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Abstract Multiple omics analyzes of Vaccinia virus (VACV) infection have defined molecular characteristics of poxvirus biology. However, little is known about the monkeypox (mpox) virus (MPXV) in humans, which has a different disease manifestation despite its high sequence similarity to VACV. Here, we perform an in-depth multi-omics analysis of the transcriptome, proteome, and phosphoproteome signatures of MPXV-infected primary human fibroblasts to gain insights into the virus-host interplay. In addition to expected perturbations of immune-related pathways, we uncover regulation of the HIPPO and TGF-β pathways. We identify dynamic phosphorylation of both host and viral proteins, which suggests that MAPKs are key regulators of differential phosphorylation in MPXV-infected cells. Among the viral proteins, we find dynamic phosphorylation of H5 that influenced the binding of H5 to dsDNA. Our extensive dataset highlights signaling events and hotspots perturbed by MPXV, extending the current knowledge on poxviruses. We use integrated pathway analysis and drug-target prediction approaches to identify potential drug targets that affect virus growth. Functionally, we exemplify the utility of this approach by identifying inhibitors of MTOR, CHUK/IKBKB, and splicing factor kinases with potent antiviral efficacy against MPXV and VACV.

Abstract Background Usher syndrome (USH) encompasses a group of disorders characterized by congenital sensorineural hearing loss (SNHL) and retinitis pigmentosa (RP). We described the clinical findings, natural history, and molecular analyses of USH patients identified during a large-scale screening to identify quantitative traits related to ocular disorders in the SardiNIA project cohort. Methods We identified 3 USH-affected families out of a cohort of 6,148 healthy subjects. 9 subjects presented a pathological phenotype, with SNHL and RP. All patients and their family members underwent a complete ophthalmic examination including best-corrected visual acuity, slit-lamp biomicroscopy, fundoscopy, fundus autofluorescence, spectral-domain optical coherence tomography, and electrophysiological testing. Audiological evaluation was performed with a clinical audiometer. Genotyping was performed using several arrays integrated with whole genome sequence data providing approximately 22 million markers equally distributed for each subject analyzed. Molecular diagnostics focused on analysis of the following candidate genes: MYO7A, USH1C, CDH23, PCDH15, USH1G, CIB2, USH2A, GPR98, DFNB31, CLRN1, and PDZD7. Results A single missense causal variant in USH2A gene was identified in homozygous status in all patients and in heterozygous status in unaffected parents. The presence of multiple homozygous patients with the same phenotypic severity of the syndromic form suggests that the Sardinian USH phenotype is the result of a founder effect on a specific pathogenic variant related haplotype. The frequency of heterozygotes in general Sardinian population is 1.89. Additionally, to provide new insights into the structure of usherin and the pathological mechanisms caused by small pathogenic in-frame variants, like p.Pro3272Leu, molecular dynamics simulations of native and mutant protein–protein and protein–ligand complexes were performed that predicted a destabilization of the protein with a decrease in the free energy change. Conclusions Our results suggest that our approach is effective for the genetic diagnosis of USH. Based on the heterozygous frequency, targeted screening of this variant in the general population and in families at risk or with familial USH can be suggested. This can lead to more accurate molecular diagnosis, better genetic counseling, and improved molecular epidemiology data that are critical for future intervention plans. Trial registration We did not perform any health-related interventions for the participants.

Abstract Machine learning can be used to define subtypes of psychiatric conditions based on shared biological foundations of mental disorders. Here we analyzed cross-sectional brain images from 4,222 individuals with schizophrenia and 7038 healthy subjects pooled across 41 international cohorts from the ENIGMA, non-ENIGMA cohorts and public datasets. Using the Subtype and Stage Inference (SuStaIn) algorithm, we identify two distinct neurostructural subgroups by mapping the spatial and temporal ‘trajectory’ of gray matter change in schizophrenia. Subgroup 1 was characterized by an early cortical-predominant loss with enlarged striatum, whereas subgroup 2 displayed an early subcortical-predominant loss in the hippocampus, striatum and other subcortical regions. We confirmed the reproducibility of the two neurostructural subtypes across various sample sites, including Europe, North America and East Asia. This imaging-based taxonomy holds the potential to identify individuals with shared neurobiological attributes, thereby suggesting the viability of redefining existing disorder constructs based on biological factors.

