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In the Emilia-Romagna region (Northern Italy), the identification and management of women at familial/hereditary risk of breast and ovarian cancer is guided by a well-established regional protocol. Here we report the results of the experience of private supplementation of public healthcare service in offering the possibility to undergo BRCA1/2 testing and/or multigene panel testing (MGPT) within a well-defined pathway to women unfulfilling regional criteria. Out of 177 patients referred to our center who underwent BRCA1/2 testing, 175 tested negative while two (1.1%) resulted carriers of pathogenic variants in BRCA2; 69 patients also underwent MGPT, and in four cases (5.8%) a pathogenic variant were found (two in ATM and one in CHEK2 and RAD51C, respectively). Overall, this private supplementation of territorial public healthcare system has made it possible to confirm the validity of regional criteria for genetic testing access (concordance: 98.9%), but also to identify carriers of pathogenic variants of BRCA1/2 that would have escaped regional protocol, to support the effectiveness of MGPT for the identification of rare cases (not BRCA) at mild/high risk, and to provide reassurance to women who were found to be non-carriers of pathogenic variants, who may benefit from a more accurate assessment of their risk. [ABSTRACT FROM AUTHOR]

Background: The severity of thyroid cancer is judged on the basis of histologic and clinical features. A limited number of studies have considered urinary metabolite signatures for its diagnosis, and no reliable urinary metabolite biomarkers have been proposed. This diagnostic method would be particularly valuable because of its non-invasive nature. Method: A nuclear magnetic resonance (NMR)-based metabolomics approach was used as the analytical platform to study the urine samples of patients with PTMC. Urine samples collected from 41 PTMC patients, 52 healthy subjects, and 13 patients with benign tumors were analyzed using 1H-NMR spectroscopy to identify metabolic changes. PLS-DA, or partial least squares discriminant analysis, was used to analyze the NMR spectra. A double cross-validation method and randomization tests were used to validate PLS-DA models. Results: Clear discriminations between PTMC patients and healthy controls, as well as between PTMC patients and patients with benign tumors were obtained. Collectively, pi-methyhistidine, trimethylamine, myo-inositol, acetate, suberate, azelate, mannitol, tau-methylhistine, ascorbate, 3-aminoisobutyric acid, 2-oxoglutarate, and methanol contributed to the discrimination. Apart from myo-inositol and methanol, all of these metabolites exhibited increased levels in the urine samples of PTMC patients as compared to that of patients with benign tumors. Conclusions: The application of this NMR-based metabolomics approach allowed the detection of anomalous metabolic traits directly connected PTMC, potentially yielding a more sensitive and comprehensive diagnostic results for PTMC. [ABSTRACT FROM AUTHOR]

Cytotoxic attack particles released by CTLs and NK cells include diverse phospholipid membrane and glycoprotein encapsulated entities that contribute to target cell killing. Supramolecular attack particles (SMAPs) are one type of particle characterized by a cytotoxic core enriched in granzymes and perforin surrounded by a proteinaceous shell including thrombospondin (TSP)-1. TSP-4 was also detected in bulk analysis of SMAPs released by CTLs; however, it has not been investigated whether TSP-4 contributes to distinct SMAP types or the same SMAP type as TSP-1 and, if in the same type of SMAP, whether TSP-4 and TSP-1 cooperate or compete. Here, we observed that TSP-4 expression increased upon CD8+ T cell activation while, surprisingly, TSP-1 was down-regulated. Correlative Light and Electron Microscopy and Stimulated Emission Depletion microscopy localized TSP-4 and TSP-1 in SMAP-containing multicore granules. Superresolution dSTORM revealed that TSP-4 and TSP-1 are usually enriched in the same SMAPs while particles with single-positive shells are rare. Retention Using Selective Hooks assays showed that TSP-4 localizes to the lytic granules faster than TSP-1 and promotes its accumulation therein. TSP-4 contributed to direct CTL-mediated killing, as previously shown for TSP-1. TSP-4 and TSP-1 were both required for latent SMAP-mediated cell killing, in which released SMAPs kill targets after removal of the CTLs. Of note, we found that chronic lymphocytic leukemia (CLL) cell culture supernatants suppressed expression of TSP-4 in CTL and latent SMAP-mediated killing. These results identify TSP-4 as a functionally important component of SMAPs and suggest that SMAPs may be targeted for immune suppression by CLL. [ABSTRACT FROM AUTHOR]

Simple Summary: Cadmium pollution, driven by human activities, is a significant stressor in aquatic ecosystems, bioaccumulating and biomagnifying in food chains. While its toxic effects on aquatic species' organs are well-documented, its impact on sensory systems, such as the olfactory system, remains understudied. This research focused on short-term exposure (96 h) to 25 µM cadmium chloride in adult zebrafish, evaluating structural and functional changes in their olfactory lamellae. Anthropic activities have significantly elevated cadmium levels, making it a significant stressor in aquatic ecosystems. Present in high concentrations across water bodies, cadmium is known to bioaccumulate and biomagnify throughout the food chain. While the toxic effects of cadmium on the organs and tissues of aquatic species are well-documented, little is known about its impact on sensory systems crucial for survival. Consequently, this study investigated the impact of short-term exposure (96 h) to 25 µM cadmium chloride on the olfactory system of adult zebrafish. The research aimed to assess structural and functional changes in the zebrafish's olfactory lamellae, providing a deeper understanding of how cadmium affects the sense of smell in this aquatic species. After exposure, cyto-anatomical alterations in the lamellae were analysed using light microscopy and immunocytochemistry. They revealed severe lamellar edema, epithelial thickening, and an increased number of apoptotic and crypt cells. Rodlet and goblet cells also increased by 3.5- and 2.5-fold, respectively, compared to control lamellae, and collagen density in the lamina propria increased 1.7-fold. Cadmium upregulated metallothioneins and increased the number of PCNA-positive cells. The olfactory function was assessed through a behavioural odour recognition test, followed by a recovery phase in which zebrafish exposed to cadmium were placed in clean water for six days. The exposed fish performed poorly, failing to reach food in five consecutive trials. However, lamellar damage was reduced after the recovery period, and their performance improved, becoming comparable to the control group. These results suggest that cadmium disrupts the sense of smell, and that recovery is possible after short-term exposure. This evidence sheds light on aspects of animal survival that are often overlooked when assessing environmental pollution. [ABSTRACT FROM AUTHOR]

Adequate implant primary stability is a key factor to obtain osseointegration and can be measured at insertion by insertion torque (IT) and at different timepoints with resonance frequency analysis (RFA), expressed as an implant stability quotient (ISQ). This retrospective study investigated the correlation between ISQ and IT at implant insertion. All patients who were eligible for this single-cohort retrospective clinical trial were treated with an immediate implant. IT parameters were recorded at implant insertion, and ISQ values were recorded at insertion and at 2-, 4-, and 12-month follow-ups. The study comprised 23 patients who received 32 implants. The mean IT value was 46.87 ± 9.66 Ncm (range: 25 to 65 Ncm), and the mean ISQ value at implant insertion was 71.45 ± 4.24 (range: 63 to 78); these values showed a statistically significant correlation (P < .0001). According to the present data and considering the implant design used in this trial, there is a statistically significant and positive correlation between IT and ISQ values. Thus, ISQ can be used as a reliable method to measure implant stability over time. [ABSTRACT FROM AUTHOR]

