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This systematic review summarizes the evidence about toe walking (TW) interventions in persons with autism. Following the PRISMA guidelines, a systematic search of MEDLINE, CINAHL, PsycINFO, The Cochrane Library, Google Scholar, and Opengrey was performed. Nine articles (all case reports or case series) were included. Methodological quality was assessed using the Mayo Evidence-Based Practice Centre tool. The included studies considered 17 subjects (16 males; age range: 4-15 years). All studies reported a reduction of TW frequency, but the follow-up was lacking in seven studies. There is a lack of high-quality studies with a sufficiently large and well-characterized sample to assess the effectiveness of TW interventions in autistic persons. These findings strongly support the need for further research in this area.

Abstract Adverse life events (e.g., severe accidents, violence/abuse, organic disorders) can elicit traumatic responses characterized by intrusive thoughts, hyperarousal, and avoidance—highlighting the need for sound assessment tools. Also, these traumatic components could heighten anxiety and depression symptoms. This study aims included to: (1) assessing the psychometric properties of the Post-Traumatic Symptom Questionnaire (PTSQ) and delineating clinical cut-offs; (2) investigating how distinct trauma components contribute to anxiety and depression symptoms. Involving 761 participants who experienced a traumatic event, Part I tested the PTSQ psychometric properties, defining clinical cut-offs. Part II tested the impact of traumatic components on anxiety and depression symptoms, using a multiple multivariate latent regression model. PTSQ exhibited exemplary fit indices and robust psychometric properties. Clinically relevant cut-offs were identified. The differential contributions of intrusion, avoidance, and hyperarousal to anxiety and depression symptoms were evaluated, elucidating the strength and nature of these relationships. This study reaffirms the PTSQ as a psychometrically sound and reliable instrument. It underscores the effects of intrusion, avoidance, and hyperarousal on anxiety and depression symptoms in individuals with traumatic experiences. These insights advocate for evidence-based interventions aimed at alleviating the psychological suffering associated with trauma components, fostering adaptation and supporting psychological health.

Abstract Evolutionarily relevant networks have been previously described in several mammalian species using time-averaged analyses of fMRI time-series. However, fMRI network activity is highly dynamic and continually evolves over timescales of seconds. Whether the dynamic organization of resting-state fMRI network activity is conserved across mammalian species remains unclear. Using frame-wise clustering of fMRI time-series, we find that intrinsic fMRI network dynamics in awake male macaques and humans is characterized by recurrent transitions between a set of 4 dominant, neuroanatomically homologous fMRI coactivation modes (C-modes), three of which are also plausibly represented in the male rodent brain. Importantly, in all species C-modes exhibit species-invariant dynamic features, including preferred occurrence at specific phases of fMRI global signal fluctuations, and a state transition structure compatible with infraslow coupled oscillator dynamics. Moreover, dominant C-mode occurrence reconstitutes the static organization of the fMRI connectome in all species, and is predictive of ranking of corresponding fMRI connectivity gradients. These results reveal a set of species-invariant principles underlying the dynamic organization of fMRI networks in mammalian species, and offer novel opportunities to relate fMRI network findings across the phylogenetic tree.

Children/adolescents with cancer can develop adverse effects impacting gross motor function. There is a lack of gross motor function assessment tools that have been validated for this population. The aim of this multicenter cross-sectional study was to preliminary validate the 88-item Gross Motor Function Measure (GMFM-88) for use in children/adolescents with cancer, exploring internal consistency and floor/ceiling effect. Inclusion criteria regarded children/adolescents diagnosed with cancer on treatment or

We analyze the predictability of daily data on the CBOE VIX and SKEW indices, used to capture the average level of risk-neutral risk and downside risk, respectively, as implied by S&P 500 index options. In particular, we use forecast models from the Heterogeneous Autoregressive (HAR) class to test whether and how lagged values of the VIX and of the SKEW may increase the forecasting power of HAR for the SKEW and the VIX. We find that a simple HAR is very hard to beat in out-of-sample experiments aimed at forecasting the VIX. In the case of the SKEW, the benchmarks (the random walk and an AR(1)) are clearly outperformed by HAR models at all the forecast horizons considered and there is evidence that special definitions of the SKEW index based on put options data only yield superior forecasts at all horizons.

