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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

Abstract Background Melanoma progression is based on a close interaction between cancer cells and immune cells in the tumor microenvironment (TME). Thus, a better understanding of the mechanisms controlling TME dynamics and composition will help improve the management of this dismal disease. Work from our and other groups has reported the requirement of an active Hedgehog-GLI (HH-GLI) signaling for melanoma growth and stemness. However, the role of the downstream GLI1 transcription factor in melanoma TME remains largely unexplored. Methods The immune-modulatory activity of GLI1 was evaluated in a syngeneic B16F10 melanoma mouse model assessing immune populations by flow cytometry. Murine polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) were differentiated from bone marrow cells and their immunosuppressive ability was assessed by inhibition of T cells. Conditioned media (CM) from GLI1-overexpressing mouse melanoma cells was used to culture PMN-MDSCs, and the effects of CM were evaluated by Transwell invasion assay and T cell inhibition. Cytokine array analysis, qPCR and chromatin immunoprecipitation were performed to explore the regulation of CX3CL1 expression by GLI1. Human monocyte-derived dendritic cells (moDCs) were cultured in CM from GLI1-silenced patient-derived melanoma cells to assess their activation and recruitment. Blocking antibodies anti-CX3CL1, anti-CCL7 and anti-CXCL8 were used for in vitro functional assays. Results Melanoma cell-intrinsic activation of GLI1 promotes changes in the infiltration of immune cells, leading to accumulation of immunosuppressive PMN-MDSCs and regulatory T cells, and to decreased infiltration of dendric cells (DCs), CD8 + and CD4 + T cells in the TME. In addition, we show that ectopic expression of GLI1 in melanoma cells enables PMN-MDSC expansion and recruitment, and increases their ability to inhibit T cells. The chemokine CX3CL1, a direct transcriptional target of GLI1, contributes to PMN-MDSC expansion and recruitment. Finally, silencing of GLI1 in patient-derived melanoma cells promotes the activation of human monocyte-derived dendritic cells (moDCs), increasing cytoskeleton remodeling and invasion ability. This phenotype is partially prevented by blocking the chemokine CCL7, but not CXCL8. Conclusion Our findings highlight the relevance of tumor-derived GLI1 in promoting an immune-suppressive TME, which allows melanoma cells to evade the immune system, and pave the way for the design of new combination treatments targeting GLI1.

The concern related to the interaction between natural events and industrial sites handling hazardous substances leading to Natech scenarios is rising. While current research primarily focuses on intense natural events, such as earthquakes and hurricanes, Natech events can also stem from lower-intensity events like cold waves. Even though their hazard to chemical industries is significant globally, there is a lack of attention and preventive investigations specifically addressing Natech accidents caused by cold waves. The present study emphasizes the importance of systematically examining safety aspects during cold waves, particularly focusing on safety barrier vulnerability and failure modes. Through detailed analysis, existing winterization measures are evaluated, strengths and areas for improvement are identified, and enhancements for winterizing and freeze protection programs are proposed. By addressing this knowledge gap, the study contributes to a better understanding of Natech accidents triggered by cold waves and provides essential insights to prevent similar incidents in the future.

Natural hazards hold the potential to impact technological infrastructure, triggering multiple disasters and exposing both the population and the environment at risk. The continuous rise in carbon emissions from anthropogenic activities has led to an escalating climate change crisis, contributing to increased frequency and severity of Natech (Natural Hazard-Triggered Technological Disasters) scenarios. These scenarios pose significant threats to critical infrastructure, including Carbon Capture and Storage (CCS) plants. CCS serves as a crucial short-term decarbonization solution able to combact global warming. However, climate change-related extreme weather events may cause Natech scenarios in CCS facilities, compromising equipment integrity and releasing stored carbon dioxide (CO2) and other substances. This exacerbates global warming, contaminates flood waters, or induces fire. The intricate link between climate change, Natech events, and resilient CCS infrastructure underscores the importance of climate change mitigation and adaptation strategies. Given the lack of literature regarding Natech scenarios affecting CCS plants, this paper investigates the CCS value chain with the objective of identifying vulnerable components to potential natural events. An inherent safety approach is applied to assess how risk increases considering natural events as potential causes of equipment failure. This study on Natech risks in CCS plants aims to enhance environmental protection, secure critical infrastructure, and foster a resilient, sustainable future.

The term NaTech was coined to describe events where natural hazards trigger technological accidents in industrial facilities. Structural damage to the installations, caused by natural events such as earthquakes or tsunami, may cause loss of containment, which may in turn lead to fires, blasts, or dispersion of toxic gases. Thus, NaTech quantitative risk assessment (QRA) requires a measure of structural risk to provide estimates of future losses and a detailed assessment of the consequences arising from such losses. This paper presents an industrial risk analysis for anchored atmospheric storage tanks subjected to tsunami hazard, by means of a multidisciplinary approach integrating structural analysis and consequence assessment. This is performed for a case study consisting of a waterfront tank farm located at a coastal Italian site. The first part of the analysis requires calculation of the structural failure rate of storage tanks that suffer content release due to damage induced by tsunami inundation, via models of probabilistic hazard for the site of interest and the vulnerability (fragility) of the examined structures. Structural failure rates are evaluated for various numbers of simultaneous waterfront storage tank failures, using tsunami fragility curves for variable tank geometry and filling level. The failure rates and consequence analysis for the tank farm are then used as input parameters for the NaTech QRA, leading to the calculation of risk figures for tsunami hazard.

The increasing threat posed by extreme natural disasters in industrial areas, where hazardous materials are handled, underscores the necessity for a robust safety management framework. Traditional safety management strategies based on the Quantitative Risk Assessment may fall short in assessing the long-term impacts of such events. Consequently, Resilience Engineering principles have been recently introduced in the context of process safety and Natech (natural hazards triggering technological disasters) accident response. Through a comprehensive review of the literature, the present study analyses existing methods for the quantitative resilience assessment of industrial systems to Natech events, focusing on chemical process plants and integrated energy systems. Moreover, the methodologies reviewed in this study are classified based on their key features, along with the resilience metrics adopted in the developed approach.

One of the potential triggers for major accidents is natural events, the so-called Natech scenarios. The attention toward these accidents has been growing over the last decades, driven by the increasing frequency of natural events and the severe consequences they can entail. Indeed, serious hazards to human health and the environment arise from major accidents. Besides impacting ecosystems, environmental harm can also pose indirect threats to the population contaminating land, surface water, and groundwater. Extensive research has been conducted on the direct risks to the population originating from fires, explosions, and toxic releases, while the assessment of environmental damages was only marginally considered. The necessity to create a methodology to evaluate damages to the environment is paramount to enable a comprehensive assessment of the risk posed by Natech accidents. The current study seeks to establish a methodological approach to assess consequences for the environment resulting from releases of Light Non-Acqueous Phase Liquids (LNAPLs) caused by Natech accidents on seawater. The methodology is applied to a fictitious case study to demonstrate its applicability and the relevance of the environmental contamination issues. The methods developed in the present study represent a step forward towards a comprehensive Natech risk assessment, paving the way for the inclusion of other environmental compartments.

