anesthesia and for anesthesia maintenance. At emergence from anesthesia, 46% of children in the premedicated group compared to 66% of children in the control group showed transient agitation. Conclusions: Midazolam/γ-cyclodextrin showed a good profile of acceptance, satisfactory anxiolytic properties, and reduced need for anesthetics when administered to children before MRI under general anesthesia.

Knowledge of hydrogen locations and protonation states is critical for a fundamental understanding of biological macromolecular function/interactions, and neutron macromolecular crystallography (NMX) is uniquely suited among the experimental structural-determination methods to provide this information. However, despite its potential, NMX remains a relatively niche technique, due to substantial limitations. This review explores NMX’s role amongst the evolving landscape of structural biology, comparing and contrasting it to the historical gold standard of X-ray macromolecular crystallography (X-ray MX) and the increasingly prevalent electron-based methods—i.e., electron microscopy (EM) and electron diffraction (ED). Forthcoming developments (e.g., the European Spallation Source in Lund, Sweden, coming online) are expected to substantially address current limitations and ensure NMX will remain relevant in the coming decades.

The ongoing occurrence of foodborne diseases and the imperative need for efficient spoilage and pathogen control in food products constitute a critical challenge for the food industry. The rising demands of consumers for safe, healthy, and clean-label food products have led to an increased interest in natural antimicrobial alternatives. Lactic acid bacteria (LAB) have proven their value in the food industry in recent years, also in reason of their antagonistic properties against undesired microbes and their significant related protechnological attributes. The natural antimicrobial compounds produced by LAB exhibit inhibitory effects on pathogens and effectively inhibit the activities of food spoilage-related organisms. Applying secondary metabolites of LAB, notably bacteriocins, organic acids, and others, has found commercial utility across multiple food sectors, effectively preventing the proliferation of undesirable microorganisms and simultaneously enhancing the sensory properties and overall quality of various food products. This review comprehensively explores the natural microbial compounds produced by LAB, specifically focusing on their antimicrobial action in supporting effective and sustainable microbial management. Additionally, it highlights their strategic application across various technological contexts within the food industry.

The use of lactic acid bacteria (LAB) for the probiotic enrichment of minimally processed fruit is a well-established practice in the literature. In addition, several LAB demonstrated a strain-specific ability to control harmful microorganisms and decay agents, improving shelf life, maintaining quality, and promoting the safety of fruits and vegetables. Edible coatings can help modulate the phenomena of gas exchange and water loss by fruits, representing protection from physical damage and spoilage phenomena linked to oxidation and the development of undesired microorganisms. At the same time, the coating can represent an innovative delivery matrix for the LAB strains of potential interest to improve safety and quality in the postharvest management of fruits. In this work, five Lactiplantibacillus plantarum strains, previously characterised for their probiotic and antifungal activity, were incorporated into a sodium alginate coating to develop edible probiotic coatings with antifungal properties for table grapes cv. Italia. The bacterial transfer and their survival were evaluated by comparing coated and uncoated table grapes during 14 days of cold storage at 4 °C. The alginate edible coating increased the number of viable cells transferred to the surface of the berries from about 5 to more than 7 Log CFU/g, with a crucial impact on the potential functional attributes of the final product. The ability of the functionalised coatings to counteract the decay development was evaluated on table grape berries artificially contaminated with Aspergillus niger CECT 2805. A significant reduction in lesion diameter was observed in the alginate coating with L. plantarum 11-A, with a reduction from 15.40 ± 1.14 mm of uncoated berries to 8.40 ± 1.14 mm of berries coated with L. plantarum 11-A. The lesion diameter reduction was also accompanied by a reduction in the symptoms of infection, such as browning around the wound. These results suggest the application of selected strains of L. plantarum as promising bio-resources to enhance the overall value of ready-to-eat fruits and vegetables, particularly in combination with edible coating as a carrier matrix. While a strain-dependent effect was not detected with respect to the improvement in the number of cells in the edible coating, a variability depending on the biotype used was detected for the properties linked to biocontrol, suggesting that the inclusion in edible packaging may represent an innovative criterion in the selection of lactobacilli to be applied postharvest.

Sardinia, located in Italy, is a significant producer of Protected Designation of Origin (PDO) sheep cheeses. In response to the growing demand for high-quality, safe, and traceable food products, the elemental fingerprints of Pecorino Romano PDO and Pecorino Sardo PDO were determined on 200 samples of cheese using validated, inductively coupled plasma methods. The aim of this study was to collect data for food authentication studies, evaluate nutritional and safety aspects, and verify the influence of cheesemaking technology and seasonality on elemental fingerprints. According to European regulations, one 100 g serving of both cheeses provides over 30% of the recommended dietary allowance for calcium, sodium, zinc, selenium, and phosphorus, and over 15% of the recommended dietary intake for copper and magnesium. Toxic elements, such as Cd, As, Hg, and Pb, were frequently not quantified or measured at concentrations of toxicological interest. Linear discriminant analysis was used to discriminate between the two types of pecorino cheese with an accuracy of over 95%. The cheese-making process affects the elemental fingerprint, which can be used for authentication purposes. Seasonal variations in several elements have been observed and discussed.

This review delves into the challenge of pediatric anesthesia, underscoring the necessity for tailored perioperative approaches due to children’s distinctive anatomical and physiological characteristics. Because of the vulnerability of pediatric patients to critical incidents during anesthesia, provider skills are of primary importance. Yet, almost equal importance must be granted to the adoption of a careful preanesthetic mindset toward patients and their families that recognizes the interwoven relationship between children and parents. In this paper, the preoperative evaluation process is thoroughly examined, from the first interaction with the child to the operating day. This evaluation process includes a detailed exploration of the medical history of the patient, physical examination, optimization of preoperative therapy, and adherence to updated fasting management guidelines. This process extends to considering pharmacological or drug-free premedication, focusing on the importance of preanesthesia re-evaluation. Structural resources play a critical role in pediatric anesthesia; components of this role include emphasizing the creation of child-friendly environments and ensuring appropriate support facilities. The results of this paper support the need for standardized protocols and guidelines and encourage the centralization of practices to enhance clinical efficacy.

In digital systems, the Residue Number System (RNS) represents an interesting alternative to the traditional two’s complement representation. Its performance and low-power properties have attracted significant research interest over the years. In this paper, RNS is used to estimate the angular position of a multi-trace electrical encoder (EE), an electro-mechanical device to measure angles at high precision widely used, for example, in antennas on-board satellites. The model of this system presents cyclic characteristics and, consequently, allows efficient use of modular arithmetic for its description. The RNS is applied to EEs equipped with more than two plates, and the absolute angle reconstruction is performed by using the Chinese Remainder Theorem (CRT). Furthermore, the use of RNS allows detection and mitigation solutions for errors due to encoders’ non-idealities and electrical noise. In this noisy context, we provide a detailed analysis of the performance of the system and propose a more robust, flexible, and easy-to-implement solution compared with the traditional methods. The results show that the RNS-based system can attenuate the noise, measure accurately the angles, and improve the overall performance.

New Public Management (NPM) is a business-oriented approach to public administration that has existed for many years. While there are mixed opinions on NPM’s level of effectiveness, I believe that the more pressing question is if it is ethical. This paper seeks to answer said question by utilizing Terry Cooper’s insights on ethics. By discussing various matters and providing multiple illustrations, such as NPM’s relationship to privatization, contrasting out, elites, and everyday citizens, this work concludes that NPM is not an ethical methodology to public administration.