Background/Objectives: Colorectal cancer (CRC) is the third leading cause of cancer death globally, with rising incidence. The immunohistochemistry (IHC) for mismatch repair (MMR) proteins is the first technique used in routine practice to evaluate an MMR status. Microsatellite instability (MSI) may be tested in case of doubt during IHC staining. This study introduces a novel high-resolution melt (HRM) protocol for MSI detection and compares it with traditional fragment length analysis (FLA) via capillary electrophoresis. Methods: A total of 100 formalin-fixed and paraffin-embedded CRC specimens were analyzed using two distinct protocols: one based on FLA (TrueMark MSI Assay kit) and another one based on HRM (AmoyDx® Microsatellite Instability Detection Kit). Results: Overall, 68 (68.0%) of the cases were MSS, and 32 (32.0%) were MSI-H. HRM analysis was first successfully carried out in all the cases. A perfect concordance in MSI evaluation between HRM and FLA was observed. HRM showed slightly shorter hands-on time and turnaround time. Conclusions: We provided evidence of the validity of this new HRM approach in determining the MSI status of colorectal carcinomas. [ABSTRACT FROM AUTHOR]

Traditional risk assessment methodologies in toxicology have relied upon animal testing, despite concerns regarding interspecies consistency, reproducibility, costs, and ethics. New Approach Methodologies (NAMs), including cell culture and multi-level omics analyses, hold promise by providing mechanistic information rather than assessing organ pathology. However, NAMs face limitations, like lacking a whole organism and restricted toxicokinetic interactions. This is an inherent challenge when it comes to the use of omics data from in vitro studies for the prediction of organ toxicity in vivo. One solution in this context are comparative in vitro–in vivo studies as they allow for a more detailed assessment of the transferability of the respective NAM data. Hence, hepatotoxic and nephrotoxic pesticide active substances were tested in human cell lines and the results subsequently related to the biology underlying established effects in vivo. To this end, substances were tested in HepaRG and RPTEC/tERT1 cells at non-cytotoxic concentrations and analyzed for effects on the transcriptome and parts of the proteome using quantitative real-time PCR arrays and multiplexed microsphere-based sandwich immunoassays, respectively. Transcriptomics data were analyzed using three bioinformatics tools. Where possible, in vitro endpoints were connected to in vivo observations. Targeted protein analysis revealed various affected pathways, with generally fewer effects present in RPTEC/tERT1. The strongest transcriptional impact was observed for Chlorotoluron in HepaRG cells (increased CYP1A1 and CYP1A2 expression). A comprehensive comparison of early cellular responses with data from in vivo studies revealed that transcriptomics outperformed targeted protein analysis, correctly predicting up to 50% of in vivo effects. [ABSTRACT FROM AUTHOR]

Geophysics is a fundamental tool to detect buried structures of archaeological interest through non-destructive techniques. The Messapian city walls in Ugento (Puglia, southern Italy) are of great archaeological importance, and some sections are still visible. In order to locate a stretch of the city walls, geophysical prospections were performed using the low-frequency electromagnetic method and ground-penetrating radar. The surveys were carried out in a peripheral area of Ugento, near a visible section of the city walls. The analysis and interpretation of the measured data revealed clear anomalies that could be ascribed to the city walls that aligned with an adjacent section of the visible walls. Archaeological excavation campaigns found a part of the walls and some important elements, as identified by the geophysical data interpretation. [ABSTRACT FROM AUTHOR]

In this paper, a new method for evaluating hot-electron degradation in p-GaN gate AlGaN/GaN power HEMTs is proposed. The method exploits a commercial parameter analyzer to study VTH and RON drifts induced by on-state stress at VDS = 50 V. The results show that VTH drift and part of the RON degradation induced by the on-state stress are recoverable and likely due to the ionization of C-related acceptors in the buffer. This was confirmed by a preliminary characterization of C-related buffer traps. Conversely, the remaining part of RON degradation (not recovered in 1000 s) was strongly affected by the surface treatment. The current level set during on-state stress affected the amount of non-recoverable degradation, confirming the involvement of hot electrons. Thanks to the monitoring of the parameters' recovery, the proposed method provides important insights into the physical mechanisms governing the parameters' degradation. This extends the capabilities of state-of-the art systems, without the need for custom setup development. [ABSTRACT FROM AUTHOR]

Background: BRCA1:c.5017_5019del (p.His1673del) is a founder variant relatively frequent in Northern Italy. Despite previous suggestion of pathogenicity, variant classification in public databases is still conflicting, needing additional evidence. Methods: Maximum likelihood penetrance of breast/ovarian and other cancer types was estimated using full pedigree data from 53 informative Italian families. The effect of the variant on BRCA1‐ABRAXAS1 interaction was assessed using a GFP‐fragment reassembly‐based PPI assay. Results were combined with additional data from multiple sources to classify the variant according to ACMG/AMP classification rules specified for BRCA1/2. Results: Variant‐carriers displayed increased risk for ovarian cancer (HR = 33.0, 95% CI = 7.0–155.0; cumulative risk at age 70 = 27.6%, 95% CI = 12.6–40.0%) but not for breast cancer (HR = 0.7, 95% CI = 0.2–2.2). An increased risk of uterine cancer (HR = 8.0, 95% CI = 1.03–61.6) emerged, warranting further evaluation. Likelihood‐ratio in favor of pathogenicity was 98898642.82 under assumption of standard BRCA1 breast and ovarian penetrance, and 104240832.84 after excluding breast cancer diagnoses (based on penetrance results). Functional analysis demonstrated that the variant abrogates the BRCA1‐ABRAXAS1 binding, supporting the PS3 code assignment within the ACMG/AMP rule‐based model. Collectively, these findings allowed to classify the variant as pathogenic. Conclusion: Pathogenicity of BRCA1:c.5017_5019del(p.His1673del) has been confirmed; however, breast cancer risk in Italian families is not increased, unlike in families from other countries and in carriers of most BRCA1 pathogenic variants. The knowledge of atypical risk profiles for this and other variants will pave the way for personalized management based on specific genotype. [ABSTRACT FROM AUTHOR]

Introduction: It has been suggested that the COVID-19 pandemic was a potentially traumatic occurrence that may have induced generalized anxiety and discomfort, particularly in susceptible populations like individuals with mental illnesses. The therapeutic approach known as eye movement desensitization and reprocessing (EMDR) has been shown to be successful in helping patients process traumatic events and restore wellbeing. Nevertheless, little is known about the precise processes through which EMDR fosters symptom recovery. Methods: In order to disentangle these issues, we conducted a randomized controlled trial (ClinicalTrials.gov Identifier NCT06110702) with 107 participants who were selected from university hospitals as a sample of investigation. Random assignments were applied to the participants in order to assign them to the experimental and control groups. The experimental group, but not the control group, underwent an 8-week EMDR intervention. Body perception, disgust, and emotions of guilt and shame, as well as mental contamination and posttraumatic and obsessive-compulsive symptoms, were investigated before and after the EMDR intervention. Results: The EMDR intervention was able to improve all of the variables investigated. Path analysis showed that body perception was able to predict both disgust and emotions of guilt and shame. Disgust was able to predict both mental contamination and obsessive-compulsive symptoms, while guilt and shame were able to predict post-traumatic symptoms. Conclusions: EMDR is an effective therapy for the treatment of post-traumatic and obsessive symptoms that acts through the promotion of improvement of the emotions of guilt/shame and disgust, respectively. Implications for clinical practice are examined. [ABSTRACT FROM AUTHOR]