Summary: Background: Efficacy and safety of onasemnogene abeparvovec (OA) for Spinal Muscular Atrophy infants under 7 months and

IntroductionPotential celiac disease (pCD) is characterized by genetic predisposition, positive anti-endomysial and anti-tissue transglutaminase antibodies, but a normal or almost normal jejunal mucosa (e.g., minor histological abnormalities without villous atrophy). To gain further insights into basic mechanisms involved in the development of intestinal villous atrophy, we evaluated and compared the microbial, lipid, and immunological signatures of pCD and atrophic CD (aCD).Materials and methodsThis study included 17 aCD patients, 10 pCD patients, and 12 healthy controls (HC). Serum samples from all participants were collected to analyze free fatty acids (FFAs). Duodenal mucosa samples of aCD and pCD patients were taken to evaluate histology, tissue microbiota composition, and mucosal immune response.ResultsWe found no significant differences in the mucosa-associated microbiota composition of pCD and aCD patients. On the other hand, in pCD patients, the overall abundance of serum FFAs showed relevant and significant differences in comparison with aCD patients and HC. In detail, compared to HC, pCD patients displayed higher levels of propionic, butyric, valeric, 2-ethylhexanoic, tetradecanoic, hexadecanoic, and octadecanoic acids. Instead, aCD patients showed increased levels of propionic, isohexanoic, and 2-ethylhexanoic acids, and a lower abundance of isovaleric and 2-methylbutyricacids when compared to HC. In addition, compared to aCD patients, pCD patients showed a higher abundance of isobutyric and octadecanoic acid. Finally, the immunological analysis of duodenal biopsy revealed a lower percentage of CD4+ T lymphocytes in pCD infiltrate compared to that observed in aCD patients. The functional characterization of T cells documented a pro-inflammatory immune response in both aCD and pCD patients, but the pCD patients showed a higher percentage of Th0/Th17 and a lower percentage of Th1/Th17.ConclusionThe results of the present study show, for the first time, that the duodenal microbiota of patients with pCD does not differ substantially from that of aCD; however, serum FFAs and local T cells displayed a distinctive profile between pCD, aCD, and HC. In conclusion, our result may help to shed new light on the “gut microbiota-immunity axis,” lipid metabolites, and duodenal immune response in overt CD and pCD patients, opening new paradigms in understanding the pathogenesis behind CD progression.

Children and adolescents affected by brain tumors are at risk for neuropsychological sequelae that need to be evaluated in order to plan adequate rehabilitation programs, and to support their development and recovery. This work aims to describe an innovative prospective observational study protocol for the early evaluation and monitoring over time of neuropsychological outcomes in this pediatric population. Pediatric patients aged 3–17 with a brain tumor diagnosis will be assessed through the use of a battery of Italian standardized neuropsychological tests, with good psychometric properties and age-appropiate, at three different time points of their clinical course: at diagnosis and before surgery (T0), after surgical removal and before the start of potential adjuvant therapies (T1), and at the one-year follow-up after potential adjuvant therapies (T2). This study will allow clinicians to support the neuropsychological development of these children by promoting appropriate and timely rehabilitation and educational programs from the early phases of their clinical course.

Natech accidents have an increasing relevance due to the growing number of such events and to their severe consequences. Climate change and global warming are intensifying the occurrence and the magnitude of climate-related natural events, further increasing the risk of cascading sequences triggered by natural disasters impacting industrial installations. The present study focuses on Natech triggered by heat waves. The features of this specific category of Natech events were investigated by past accident analysis, collecting an extended dataset of past events. The dataset analysis allowed the identification of the key factors that characterize these accident scenarios, such as the direct causes, the technological scenario that occurred, the substance categories, and the equipment items more frequently involved. The main direct cause of accidents resulted in an internal pressure increase, exceeding equipment design limits. Fire scenarios represent the most important category of technological scenarios that occurred. Besides equipment items handling liquid and gaseous hydrocarbons, waste storage and processing systems also resulted frequently in accidents, due to the self-decomposition and self-ignition phenomena. The analysis of past accidents also allowed identifying some lessons learned, useful to identify specific actions aimed at preventing and/or mitigating the possible occurrence of these accident scenarios.

Accidents triggered by natural events are becoming an increasing issue for policy-makers and industrial practitioners in the last decades. These events are called Natech (natural hazards triggering technological disasters), and their study is critical due to an increase in both the frequency and the magnitude of the consequences. Considering the possible failure of safety systems and the several equipment items potentially involved in the accidents due to the occurrence of multiple simultaneous failures and cascading events, the emergency response results to be a crucial aspect in the risk assessment and management of Natech events. Despite this, the emergency response can also be affected by the occurrence of natural events. The purpose of the present work is to understand the effects of natural events on emergency response. To reach this goal, some relevant past accidents are studied. The result of the analysis allows highlighting the effects of the natural events on the emergency response. Moreover, lessons learned on the critical elements of the emergency response are derived when considering Natech accidents and related cascading events.

Wildfires are uncontrolled fires involving the combustion of wild vegetation. When a wildfire front approaches the Wildland-Industrial Interface there can be a serious threat for process and storage equipment items located at the plant boundary. Ensuring the integrity of such equipment prevents the fire from spreading inside the plant site and causing major accidents such as fire, explosion, and toxic gas dispersion. The provision of adequate clearance areas is paramount since the early stages of the plant design. Once the facility is built, the implementation of safety measures can protect industrial items and ensure tank integrity. A tailored methodology for the calculation of safety distances between wild vegetation and tanks accounting for the safety system was developed and applied to a case study. The outcomes provide useful information on the effectiveness of safety measures for the protection of industrial items exposed to wildfire.

The release of hazardous materials induced by natural events affecting industrial facilities presents peculiar characteristics because of the huge potential extension of the affected areas. The reduction of both the likelihood and the magnitude of such events represents an essential step to reduce the risk associated with Natech accidents. Nevertheless, the evaluation of damage to the environment in Natech events has been poorly addressed. In the present study, past accidents analysis was carried out, using both a detailed description of specific accidents and an extended database of Natech events. Lessons learnt as well as possible common patterns and main features related to such accidents were identified and discussed. The results of the present study can be intended as a preliminary step for the development of models for the quantitative assessment of damage to the environment in major accidents caused by natural events.

AimEmotional dysregulation (ED), defined by deficits in the ability to monitor and modulate the valence, intensity, and expression of emotions, is typically expressed with irritability, tantrums, mood fluctuations, and self-harm in young children with autism spectrum disorder (ASD). Although ED does not represent a diagnostic feature of ASD, its manifestations are an important contributor to functional impairment and clinical referral. This study aims to examine the relationship between ED and adaptive functioning in preschoolers clinically referred for ASD or other neurodevelopmental disorders.MethodsA sample of 100 children (74% males, mean age 39.4 ± 12.3 months), consecutively referred to a university clinic for neurodevelopmental disorders, received clinical assessments of psychopathology with the CBCL and the Autism Diagnostic Interview-Revised, of ED- with the CBCL-Attention, Anxious/Depressed, and Aggression index (CBCL-AAA), of autism symptom severity with the ADOS-2 Calibrated Severity Score (ADOS-CSS), and of global developmental/cognitive delay (GDD) with the WPPSI-IV or other age-appropriate standardized scales. Adaptive functioning was measured with the ABAS-II. Sixty-five children met DSM-5 criteria for ASD. Multivariate regression models were applied to evaluate the relative contribution of ED, ASD severity and GDD to the ABAS-II general (GAC), conceptual (CAD), social (SAD), and practical (PAD) adaptive functioning domains.ResultsOverall (n = 100), lower adaptive functioning was associated with higher CBCL-AAA (p = 0.003), higher ADOS-CSS (p < 0.001), and presence of GDD (p = 0.023). In the ASD group (n = 65), worse CAD was predicted by GDD (p = 0.016), and worse SAD and PAD by higher ADOS-CSS (p = 0.032) and ED (p = 0.002). No sex differences were detected in the study variables.ConclusionTogether with the severity of global developmental delay and of autism symptoms, ED is a significant contributor to impairment in adaptive functioning among young children with a neurodevelopmental disorder and, in particular, with ASD. ED could represent a specific target for early interventions aimed at enhancing adaptive functioning in early childhood.

