Search

Abstract Background Phelan-McDermid syndrome (PMS) is caused by monoallelic loss or inactivation at the SHANK3 gene, located in human chr 22q13.33, and is often associated with Autism Spectrum Disorder (ASD). Objectives To assess the clinical and developmental phenotype in a novel sample of PMS patients, including for the first time auxometric trajectories and serotonin blood levels. Methods 70 Italian PMS patients were clinically characterized by parental report, direct medical observation, and a thorough medical and psychodiagnostic protocol. Serotonin levels were measured in platelet-rich plasma by HPLC. Results Our sample includes 59 (84.3%) cases with chr. 22q13 terminal deletion, 5 (7.1%) disruptive SHANK3 mutations, and 6 (8.6%) ring chromosome 22. Intellectual disability was present in 69 (98.6%) cases, motor coordination disorder in 65 (92.9%), ASD in 20 (28.6%), and lifetime bipolar disorder in 12 (17.1%). Prenatal and postnatal complications were frequent (22.9%-48.6%). Expressive and receptive language were absent in 49 (70.0%) and 19 (27.1%) cases, respectively. Decreased pain sensitivity was reported in 56 (80.0%), hyperactivity in 49 (80.3%), abnormal sleep in 45 (64.3%), congenital dysmorphisms in 35 (58.3%), chronic stool abnormalities and especially constipation in 29 (41.4%). Parents reported noticing behavioral abnormalities during early childhood immediately after an infective episode in 34 (48.6%) patients. Brain MRI anomalies were observed in 53 (79.1%), EEG abnormalities in 16 (23.5%), kidney and upper urinary tract malformations in 18 (28.1%). Two novel phenotypes emerged: (a) a subgroup of 12/44 (27.3%) PMS patients displays smaller head size at enrollment (mean age 11.8 yrs) compared to their first year of neonatal life, documenting a deceleration of head growth (p

Abstract A portion of multiple myeloma (MM) patients relapse early or do not respond to first line treatment. Identification of possible clinical and or biological features of these patients remains an unmet medical need. In this study we assesed the predictive markers for early relapse MM, defined as a progressive disease that occurred within 18 months, from autologoust stem cell transplantation (ASCT) in MM patients who did not have primary refractory disease. 74 consecutive MM patients were included in the study that received intensive therapy with ASCT. The study was able to identify the main features of newly diagnosed ER MM patients eligible for ASCT identifying the IgA isotype and the R2‐ISS score system as the main predictive prognostic factors for ER in this cohort of MM patients.

Aim To determine the prevalence and characteristics of pulmonary embolism (PE) in patients presenting with haemoptysis. Additionally, we assessed the efficiency and failure rates of different clinical diagnostic algorithms for PE in this patient population. Methods We enrolled consecutive adult patients who presented to nine Italian emergency departments with haemoptysis as the primary complaint. PE diagnosis was ruled out in patients with a low pre-test probability in combination with a negative age-adjusted D-dimer (referred to as the “age-adjusted” D-dimer strategy), a negative computed tomography pulmonary angiography or when a clear alternative source of bleeding was identified, along with negative findings for venous thromboembolism during a 30-day follow-up. Results A total of 546 patients were included in the study. The prevalence of PE, including the 30-day follow-up, was 4.2% (95% CI 2.7–6.3%). The majority of these cases (78%) exhibited distal (segmental or subsegmental) emboli and there were no PE-related fatalities. The “age-adjusted” D-dimer strategy initially excluded PE in 24% of patients (95% CI 21–28%), with a failure rate of 0.8% (95% CI 0.0–4.1%). Retrospectively applied, the “clinical probability-adjusted” D-dimer strategies, specifically the YEARS and Pulmonary Embolism Graduated d-Dimer (PEGeD) algorithms, excluded PE in a significantly higher proportion (30% and 32%, respectively) compared with the “age-adjusted” D-dimer strategy (p