The article presents the initial results of research using statistical analysis to demonstrate the emergence of a new meaning of the idiomatic expression italiani brava gente linked to the history of the Italian colonialism. The idiomatic expression, who comes from the title of a 1964 by director De Santis (Italiani, brava gente), revives the myth of Italians who, unlike their Germans allies in the Second World War, stood out for their sense of good-naturedness and humanity, their inability to carry out atrocities in war, and their lack of racism and xenophobia. Starting from 2005, with the publication of a book by the historian Angelo Del Boca (Italiani, brava gente?), the idiomatic expression has definitively acquired a new meaning that links it in a critical sense to the history of Italian colonialism. To demonstrate the emergence of this new meaning, a collection of 292 articles from the historical archive of the newspaper «la Repubblica» where the idiomatic expression appears was analysed. The collection was divided into two sections: in the first, articles published from 1984 to 2005; in the second, articles produced from 2005 (after the edition of Del Boca's book) to 31 October 2023. The results highlight that in the second group, there is a greater number of articles in which the idiomatic expression with the new meaning is used, and there is a greater frequency of words with lexical bases linked to the semantic field of Italian colonialism. This is preliminary research wich, despite already having a statistical value, will later be expanded with the consideration of other material, linked as well to the publishing sector. [ABSTRACT FROM AUTHOR]

Background: Automated pupillometry (AP) is a handheld, non-invasive tool that is able to assess pupillary light reflex dynamics and is useful for the detection of intracranial hypertension. Limited evidence is available on acute ischemic stroke (AIS) patients. The primary objective was to evaluate the ability of AP to discriminate AIS patients from healthy subjects (HS). Secondly, we aimed to compute a predictive score for AIS diagnosis based on clinical, demographic, and AP variables. Methods: We included 200 consecutive patients admitted to a comprehensive stroke center who underwent AP assessment through NPi-200 (NeurOptics®) within 72 h of stroke onset and 200 HS. The mean values of AP parameters and the absolute differences between the AP parameters of the two eyes were considered in the analyses. Predictors of stroke diagnosis were identified through univariate and multivariate logistic regressions; we then computed a nomogram based on each variable's β coefficient. Finally, we developed a web app capable of displaying the probability of stroke diagnosis based on the predictive algorithm. Results: A high percentage of pupil constriction (CH, p < 0.001), a low constriction velocity (CV, p = 0.002), and high differences between these two parameters (p = 0.036 and p = 0.004, respectively) were independent predictors of AIS. The highest contribution in the predictive score was provided by CH, the Neurological Pupil Index, CV, and CV absolute difference, disclosing the important role of AP in the discrimination of stroke patients. Conclusions: The results of our study suggest that AP parameters, and in particular, those concerning pupillary constriction, may be useful for the early diagnosis of AIS. [ABSTRACT FROM AUTHOR]

Background BRCA1/2 testing is crucial to guide clinical decisions in patients with hereditary breast/ovarian cancer, but detection of variants of uncertain significance (VUSs) prevents proper management of carriers. The ENIGMA (Evidence-based Network for the Interpretation of Germline Mutant Alleles) BRCA1/2 Variant Curation Expert Panel (VCEP) has recently developed BRCA1/2 variant classification guidelines consistent with ClinGen processes, specified against the ACMG/AMP (American College of Medical Genetics and Genomics/Association for Molecular-Pathology) classification framework. Methods The ClinGen-approved BRCA1/2-specified ACMG/AMP classification guidelines were applied to BRCA1/2 VUSs identified from 2011 to 2022 in a series of patients, retrieving information from the VCEP documentation, public databases, literature and ENIGMA unpublished data. Then, we critically re-evaluated carrier families based on new results and checked consistency of updated classification with main sources for clinical interpretation of BRCA1/2 variants. Results Among 166 VUSs detected in 231 index cases, 135 (81.3%) found in 197 index cases were classified by applying BRCA1/2-specified ACMG/AMP criteria: 128 (94.8%) as Benign/Likely Benign and 7 (5.2%) as Pathogenic/Likely Pathogenic. The average time from the first report as 'VUS' to classification using this approach was 49.4 months. Considering that 15 of these variants found in 64 families had already been internally reclassified prior to this work, this study provided 121 new reclassifications among the 151 (80.1%) remaining VUSs, relevant to 133/167 (79.6%) families. Conclusions These results demonstrated the effectiveness of new BRCA1/2 ACMG/AMP classification guidelines for VUS classification within a clinical cohort, and their important clinical impact. Furthermore, they suggested a cadence of no more than 3 years for regular review of VUSs, which however requires time, expertise and resources. [ABSTRACT FROM AUTHOR]

This study explores the application of Machine Learning (ML) and citizen engagement in improving road safety for vulnerable populations (pedestrians, cyclists) in Genoa, Italy. Aligned with the UN's 2030 Agenda for Sustainable Development, the project aims for a 50% reduction in traffic accidents by 2030.The AI4PublicPolicy initiative introduces the Virtual Policy Management Environment (VPME) platform. VPME utilizes ML, Deep Learning (DL), Natural Language Processing (NLP), and chatbots to empower the policy development lifecycle. Citizen feedback is integrated through workshops and surveys, fostering a citizen-centric approach. The Genoa pilot program demonstrates VPME's capabilities. ML models analyse historical accident and Geographic Information Systems (GIS) data to predict future high-risk areas. These predictions inform resource allocation and targeted interventions for pedestrian crossings and school walking routes ("Pedibus"). Dashboards visualize the model outputs, allowing users to assess risk levels and predict accident occurrences. Future improvements include incorporating additional data sources (demographics, real-time traffic) for enhanced model accuracy. Citizen engagement played a vital role. Co-creation workshops facilitated stakeholder participation in defining Use Cases, User Stories, and project objectives. Discussions focused on integrating data from environmental, traffic, and citizen reporting systems with VPME solutions. Participants evaluated the project approach and provided valuable feedback. The project highlights the potential of AI and citizen collaboration for data-driven policymaking. This approach empowers municipalities to make informed decisions that prioritize public safety and well-being. [ABSTRACT FROM AUTHOR]

Background.: This study evaluated the gingival crevicular fluid (GCF) and Peri- implant crevicular fluid (PICF) concentrations of interleukin-1 beta (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) and active metalloproteinase-8 (a-MMP-8) in sites with healthy conditions vs. sites affected by periodontitis (PER) and peri-implantitis (PIM). Methods.: Periodontally healthy (PH) sites with PER, sites with peri-implant health (PIH), and sites with PIM were investigated intra-individually, according to the inclusion criteria of each group. Probing pocket depth (PPD), plaque index, gingival index, and the presence or absence of bleeding on probing (BoP) were evaluated. In GCF and PICF samples, IL-1β, IL-6, and TNF-α were quantified by ELISA Duoset® kit in combination with Ultramark® micro-ELISA digital reader; a-MMP8 concentration was analyzed by a chairside test (Perio/ImplantSafe®) in combination with a digital reader (ORALyzer®). Results.: The concentrations of IL-6 and IL-1β, TNF-α, and a-MMP-8 were significantly higher in the PIM and PER sites compared to healthy sites (P <0.05).>P<0.05),>P>0.05). Conclusion.: aMMP-8, IL-6, IL-1β, and TNF-α presented higher GCF/PICF concentrations in diseased periodontal and peri-implant sites. However, only the concentrations of IL-1β and a-MMP-8 were significantly higher in PIM than in PER sites. [ABSTRACT FROM AUTHOR]