Societal Impact Statement The legume crop cowpea is grown worldwide, but 90% of the world's total share is produced in Africa. It is a promising species due to its resilience properties, balance of macro and micronutrients and presence of health‐promoting bioactive compounds. In African countries, cowpea has a crucial role in guaranteeing food security as a subsistence crop for families and commercial income for small farmers. The discovery of compounds with high nutraceutical value and bioactive properties supports socio‐economic policies to improve health and nutrition, especially in low‐ and middle‐income countries. In turn, this encourages biodiversity protection and crop enhancement programmes. Summary Bowman–Birk protease inhibitors (BBIs) are a restricted group of small proteins in plants mainly involved in defence mechanisms against pests. BBIs are demonstrated to be active components capable of reducing the viabilities of different cancer cell lines. BBI bioactivity is directly linked to the inhibition capacity, but the variability and the efficiency against the physiological targets of different BBI isoforms remain still unexplored. We analysed the natural genetic diversity of two main genes encoding BBI trypsin‐trypsin (BBI‐TT) and trypsin‐chymotrypsin (BBI‐TC) in wild and domesticated cowpea samples mainly spread in Sub‐Saharan Africa. We analysed DNA sequences and respective amino acidic isoforms/isoproteins to explore signs of natural selection and haplotype relationships. Moreover, we calculated the binding energy between BBIs and their biological targets to identify which are the most efficient inhibitors and their geographical locations. We found a high level of haplotype diversity for both genes, almost exclusively in wild accessions and detected positive and negative selection signals in the amino acid sequences. Furthermore, in the wild diversity pool, some BBI‐TT and BBI‐TC mature proteins were potentially better interactors with the physiological targets. The long interaction between plant‐pathogen has selected new and useful isoforms in wild lineages that have allowed the chances of survival of the species to improve. On the other hand, the domestication process has produced an intense bottleneck leaving only poorly efficient BBI variants. In addition to providing information on the natural diversity and evolution of BBIs, our work discusses the potential applications in agriculture and human health.

Abstract: The minimally invasive endodontic access is not directly associated with tooth discoloration in the presence of bioceramic or epoxy resin-based root canal sealers. This study aimed to evaluate the influence of minimally invasive access and endodontic sealer composition on the color stability of endodontically-treated teeth, the restorative material adaptation, and the presence of remaining filling material in the pulp chamber. Endodontic access surgery was performed in maxillary central incisors, either through conservative or minimally invasive approaches, and the root was filled with AH Plus or Bio-C Sealer. The crown color was measured with a spectrophotometer at baseline and after root obturation, restoration, and specimen storage for one year in an oven. The occurrence of voids in the restoration and the remaining filling material was analyzed using micro-CT scans. The Yellowness Index (YI) and color changes (∆E00) were calculated after each color measurement. Data of micro-CT were submitted to 2-way ANOVA, and YI and ∆E00 were analyzed with repeated-measures ANOVA. Pair-wise comparisons were performed with Tukey's test (α = 0.05). The experimental conditions had no effect on the presence of the remaining material. The minimally invasive access associated with Bio-C Sealer resulted in more voids between the restoration and the remaining filling material. Only the evaluation time affected YI and ∆E00 values. Specimens became more yellow after filling and storage in the oven (the highest ∆E00 values). The present study showed that sealer and minimally invasive cavities are not associated with crown color stability following endodontic treatment.

IntroductionThe Brief Index of Sexual Functioning for Women (BISF-W) is an international 4-factors tool assessing qualitative and quantitative aspects of sexual experiences in women, both in clinical and experimental settings. The present research aims at validating an Italian version of the BISF-W, to develop a BISF version for men (BISF-M) to fill the gap in the existing sexual function evaluation tools in Italy and to analyze gender and age groups differences in the BISF factors.MethodsThe research included 6,355 women, aged from 18 to 65 (M = 34.94, SD = 10.52) and 2,207 men, aged from 18 to 80 (M = 38.25, SD = 13.67), who completed the BISF-W and BISF-M. The Quality of Marriage Index (QMI) was administrated to both samples for testing divergent validity, while Female Sexual Function Index (FSFI) and the International Index of Erectile Function (IIEF) were administered for testing convergent validity. Correlation analysis, MANOVA between gender and age and Confirmatory Factor Analysis were conducted.ResultsThe CFAs confirmed that the proposed 4-factor model (Dyadic, Solitaire and Anal Sexuality, and Sexual Difficulties) is suitable both for the BISF-W and the BISF-M, demonstrated strong psychometric properties for assessing sexual functioning in both genders, with dyadic sexuality being the most important factor. MANOVA analysis showed significative differences in the factors’ scores, according to gender and age.DiscussionThe BISF-W and the BISF-M are promising tools to address sexual functioning in individuals and couples, both in clinical and non-clinical settings. Gender and age differences are discussed regarding the potential use of BISF in the therapeutic context.