Abstract Background To test whether known prognosticators of COVID-19 maintained their stratification ability across age groups. Methods We performed a retrospective study. We included all patients (n = 2225), who presented to the Emergency Department of the Careggi University Hospital for COVID-19 in the period February 2020—May 2021, and were admitted to the hospital. The following parameters were analyzed as dichotomized: 1) SpO2/FiO2 ≤ or > 214; 2) creatinine 82). The primary end-point was in-hospital mortality. Results By the univariate analysis, the aforementioned dichotomized variables demonstrated a significant association with in-hospital mortality in all subgroups. We introduced them in a multivariate model: in G1 SpO2/FiO2 ≤ 214 (Relative Risk, RR 15.66; 95%CI 3.98–61,74), in G2 creatinine ≥ 1.1 mg/L (RR 2.87, 95%CI 1.30–6.32) and LDH ≥ 250 UI/L (RR 8.71, 95%CI 1,15–65,70), in G3 creatinine ≥ 1.1 mg/L (RR 1.98, 95%CI 1,17–3.36) and CRP ≥ 60 ng/L (RR 2.14, 95%CI 1.23–3.71), in G4 SpO2/FiO2 ≤ 214 (RR 5.15, 95%CI 2.35–11.29), creatinine ≥ 1.1 mg/L (RR 1.75, 95%CI 1.09–2.80) and CRP ≥ 60 ng/L (RR 1.82, 95%CI 1.11–2.98) were independently associated with an increased in-hospital mortality. Conclusions A mild to moderate respiratory failure showed an independent association with an increased mortality rate only in youngest and oldest patients, while kidney disease maintained a prognostic role regardless of age.

IntroductionPolycythemia vera (PV) is a JAK2-mutated myeloproliferative neoplasm (MPN) characterized by clonal erythrocytosis and an intrinsic risk of transformation into acute myeloid leukemia (AML), known as blast-phase (BP) disease, a condition typified by dismal prognosis. In PV, the evolution to BP generally occurs through an overt fibrotic progression, represented by the post-PV myelofibrotic (MF) stage. However, direct leukemic transformation from PV may also occur in up to ~50% of patients. In this study, we sought to shed light on the morphological, clinical, and molecular features that may differentiate BP arising from a direct transition from the PV stage (post-PV-BP) from those evolving through a diagnosis of post-PV myelofibrosis (post-PV-MF-BP). Methods and resultsWe retrospectively analyzed a cohort of post-PV-BP (n=5) and post-PV-MF-BP (n=5). We found that BP arising from PV directly displayed significantly lower leukocyte count (median 2.93 × 109/L, range: 2.30–39.40 vs. median 41.05 × 109/L, range: 5.46–58.01; P=0.03), and spleen diameter (14.0 cm, range: 11.5–20.0 vs. 25.5 cm, range: 18–26; P=0.03) as compared to those experiencing an overt fibrotic stage. The most striking differences emerged from bone marrow (BM) morphological analysis: all post-PV-BP were characterized by significantly higher cellularity (median 70%, range: 60%–98% vs. 28%, range: 2%–41%, P=0.0245), lower degree of fibrosis (fibrosis grade 1 vs. fibrosis grade 3 in all cases, P=0.008) and dysplastic features involving all three lineages, most prominently the erythroid and megakaryocytic compartment. Next-generation sequencing (NGS) analysis revealed that post-PV-BP cases were enriched in mutations located in genes involved in DNA methylation such as DNMT3A, IDH1/2, and TET2 (45% vs. 15%, P=0.038). DiscussionWith all the limits of the small number of patients for each cohort, our data suggest that BPs that arise directly from PV present a peculiar phenotype, consistent with the molecular signature of the disease, typified by mutations of genes occurring with a high frequency in Myelodysplastic Syndromes (MDS) and MDS/MPN. Further studies in larger cohorts are warranted to translate these observations into robust evidence that may advise therapeutic choices.

Plasma of COVID-19 patients contains a strong metabolomic/lipoproteomic signature, revealed by the NMR analysis of a cohort of >500 patients sampled during various waves of COVID-19 infection, corresponding to the spread of different variants, and having different vaccination status. This composite signature highlights common traits of the SARS-CoV-2 infection. The most dysregulated molecules display concentration trends that scale with disease severity and might serve as prognostic markers for fatal events. Metabolomics evidence is then used as input data for a sex-specific multi-organ metabolic model. This reconstruction provides a comprehensive view of the impact of COVID-19 on the entire human metabolism. The human (male and female) metabolic network is strongly impacted by the disease to an extent dictated by its severity. A marked metabolic reprogramming at the level of many organs indicates an increase in the generic energetic demand of the organism following infection. Sex-specific modulation of immune response is also suggested.