In this work, a three-dimensional fluid-structural and vibro-acoustics coupled model of a gear pump is presented. Gear pumps represent the majority of the positive displacement machines used for flow generation in fluid power systems. Typically, the dynamics of gear pumps are dependent on the characteristics of the fluid dynamics inside the pump, which translates into vibrations to the housing. These vibrations then propagate to the surrounding medium and emit sound. The purpose of this study is to propose a three-dimensional fully integrated computational model to simulate the complete gear pump behaviour from the fluid dynamics to the structural vibrations, up to the vibroacoustic response. In this hybrid configuration, a transient CFD (Computational Fluid Dynamics) model is first developed to simulate the 3D flow field with a deforming and re-meshing approach to take into account the variation of the volume between the gears. Second, the internal pressure field calculated at each time step is then used as a loading into a structural FEM (Finite Element Method) model of the gear pump to compute the actual stresses and deformations of the housing. Third, the results of the structural response are used as excitation in a vibroacoustic sub-model to simulate the radiated noise using a high-order FEM technique. The comparison between the numerical and experimental flow curves validates the CFD model. The sound power calculations from the vibroacoustic model show good comparison with the sound intensity measurements around the pump casing, confirming the validity of the proposed coupled model. The described CFD-FEM approach proves to be a powerful gear pump design tool: it provides a reliable estimate of gear pump working parameters such as fluid power and vibroacoustic characteristics, starting from the CAD (Computer-Aided Design) geometry of the components. Furthermore, being one of the first multi-domain simulation models of a gear pump, this work can be useful to researchers as a starting point to correlate the noise emitted with the internal flow in full 3D conditions. [ABSTRACT FROM AUTHOR]

This review summarizes the current knowledge on immune defence activities of the European sea bass Dicentrarchus labrax by reporting the consistent amount of work done on this economically-important species. A draft genome sequence is available for this species, together with whole transcriptomes from lymphoid and nonlymphoid tissues. Available full-length coding sequences of many immunoregulatory and immune-related genes allow for targeted quantitative PCR analysis, nowadays needed for -omics data verification, ex vivo and in vitro. The first anti-T cells monoclonal antibody teleost-wise was obtained in sea bass, followed by several monoclonal and polyclonal markers of lymphocyte populations, namely T cells (pan-T, CD3e, TcR?, CD45), and B cells (IgM, IgT, IgD). The combined use of molecular and biochemical tools enabled investigations on innate and acquired immune responses of sea bass in unstimulated/stimulated fish, along the development and under variable environmental conditions and food regimes. An overview of sea bass viral and bacterial pathogens and available vaccines against these microorganisms is also provided. The knowledge accumulated in the past 25 years validates the European sea bass as a reference marine model in the field of fish immunology. [ABSTRACT FROM AUTHOR]

Phase Change Materials (PCMs), among the existing thermal storage technologies, are characterized by higher storage densities than conventional storage systems, and absorb and release thermal energy at nearly constant temperatures. In recent years, the potential advantages that can be obtained by the integration of these materials into refrigeration machines have attracted the attention of specialized literature. Indeed, PCMs can allow a more efficient operation through an appropriate increase in thermal inertia, for applications relative to air conditioning in both internal residential environments and inside vehicles for the transport of people, and also in the case of machines used in the field of food refrigeration. Furthermore, in recent years, innovative solutions with integrated PCM have also been analyzed, aiming at enhancing the usability and transportability of refrigeration systems, as well as increasing the energy efficiency and reducing environmental impact. In this context, the present work focuses on the experimental characterization and numerical simulation of a cooling system with integrated PCM. In particular, the cooling system, designed for a personal cooling application, is experimentally analyzed by varying the configuration of the PCM-based condenser, while the numerical simulations have been realized to validate a simulation tool that could be used for the design and optimization of the PCM condenser configuration. The results allow us to identify the main characteristics of the analyzed personal cooling system, namely, the cooling capacity and operating autonomy, and to point out the utility and the limits of the developed simulation tool. Among the various configurations analyzed, the best one in terms of refrigeration power and autonomy is the one characterized by the highest heat transfer surface of the heat exchanger, with the refrigerant compressor at 50% power. [ABSTRACT FROM AUTHOR]

The article explores the impact of racial hierarchies and historical legacies of the Belgian Congo and Southern Rhodesia on the Jews of Rhodes, Greece and how the social implications of these African contexts shaped a diaspora. Topics discussed include influence of Italian and British colonial rule on the Jews of Rhodes, nationhood and colonialism before the Holocaust, decolonization and end of the Jewish quarter after the Holocaust, and Jewish traces of racism and colonial violence.

The aim of the present study was to retrospectively evaluate the longevity of teeth and implants during a long-term period in a cohort of periodontally compromised patients, treated and maintained in a private specialist periodontal practice, and to analyze the associated risk factors. Fifty-eight patients (30 men, 28 women) who had received active periodontal therapy (APT) and regular periodontal maintenance (PM) = 10 years were included and evaluated. The following were evaluated: (1) statistically significant differences of clinical parameters assessed at six tooth or implant sites (plaque scores, bleeding score, periodontal probing depth, bleeding on probing, and gingival recession) and radiographic parameters (mesial and distal bone crest loss) between patients with and without tooth/implant loss during PM; and (2) associations between the number of teeth and implants lost and potential risk factors. During PM, the overall average tooth loss was 0.07 teeth/patient/year (0.04 teeth/patient/year for periodontal reasons), while the overall average implant loss was 0.4 implants/patient/year. The overall implant failure was 10.08%, and the rate of implant failure due to biologic reasons was 9.8%. Incidence of implant failures in patients with vs without recurrent periodontal disease was 83.3% vs 16.7% (P < .05). Results showed that in chronic periodontitis patients, ATP followed by long-term PM is successful in keeping the majority of periodontally compromised teeth. In the same patients, a higher tendency for implant loss than tooth loss was found. [ABSTRACT FROM AUTHOR]

Due to the unavailability of up-to-date and georeferenced information about Lisbon's existing solar energy systems, tracking the progress of solar energy in relation to the city's Climate Action Plans 2030 is a complex task, thus hindering the potential of data-driven decision-making for a targeted implementation of photovoltaics (PV) in buildings and urban infrastructure. To overcome the challenges posed, an integrated approach to accelerate policy-making based on artificial intelligence (AI) resources and local citizens' and stakeholders' participation is developed and piloted in Lisbon. Recurring to a two-step AI model setup to identify and geolocate PV systems, key policy indicators are calculated to inform policymakers about the evolution of PV deployment in the city and contribute to tailor future incentives tomore depressed or energy poor districts. The AI model based on open data orthophotos from 2016 allowed estimates for the installed peak power at the city level, in that year, to be delivered in a few minutes, whereas manual inspection of aerial images will have taken several months. Although the PV capacity determined is 30% lower than the historical official numbers, the proof of concept for the proposed framework is achieved and validated by local stakeholders. [ABSTRACT FROM AUTHOR]

Objective: A significant body of research has suggested that the contraction of SARS-CoV-2 may cause memory impairment, even in the months following recovery. In this regard, studies suggest that COVID-19 predominantly targets structures and cortices within the temporal lobe, and the hippocampus, a critical brain structure for memory and spatial navigation. The purpose of this study was to investigate the potential impact of the COVID-19 pandemic on subjective memory complaints, which represent an individual’s perception of subtle changes in memory in the absence of an objective memory impairment. Method: to explore how the COVID-19 pandemic may affect subjective memory complaints, we incorporated ad hoc self-reported measures of subjective memory complaints, the "Subjective Memory Complaints Questionnaire" (SMCQ) and the "Prospective and Retrospective Memory Questionnaire" (PRMQ), in our crosssectional study. Both measures referred to two periods: the pre-pandemic period (T0) and the moment of survey administration (T1) (December 28th, 2021, to February 6th, 2022). Results: 207 Italian participants accessed the survey, out of which 189 participants were included in the final sample. The majority of the participants were females, and their age ranged from 55 to 65 years. The study revealed a significant increase in the total PRMQ score at T1 compared to T0 (p = 0.02). However, no significant differences were found between PRMQ and SMCQ scores of COVID-19-negative individuals and those who tested positive for COVID-19 in the last 12 months from the date of completing the survey. McNemar's test showed a statistically significant increase in the score of item 1 (“Do you think that you have a memory problem?” (p = 0.016) and item 10 (“Do you lose objects more often than you did previously”) (0.019) of the SMCQ, while for the PRMQ, significant increases were found in several individual items. Conclusions: our study suggests that subjective memory complaints increased during the pandemic, potentially due to the compound effects of stress and social isolation, rather than solely due to COVID-19 infection. Although a marginal association between COVID-19 and reported prospective memory issues was detected, further investigation is warranted to understand its persistent effects. [ABSTRACT FROM AUTHOR]