Accurate cave surveying is crucial for understanding their genesis, current state, and potential hazards, especially in challenging environments marked by limited accessibility and poor visibility. This study applies geomatics techniques, including Terrestrial Laser Scanning (TLS), SLAM-based Mobile Mapping Systems (MMS), and digital photogrammetry, to create three-dimensional models of artificial caves in Gravina in Puglia, Apulia region, southern Italy. The research aims to assess these methodologies' accuracy, reliability, and performance for structural monitoring and hazard assessment. Despite challenges such as rough conditions, limited accessibility and poor visibility, the study reveals promising insights into the capabilities of these techniques for efficient surveying in complex underground environments. While highlighting the potential of MMS for cost-effective and rapid data acquisition, digital photogrammetry using spherical cameras also emerges as a viable alternative, offering comprehensive data collection capabilities with minimal capture time. Further research is warranted to optimize these techniques for enhanced hazard assessment and structural monitoring in challenging underground environments.

Abstract Background The challenge of addressing obesity persists in healthcare, necessitating nuanced approaches and personalized strategies. This study aims to evaluate the effects of diverse therapeutic interventions on anthropometric and biochemical parameters in individuals with overweight and obesity within a real-world clinical context. Methods A retrospective analysis was conducted on 192 patients (141 females, 51 males) aged 18 to 75, with a BMI ranging from 25 to 30 (14.1%) and BMI ≥ 30 (85.9%), observed over a 12-month period at our Endocrinology Unit. Treatment cohorts comprised individuals following different regimens: Mediterranean Diet (MD), with an approximate daily intake of 1500 kcal for women and 1800 kcal for men (71% patients); Ketogenic Diet (KD), utilizing the VLCKD protocol characterized by a highly hypocaloric dietary regimen

IntroductionIn recent years, the increasing presence of refugees and asylum seekers displaced from their country of origin, determined significant social, economic, humanitarian and public health implications in host countries, including Italy. These populations are exposed to several potential stressful experiences which make them vulnerable to psychological distress. In fact, the majority of studies addressing the topic found a higher prevalence of mental disorders, especially post-traumatic stress disorder and major depressive disorder, in refugees and asylum seekers with respect to the general population. However, heterogeneous prevalence rates have been reported among studies, due to methodological factor as well as to the impact of a variety of risk factors related to stressful experiences lived in the country of origin, during the migration journey and in the host country.ObjectivesThe aim of the present study was to assess the prevalence of the main psychiatric diagnoses in a large group of adult refugees and asylum seekers (N=303) in the reception centers of two provinces of the Campania region, as well as to investigate the impact of potential risk factors on the occurrence of psychiatric disorders.MethodsThe diagnosis of psychiatric disorders and the identification of subjects at high risk to develop psychosis were carried out by means of structured diagnostic interviews. The following variables were explored as potential risk/protective factors to the occurrence of psychiatric disorders: socio-demographic variables, migration status (refugees/asylum seekers) and characteristics of the reception center,assessed by means of an ad hoc questionnaire; cognitive indices assessed by using standardized neuropsychological tests; traumatic experiences and level of political terror in the country of origin, assessed by means of reliable and valid self-report questionnaires.ResultsAt least one mental disorder was found in 29.7% of the sample. Most prevalent diagnoses were depressive disorders, anxiety disorders and PTSD. Women showed, with respect to men, a higher prevalence of anxiety disorders, higher trauma levels, and came from more at-risk countries. Higher trauma levels, better cognitive abilities and unemployment and refugee status were associated to the presence of a current psychiatric disorder in the whole sample.ConclusionsOur findings showed a higher prevalence of depressive disorders and PTSD in the sample of refugees and asylum seekers with respect to the general population and highlighted the role of potential risk factors whose identification may guide the implementation of preventive strategies and early treatments in these people.