Abstract The Arctic marine environment is highly affected by global warming with notable changes in habitat conditions, which have great consequences on migrating species. For example, the timing of their migration can be altered leading to changes in their occurrence in suitable areas, which are critical for their survival. In this study, seven years of acoustic data were analysed in Svalbard Islands from 2014 to 2020, revealing that the occurrence of fin whales (Balaenoptera physalus) happened all year-round. The sea surface temperature recorded reveals conditions which could be favorable for these species to persist until the Polar Night. The occurrence of songs indicated that certain individuals did not undertake the migratory journey through the southern breeding grounds, possibly using the area for mating purposes. The analyses of the Inter-Note-Interval (INI) demonstrated that over the years songs with different patterns were found. This suggests that either the fin whales are able to switch their INI patterns or that populations with different INIs are visiting during the Winter. Therefore, this study unveils the undertaking of an alternative strategy to migration movements, and the possible potential origin of the fin whales overwintering in Svalbard.

In this paper we assess how intra-day electricity prices can improve the prediction of zonal day-ahead wholesale electricity prices in Italy. We consider linear autoregressive models with exogenous variables (ARX) with and without interactions among predictors, and non-parametric models taken from the machine learning literature. In particular, we implement Random Forests and support vector machines, which should automatically capture the relevant interactions among predictors. Given the large number of predictors, ARX models are also estimated using LASSO regularization, which improves predictions when regressors are many and selects the important variables. In addition to zonal intra-day prices, among the predictors we include also the official demand forecasts and wind generation expectations. Our results show that the prediction performance of the simple ARX model is mostly superior to those of machine learning models. The analysis of the relevance of exogenous variables, using variable importance measures, reveals that intra-day market information successfully contributes to the forecasting performance, although the impact differs among the estimated models.

Abstract In this work, we investigate the correlation between ragweed pollen concentration and conjunctival, nasal, and asthma symptom severity in patients allergic to ragweed pollen using ambient pollen exposure in the Milan area during the 2014 ragweed season We calculate the pollen/symptom thresholds and we assess the effectiveness of ragweed allergen immunotherapy (AIT). A total of 66 participants allergic to ragweed (Amb a 1) were enrolled in the study and divided into two groups: AIT treated (24) and no AIT treated (42). Pollen counts and daily symptom/medication patient diaries were kept. Autoregressive distributed lag models were used to develop predictive models of daily symptoms and evaluate the short-term effects of temporal variations in pollen concentration on the onset of symptoms. We found significant correlations between ragweed pollen load and the intensity of symptoms for all three symptom categories, both in no AIT treated (τ = 0.341, 0.352, and 0.721; and ρ = 0.48, 0.432, and 0.881; p-value

Introduction: Bottom ashes (BA) from municipal solid waste incinerators (MSWIs) are currently classified by the European Waste Catalogue as industrial non-hazardous waste. To promote their reuse, identification and characterization of the heavy metal-bearing phases (both glass and minerals), as well as their weathering behavior, must be addressed for what concern the chemical composition, mineralogical phases, and in high concentrations and pollutants’ mobility. An important point to be noted is whether the results from a given plant can be generalized.Materials and methods: In this work, BA from five waste-to-energy (WtE) plants in northern Italy were sorted based on different grain sizes. The area showed similar MSW production, collected from a culturally homogeneous area, and similar collection management. For each grain size, a mineralogical, chemical, and physical characterization was carried out using XRF, XRD, TGA, and the leaching test.Results and discussion: We found that for major elements, the average chemical composition of the incinerators is similar, with some differences in minor elements. Ferrara (FE) and Forlì-Cesena (FC) BA show portlandite, higher ettringite, and less amorphous than the Torino (TO), Parma (PR), and Piacenza (PC) BA. This affects the pH, the release, and toxicity of the leachates. In FE and FC ashes, ettringite is insoluble, and we not only have low sulfate but also Ni and Ba beyond reglementary limits, suggesting that Ni and Ba are present as hydroxides with portlandite, which are soluble. In TO, PR, and PC, Cr and sulfates are beyond limits, suggesting that Cr comes from dissolution in ettringite. Cu and Cl are always beyond limits; the dissolution of chlorides accounts for only 30%–35% of the global Cl leachate. We observe that in the assessment of the potential toxicity of the ashes, mineralogy has a higher effect than the bulk chemical composition. Grain size sorting, although useful together with other techniques, is not by itself able to comply with the PTE risk level.Conclusion: The findings contribute to the development of efficient treatment strategies for BA, highlighting the need for a more thorough investigation to understand composition and properties and to find innovative ways to reuse, promoting the circular economy and sustainable waste management practices.