Objective: Prior research has suggested a possible connection between vaccination and manifestations of Sickness Behavior; however, a need remains to first delve deeper into this association and second examine how Interoceptive Awareness and emotional factors may modulate individuals' perceptions of their health status post vaccination. Method: An online retrospective cross-sectional survey of 647 individuals who received a COVID-19 vaccination was conducted. Together with vaccination side effects, socio-demographic characteristics, health status, level of concern about vaccination, and Interoceptive Awareness were collected at the baseline level. Mood, sleep, and Sickness Behavior were assessed at baseline and after vaccination. Data were analyzed using inferential statistics and machine learning techniques. Results: After vaccination, there was a significant increase in Sickness Behavior levels (mean (±SD) SicknessQ T0 = 1.57 (±2.72), mean (±SD) SicknessQ T1 = 5.54 (±5.51); p-value = 0.001; ES = 0.77). A Machine Learning analysis revealed specific patterns of individual dispositions (sex and age), baseline emotional characteristics (levels of depression, anxiety, stress, and concern about adverse reactions), as well as some components of Interoceptive Awareness (Noticing, Body Listening, and Attention Regulation), as predictors of high levels of Sickness Behavior, both in terms of overall scores (JRIP: 72.65% accuracy, AUC = 0.692, d = 0.709; F1 = 0.726) and individual items (JRIP: 75.77% accuracy, AUC = 0.694; d = 0.717; F1 = 0.754). Conclusions: Our results provide new insight into post-immune reactions by highlighting the contribution of Interoceptive Awareness in modulating the severity of Sickness Behavior. This sheds light on the role of awareness of bodily sensations in modulating perceptions of health status, helping to identify the characteristics that make individuals more prone to feeling sick. [ABSTRACT FROM AUTHOR]

This paper analyses the consequences on demographic changes observed in the municipalities of Abruzzo region after the earthquake of L'Aquila in 2009. Relying on Italian National Institute of Statistics (Istat) data on the population in the municipalities, we aim to understand how population growth changed after the earthquake, analysing population dynamics both in the municipalities affected by the earthquake and in the other municipalities of the Abruzzo region. We apply a spatial regression model to understand the associations between population growth, the earthquake, and some demographic and economic variables, taking into account the spatial autocorrelation. Our findings confirm the importance of space and the close association of the population dynamics after the earthquake with the population age structure, both in the pre‐existing situation and in the subsequent dynamics. Population trends in the Abruzzo region were closely associated with the pre‐existing vulnerabilities. The effect of the earthquake was strong in the crater municipalities in the period immediately after the shock, while it petered out over time. A destructive earthquake implies a tremendous shock, however, in places that are already suffering from demographic, social, and economic fragility, pre‐existing factors can act equally or even more strongly on the population dynamics in the medium term. Hence, in the medium period, the characteristics of the population and socio‐economic context are stronger than in the short one, and also the effect that space and territorial contiguities have on these and other nonobservable variables is stronger than in the short period. [ABSTRACT FROM AUTHOR]

Dissociative disorders (DDs) are characterized by a discontinuity in the normal integration of consciousness, memory, identity, emotion, perception, bodily representation, motor control, and action. The life-threatening coronavirus disease 2019 (COVID-19) pandemic has been identified as a potentially traumatic event and may produce a wide range of mental health problems, such as depression, anxiety disorders, sleep disorders, and DD, stemming frompandemic- related events, such as sickness, isolation, losing loved ones, and fear for one's life. In our conceptual analysis, we introduce the contribution of the structural dissociation of personality (SDP) theory and polyvagal theory to the conceptualization of the COVID-19 pandemic-triggered DD and the importance of assessing perceived safety in DD through neurophysiologically informed psychometric tools. In addition, we analyzed the contribution of eye movement desensitization and reprocessing (EMDR) to the treatment of the COVID- 19 pandemic-triggered DD and suggest possible neurobiological mechanisms of action of the EMDR. In particular, we propose that, through slow eye movements, the EMDR may promote an initial non-rapid-eye-movement sleep stage 1-like activity, a subsequent access to a slow-wave sleep activity, and an oxytocinergic neurotransmission that, in turn, may foster the functional coupling between paraventricular nucleus and both sympathetic and parasympathetic cardioinhibitory nuclei. Neurophysiologically informed psychometric tools for safety evaluation in DDs are discussed. Furthermore, clinical and public health implications are considered, combining the EMDR, SDP theory, and polyvagal conceptualizations in light of the potential dissociative symptomatology triggered by the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Association of advanced age, neoplastic disease and immunocompromission (IC) may lead to surgical emergencies. Few data exist about this topic. Present study reports the preliminary data from the WIRES-T trial about patients managed for colorectal neoplastic emergencies in immunocompromised patients. The required data were taken from a prospective observational international register. The study was approved by the Ethical Committee with approval n. 17575; ClinicalTrials.gov Identifier: NCT03643718. 839 patients were collected; 753 (80.7%) with mild–moderate IC and 86 (10.3%) with severe. Median age was 71.9 years and 73 years, respectively, in the two groups. The causes of mild–moderate IC were reported such malignancy (753–100%), diabetes (103–13.7%), malnutrition (26–3.5%) and uremia (1–0.1%), while severe IC causes were steroids treatment (14–16.3%); neutropenia (7–8.1%), malignancy on chemotherapy (71–82.6%). Preoperative risk classification were reported as follow: mild–moderate: ASA 1–14 (1.9%); ASA 2–202 (26.8%); ASA 3–341 (45.3%); ASA 4–84 (11.2%); ASA 5–7 (0.9%); severe group: ASA 1-1 patient (1.2%); ASA 2–16 patients (18.6%); ASA 3–41 patients (47.7%); ASA 4–19 patients (22.1%); ASA 5–3 patients (3.5%); lastly, ASA score was unavailable for 105 cases (13.9%) in mild–moderate group and in 6 cases (6.9%) in severe group. All the patients enrolled underwent urgent/emergency surgery Damage control approach with open abdomen was adopted in 18 patients. Mortality was 5.1% and 12.8%, respectively, in mild–moderate and severe groups. Long-term survival data: in mild–moderate disease-free survival (median, IQR) is 28 (10–91) and in severe IC, it is 21 (10–94). Overall survival (median, IQR) is 44 (18–99) and 26 (20–90) in mild–moderate and severe, respectively; the same is for post-progression survival (median, IQR) 29 (16–81) and 28, respectively. Univariate and multivariate analyses showed as the only factor influencing mortality in mild–moderate and severe IC is the ASA score. Colorectal neoplastic emergencies in immunocompromised patients are more frequent in elderly. Sigmoid and right colon are the most involved. Emergency surgery is at higher risk of complication and mortality; however, management in dedicated emergency surgery units is necessary to reduce disease burden and to optimize results by combining oncological and acute care principles. This approach may improve outcomes to obtain clinical advantages for patients like those observed in elective scenario. Lastly, damage control approach seems feasible and safe in selected patients. [ABSTRACT FROM AUTHOR]