After two decades of psychological research into travel behavior, one would anticipate a thorough understanding of the cognitive processes guiding travel choices. However, the intricate and unpredictable nature of mobility dynamics often obstructs efforts to promote sustainable travel behaviors. While hybrid choice models (HCMs) incorporating latent variables prove invaluable in analyzing travel behavior, there remains a critical need for further exploration into effectively managing these variables. Typically assessed at singular time points, these variables pose challenges in analyzing individual characteristics based on their fluctuations. Moreover, deriving actionable policy implications from HCMs is challenging due to the inherent nature of psycho-attitudinal variables, which exhibit limited responsiveness to alterations in alternatives. Only a significant disruptive event could induce notable shifts in individuals’ psycho-attitudinal characteristics. The objective of this paper is to investigate two aspects: i) to study if and how norms, intentions and perceived behavioral control change after a strong shock such as the pandemic, and ii) to analyze the differences in the HCMs results estimated by using data collected before and after the shock. The study involves a panel dataset gathered during a VTBC Program which involved three phases, two of which before and straight after the first lockdown. Our results show that norms were less impacted by COVID-19 and lost importance post-lockdown. There was a notable decline in the intention to use sustainable modes and an increase in car usage, with significant differences in perceived behavioral control between those who maintain and those who change their transport modes.

The aim of the present study was to explore the relationship between gaze behaviour, motor responses and the direction of visual attention when different levels of basketball players were engaged in a basketball three-point shot. Twelve near-experts and 12 amateur basketball players, wearing an eye tracker and an inertial sensor, performed 20 shots on a basketball field, receiving the ball from a teammate, who then acted as the opponent. The trial sequence was subdivided into catching, aiming and ball flight phases. The analysis demonstrated that near-experts exhibited longer fixation durations and saccades of lower amplitude and peak velocity than amateurs. The gaze behaviour showed that all players utilized fixations during the last part of the catching phase, during most of the aiming phase, and during the final part of the ball flight phase. The greatest number of saccades was exhibited between the aiming and the ball flight phases, when the ball was released by the players. Saccades were oriented toward the teammate during the catching phase. Instead, during the aiming and ball flight phases, saccade orientations were not polarized toward a specific visual cue. In conclusion, vision plays a critical role in every aspect of the three-point shot in basketball, from catching the ball, to aiming preparation, and shot execution. It is a key factor in decision-making, spatial awareness, and overall performance in team sports.

Previous studies indicated atypical Theory of Mind (ToM) abilities in individuals with autism spectrum disorder (ASD) at different ages. However, research focused on adolescents with ASD is still rare. This study aims to fill the gaps in the literature, by investigating ToM abilities in adolescents with ASD and in a group of typically developing ones. We applied the Theory of Mind Assessment Scale (Th.o.m.a.s.), a semi-structured interview that allows a multi-dimensional measurement of ToM, including different perspectives (first/s-order, first/third-person, egocentric/allocentric), various mental states (emotions, desires, beliefs) and metacognitive abilities related with mental states (awareness, relation, and strategies). The results indicated that ToM develops atypically in ASD, with strengths and weaknesses. First, participants with ASD were comparable to controls in some specific ToM aspects, i.e., third-person ToM, both from an egocentric and an allocentric perspective. However, they were significantly weaker in attributing an understanding of the mental states of others, both in first- and second-order ToM scenarios. Second, they showed the same level of awareness about mental states as controls, but they were significantly weaker in conceptualizing the relationship between mental states and behavior. Also, they found it very difficult to think about possible strategies that they or others might employ to realize desires and needs. Finally, they performed similarly to controls in understanding emotions, while they poorly understood desires and beliefs. These results point out the distinctive characteristics of ToM development in individuals with ASD, with important implications for individualized interventions.