A previously-reported cadmium-based two-periodic metal-organic framework [Cd1.5(BTC)(H2O)4.5]n·nH2O (CP1) has been re-synthesized, where H3BTC = 1,3,5-benzenetricarboxylic acid. CP1 was characterized with single crystal X-ray diffraction (SCXRD), powder X-ray diffraction (PXRD) followed by various thermal analyses such as thermogravimetric analysis (TGA), hot stage microscopy (HSM) and differential scanning calorimetry (DSC). CP1 is composed of 2-periodic layers, which are interdigitated. Heating can effectively remove the uncoordinated and coordinated water molecules resulting in an amorphous product CP1′. The original framework can be regenerated by readsorption of water from the atmosphere, indicating that the dehydration is reversible.

Limnospira fusiformis (also known as Spirulina) is a cyanobacterium that is widely cultivated due to its economic importance. It has specific pigments such as phycocyanin that allow it to grow at different light wavelengths compared to other cultivated algae. Our study investigated the effect of yellow (590 nm) and blue (460 nm) light fields on various biochemical features, including the pigment concentration, protein content, dry weight, and cell ultrastructure of L. fusiformis. Our findings revealed that biomass growth was faster in yellow light compared to blue light, with a higher relative amount of proteins even after one day of exposure. However, after eight days, the relative protein content in yellow versus blue light was not statistically different. Furthermore, in yellow light, we observed a decrease in chlorophyll a, an increase in cyanophycin granules, and an increase in the amount of dilated thylakoids. On the other hand, in blue light, there was an increase in phycocyanin after one day, along with an increase in electron-dense bodies, which are attributable to carboxysomes. However, after eight days, the differences in pigment content compared to the control were not statistically significant. Our study showed that using specific wavelengths during the harvesting phase of spirulina growth can enhance phycocyanin content with blue light (after one day) and biomass, growth rates, and protein content with yellow light after six days. This highlights the biotechnological potential of this approach.

Abstract Breast cancer is the leading cause of cancer death among women worldwide. Blocking a single signaling pathway is often an ineffective therapy, especially in the case of aggressive or drug-resistant tumors. Since we have previously described the mechanism involved in the crosstalk between Retinoic Acid system and protein kinase C (PKC) pathway, the rationale of our study was to evaluate the effect of combining all-trans-retinoic acid (ATRA) with a classical PCK inhibitor (Gö6976) in preclinical settings. Employing hormone-independent mammary cancer models, Gö6976 and ATRA combined treatment induced a synergistic reduction in proliferative potential that correlated with an increased apoptosis and RARs modulation towards an anti-oncogenic profile. Combined treatment also impairs growth, self-renewal and clonogenicity potential of cancer stem cells and reduced tumor growth, metastatic spread and cancer stem cells frequency in vivo. An in-silico analysis of “Kaplan–Meier plotter” database indicated that low PKCα together with high RARα mRNA expression is a favorable prognosis factor for hormone-independent breast cancer patients. Here we demonstrate that a classical PKC inhibitor potentiates ATRA antitumor effects also targeting cancer stem cells growth, self-renewal and frequency.

Metabolomics and lipidomics have been used in several studies to define the biochemical alterations induced by COVID-19 in comparison with healthy controls. Those studies highlighted the presence of a strong signature, attributable to both metabolites and lipoproteins/lipids. Here, 1H NMR spectra were acquired on EDTA-plasma from three groups of subjects: i) hospitalized COVID-19 positive patients (≤21 days from the first positive nasopharyngeal swab); ii) hospitalized COVID-19 positive patients (>21 days from the first positive nasopharyngeal swab); iii) subjects after 2–6 months from SARS-CoV-2 eradication. A Random Forest model built using the EDTA-plasma spectra of COVID-19 patients ≤21 days and Post COVID-19 subjects, provided a high discrimination accuracy (93.6%), indicating both the presence of a strong fingerprint of the acute infection and the substantial metabolic healing of Post COVID-19 subjects. The differences originate from significant alterations in the concentrations of 16 metabolites and 74 lipoprotein components. The model was then used to predict the spectra of COVID-19>21 days subjects. In this group, the metabolite levels are closer to those of the Post COVID-19 subjects than to those of the COVID-19≤21 days; the opposite occurs for the lipoproteins. Within the acute phase patients, characteristic trends in metabolite levels are observed as a function of the disease severity. The metabolites found altered in COVID-19≤21 days patients with respect to Post COVID-19 individuals overlap with acute infection biomarkers identified previously in comparison with healthy subjects. Along the trajectory towards healing, the metabolome reverts back to the “healthy” state faster than the lipoproteome. Author summary 1H NMR spectra of EDTA-plasma from 246 COVID-19-positive subjects in the acute phase of infection were compared to those of 95 COVID-19-recovered subjects. The two cohorts are largely different (discrimination accuracy > 93%) due to a pool of 16 metabolites and 74 lipoprotein parameters significantly up- or down-regulated in the patients and within the healthy range in the recovered subjects. In 28 post-acute COVID-19-positive patients, the metabolites levels are reverted back to normality whereas the lipoprotein parameters are still altered. Therefore, the metabolite biomarkers might be used as the timeliest sign of the individual response to treatment or spontaneous healing.