The aim of this study was to establish the possible effect of age, corticosteroid treatment and brain dystrophin involvement on motor function in young boys affected by Duchenne Muscular Dystrophy who were assessed using the North Star Ambulatory Assessment between the age of 4 and 7 years. The study includes 951 North Star assessments from 226 patients. Patients were subdivided according to age, to the site of mutation and therefore to the involvement of different brain dystrophin isoforms and to corticosteroids duration. There was a difference in the maximum North Star score achieved among patients with different brain dystrophin isoforms (p = 0.007). Patients with the involvement of Dp427, Dp140 and Dp71, had lower maximum NSAA scores when compared to those with involvement of Dp427 and Dp140 or of Dp427 only. The difference in the age when the maximum score was achieved in the different subgroups did not reach statistical significance. Using a linear regression model on all assessments we found that each of the three variables, age, site of mutation and corticosteroid treatment had an influence on the NSAA values and their progression over time. A second analysis, looking at 12-month changes showed that within this time interval the magnitude of changes was related to corticosteroid treatment but not to site of mutation. Our findings suggest that each of the considered variables appear to play a role in the progression of North Star scores in patients between the age of 4 and 7 years and that these should be carefully considered in the trial design of boys in this age range.

Summary: Urinary stem cells (USCs) are a non-invasive, simple, and affordable cell source to study human diseases. Here we show that USCs are a versatile tool for studying Duchenne muscular dystrophy (DMD), since they are able to address RNA signatures and atypical mutation identification. Gene expression profiling of DMD individuals’ USCs revealed a profound deregulation of inflammation, muscle development, and metabolic pathways that mirrors the known transcriptional landscape of DMD muscle and worsens following USCs’ myogenic transformation. This pathogenic transcription signature was reverted by an exon-skipping corrective approach, suggesting the utility of USCs in monitoring DMD antisense therapy. The full DMD transcript profile performed in USCs from three undiagnosed DMD individuals addressed three splicing abnormalities, which were decrypted and confirmed as pathogenic variations by whole-genome sequencing (WGS). This combined genomic approach allowed the identification of three atypical and complex DMD mutations due to a deep intronic variation and two large inversions, respectively. All three mutations affect DMD gene splicing and cause a lack of dystrophin protein production, and one of these also generates unique fusion genes and transcripts. Further characterization of USCs using a novel cell-sorting technology (Celector) highlighted cell-type variability and the representation of cell-specific DMD isoforms. Our comprehensive approach to USCs unraveled RNA, DNA, and cell-specific features and demonstrated that USCs are a robust tool for studying and diagnosing DMD.

Background: Hospitals can be especially stressful for children with autism spectrum disorder (ASD) due to the communication and social skills deficits, lower capacity to adapt to disruption, and sensory hypersensitivity that are typical of these patients. Purpose: This study investigated how health-care professionals (HPs) experienced the clinical care and management of children with ASD undergoing medical testing in a day hospital setting, and assessed the rate of successful completion of laboratory tests and instrumental examinations. Methods: A cross-sectional questionnaire was administered to 45 HPs, inquiring about their experience in obtaining blood and urine tests, ECG, audiometry, and EEG from children with ASD. The clinical sample included 153 consecutively referred children with ASD (74.5% males, mean age 5.6 years) undergoing a medical diagnostic work-up as part of their diagnostic evaluation. The success rate of completing the various assessments was examined. Results: HPs identified aggressive behavior and communication deficits as the major challenges when providing care to children with ASD. The parents were seen as an important resource for managing the children. The completion rate of the laboratory tests and instrumental examinations was high (between 88.5% and 98.4% according to the specific type of examination). The lowest non-completion rate was found for the EEG (12.5%). Conclusions: Despite considerable challenges being reported by HPs in managing children with ASD, the scheduled assessments could be completed in the large majority of cases. Targeted approaches to preventing aggressive behaviors and obviating the communication barriers in children with ASD undergoing hospital exams are warranted.

We present a catalog of the millimeter-wave (mm-wave) continuum properties of 98 nearby ( z < 0.05) active galactic nuclei (AGNs) selected from the 70 month Swift/BAT hard-X-ray catalog that have precisely determined X-ray spectral properties and subarcsecond-resolution Atacama Large Millimeter/submillimeter Array Band 6 (211–275 GHz) observations as of 2021 April. Due to the hard-X-ray (>10 keV) selection, the sample is nearly unbiased for obscured systems at least up to Compton-thick-level obscuration, and provides the largest number of AGNs with high-physical-resolution mm-wave data (≲100–200 pc). Our catalog reports emission peak coordinates, spectral indices, and peak fluxes and luminosities at 1.3 mm (230 GHz). Additionally, high-resolution mm-wave images are provided. Using the images and creating radial surface brightness profiles of mm-wave emission, we identify emission extending from the central sources and isolated blob-like emission. Flags indicating the presence of these emission features are tabulated. Among 90 AGNs with significant detections of nuclear emission, 37 AGNs (≈41%) appear to have both or one of extended or blob-like components. We, in particular, investigate AGNs that show well-resolved mm-wave components and find that these seem to have a variety of origins (i.e., a jet, radio lobes, a secondary AGN, stellar clusters, a narrow-line region, galaxy disk, active star formation regions, or AGN-driven outflows), and some components have currently unclear origins.

We present two independent measurements of stellar velocity dispersions ( σ _⋆ ) from the Ca ii H+K λ 3969, 3934 and Mg i b λ 5183, 5172, 5167 region (3880–5550 Å) and the calcium triplet region (8350–8750 Å) for 173 hard X-ray-selected Type 1 active galactic nuclei (AGNs; z ≤ 0.08) from the 105 month Swift-BAT catalog. We construct one of the largest samples of local Type 1 AGNs that have both single-epoch virial black hole mass ( M _BH ) estimates and σ _⋆ measurements obtained from high spectral resolution data, allowing us to test the usage of such methods for supermassive black hole studies. We find that the two independent σ _⋆ measurements are highly consistent with each other, with an average offset of only 0.002 ± 0.001 dex. Comparing M _BH estimates based on broad emission lines and stellar velocity dispersion measurements, we find that the former is systematically lower by ≈0.12 dex. Consequently, Eddington ratios estimated through broad-line M _BH determinations are similarly biased (but in the opposite way). We argue that the discrepancy is driven by extinction in the broad-line region. We also find an anticorrelation between the offset from the M _BH – σ _⋆ relation and the Eddington ratio. Our sample of Type 1 AGNs shows a shallower M _BH – σ _⋆ relation (with a power-law exponent of ≈3.5) compared with that of inactive galaxies (with a power-law exponent of ≈4.5), confirming earlier results obtained from smaller samples.