Aim: The goal of the presented study is to evaluate the influence of material properties on the modulus of elasticity of autoclaved aerated concrete masonry. In addition, it was assessed the reliability of the KE value included in the Eurocode 6 to calculate the modulus of elasticity of AAC masonry in relation to its characteristic compressive strength. Method: An experimental campaign for the determination of modulus of elasticity of AAC masonry with a characteristic compressive strength in the range of 1.3‐2.0 MPa, was carried out. AAC units from different plants in Europe have been tested as well as the thin layer mortar used for the samples. The values of bulk density range between 270 and 350 kg/m3. Moreover, the testing comprised the determination of compressive strength as well as modulus of elasticity of masonry erected by using these blocks. Basis for testing of the compressive strength and modulus of elasticity was EN 1052‐1. Results: The experimental results were compared with the values of modulus of elasticity E calculated according to EN 1996‐1‐1. The comparison shows how the current range of values of KE reported by the German annex DIN EN 1996‐1‐1/NA fits well to the experimental results obtained. [ABSTRACT FROM AUTHOR]

Background: Recent studies on masonry infills have shown that damages can be more serious when frame and infill are coupled. Although the discussion on out‐of‐plane (OOP) stability and strength of isolated infills is still open, the development of solutions able to assure the decoupling of infill panels respect to structural frame seems to be the most promising in terms of damage prevention of the building. Aim: A system for decoupling the RC frame and the aerated autoclaved concrete (AAC) masonry infill reinforced with textile reinforced mortar (TRM) is presented. The goal is to analyze the potential of this system to face the OOP actions caused by a seismic event. Method: In this system, the frame is free to deform in its plane, without interaction with the AAC infill, which is supported by retaining brackets at the top. These brackets allow relative in‐plane displacements between the RC frame and the masonry infill and avoid OOP overturning of the infill. Results: The paper shows the design of the system and provides an overview of the seismic capacities validated by testing on the system components. Based on the analysis and comparison of the test results, the performance and effectiveness of the proposed system are presented. [ABSTRACT FROM AUTHOR]

Aim: In this paper, a comparative study on the initial shear strength of aerated autoclaved concrete (AAC) masonry is presented. Shear tests were carried out according to EN 1052–3 to characterize the shear‐bond behavior of masonry assemblages constructed with AAC blocks with different compressive strengths. Method: To assess the influence of the axial pre‐compression on shear strength, the two different testing procedures suggested in EN 1052–3 were followed and compared. The first procedure (called A) imposes three levels of axial pre‐compression, in the second procedure (called B) shear tests are carried out without axial pre‐compression. Results: For tests performed according to the procedure A, the dispersion of values of the shear strength increases as the pre‐compression level decreases. The so obtained mean values of the initial shear strength are close to the characteristic value suggested by Eurocode 6 (EN 1996–1–1). For tests performed according to the procedure B. often the mean value of the initial shear strength is higher than the value obtained for the procedure A. However, in this case most of the specimens were characterized by crushing or by a splitting failure in the units. Conclusions: According to the authors' opinion, the higher values of initial shear strength obtained with the procedure B can be justified in view of some criticisms probably caused by the rotation of the blocks in the test setup. [ABSTRACT FROM AUTHOR]

Background: Patients' adherence to medical prescription during pre- and post- liver transplant phases is crucial to prevent treatment inefficacy. Literature has highlighted the urge of performing a psychological characterization to prevent post-intervention relapses and to impede treatment non-adherence behavior. The aim of this study is to define an "adherence core" by investigating personality traits, cognitive functions, and affective symptoms of patients waiting for liver transplant to enhance treatment effectiveness. We hypothesize a negative correlation between depressive and anxious symptoms and cognitive abilities and a positive association between some personality traits (Openmindedness, Conscientiousness and Extraversion) and cognitive functions. Materials and methods: Forty-six candidates (23 females, mean age: 56.02±7.81 years, range: 39-76) for liver transplantation were assessed utilizing the following psychometric tools: State-Trait Anxiety Inventory Form Y1 and Form Y2, Big Five Questionnaire and Beck Depression Inventory 2. Cognitive assessment included: Coloured Progressive Matrices, Rey's 15-word list, Semantic Incidental Memory Test for Adults, Attentional Matrices Test and Corsi Block-tapping Test. Results: The findings showed that education level negatively correlated with trait anxiety and positively correlated with Open-mindedness and Emotional Stability. Coloured Progressive Matrices negatively correlated with trait anxiety and depressive symptoms and positively correlated with Emotional Stability and Open-mindedness. Significant correlations were also shown between cognitive tests. Rey Immediate Recall scores showed positive correlation with: Rey Delayed Recall, Semantic Incidental Memory, and Attentional Matrices. Moreover, the findings demonstrated a positive correlation between trait anxiety and depressive symptoms, as well as a negative correlation between trait anxiety and Emotional Stability. Additionally, state anxiety was found to be positively correlated with depressive symptoms and negatively correlated with Energy and Open-mindedness. Discussion: Higher fluid abilities, with lower degree of depression state, less pronounced anxious trait, and more open-minded personality can potentially aid patients in managing the distress associated with pre- and post-transplantation, ultimately resulting in optimal adherence. Furthermore, the positive association observed between the attention and memory domains might suggest their significant involvement in predicting adherence trajectories. In line with literature highlighting the paramount role of psychological factors in recovering from organ transplant, this study paves the road for the potentiation of individual resources and weaknesses identification to reduce relapses and healthcare costs. However, small sample size and lack of causality direction of results prevent robust conclusions. [ABSTRACT FROM AUTHOR]

The role of the magnesium (Mg) doping and its electrical activation on the off-state of p-GaN/AlGaN/GaN HEMTs has been investigated in this work. Firstly, the effect of different Mg doping profiles has been studied via the help of Technology Computer-Aided Design (TCAD) simulations, with the objective of analyzing the band diagrams of the structure. Then, it has been shown how experimental Capacitance–Voltage measurements can be useful to obtain information on the net acceptor concentration in the p-GaN. As a result, devices with an undoped (magnesium-free) GaN gate have been experimentally compared to devices whose p-GaN gate has been activated via a reference annealing process. Finally, results on a device characterized by an improved p-GaN activation have been presented and compared, showing improvements on several parameters of both off- and on-state, thus underlining the key role of the Mg activation process in the overall performances of normally-off GaN HEMTs. [ABSTRACT FROM AUTHOR]

Trans-axillary robot-assisted total thyroidectomy (RATT) is nowadays worldwide accepted but the completeness obtained by RATT is still debated. The Aim of this study was to compare the completeness and safety of RATT with conventional open thyroidectomy (OT). We enrolled patients with nontoxic multinodular goiter, cytologically indeterminate nodules and well differentiated thyroid cancer without local and/or distant metastasis. In all cases the biggest nodule should be < 6 cm. The surgical completeness was evaluated by means of serum thyroglobulin (hs-Tg) and neck ultrasound (nUS) performed three months postoperatively. 100 patients underwent either RATT or OT. The type of surgical procedure was chosen by patients. They were then divided in two subgroups based on benign or malignant histology. There were no significant differences in the postoperatively values of hs-Tg in patients operated with RATT or OT, both in benign and malignant subgroups. The post-operative thyroid remnant volume estimated by nUS was not significantly different between the two groups, both in benign and malignant subgroups. We also analyzed the difference of the volume of the thyroid remnant ipsilateral to the axillary access vs that of the remnant on the contralateral side and there was not significantly difference in both subgroups. RATT was demonstrated to determine a comparable surgical completeness as OT, both in benign and malignant thyroid diseases, with no differences in the prevalence of surgical complications. In our hands the surgical completeness of RATT by a single trans-axillary was satisfying. [ABSTRACT FROM AUTHOR]