Background and AimsThe risk of disease progression in MASH increases proportionally to the pathological stage of fibrosis. This latter is evaluated through a semi-quantitative process, which has limited sensitivity in reflecting changes in disease or response to treatment. This study aims to test the clinical impact of Artificial Intelligence (AI) in characterizing liver fibrosis in MASH patients.MethodsThe study included 60 patients with clinical pathological diagnosis of MASH. Among these, 17 received a medical treatment and underwent a post-treatment biopsy. For each biopsy (n = 77) a Sirius Red digital slide (SR-WSI) was obtained. AI extracts >30 features from SR-WSI, including estimated collagen area (ECA) and entropy of collagen (EnC).ResultsAI highlighted that different histopathological stages are associated with progressive and significant increase of ECA (F2: 2.6% ± 0.4; F3: 5.7% ± 0.4; F4: 10.9% ± 0.8; p: 0.0001) and EnC (F2: 0.96 ± 0.05; F3: 1.24 ± 0.06; F4: 1.80 ± 0.11, p: 0.0001); disclosed the heterogeneity of fibrosis among pathological homogenous cases; revealed post treatment fibrosis modification in 76% of the cases (vs 56% detected by histopathology).ConclusionAI characterizes the fibrosis process by its true, continuous, and non-categorical nature, thus allowing for better identification of the response to anti-MASH treatment.

Abstract Objective Neoadjuvant chemotherapy (NACT) has become the standard of care for patients with triple-negative breast cancer (TNBC) with tumors > 1 cm or positive axillary nodes. Pathologic complete response (pCR) has been used as an endpoint to select patients for treatment scaling. This study aimed to examine the benefit of adding adjuvant capecitabine for TNBC patients who did not achieve pCR after standard NACT in a real-world scenario. Methods This retrospective cohort study included all patients with TNBC who underwent NACT between 2010 and 2020. Clinicopathological data were obtained from the patient records. Univariate and multivariate analyses were conducted at the 5 years follow-up period. Results We included 153 patients, more than half of whom had stage III (58.2%) and high-grade tumors (60.8%). The overall pCR rate was 34.6%, and 41% of the patients with residual disease received adjuvant capecitabine. Disease-specific survival (DSS) among the patients who achieved pCR was significantly higher (p

Summary: Neurons in the primary cortex carry sensory- and behavior-related information, but it remains an open question how this information emerges and intersects together during learning. Current evidence points to two possible learning-related changes: sensory information increases in the primary cortex or sensory information remains stable, but its readout efficiency in association cortices increases. We investigated this question by imaging neuronal activity in mouse primary somatosensory cortex before, during, and after learning of an object localization task. We quantified sensory- and behavior-related information and estimated how much sensory information was used to instruct perceptual choices as learning progressed. We find that sensory information increases from the start of training, while choice information is mostly present in the later stages of learning. Additionally, the readout of sensory information becomes more efficient with learning as early as in the primary sensory cortex. Together, our results highlight the importance of primary cortical neurons in perceptual learning.

Abstract Aberrant motor-sensory predictive functions have been linked to symptoms of psychosis, particularly reduced attenuation of self-generated sensations and misattribution of self-generated actions. Building on the parallels between prediction of self- and other-generated actions, this study aims to investigate whether individuals with psychosis also demonstrate abnormal perceptions and predictions of others’ actions. Patients with psychosis and matched controls completed a two-alternative object size discrimination task. In each trial, they observed reaching actions towards a small and a large object, with varying levels of temporal occlusion ranging from 10% to 80% of movement duration. Their task was to predict the size of the object that would be grasped. We employed a novel analytic approach to examine how object size information was encoded and read out across progressive levels of occlusion with single-trial resolution. Patients with psychosis exhibited an overall pattern of reduced and discontinuous evidence integration relative to controls, characterized by a period of null integration up to 20% of movement duration, during which they did not read any size information. Surprisingly, this drop in accuracy in the initial integration period was not accompanied by a reduction in confidence. Difficulties in action prediction were correlated with the severity of negative symptoms and impaired functioning in social relationships.

Abstract Measures of functional connectivity have played a central role in advancing our understanding of how information is transmitted and processed within the brain. Traditionally, these studies have focused on identifying redundant functional connectivity, which involves determining when activity is similar across different sites or neurons. However, recent research has highlighted the importance of also identifying synergistic connectivity—that is, connectivity that gives rise to information not contained in either site or neuron alone. Here, we measured redundant and synergistic functional connectivity between neurons in the mouse primary auditory cortex during a sound discrimination task. Specifically, we measured directed functional connectivity between neurons simultaneously recorded with calcium imaging. We used Granger Causality as a functional connectivity measure. We then used Partial Information Decomposition to quantify the amount of redundant and synergistic information about the presented sound that is carried by functionally connected or functionally unconnected pairs of neurons. We found that functionally connected pairs present proportionally more redundant information and proportionally less synergistic information about sound than unconnected pairs, suggesting that their functional connectivity is primarily redundant. Further, synergy and redundancy coexisted both when mice made correct or incorrect perceptual discriminations. However, redundancy was much higher (both in absolute terms and in proportion to the total information available in neuron pairs) in correct behavioural choices compared to incorrect ones, whereas synergy was higher in absolute terms but lower in relative terms in correct than in incorrect behavioural choices. Moreover, the proportion of redundancy reliably predicted perceptual discriminations, with the proportion of synergy adding no extra predictive power. These results suggest a crucial contribution of redundancy to correct perceptual discriminations, possibly due to the advantage it offers for information propagation, and also suggest a role of synergy in enhancing information level during correct discriminations.