1ES1927+654 is a nearby active galactic nucleus (AGN) that has shown an enigmatic outburst in optical/UV followed by X-rays, exhibiting strange variability patterns at timescales of months to years. Here we report the unusual X-ray, UV, and radio variability of the source in its postflare state (2022 January–2023 May). First, we detect an increase in the soft X-ray (0.3–2 keV) flux from 2022 May to 2023 May by almost a factor of 5, which we call the bright soft state. The hard X-ray 2–10 keV flux increased by a factor of 2, while the UV flux density did not show any significant changes (≤30%) in the same period. The integrated energy pumped into the soft and hard X-rays during this period of 11 months is ∼3.57 × 10 ^50 erg and 5.9 × 10 ^49 erg, respectively. From the energetics, it is evident that whatever is producing the soft excess (SE) is pumping out more energy than either the UV or hard X-ray source. Since the energy source presumably is ultimately the accretion of matter onto the supermassive black hole, the SE-emitting region must be receiving the majority of this energy. In addition, the source does not follow the typical disk–corona relation found in AGNs, neither in the initial flare (from 2017 to 2019) nor in the current bright soft state (2022–2023). We found that the core (

Roughly one third of the sources in the Fermi-LAT catalogs are listed as unidentified/unassociated γ -ray sources (UGS), i.e., they lack a low-energy counterpart. In addition, there is a growing population of blazars of uncertain type (BCUs). Spectroscopic observations are crucial to confirm the blazar nature of the UGSs candidate counterparts and BCUs. Hence, in 2013 we started an optical spectroscopic campaign to carry out the identifications and classifications. In this paper, as a continuation of the campaign we report the spectra of 39 sources: the sample comprises 37 sources classified as BCUs, one source classified as a BL Lac in the Fourth Source Catalog of the Fermi-LAT (4FGL), and one source classified as UGS. We classify 19 of the sources in the sample as BL Lacs, 13 as blazars with nonnegligible host-galaxy emission, six as Flat Spectrum Radio Quasars, and one as a normal elliptical galaxy. The source listed as BL Lac in the 4FGL seems to be a blazar with nonnegligible host-galaxy emission in our observations, most likely due to an ongoing quiescent state. We classified the UGS source as a BL Lac. Six out of the 39 sources were previously reported in the campaign; in general, both the classifications and redshifts are in agreement, except for one of them with no redshift reported before. Altogether, we provided reliable redshift estimates to 21 out of the 39 sources. Finally, we describe the statistics of the data collected in our campaign so far.

In clinical practice and research, innovative digital technologies have been proposed for the characterization of neuromuscular and movement disorders through objective measures. Among these, wearable devices prove to be a suitable solution for tele-monitoring, tele-rehabilitation, and daily activities monitoring. Inertial Measurement Units (IMUs) are low-cost, compact, and easy-to-use wearable devices that evaluate kinematics during different movements. Kinematic variables could support the clinical evaluation of the progression of some neuromuscular diseases and could be used as outcome measures. The current review describes the use of IMUs for the biomechanical assessment of meaningful outcome measures in individuals affected by Duchenne muscular dystrophy (DMD). The PRISMA methodology was used and the search was conducted in different databases (Scopus, Web of Science, PubMed). A total of 23 articles were examined and classified according to year of publication, ambulatory/non-ambulatory subjects, and IMU positioning on human body. The analysis points out the recent regulatory identification of Stride Velocity 95th Centile as a new endpoint in therapeutic DMD trials when measured continuously from a wearable device, while only a few studies proposed the use of IMUs in non-ambulatory patients. Clinical recognition of reliable and accurate outcome measures for the upper body is still a challenge.

Research on the association between callous–unemotional (CU) traits and intelligence yielded contradictory results. Moreover, several previous studies focused on global intelligence scores or verbal vs. nonverbal/performance abilities usually evaluated with short/abbreviated instruments. The current study builds on these previous works and explores the link between CU traits and intelligence using the full version of the Wechsler Intelligence Scale for Children—4th Edition (WISC-IV), which provides four different verbal and nonverbal abilities scores. This guarantees a more detailed evaluation of children’s intelligence and its relation to CU traits. The sample included children (N = 149; age 6–14 years old) with severe behavioral problems. Clinicians administered the WISC-IV, and parents completed questionnaires evaluating the child’s externalizing problems and CU traits. Findings showed that CU traits were associated with lower verbal comprehension scores after also controlling for gender, age, externalizing problems, and the other WISC-IV indexes. In addition, CU traits and externalizing problems did not interact in predicting the WISC-IV indexes, and there were no significant differences in the WISC-IV indexes between children with CU traits and high vs. low externalizing problems. The current study suggests the relevance of assessing and addressing verbal abilities in children with behavioral problems and CU traits.

Abstract Background In addition to morphological and cytogenetic features, acute myeloid leukemias are characterized by mutations that can be used for target-therapy; also the minimal/measurable residual disease (MRD) could be an important prognostic factor. The purpose of this retrospective study was to investigate if somatic mutations could represent an additional prognostic value in respect of MRD alone. Method At baseline, 98 patients were tested for NPM1, FLT3, and for WT1 expression; 31 for ASXL1, TET2, IDH1, IDH2, N-RAS, WT1, c-KIT, RUNX1, and DNMT3A. The same genes have been also tested after induction and consolidation. Results Overall, 60.2% of our patients resulted mutated: 24.5% carried mutations of FLT3-ITD, 38.7% of NPM1, 48.4% of c-KIT, 25.8% of N-RAS and 19.3% of IDH2. The probability of achieving a complete response (CR) was higher for younger patients, with low ELN risk score, NPM1-mutated, with low WT1 levels, and without FLT3. The presence of additional mutations represented a poor predictive factor: only 19% of these cases achieved CR in comparison to 43% of subjects without any of it. Concerning survival, it was conditioned by a lower ELN risk score, younger age, reduction > 1 log of the NPM1 mutational burden, disappearance of FLT3 mutations and lower WT1 expression. Regarding the role of the additional mutations, they impaired the outcome of 20% of the already MRD-negative patients. Concerning the possibility of predicting relapse, we observed an increase of the NPM1 mutational burden at the time-point immediately preceding the relapse (about 2 months earlier) in 50% of subjects. Similarly concerning WT1, an increase of its expression anticipated disease recurrence in 64% of cases. Conclusions We demonstrated that additional somatic mutations are able to impair outcome of the already MRD-negative subjects. About MRD, we suggest a prognostic role also for the WT1 expression. Finally, we considered as relevant the assessment of NPM1 quantity clearance instead of the presence/absence of mutations alone. Still remains in doubt the utility in terms of long-term prognosis of a baseline more complex mutational screening; we could hypothesize that it would be useful for those patients where other markers are not available or who reached the MRD negativity.

Wildfires approaching the Wildland-Industrial Interfaces can be a serious threat for industrial items located at the plant boundary. These items are typically storage tanks involving large amounts of hazardous substances. Ensuring their integrity is of paramount importance to prevent the wildfire spread inside the industrial plant, avoiding the occurrence of major accidents such as fires, explosions and toxic releases. A methodology for the evaluation of safety distances between tanks and vegetation for the protection from wildfire hazard was developed and applied to a case study. The outcomes provide useful information for an effective emergency response planning in the case of wildfire. Moreover, the results obtained rise concern about the appropriateness of clearance areas between the vegetation and industrial areas currently adopted.