The aim of the present prospective study was to evaluate the stability of peri-implant soft tissue and the stability of the implant-gingival unit (IGU) around one-stage titanium implants with a laser-microgrooved collar surface following 3 years of loading. Thirty one-stage titanium implants with a laser-microgrooved collar surface were placed in 30 partially edentulous patients. Clinical and radiographic examinations were carried out at implant placement, after a period of 4 to 6 months free of masticatory loading, and after 3 years of function. Plaque Index (PI), modified sulcus bleeding index (SBI), probing depth (PD), distance between the implant coronal margin and the mucosal margin (DIM), clinical attachment level (CAL), and keratinized tissue width (KTW) and thickness (KTT) were recorded. Radiographic marginal bone levels (MBL) were assessed at the mesial (MI) and distal (DI) aspects of implant sites. In addition, the influence of KTT on IGU stability was investigated. No implants failed during the follow-up period. Compared to baseline, PI, BPI, PD, DIM, CAL, KTW, MBL, and IGU showed differences that were not statistically significant (P > .05). Moreover, IGU didn't show a statistical correlation with KTT. Within the limitations of the present study, it can be concluded that around one-stage implants with laser-microgrooved collar, the peri-implant tissues and IGU remain stable over the three evaluation periods. [ABSTRACT FROM AUTHOR]

The aim of the present randomized study was to radiographically evaluate the early marginal bone remodeling (EMBR) around one-stage implants with a collar surface that is laser-microtextured (LM), placed with the mirograp/interface at different levels relative to the bone crest, and to clinically evaluate the influence of keratinized tissue thickness (KTT) on outcomes. Thirty partially edentulous patients were selected to each receive at least two one-stage implants with LM collars placed at different depth levels in the mandible and maxilla: one implant placed at an equicrestal level (E group) and one implant placed at a supracrestal level (SP group). Rank-based analysis of variance test was used for statistical comparison between groups. Before loading, the E and SP groups showed a mean marginal bone loss of 0.03 ± 0.04 mm and 0.02 ± 0.03 mm, respectively, without a statistically significant difference (P > .05) between the groups. Moreover, no statistically significant correlation between EMBR and the amount of KTT was found (P > .05). Within the limitations of the present study, it can be concluded that neither the vertical position of the microgap/interface of one-stage implants with an LM surface nor the thickness of keratinized tissue around the implant site influences the amount of EMBR. [ABSTRACT FROM AUTHOR]

A detailed multi-scale investigation of the geotechnical, chemical and mineralogical properties was conducted on contaminated sediment samples collected within the Mar Piccolo, a marine basin in the south of Italy. The basin is located close to one of the most important industrial sites in Europe, which has also been declared 'at high risk of environmental crisis' and prioritised for remediation activities. A multidisciplinary investigation campaign showed that the samples collected close to the sea floor are characterised by high values of both heavy metals and organic pollutants and by the presence of significant amount of organic matter. Several samples in the top layer exhibited peculiar geotechnical properties, in terms of plasticity and activity indexes, compressibility and hydraulic permeability. While the prime suspect for such unconventional behaviour was chemo-mechanical coupling between the soil skeleton and contaminants, it turned out that the biogeochemical degradation of organic matter and the presence of microfossils and diatoms is likely to affect significantly the micro to macro behaviour of polluted marine sediments. [ABSTRACT FROM AUTHOR]

Current methods for near real-time estimation of effective reproduction numbers from surveillance data overlook mobility fluxes of infectors and susceptible individuals within a spatially connected network (the metapopulation). Exchanges of infections among different communities may thus be misrepresented unless explicitly measured and accounted for in the renewal equations. Here, we first derive the equations that include spatially explicit effective reproduction numbers, Rk(t), in an arbitrary community k. These equations embed a suitable connection matrix blending mobility among connected communities and mobility-related containment measures. Then, we propose a tool to estimate, in a Bayesian framework involving particle filtering, the values of Rk(t) maximizing a suitable likelihood function reproducing observed patterns of infections in space and time. We validate our tools against synthetic data and apply them to real COVID-19 epidemiological records in a severely affected and carefully monitored Italian region. Differences arising between connected and disconnected reproduction numbers (the latter being calculated with existing methods, to which our formulation reduces by setting mobility to zero) suggest that current standards may be improved in their estimation of disease transmission over time. [ABSTRACT FROM AUTHOR]

Despite significant therapeutic advances, metastatic CRPC (mCRPC) remains a lethal disease. Mutations in homologous recombination repair (HRR) genes are frequent in mCRPC, and tumors harboring these mutations are known to be sensitive to PARP inhibitors. The aim of this study was to verify the technical effectiveness of this panel in the analysis of mCRPC, the frequency and type of mutations in the BRCA1/BRCA2 genes, as well as in the homologous recombination repair (HRR) genes. A total of 50 mCRPC cases were analyzed using a multi-gene next-generation sequencing panel evaluating a total of 1360 amplicons in 24 HRR genes. Of the 50 cases, 23 specimens (46.0%) had an mCRPC harboring a pathogenic variant or a variant of uncertain significance (VUS), whereas in 27 mCRPCs (54.0%), no mutations were detected (wild-type tumors). BRCA2 was the most commonly mutated gene (14.0% of samples), followed by ATM (12.0%), and BRCA1 (6.0%). In conclusion, we have set up an NGS multi-gene panel that is capable of analyzing BRCA1/BRCA2 and HRR alterations in mCRPC. Moreover, our clinical algorithm is currently being used in clinical practice for the management of patients with mCRPC. [ABSTRACT FROM AUTHOR]

Background: In psychopathologies characterized by compulsive decision-making, core impairments include cognitive inflexibility and excessive sensitivity to rewards. It has been posited that traits shared by nonclinical individuals and psychiatric patients could help explain the pathogenesis of compulsive decision-making. Methods: To investigate whether cognitive inflexibility predisposes nonclinical individuals to poor choices and hyper-reactivity to reward, we recruited people with high and low scores for cognitive persistence and used the Iowa Gambling Task to assess decision-making and cardiac reactivity to monetary gains/losses. Results: As is frequently observed in psychophysiological research, the data indicated discrepancies among self-reports, behavior, and physiology. Cognitive inflexibility was not related to worse performance; however, monetary gains, in line with the literature, prompted marked cardiac accelerations. Consistent with our research goal, only inflexible participants showed large cardiac accelerations during the largest monetary wins. Discussion: Taken together, the data confirm an association between cognitive persistence and physiological reward sensitivity in a nonclinical population. The findings are in line with recent theories on the development of compulsive behaviors that consider cognitive inflexibility as a transdiagnostic impairment and predisposing factor for excessive reactivity to rewards, and might act both as a preexisting individual trait and drug-induced deficit. [ABSTRACT FROM AUTHOR]

Background: The surgical treatment for perforated peptic ulcers (PPUs) can be safely performed laparoscopically. This study aimed to compare the outcomes of patients who received different surgical approaches for PPU and to identify the predictive factors for conversion to open surgery. Methods: This retrospective study analyzed patients treated for PPUs from 2002 to 2020. Three groups were identified: a complete laparoscopic surgery group (LG), a conversion to open group (CG), and a primary open group (OG). After univariate comparisons, a multivariate analysis was conducted to identify the predictive factors for conversion. Results: Of the 175 patients that underwent surgery for PPU, 104 (59.4%) received a laparoscopic-first approach, and 27 (25.9%) required a conversion to open surgery. Patients treated directly with an open approach were older (p < 0.0001), had more comorbidities (p < 0.0001), and more frequently had a previous laparotomy (p = 0.0001). In the OG group, in-hospital mortality and ICU need were significantly higher, while the postoperative stay was longer. Previous abdominal surgery (OR 0.086, 95% CI 0.012–0.626; p = 0.015), ulcer size (OR 0.045, 95% CI 0.010–0.210; p < 0.0001), and a posterior ulcer location (OR 0.015, 95% CI 0.001–0.400; p = 0.012) were predictive factors for conversion to an open approach. Conclusion: This study confirms the benefits of the laparoscopic approach for the treatment of PPUs. Previous laparotomies, a greater ulcer size, and a posterior location of the ulcer are risk factors for conversion to open surgery during laparoscopic repair. [ABSTRACT FROM AUTHOR]