Conjugated linoleic acid (CLA) isomers exhibit anti-inflammatory properties within the central nervous system (CNS). This study investigated the effects of CLA isomers c9,t11 and t10,c12 on fatty acid (FA) and N-acylethanolamine (NAE) profiles and their association with pro-inflammatory molecule expression in BV-2 microglia cell line, the CNS's resident immune cells responsible for maintaining neuronal activity and immune homeostasis. BV-2 cells were treated with 25 μM of c9,t11-CLA, t10,c12-CLA, or oleic acid (OA) for 24 h, followed by lipopolysaccharide (LPS) stimulation. After treatment, the cell's FA and NAE profiles and pro-inflammatory molecule expression were analyzed. Our results demonstrated that CLA isomers mitigate LPS-induced morphological changes in BV-2 cells and reduce gene expression and protein levels of inflammatory markers. This effect was linked to an upregulation of acyl-CoA oxidase 1, a key enzyme in the anti-inflammatory peroxisomal beta-oxidation pathway that efficiently metabolizes CLA isomers. Notably, t10,c12-CLA significantly suppressed stearoyl-CoA desaturase 1, impacting monounsaturated fatty acid synthesis. The NAEs profile was remarkably altered by CLA isomers, with a significant release of the anti-neuroinflammatory mediator docosahexaenoic acid (DHA)-derived N-acylethanolamine (DHAEA). In conclusion, our findings suggest that the anti-neuroinflammatory effects of CLA isomers are due to their unique influences on FA metabolism and the modulation of bioactive FA-derived NAEs, highlighting a potential strategy for nutritional intervention in conditions characterized by neuroinflammation.

Polar sea surface height observation by radar altimeters requires missions with high-latitude orbit and specific processing to observe the sea-ice-covered region within fractures in the ice. Here, we combine sea surface height estimates from different radar satellites over the ice-free and ice-covered polar oceans to create cross-calibrated along-tracks and gridded products over the Arctic Ocean (2011–2021) and the Southern Ocean (2013–2021). The sea surface height from our regional polar products is in great agreement with tide gauges and bottom pressure recorders at monthly timescales in seasonally to year-round ice-covered regions. Thanks to the use of several missions and the mapping strategy, our multi-mission products have a greater resolution than mono-mission products. Part of the sea level variability of the Arctic Ocean product is related to the Arctic Oscillation atmospheric circulation. At long term, the Arctic altimetry sea level is coherent with in-situ steric height evolution in the Beaufort gyre, and negative sea level trends over the 10-year period are observed in the East Siberian slope region, which may be related to the local freshwater decrease observed by other studies. Our regional polar sea level products are limited by current understanding of the sea-ice lead measurements, and homogenization of these polar products with global sea level products needs to be tackled.

Pulsed Electromagnetic Field (PEMF) therapy is a non-invasive treatment that utilizes electromagnetic fields to stimulate and promote natural healing processes within the body. PEMF therapy works by emitting low-frequency electromagnetic pulses, which penetrate deep into tissues and cells, enhancing cellular function and health. PEMF applications are vast, ranging from enhancing recovery in athletes to supporting overall well-being in everyday individuals. PEMF therapy is increasingly recognized in the realm of sports and physical activity for its profound benefits in enhancing performance, accelerating recovery, and preventing injuries. By improving circulation, enhancing tissue oxygenation, and promoting the body's natural healing processes, PEMF therapy has become an invaluable tool in sports medicine, contributing to optimized physical health and prolonged athletic careers. In this review, we explore the effects of PEMF on exercise and the underlying physiological mechanisms.