Aim: The coronavirus disease 2019 (COVID-19) pandemic has abruptly changed the life of millions as travel and social contacts have been severely restricted. We assessed the psychological impact of COVID-19 on adults and children, with special attention to health care workers (HCWs).Methods: A self-rated online survey, including the Impact of Event Scale-Revised (IES-R) for adults and the Children Revised Impact of Event Scale-Revised-13 items (CRIES-13) for their 8–18-year-old offspring, was conducted in Italy on March 20–26, 2020. Linear mixed-effects models were applied to the data, accounting for age, sex, education, and other demographic characteristics.Results: Data were available from 2,419 adults (78.4% females, mean age 38.1 ± SD 13.1 years; 15.7% HCW) and 786 children (50.1% male, mean age 12.3 ± 3.2 years). Median (IQR) IES-R score was 30.0 (21.0–40.0), corresponding to mild psychological impact, with 33.2% reporting severe psychological impact. IES-R was lower in HCWs (29.0) than non-HCWs (31.0), but HCWs directly involved in COVID-19 care had higher scores [33.0 (26.0–43.2)] than uninvolved HCWs [28.0 (19.0–36.0)]. Median CRIES-13 score was [21.0 (11.0–32.0)], with 30.9% of the children at high risk for post-traumatic stress disorder. Parent and child scores were correlated.Conclusions: Up to 30% of adult and children in the pandemic area are at high risk for post-traumatic stress disturbances. The risk is greater for HCWs directly involved in COVID-19 care and for their children.

Background and aimGut microbiota (GM) can support colorectal cancer (CRC) progression by modulating immune responses through the production of both immunostimulatory and/or immunosuppressive cytokines. The role of IL-9 is paradigmatic because it can either promote tumor progression in hematological malignancies or inhibit tumorigenesis in solid cancers. Therefore, we investigate the microbiota–immunity axis in healthy and tumor mucosa, focusing on the correlation between cytokine profile and GM signature.MethodsIn this observational study, we collected tumor (CRC) and healthy (CRC-S) mucosa samples from 45 CRC patients, who were undergoing surgery in 2018 at the Careggi University Hospital (Florence, Italy). First, we characterized the tissue infiltrating lymphocyte subset profile and the GM composition. Subsequently, we evaluated the CRC and CRC-S molecular inflammatory response and correlated this profile with GM composition, using Dirichlet multinomial regression.ResultsCRC samples displayed higher percentages of Th17, Th2, and Tregs. Moreover, CRC tissues showed significantly higher levels of MIP-1α, IL-1α, IL-1β, IL-2, IP-10, IL-6, IL-8, IL-17A, IFN-γ, TNF-α, MCP-1, P-selectin, and IL-9. Compared to CRC-S, CRC samples also showed significantly higher levels of the following genera: Fusobacteria, Proteobacteria, Fusobacterium, Ruminococcus2, and Ruminococcus. Finally, the abundance of Prevotella spp. in CRC samples negatively correlated with IL-17A and positively with IL-9. On the contrary, Bacteroides spp. presence negatively correlated with IL-9.ConclusionsOur data consolidate antitumor immunity impairment and the presence of a distinct microbiota profile in the tumor microenvironment compared with the healthy mucosa counterpart. Relating the CRC cytokine profile with GM composition, we confirm the presence of bidirectional crosstalk between the immune response and the host’s commensal microorganisms. Indeed, we document, for the first time, that Prevotella spp. and Bacteroides spp. are, respectively, positively and negatively correlated with IL-9, whose role in CRC development is still under debate.

IntroductionThe aim of this study was to report 36-month longitudinal changes using the North Star Ambulatory Assessment (NSAA) in ambulant patients affected by Duchenne muscular dystrophy amenable to skip exons 44, 45, 51 or 53.Materials and methodsWe included 101 patients, 34 had deletions amenable to skip exon 44, 25 exon 45, 19 exon 51, and 28 exon 53, not recruited in any ongoing clinical trials. Five patients were counted to skip exon 51 and 53 since they had a single deletion of exon 52.ResultsThe difference between subgroups (skip 44, 45, 51 and 53) was significant at 12 (p = 0.043), 24 (p = 0.005) and 36 months (p≤0.001).DiscussionMutations amenable to skip exons 53 and 51 had lower baseline values and more negative changes than the other subgroups while those amenable to skip exon 44 had higher scores both at baseline and at follow up.ConclusionOur results confirm different progression of disease in subgroups of patients with deletions amenable to skip different exons. This information is relevant as current long term clinical trials are using the NSAA in these subgroups of mutations.

Eosinophilic granulomatosis with polyangiitis (EGPA) is an anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. A genome-wide association study showed a correlation between ANCA-negative EGPA and variants of genes encoding proteins with intestinal barrier functions, suggesting that modifications of the mucosal layer and consequent gut dysbiosis might be involved in EGPA pathogenesis. Here, we characterized the gut microbiota (GM) composition and the intestinal immune response in a cohort of EGPA patients. Faeces from 29 patients and 9 unrelated healthy cohabitants were collected, and GM and derived metabolites’ composition were compared. Seven intestinal biopsies from EGPA patients with gastrointestinal manifestations were analysed to assess the T-cell distribution and its correlation with GM and EGPA clinical and laboratory features. No significant differences in GM composition, nor in the total amount of faecal metabolites, emerged between patients and controls. Nevertheless, differences in bacterial taxa abundances and compositional GM-derived metabolites profile were observed. Notably, an enrichment of potential pathobionts (Enterobacteriacee and Streptococcaceae) was found in EGPA, particularly in patients with active disease, while lower levels were found in patients on immunosuppression, compared with non-immunosuppressed ones. Significantly lower amounts of hexanoic acid were found in patients, compared to controls. The analysis of the immune response in the gut mucosa revealed a high frequency of IFN-γ/IL-17-producing T lymphocytes, and a positive correlation between EGPA disease activity and intestinal T-cell levels. Our data suggest that an enrichment in potential intestinal pathobionts might drive an imbalanced inflammatory response in EGPA.

Abnormalities in the plasma amino acid and/or urinary organic acid profile have been reported in autism spectrum disorder (ASD). An imbalance between excitatory and inhibitory neuronal activity has been proposed as a mechanism to explain dysfunctional brain networks in ASD, as also suggested by the increased risk of epilepsy in this disorder. This study explored the possible association between presence of EEG paroxysmal abnormalities and the metabolic profile of plasma amino acids and urinary organic acids in children with ASD. In a sample of 55 children with ASD (81.8% male, mean age 53.67 months), EEGs were recorded, and 24 plasma amino acids and 56 urinary organic acids analyzed. EEG epileptiform discharges were found in 36 (65%) children. A LASSO regression, adjusted by age and sex, was applied to evaluate the association of plasma amino acids and urinary organic acids profiles with the presence of EEG epileptiform discharges. Plasma levels of threonine (THR) (coefficient = −0.02, p = 0.04) and urinary concentration of 3-Hydroxy-3-Methylglutaric acid (HMGA) (coefficient = 0.04, p = 0.02) were found to be associated with the presence of epileptiform discharges. These results suggest that altered redox mechanisms might be linked to epileptiform brain activity in ASD.

The increase both in frequency and magnitude of natural events makes the study of the interaction between natural events and industrial facilities of paramount importance. Natural events may affect facilities leading to major accidents (e.g. explosion, fire, …) and these events are called NaTech (natural hazards triggering technological disasters). Extreme temperatures are one of the causes of NaTechs and the first step in studying their interaction with industrial facilities is given by the historical analysis of past accidents, being essentially the only source of information. To do this, a dataset of 305 past events was collected and analysed in order to highlight the main features of these accidents, such as the trend over the years, the geographical location, the final scenarios and the type of industrial sectors involved.