The incomplete partition type III is a severe cochlear malformation present in X-linked deafness. It is a rare, non-syndromic cause of severe to profound mixed hearing loss, often progressive. The complete absence of bony modiolus and the wide communication between the cochlea and the internal auditory canal make cochlear implantation challenging, with still no consensus on the management of these patients. To the best of our knowledge, no results have ever been published in the literature on the treatment of these patients with hybrid stimulation (bone and air). We present three cases in which this hybrid stimulation gave better audiological results then air stimulation alone. A literature review on audiological results of the current treatment options in children affected by IPIII malformation was conducted independently by two researchers. Ethical considerations on the treatment of these patients were conducted by the Bioethics department of the University of Insubria. In two of the patients, the bone–air stimulation, associated with prosthetic–cognitive rehabilitation, meant that surgery was avoided, obtaining similar communication performances of those present in the literature. We believe that, when the bone threshold appears partially preserved, a stimulation through the bone or hybrid modality, such as the Varese B.A.S. stimulation, should be attempted. [ABSTRACT FROM AUTHOR]

A piece of historical research about the construction of the ancient Arch of Taq-iKisra, part of the imperial palace of the Sasanian Empire in the city of Ctesiphon, has been carried out. The information obtained, an analysis using graphic statics, the use of a physical model with hanging chains, and an ad hoc optimization program written in MATLAB have shown that the designer of this sixth century ad arch, a Byzantine named Farghán, was aware of the effects of the uneven distribution of loads and the differential settlements of the foundations on the equilibrium shape of structures working exclusively in compression and was able to control them. This discovery predates the earliest statement about the link between the shape of the catenary and that of an arch, by Robert Hooke, by eleven centuries and makes this building relevant not only because of its historical, archaeological, and architectural importance, but also because of its importance in the history of structural engineering. The building is currently in need of restoration to stop its collapse, and an awareness of the way it was designed could be of practical use for the definition of the intervention needed. [ABSTRACT FROM AUTHOR]

Simple Summary: Ovarian cancer (OC) is a highly lethal malignancy. Major improvements in treatment are expected from the identification of molecular features that may predict outcome or be used as therapeutic targets. Among genetic defects relevant for OC are those of BRCA1 and BRCA2 genes. Indeed, at least 20% of OC patients carry inherited or acquired BRCA1/2 pathogenic variants, the identification of which is important for treatment and prevention. A comprehensive study of 30 OC patients revealed that 7 (23%) had BRCA alterations (6 inherited and 1 acquired) detectable by usual clinical testing, while another 5 patients (17%) showed epigenetic silencing of BRCA1 in the tumor, which would have escaped standard sequencing analysis, and one had an inherited variant in another gene: RAD51C, involved in the same DNA repair mechanism as BRCA1 and BRCA2. Patients with BRCA deficit showed greater genomic instability, but better survival, than those with no evidence of BRCA deficit. BRCA testing is recommended in all Ovarian Cancer (OC) patients, but the optimal approach is debated. The landscape of BRCA alterations was explored in 30 consecutive OC patients: 6 (20.0%) carried germline pathogenic variants, 1 (3.3%) a somatic mutation of BRCA2, 2 (6.7%) unclassified germline variants in BRCA1, and 5 (16.7%) hypermethylation of the BRCA1 promoter. Overall, 12 patients (40.0%) showed BRCA deficit (BD), due to inactivation of both alleles of either BRCA1 or BRCA2, while 18 (60.0%) had undetected/unclear BRCA deficit (BU). Regarding sequence changes, analysis performed on Formalin-Fixed-Paraffin-Embedded tissue through a validated diagnostic protocol showed 100% accuracy, compared with 96.3% for Snap-Frozen tissue and 77.8% for the pre-diagnostic Formalin-Fixed-Paraffin-Embedded protocol. BD tumors, compared to BU, showed a significantly higher rate of small genomic rearrangements. After a median follow-up of 60.3 months, the mean PFS was 54.9 ± 27.2 months in BD patients and 34.6 ± 26.7 months in BU patients (p = 0.055). The analysis of other cancer genes in BU patients identified a carrier of a pathogenic germline variant in RAD51C. Thus, BRCA sequencing alone may miss tumors potentially responsive to specific treatments (due to BRCA1 promoter methylation or mutations in other genes) while unvalidated FFPE approaches may yield false-positive results. [ABSTRACT FROM AUTHOR]

Background: Monitoring antibody response following SARS-CoV-2 vaccination is strategic, and neutralizing antibodies represent the gold standard. The neutralizing response to Beta and Omicron VOCs was evaluated versus the gold standard by a new commercial automated assay. Methods: Serum samples from 100 healthcare workers from the Fondazione Policlinico Universitario Campus Biomedico and the Pescara Hospital were collected. IgG levels were determined by chemiluminescent immunoassay (Abbott Laboratories, Wiesbaden, Germany) and serum neutralization assay as the gold standard. Moreover, a new commercial immunoassay, the PETIA test Nab (SGM, Rome, Italy), was used for neutralization evaluation. Statistical analysis was performed with R software, version 3.6.0. Results: Anti-SARS-CoV-2 IgG titers decayed during the first ninety days after the vaccine second dose. The following booster dose significantly (p < 0.001) increased IgG levels. A correlation between IgG expression and neutralizing activity modulation was found with a significant increase after the second and the third booster dose (p < 0.05. Compared to the Beta variant of the virus, the Omicron VOC was associated with a significantly larger quantity of IgG antibodies needed to achieve the same degree of neutralization. The best Nab test cutoff for high neutralization titer (≥1:80) was set for both Beta and Omicron variants. Conclusion: This study correlates vaccine-induced IgG expression and neutralizing activity using a new PETIA assay, suggesting its usefulness for SARS-CoV2 infection management. [ABSTRACT FROM AUTHOR]

Hearing loss is the most frequent sensorineural disorder, affecting approximately 1:1000 newborns. Hereditary forms (HHL) represent 50–60% of cases, highlighting the relevance of genetic testing in deaf patients. HHL is classified as non-syndromic (NSHL—70% of cases) or syndromic (SHL—30% of cases). In this study, a multistep and integrative approach aimed at identifying the molecular cause of HHL in 102 patients, whose GJB2 analysis already showed a negative result, is described. In NSHL patients, multiplex ligation probe amplification and long-range PCR analyses of the STRC gene solved 13 cases, while whole exome sequencing (WES) identified the genetic diagnosis in 26 additional ones, with a total detection rate of 47.6%. Concerning SHL, WES detected the molecular cause in 55% of cases. Peculiar findings are represented by the identification of four subjects displaying a dual molecular diagnosis and eight affected by non-syndromic mimics, five of them presenting Usher syndrome type 2. Overall, this study provides a detailed characterisation of the genetic causes of HHL in the Italian population. Furthermore, we highlighted the frequency of Usher syndrome type 2 carriers in the Italian population to pave the way for a more effective implementation of diagnostic and follow-up strategies for this disease. [ABSTRACT FROM AUTHOR]