We advocate for a new paradigm of cosmological likelihood-based inference, leveraging recent developments in machine learning and its underlying technology, to accelerate Bayesian inference in high-dimensional settings. Specifically, we combine (i) emulation, where a machine learning model is trained to mimic cosmological observables, e.g. CosmoPower-JAX; (ii) differentiable and probabilistic programming, e.g. JAX and NumPyro, respectively; (iii) scalable Markov chain Monte Carlo (MCMC) sampling techniques that exploit gradients, e.g. Hamiltonian Monte Carlo; and (iv) decoupled and scalable Bayesian model selection techniques that compute the Bayesian evidence purely from posterior samples, e.g. the learned harmonic mean implemented in harmonic. This paradigm allows us to carry out a complete Bayesian analysis, including both parameter estimation and model selection, in a fraction of the time of traditional approaches. First, we demonstrate the application of this paradigm on a simulated cosmic shear analysis for a Stage IV survey in 37- and 39-dimensional parameter spaces, comparing $\Lambda$CDM and a dynamical dark energy model ($w_0w_a$CDM). We recover posterior contours and evidence estimates that are in excellent agreement with those computed by the traditional nested sampling approach while reducing the computational cost from 8 months on 48 CPU cores to 2 days on 12 GPUs. Second, we consider a joint analysis between three simulated next-generation surveys, each performing a 3x2pt analysis, resulting in 157- and 159-dimensional parameter spaces. Standard nested sampling techniques are simply unlikely to be feasible in this high-dimensional setting, requiring a projected 12 years of compute time on 48 CPU cores; on the other hand, the proposed approach only requires 8 days of compute time on 24 GPUs. All packages used in our analyses are publicly available.

Left-right asymmetry is an important organizing feature of the healthy brain that may be altered in schizophrenia, but most studies have used relatively small samples and heterogeneous approaches, resulting in equivocal findings. We carried out the largest case-control study of structural brain asymmetries in schizophrenia, with MRI data from 5,080 affected individuals and 6,015 controls across 46 datasets, using a single image analysis protocol. Asymmetry indexes were calculated for global and regional cortical thickness, surface area, and subcortical volume measures. Differences of asymmetry were calculated between affected individuals and controls per dataset, and effect sizes were meta-analyzed across datasets. Small average case-control differences were observed for thickness asymmetries of the rostral anterior cingulate and the middle temporal gyrus, both driven by thinner left-hemispheric cortices in schizophrenia. Analyses of these asymmetries with respect to the use of antipsychotic medication and other clinical variables did not show any significant associations. Assessment of age- and sex-specific effects revealed a stronger average leftward asymmetry of pallidum volume between older cases and controls. Case-control differences in a multivariate context were assessed in a subset of the data (N = 2,029), which revealed that 7% of the variance across all structural asymmetries was explained by case-control status. Subtle case-control differences of brain macrostructural asymmetry may reflect differences at the molecular, cytoarchitectonic, or circuit levels that have functional relevance for the disorder. Reduced left middle temporal cortical thickness is consistent with altered left-hemisphere language network organization in schizophrenia.

Emerging evidence suggests brain white matter alterations in adolescents with early-onset psychosis (EOP; age of onset

Schizophrenia (SZ) is associated with an increased risk of life-long cognitive impairments, age-related chronic disease, and premature mortality. We investigated evidence for advanced brain ageing in adult SZ patients, and whether this was associated with clinical characteristics in a prospective meta-analytic study conducted by the ENIGMA Schizophrenia Working Group. The study included data from 26 cohorts worldwide, with a total of 2803 SZ patients (mean age 34.2 years; range 18-72 years; 67% male) and 2598 healthy controls (mean age 33.8 years, range 18-73 years, 55% male). Brain-predicted age was individually estimated using a model trained on independent data based on 68 measures of cortical thickness and surface area, 7 subcortical volumes, lateral ventricular volumes and total intracranial volume, all derived from T1-weighted brain magnetic resonance imaging (MRI) scans. Deviations from a healthy brain ageing trajectory were assessed by the difference between brain-predicted age and chronological age (brain-predicted age difference [brain-PAD]). On average, SZ patients showed a higher brain-PAD of +3.55 years (95% CI: 2.91, 4.19; I2 = 57.53%) compared to controls, after adjusting for age, sex and site (Cohen's d = 0.48). Among SZ patients, brain-PAD was not associated with specific clinical characteristics (age of onset, duration of illness, symptom severity, or antipsychotic use and dose). This large-scale collaborative study suggests advanced structural brain ageing in SZ. Longitudinal studies of SZ and a range of mental and somatic health outcomes will help to further evaluate the clinical implications of increased brain-PAD and its ability to be influenced by interventions.