SARS-CoV-2 is the viral agent responsible for the pandemic that in the first months of 2020 caused about 400,000 deaths. Among compounds proposed to fight the SARS-CoV-2-related disease (COVID-19), tyrosine kinase inhibitors (TKIs), already effective in Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL) and chronic myeloid leukemia (CML), have been proposed on the basis of their antiviral action already demonstrated against SARS-CoV-1. Very few cases of COVID-19 have been reported in Ph+ ALL and in CML Italian cohorts; authors suggested that this low rate of infections might depend on the use of TKIs, but the biological causes of this phenomenon remain unknown. In this study, the CML model was used to test if TKIs would sustain or not the viral replication and if they could damage patient immunity. Firstly, the infection and replication rate of torquetenovirus (TTV), whose load is inversely proportional to the host immunological control, have been measured in CML patients receiving nilotinib. A very low percentage of subjects were infected at baseline, and TTV did not replicate or at least showed a low replication rate during the follow-up, with a mean load comparable to the measured one in healthy subjects. Then, after gene expression profiling experiments, we found that several “antiviral” genes, such as CD28 and IFN gamma, were upregulated, while genes with “proviral” action, such as ARG-1, CEACAM1, and FUT4, were less expressed during treatment with imatinib, thus demonstrating that TKIs are not detrimental from the immunological point of view. To sum up, our data could offer some biological explanations to the low COVID-19 occurrence in Ph+ ALL and CML patients and sustain the use of TKIs in COVID-19, as already proposed by several international ongoing studies.

Summary: The Tn antigen is a well-known tumor-associated carbohydrate determinant, often incorporated in glycopeptides to develop cancer vaccines. Herein, four copies of a conformationally constrained mimetic of the antigen TnThr (GalNAc-Thr) were conjugated to the adjuvant CRM197, a protein licensed for human use. The resulting vaccine candidate, mime[4]CRM elicited a robust immune response in a triple-negative breast cancer mouse model, correlated with high frequency of CD4+ T cells and low frequency of M2-type macrophages, which reduces tumor progression and lung metastasis growth. Mime[4]CRM-mediated activation of human dendritic cells is reported, and the proliferation of mime[4]CRM-specific T cells, in cancer tissue and peripheral blood of patients with breast cancer, is demonstrated. The locked conformation of the TnThr mimetic and a proper presentation on the surface of CRM197 may explain the binding of the conjugate to the anti-Tn antibody Tn218 and its efficacy to fight cancer cells in mice.

Although Attention Deficit Hyperactivity Disorder (ADHD) has been related to an increased risk for behavioral addictions, the relationship between ADHD and Internet Gaming Disorder (IGD) is still debated. The aim of this study is to address this topic by exploring the prevalence of IGD in a consecutive sample of ADHD youth, compared to a normal control group, and by assessing selected psychopathological and cognitive features in ADHD patients with and without IGD. One hundred and eight patients with ADHD (mean age 11.7 ± 2.6 years, 96 males) and 147 normal controls (NC) (mean age 13.9 ± 3.0 years, 114 males) were included in the study and received structured measures for IGD. In the ADHD group, 44% of the sample were above the IGD cut-off, compared to 9.5% in the NC group. ADHD patients with IGD presented with greater severity and impairment, more severe ADHD symptomatology, more internalizing symptoms, particularly withdrawal/depression and socialization problems, and more prominence of addiction and evasion dimensions. A binary logistic regression showed that the degree of inattention presented a greater weight in determining IGD. These findings may be helpful for identifying, among ADHD patients, those at higher risk for developing a superimposed IGD.

We present the active galactic nucleus (AGN) catalog and optical spectroscopy for the second data release of the Swift BAT AGN Spectroscopic Survey (BASS DR2). With this DR2 release we provide 1449 optical spectra, of which 1182 are released for the first time, for the 858 hard-X-ray-selected AGNs in the Swift BAT 70-month sample. The majority of the spectra (801/1449, 55%) are newly obtained from Very Large Telescope (VLT)/X-shooter or Palomar/Doublespec. Many of the spectra have both higher resolution ( R > 2500, N ∼ 450) and/or very wide wavelength coverage (3200–10000 Å, N ∼ 600) that are important for a variety of AGN and host galaxy studies. We include newly revised AGN counterparts for the full sample and review important issues for population studies, with 47 AGN redshifts determined for the first time and 790 black hole mass and accretion rate estimates. This release is spectroscopically complete for all AGNs (100%, 858/858), with 99.8% having redshift measurements (857/858) and 96% completion in black hole mass estimates of unbeamed AGNs (722/752). This AGN sample represents a unique census of the brightest hard-X-ray-selected AGNs in the sky, spanning many orders of magnitude in Eddington ratio ( L / L _Edd = 10 ^−5 –100), black hole mass ( M _BH = 10 ^5 –10 ^10 M _⊙ ), and AGN bolometric luminosity ( L _bol = 10 ^40 –10 ^47 erg s ^−1 ).

We present the BAT AGN Spectroscopic Survey (BASS) Near-infrared Data Release 2 (DR2), a study of 168 nearby ( $\bar{z}=0.04$ , z < 0.6) active galactic nuclei (AGN) from the all-sky Swift Burst Array Telescope X-ray survey observed with the Very Large Telescope (VLT)/X-shooter in the near-infrared (NIR; 0.8–2.4 μ m). We find that 49/109 (45%) Seyfert 2 and 35/58 (60%) Seyfert 1 galaxies observed with VLT/X-shooter show at least one NIR high-ionization coronal line (CL; ionization potential χ > 100 eV). Comparing the emission of the [Si vi ] λ 1.9640 CL with the X-ray emission for the DR2 AGN, we find a significantly tighter correlation, with a lower scatter (0.37 dex) than that for the optical [O iii ] λ 5007 line (0.71 dex). We do not find any correlation between CL emission and the X-ray photon index Γ. We find a clear trend of line blueshifts with increasing ionization potential in several CLs, such as [Si vi ] λ 1.9640, [Si x ] λ 1.4300, [S viii ] λ 0.9915, and [S ix ] λ 1.2520, indicating the radial structure of the CL region. Finally, we find a strong underestimation bias in black hole mass measurements of Sy 1.9 using broad H α due to the presence of significant dust obscuration. In contrast, the broad Pa α and Pa β emission lines are in agreement with the M – σ relation. Based on the combined DR1 and DR2 X-shooter sample, the NIR BASS sample now comprises 266 AGN with rest-frame NIR spectroscopic observations, the largest set assembled to date.

Virial black hole (BH) mass ( M _BH ) determination directly involves knowing the broad-line region (BLR) clouds’ velocity distribution, their distance from the central supermassive BH ( R _BLR ), and the virial factor ( f ). Understanding whether biases arise in M _BH estimation with increasing obscuration is possible only by studying a large ( N > 100) statistical sample of obscuration-unbiased (hard) X-ray-selected active galactic nuclei (AGNs) in the rest-frame near-infrared (0.8–2.5 μ m) since it penetrates deeper into the BLR than the optical. We present a detailed analysis of 65 local Burst Alert Telescope (BAT) selected Seyfert galaxies observed with Magellan/FIRE. Adding these to the near-infrared BAT AGN spectroscopic survey database, we study a total of 314 unique near-infrared spectra. While the FWHMs of H α and near-infrared broad lines (He i , Pa β , Pa α ) remain unbiased to either BLR extinction or X-ray obscuration, the H α broad-line luminosity is suppressed when N _H ≳ 10 ^21 cm ^−2 , systematically underestimating M _BH by 0.23–0.46 dex. Near-infrared line luminosities should be preferred to H α until N _H < 10 ^22 cm ^−2 , while at higher obscuration a less-biased R _BLR proxy should be adopted. We estimate f for Seyfert 1 and 2 using two obscuration-unbiased M _BH measurements, i.e., the stellar velocity dispersion and a BH mass prescription based on near-infrared and X-ray, and find that the virial factors do not depend on the redshift or obscuration, but some broad lines show a mild anticorrelation with M _BH . Our results show the critical impact obscuration can have on BLR characterization and the importance of the near-infrared and X-rays for a less-biased view of the BLR.