The Authors report an accidental gas exposure of Chlorine gas in a worker. This accident is very uncommon and can lead to important life-threatening conditions, such as Reactive Airway Disfunction Syndrome (RADS) and Acute Respiratory Distress Syndrome (ARDS) with important pulmonary disfunctions and even death. This syndrome results are reversible when a quick and appropriate intensive treatment is performed.

Even if mind wandering (MW) and mindfulness have traditionally been intended as separate and antithetical constructs, the roles of these 2 mental states on creative behavior were jointly explored in this article. In particular, MW was analyzed in light of a recent approach suggesting a differentiation between deliberate and spontaneous MW, whereas mindfulness was analyzed by distinguishing its 5 different constitutional dimensions: observing, acting with awareness, describing, nonreactivity, and nonjudging. The influence on creativity of these 2 mental states was analyzed using a sample of 77 undergraduate students both on a performance index (i.e., originality) and on a self-report index (i.e., creative achievement). Results showed that MW and mindfulness dimensions predicted creative behavior both alone and in combination, suggesting a complex interdependence between these 2 mental states within the creative thinking process. In particular, the critical importance of distinguishing between deliberate and spontaneous MW was revealed by a final path analysis, which revealed the opposite effects of these 2 dimensions on originality and creative achievement. That is, deliberate MW positively predicted creative performance, whereas spontaneous MW was negatively associated with such performance. Moreover, the nonreactivity and awareness dimensions of mindfulness, the latter in interaction with deliberate MW, emerged as main predictors of response originality. Finally, the describing facet of mindfulness predicted creative achievement both directly and indirectly through an interaction with deliberate MW. The implications emerging from the adoption of a multi-dimensional approach to the analysis of MW and mindfulness in the study of creativity are discussed herein.

Acute rheumatic fever (ARF) is a non-septic complication of group A β-hemolytic streptococcal (GAS) throat infection. Since 1944, ARF diagnosis relies on the Jones criteria, which were periodically revised. The 2015 revision of Jones criteria underlines the importance of knowing the epidemiological status of its own region with updated data. This study aims to describe ARF features in a retrospective cohort retrieved over a 10-year timespan (2009–2018) and to report the annual incidence of ARF among children in the Province of Monza-Brianza, Lombardy, Italy during the same period. This is a multicentric cross-sectional/retrospective study; 70 patients (39 boys) were diagnosed with ARF. The median age at diagnosis was 8.5 years (range, 4–14.2 years). Overall, carditis represented the most reported major Jones criteria followed by arthritis and chorea (40, 27, and 20 cases, respectively). In order to calculate the annual incidence of ARF, only children resident in the Province of Monza-Brianza were included in this part of the analysis. Therefore, 47 patients aged between 5 and 14 years were identified. The median incidence during the study time was 5.7/100,000 (range, 2.8–8.3/100,000). In the Province of Monza-Brianza, we found an incidence rate of ARF among children aged 5–14 years constantly above the threshold of low-risk area as defined in the 2015 revision of Jones criteria. Therefore, the diagnosis of ARF should be based on the moderate–high-risk set of Jones criteria. However, given the burden of secondary prophylaxis, expert opinion is advisable when the diagnosis of ARF is uncertain.