Background: Adverse life occurrences (e.g., severe accidents, violence/abuse, organic disorders such as COVID-19) can elicit traumatic responses that heighten fear, anxiety, and depression. However, scientific research has shown that certain variables, such as self-esteem, based on theories like terror management theory (TMT) and the anxiety-buffering hypothesis (ABH), can mitigate the negative effects of trauma. This study aimed to test the ABH by assessing the buffering role of self-esteem in the relationships among the impact of traumatic experiences, fear, anxiety, and depression. Method: An observational research design was used. This study involved 321 participants who experienced COVID-19 as a traumatic experience. A sequential multiple-mediation model with observed variables (path analysis) was used to test the impact of the traumatic experience on fear, anxiety, and depression, examining the protective role of self-esteem. Results: A path analysis revealed that fear and anxiety mediated the relationship between the impact of the traumatic experience of COVID-19 and depression. Additionally, in line with the ABH, self-esteem was found to mediate the relationship between the predictors and their adverse psychological consequences. This suggests that self-esteem played a buffering role, mitigating the negative impact of traumatic experiences on mental health outcomes. Conclusions: These findings underscore the central mediating role of self-esteem, as well as fear and anxiety, in the pathway from trauma-related factors to depression. These insights advocate for evidence-based interventions aimed at alleviating the psychological suffering associated with traumatic experiences, fostering adaptation, and supporting psychological health.

The literature on COVID-19 continues to increase daily. Cognitive sequelae associated with COVID-19 infection still draw the attention of the scientific community given the lack of consensus about their existence, etiology, characterization and reversibility. The aim of this study is to provide a neuropsychological identikit for younger (

Background/Objectives: Rett syndrome is a rare neurodevelopmental disorder that can severely affect motor functioning, particularly walking. Previous training programs proposed treadmills as tools to increase walking endurance of patients with Rett syndrome, but these trainings did not include virtual reality (VR). The aim of this study was to assess the feasibility of a short treadmill training coupled to VR in girls with Rett syndrome. Methods: Nine patients with Rett syndrome underwent a 3-day treadmill walking program performed in semi-immersive VR. During the training, the happiness index and performance metrics were collected. At the end of the training parents filled out the Suitability Evaluation Questionnaire (SEQ) and, when feasible, patients underwent a gait assessment. Results: All the subjects recruited performed the three GRAIL sessions and parents showed a good satisfaction and considered the integration of treadmill and VR a good possibility for future rehabilitative programs. Participants showed greater satisfaction in environments requiring walking and their attention increased during training sessions, hypothesizing the feasibility of longer trainings with treadmill and VR. Data collected from gait analysis provided insights, although preliminary, concerning differences in gait pattern amongst the recruited subjects. Conclusions: Despite the small sample size and limited training duration, the paper suggests that a walking training with a treadmill combined with VR can represent a new strategy for Rett rehabilitation.

Predicting range shifts of marine species under different CO2 emission scenarios is of paramount importance to understand spatial potential changes in a context of climate change and to ensure appropriate management, in particular in areas where resources are critical to fisheries. Important tools which use environmental variables to infer range limits and species habitat suitability are the species distribution models or SDMs. In this work, we develop an ensemble species distribution model (e-SDM) to assess past, present and future distributions under Representative Concentration Pathway (RCP) 8.5 of nine demersal species and hotspot areas for their two life stages (adult and juvenile) in the Adriatic and Western Ionian Seas in four time windows (1999-2003, 2014-2018, 2031-2035 and 2046-2050). The e-SDM has been developed using three different models (and sub-models), i.e. (i) generalized additive models (GAM), (ii) generalized linear mixed model (GLMM), (iii) gradient boosting machine (GBM), through the combination of density data in terms of numbers of individuals km2 and environmental variables. Then, we have determined the changes in the aggregation hotspots and distributions. Finally, we assess gains and losses areas (i.e. occupation area) in the future climate change scenario as new potential range shifts for the nine species and their life stages. The results show that densities of some key commercial species, such as Merluccius merluccius (European hake), Mullus barbatus (red mullet), and Lophius budegassa (anglerfish) will be shifting northwards.