We present new central stellar velocity dispersions for 484 Sy 1.9 and Sy 2 from the second data release of the Swift/BAT AGN Spectroscopic Survey (BASS DR2). This constitutes the largest study of velocity dispersion measurements in X-ray-selected obscured active galactic nuclei (AGN) with 956 independent measurements of the Ca ii H and K λ 3969, 3934 and Mg I λ 5175 region (3880–5550 Å) and the calcium triplet region (8350–8730 Å) from 642 spectra mainly from VLT/X-Shooter or Palomar/DoubleSpec. Our sample spans velocity dispersions of 40–360 km s ^1 , corresponding to 4–5 orders of magnitude in black hole mass ( M _BH = 10 ^5.5−9.6 M _⊙ ), bolometric luminosity ( L _bol ∼ 10 ^42–46 erg s ^−1 ), and Eddington ratio ( L / L _Edd ∼ 10 ^−5 to 2). For 281 AGN, our data and analysis provide the first published central velocity dispersions, including six AGN with low-mass black holes ( M _BH = 10 ^5.5−6.5 M _⊙ ), discovered thanks to high spectral resolution observations ( σ _inst ∼ 25 km s ^−1 ). The survey represents a significant advance with a nearly complete census of velocity dispersions of hard X-ray–selected obscured AGN with measurements for 99% of nearby AGN ( z < 0.1) outside the Galactic plane (∣ b ∣ > 10°). The BASS AGN have much higher velocity dispersions than the more numerous optically selected narrow-line AGN (i.e., ∼150 versus ∼100 km s ^−1 ) but are not biased toward the highest velocity dispersions of massive ellipticals (i.e., >250 km s ^−1 ). Despite sufficient spectral resolution to resolve the velocity dispersions associated with the bulges of small black holes (∼10 ^4–5 M _⊙ ), we do not find a significant population of super-Eddington AGN. Using estimates of the black hole sphere of influence from velocity dispersion, direct stellar and gas black hole mass measurements could be obtained with existing facilities for more than ∼100 BASS AGN.

We present measurements of broad emission lines and virial estimates of supermassive black hole masses ( M _BH ) for a large sample of ultrahard X-ray-selected active galactic nuclei (AGNs) as part of the second data release of the BAT AGN Spectroscopic Survey (BASS/DR2). Our catalog includes M _BH estimates for a total of 689 AGNs, determined from the H α , H β , Mg ii λ 2798, and/or C iv λ 1549 broad emission lines. The core sample includes a total of 512 AGNs drawn from the 70 month Swift/BAT all-sky catalog. We also provide measurements for 177 additional AGNs that are drawn from deeper Swift/BAT survey data. We study the links between M _BH estimates and line-of-sight obscuration measured from X-ray spectral analysis. We find that broad H α emission lines in obscured AGNs ( $\mathrm{log}({N}_{{\rm{H}}}/{\mathrm{cm}}^{-2})\gt 22.0$ ) are on average a factor of ${8.0}_{-2.4}^{+4.1}$ weaker relative to ultrahard X-ray emission and about ${35}_{-12}^{\,+7}$ % narrower than those in unobscured sources (i.e., $\mathrm{log}({N}_{{\rm{H}}}/{\mathrm{cm}}^{-2})\lt 21.5$ ). This indicates that the innermost part of the broad-line region is preferentially absorbed. Consequently, current single-epoch M _BH prescriptions result in severely underestimated (>1 dex) masses for Type 1.9 sources (AGNs with broad H α but no broad H β ) and/or sources with $\mathrm{log}({N}_{{\rm{H}}}/{\mathrm{cm}}^{-2})\gtrsim 22.0$ . We provide simple multiplicative corrections for the observed luminosity and width of the broad H α component ( L [bH α ] and FWHM[bH α ]) in such sources to account for this effect and to (partially) remedy M _BH estimates for Type 1.9 objects. As a key ingredient of BASS/DR2, our work provides the community with the data needed to further study powerful AGNs in the low-redshift universe.

We determine the low-redshift X-ray luminosity function, active black hole mass function (BHMF), and Eddington ratio distribution function (ERDF) for both unobscured (Type 1) and obscured (Type 2) active galactic nuclei (AGNs), using the unprecedented spectroscopic completeness of the BAT AGN Spectroscopic Survey (BASS) data release 2. In addition to a straightforward 1/ V _max approach, we also compute the intrinsic distributions, accounting for sample truncation by employing a forward-modeling approach to recover the observed BHMF and ERDF. As previous BHMFs and ERDFs have been robustly determined only for samples of bright, broad-line (Type 1) AGNs and/or quasars, ours are the first directly observationally constrained BHMF and ERDF of Type 2 AGNs. We find that after accounting for all observational biases, the intrinsic ERDF of Type 2 AGNs is significantly more skewed toward lower Eddington ratios than the intrinsic ERDF of Type 1 AGNs. This result supports the radiation-regulated unification scenario, in which radiation pressure dictates the geometry of the dusty obscuring structure around an AGN. Calculating the ERDFs in two separate mass bins, we verify that the derived shape is consistent, validating the assumption that the ERDF (shape) is mass-independent. We report the local AGN duty cycle as a function of mass and Eddington ratio, by comparing the BASS active BHMF with the local mass function for all supermassive black holes. We also present the $\mathrm{log}N-\mathrm{log}S$ of the Swift/BAT 70 month sources.

We present the second catalog and data release of optical spectral line measurements and active galactic nucleus (AGN) demographics of the BAT AGN Spectroscopic Survey, which focuses on the Swift-BAT hard X-ray detected AGNs. We use spectra from dedicated campaigns and publicly available archives to investigate spectral properties of most of the AGNs listed in the 70 month Swift-BAT all-sky catalog; specifically, 743 of the 746 unbeamed and unlensed AGNs (99.6%). We find a good correspondence between the optical emission line widths and the hydrogen column density distributions using the X-ray spectra, with a clear dichotomy of AGN types for N _H = 10 ^22 cm ^−2 . Based on optical emission-line diagnostics, we show that 48%–75% of BAT AGNs are classified as Seyfert, depending on the choice of emission lines used in the diagnostics. The fraction of objects with upper limits on line emission varies from 6% to 20%. Roughly 4% of the BAT AGNs have lines too weak to be placed on the most commonly used diagnostic diagram, [O iii ] λ 5007/H β versus [N ii ] λ 6584/H α , despite the high signal-to-noise ratio of their spectra. This value increases to 35% in the [O iii ] λ 5007/[O ii ] λ 3727 diagram, owing to difficulties in line detection. Compared to optically selected narrow-line AGNs in the Sloan Digital Sky Survey, the BAT narrow-line AGNs have a higher rate of reddening/extinction, with H α /H β > 5 (∼36%), indicating that hard X-ray selection more effectively detects obscured AGNs from the underlying AGN population. Finally, we present a subpopulation of AGNs that feature complex broad lines (34%, 250/743) or double-peaked narrow emission lines (2%, 17/743).