In the present study we investigated whether and how age group, dimensions of well-being and their interactions predicted the phenomenological properties of semantic self-images, taking also into account the different levels of accessibility of self-images (i.e., order of generation). Results on the first self-image revealed that, independently of age, higher levels of life satisfaction predicted higher likelihood of positive than negative statement and higher levels of negative affect and life satisfaction predicted higher levels of personal relevance of the self-image. When all self-images were considered, for higher levels of life satisfaction neutral and positive self-images were more likely than negative ones, and for lower levels of positive affect, neutral images were more likely than negative ones. Moreover, young adults were more likely than older adults to report neutral rather than negative self-images and, for higher levels of positive affect, they were more likely to report neutral and positive images instead of negative ones. These results suggest that the accessibility of semantic self-images should be taken into account in the investigation of the complex association between well-being and semantic self-images. Theoretical and practical implications of these results are discussed.

A patient presenting an ST-segment elevation could represent a life-threatening condition in Emergency Department (ED). This case shows how sometimes, a chronic, and more often, an acute abuse of alcohol is related to important harmful effects on myocardial contractility. The authors present a case of a 19-year-old male of oriental-Asiatic origin admitted unconscious to ED with alcoholic fetor: on electrocardiogram a significant and widespread STsegment elevation was observed. A bedside echocardiography showed no abnormalities in segmental kinetics; therefore electrocardiogram- alterations could be related to a coronary spasm. The literature is poor about this effect induced by acute alcohol ingestion: the pathophysiological mechanism at the base of the abnormal muscle contractility, seems to be related to an impairment in cyclic guanosine monophosphate production, although a second and less probable hypothesis could be an altered intracellular concentration of calcium levels.

Mind wandering (MW) refers to the shift of attention away from a primary task and/or external environment towards thoughts unrelated to the task. Recent evidence has shown that pupillometry can be used as an objective marker of the onset and maintenance of externally-driven MW episodes. In the present study we aimed to further investigate pupillary changes associated with the onset and duration of self-reported MW episodes. We used a modified version of the joint behavioural-pupillometry paradigm we recently introduced. Participants were asked to perform a monotonous vigilance task which was intermixed with task-irrelevant cue-phrases (visually presented verbal cues); they were instructed to interrupt the task whenever a thought came to mind (self-caught method) and to indicate the trigger of their thought, if any. We found systematic pupil dilation after the presentation of verbal cues reported to have triggered MW, compared with other verbal cues presented during a supposedly on-task period (i.e., the period immediately following the resuming of the task after a self-caught interruption and MW report). These results confirm that pupil diameter is sensitive to the changes associated with the onset of MW and its unfolding over time. Moreover, by computing the latency between the trigger presentation and the task interruption (self-catch), we could also estimate the duration of MW episodes triggered by verbal cues. However, a high variability was found, implying very large inter-event variability, which could not be explained by any of the MW properties we acquired (including: temporal focus, specificity, emotional valence). Our behavioural and pupillometry findings stress the need for objective measures about the temporal unfolding of MW (while most studies focus on arbitrary time-window preceding self-reports of MW).

The purpose of this analytical study was to develop an advanced formulation of medical Cannabis oil (MCO) comparing the chemical profile of different extracts obtained with two existing methods (SIFAP and CALVI) and one original upgraded (CERFIT) method. Preparation methods were applied with varying solvent, temperature, and duration of the decarboxylation and extraction steps. HPLC-MS/MS TSQ and GC/FID-HS analyses were performed to investigate cannabinoid and terpene contents in the three oil extracts. Cannabinoids profile remained comparable between the formulations. CERFIT extracts exhibited a superior quantity of total terpene hydrocarbon forms (e.g., limonene and α-pinene) with no degradation occurrence (i.e., oxidized terpenes not quantifiable). Thus, this new method optimized the phytochemical profile of the MCO presenting a value opportunity to obtain a standardized high-level therapeutic product.

Observing how children manipulate objects while they are playing can help detect possible autism spectrum disorders (ASD) at an early stage. For this purpose, specialists seek the so-called “red-flags” of motor signature of ASD for more precise diagnostic tests. However, a significant drawback to achieve this is that the observation of object manipulation by the child very often is not naturalistic, as it involves the physical presence of the specialist and is typically performed in hospitals. In this framework, we present a novel Internet of Things support in the form factory of a smart toy that can be used by specialists to perform indirect and non-invasive observations of the children in naturalistic conditions. While they play with the toy, children can be observed in their own environment and without the physical presence of the specialist. We also present the technical validation of the technology and the study protocol for the refinement of the diagnostic practice based on this technology.