In this study, we use the Swift/BAT AGN sample, which has received extensive multiwavelength follow-up analysis as a result of the BAT AGN Spectroscopic Survey, to develop a diagnostic for nuclear obscuration by examining the relationship between the line-of-sight column densities ( N _H ), the 2–10 keV to 12 μ m luminosity ratio, and WISE mid-infrared colors. We demonstrate that heavily obscured AGNs tend to exhibit both preferentially “redder” mid-infrared colors and lower values of L _X,Obs. / L _12 _μ _m than less obscured AGNs, and we derive expressions relating N _H to the L _X,Obs. / L _12 _μ _m and L _22 _μ _m / L _4.6 _μ _m luminosity ratios, as well as develop diagnostic criteria using these ratios. Our diagnostic regions yield samples that are ≳80% complete and ≳60% pure for AGNs with log( N _H /cm ^−2 ) ≥ 24, as well as ≳85% pure for AGNs with $\mathrm{log}({N}_{{\rm{H}}}/{\mathrm{cm}}^{-2})\gtrsim 23.5$ . We find that these diagnostics cannot be used to differentiate between optically star-forming galaxies and active galaxies. Further, mid-IR contributions from host galaxies that dominate the observed 12 μ m emission can lead to larger apparent X-ray deficits and redder mid-IR colors than the AGNs would intrinsically exhibit, though this effect helps to better separate less and more obscured AGNs. Finally, we test our diagnostics on two catalogs of AGNs and infrared galaxies, including the XMM-Newton XXL-N field, and we identify several known Compton-thick AGNs, as well as a handful of candidate heavily obscured AGNs based upon our proposed obscuration diagnostics.

The BAT AGN Spectroscopic Survey (BASS) is designed to provide a highly complete census of the key physical parameters of the supermassive black holes (SMBHs) that power local active galactic nuclei (AGNs) ( z ≲ 0.3), including their bolometric luminosity ( L _bol ), black hole (BH) mass ( M _BH ), accretion rates ( L _bol / L _Edd ), line-of-sight gas obscuration ( N _H ), and the distinctive properties of their host galaxies (e.g., star formation rates, masses, and gas fractions). We present an overview of the second data release of BASS (DR2), an unprecedented spectroscopic AGN survey in spectral range, resolution, and sensitivity, including 1449 optical (∼3200 Å–1 μ m) and 233 near-IR (1–2.5 μ m) spectra for the brightest 858 ultrahard X-ray (14–195 keV) selected AGNs across the entire sky and essentially all levels of obscuration. This release provides a highly complete set of key measurements (emission-line measurements and central velocity dispersions), with 99.9% measured redshifts and 98% BH masses estimated (for unbeamed AGNs outside the Galactic plane). The BASS DR2 AGN sample represents a unique census of nearby powerful AGNs, spanning over 5 orders of magnitude in AGN bolometric luminosity ( L _bol ∼ 10 ^40 –10 ^47 erg s ^−1 ), BH mass ( M _BH ∼ 10 ^5 –10 ^10 M _⊙ ), Eddington ratio ( L _bol / L _Edd ≳ 10 ^−5 ), and obscuration ( N _H ∼ 10 ^20 –10 ^25 cm ^−2 ). The public BASS DR2 sample and measurements can thus be used to answer fundamental questions about SMBH growth and its links to host galaxy evolution and feedback in the local universe, as well as open questions concerning SMBH physics. Here we provide a brief overview of the survey strategy, the key BASS DR2 measurements, data sets and catalogs, and scientific highlights from a series of DR2-based works pursued by the BASS team.

Background: Beside the core symptoms, patients with attention-deficit/hyperactivity disorder (ADHD) frequently show relevant difficulty in developing relationships with peers. Although ADHD symptoms may account for social impairment, deficits in cognitive and/or affective empathy have also been involved. Our aim was to investigate the effect of methylphenidate (MPH) treatment on affective and cognitive empathy. Methods: Sixty-one drug-naïve youths with ADHD (age range 6 to 17 years, mean 10.3 ± 2.8 years, 51 males) naturalistically treated with MPH monotherapy were followed up for 6 months for ADHD symptoms and empathy, measured with the Basic Empathy Scale. Results: After being treated with MPH, the patients showed a significant improvement in affective and cognitive empathy scores. Linear regression models showed that changes in inattention symptoms predicted changes in affective but not in cognitive empathy, while changes in the hyperactivity/impulsivity symptoms did not predict changes in affective or cognitive empathy. Conclusions: Our study provides a further contribution for a better understanding of the possible effects of the MPH on youth’s characteristics.

Pancreatic cancer (PC) still represents an unresolved therapeutic challenge due to the associated poor prognosis and the lack of responsiveness to current treatments. Surgery, followed by adjuvant therapy, is the only potentially curative treatment for PC; however, only 20% of PC patients have a potential resectable disease at diagnosis and the overall 5-year survival rate does not exceed 20%. In this context, better, more effective strategies are needed. Immunotherapy is an interesting approach for cancer treatments, but increasing evidence testifies that the immune system plays contrasting roles in both tumour elimination and tumour progression. In particular, PC is considered relatively immune resistant due to the characteristic fibrosis, the presence of immunosuppressive cells, and the compact extracellular matrix that defines the tumour microenvironment and allows for the growth of cancer cells. Despite this, there is evidence that PC cells are able to induce an anti-tumour immune response that can impact the disease course. More recently, it has become clear that PC activates both the anti-cancer immune response and the immunosuppressive effects of the immune system; therefore, for the immune-therapeutic strategies to be effective, they should involve not only the stimulation of the immune system but also the control of the immunosuppressive milieu. In this review, we discuss the dual role of immune cells in the onset and progression of PC.

Background and Rationale: Among the key players in the pathogenesis of Amyotrophic Lateral Sclerosis (ALS), microglia and T regulatory lymphocytes (Treg) are candidate cells for modifying the course of the disease. The gut microbiota (GM) acts by shaping immune tolerance and regulating the Treg number and suppressive function, besides circulating neuropeptides, and other immune cells that play in concert through the gut-brain axis. Previous mouse models have shown an altered enteric flora in early stage ALS, pointing to a possible GM role in ALS pathogenesis. Fecal Microbial Transplantation (FMT) is a well-known therapeutic intervention used to re-establish the proper microenvironment and to modulate enteric and systemic immunity.Methods: We are going to perform a multicenter randomized double-blind clinical trial employing FMT as a therapeutic intervention for ALS patients (NCT0376632). Forty-two ALS patients, at an early stage, will be enrolled with a 2:1 allocation ratio (28 FMT-treated patients vs. 14 controls). Study duration will be 12 months per patient. Three endoscopic procedures for intestinal biopsies in FMT and control groups are predicted at baseline, month 6 and month 12; at baseline and at month 6 fresh feces from healthy donors will be infused at patients in the intervention arm. The primary outcome is a significant change in Treg number between FMT-treated patients and control arm from baseline to month 6. Secondary outcomes include specific biological aims, involving in-depth analysis of immune cells and inflammatory status changes, central and peripheral biomarkers of ALS, besides comprehensive analysis of the gut, saliva and fecal microbiota. Other secondary aims include validated clinical outcomes of ALS (survival, forced vital capacity, and modifications in ALSFRS-R), besides safety and quality of life.Expected Results: We await FMT to increase Treg number and suppressive functionality, switching the immune system surrounding motorneurons to an anti-inflammatory, neuroprotective status. Extensive analysis on immune cell populations, cytokines levels, and microbiota (gut, fecal and saliva) will shed light on early processes possibly leading the degenerative ALS course.Conclusions: This is the first trial with FMT as a potential intervention to modify immunological response to ALS and disease progression at an early stage.