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Electric vehicles (EVs) are quickly replacing internal combustion cars, which will soon become obsolete. Nonetheless, how drivers' perception and cognition deal with certain features of EVs remains largely unknown. In this study we focus on the role of in-car sound, specifically the artificial engine sounds, on drivers' speed perception and control. Previous studies indicate that removing or reducing engine sound leads drivers to underestimate speed and, consequently, to drive faster. Furthermore, evidence suggests that specific sound frequencies could play a role in this process, highlighting the importance of in-car sound features. We consider benefits and limitations of different research paradigms used in the field (mostly video based technique and driving simulation) and we propose an experimental protocol to systematically investigate the phenomenon. Finally, we suggest that the wider use of psychophysical methods on video recordings would benefit the research in the field and overcome some limitations of simulation studies.

Recent studies have shown correlations between the microbiota’s composition and various health conditions. Machine learning (ML) techniques are essential for analyzing complex biological data, particularly in microbiome research. ML methods help analyze large datasets to uncover microbiota patterns and understand how these patterns affect human health. This study introduces a novel approach combining statistical physics with the Monte Carlo (MC) methods to characterize bacterial species in the human microbiota. We assess the significance of bacterial species in different age groups by using notions of statistical distances to evaluate species prevalence and abundance across age groups and employing MC simulations based on statistical mechanics principles. Our findings show that the microbiota composition experiences a significant transition from early childhood to adulthood. Species such as Bifidobacterium breve and Veillonella parvula decrease with age, while others like Agathobaculum butyriciproducens and Eubacterium rectale increase. Additionally, low-prevalence species may hold significant importance in characterizing age groups. Finally, we propose an overall species ranking by integrating the methods proposed here in a multicriteria classification strategy. Our research provides a comprehensive tool for microbiota analysis using statistical notions, ML techniques, and MC simulations.

BACKGROUND: The Immunoscore (IS) is a quantitative digital pathology assay that evaluates the immune response in cancer patients. This study reports on the reproducibility of pathologists visual assessment of CD3+- and CD8+-stained colon tumors, compared to IS quantification. METHODS: An international group of expert pathologists evaluated 540 images from 270 randomly selected colon cancer (CC) cases. Concordance between pathologists T-score, corresponding hematoxylin-eosin (H&E) slides, and the digital IS was evaluated for two- and three-category IS. RESULTS: Non-concordant T-scores were reported in more than 92% of cases. Disagreement between semi-quantitative visual assessment of T-score and the reference IS was observed in 91% and 96% of cases before and after training, respectively. Statistical analyses showed that the concordance index between pathologists and the digital IS was weak in two- and three-category IS, respectively. After training, 42% of cases had a change in T-score, but no improvement was observed with a Kappa of 0.465 and 0.374. For the 20% of patients around the cut points, no concordance was observed between pathologists and digital pathology analysis in both two- and three-category IS, before or after training (all Kappa < 0.12). CONCLUSIONS: The standardized IS assay outperformed expert pathologists T-score evaluation in the clinical setting. This study demonstrates that digital pathology, in particular digital IS, represents a novel generation of immune pathology tools for reproducible and quantitative assessment of tumor-infiltrated immune cell subtypes.

RESUMO O referido projeto se caracteriza nas implicações relacionais do desenvolvimento sociomoral da teoria psicogenética em Piaget sobre a construção cognoscente da ética nos vieses pessoais e em referenciais da dialética discursiva na linguística. Foram parametrizados a dados funcionais de treinamento e teste em um classificador de categorias urbano-sociais em uma abordagem analítica textual por Processamento de Linguagem Natural (PLN), e baseado no mecanismo de atenção adaptada Transformers. Nessa perspectiva, desenvolveu-se uma metodologia de mitigação de viés para a reestruturação do crivo e critério que datasets multimodais são retreinados, retestados e reavaliados. Finalmente, verificou-se e validou-se a heterogeneidade da ética comum coletiva humana, sobre inferências interpretativas, insights e tendências sociais reais que a relação cidade/cidadão aborda o “social sensing” na identificação de problemas público-sociais.

Abstract Background Urogenital schistosomiasis is caused by the parasitic trematode Schistosoma haematobium. Sensitive and specific point-of-care diagnostics are needed for elimination of this disease. Recombinase polymerase amplification (RPA) assays meet these criteria, and an assay to diagnose S. haematobium has been developed (Sh-RPA). However, false-positive results can occur, and optimisation of reaction conditions to mitigate these is needed. Ease of use and compatibility of DNA extraction methods must also be considered. Methods Using synthetic DNA, S. haematobium genomic DNA (gDNA), and urine samples from clinical cases, Sh-RPA reactions incorporating different betaine concentrations (0 M, 1 M, 2.5 M, 12.5 M) and the sample-to-water ratios were tested to determine effects on assay specificity and sensitivity. In addition, five commercial DNA extraction kits suitable for use in resource-limited settings were used to obtain gDNA from single S. haematobium eggs and evaluated in terms of DNA quality, quantity, and compatibility with the Sh-RPA assay. All samples were also evaluated by quantitative polymerase chain reaction (qPCR) to confirm DNA acquisition. Results The analytical sensitivity of the Sh-RPA with all betaine concentrations was ≥ 10 copies of the synthetic Dra1 standard and 0.1 pg of S. haematobium gDNA. The addition of betaine improved Sh-RPA assay specificity in all reaction conditions, and the addition of 2.5 M of betaine together with the maximal possible sample volume of 12.7 µl proved to be the optimum reaction conditions. DNA was successfully isolated from a single S. haematobium egg using all five commercial DNA extraction kits, but the Sh-RPA performance of these kits varied, with one proving to be incompatible with RPA reactions. Conclusions The addition of 2.5 M of betaine to Sh-RPA reactions improved reaction specificity whilst having no detrimental effect on sensitivity. This increases the robustness of the assay, advancing the feasibility of using the Sh-RPA assay in resource-limited settings. The testing of commercial extraction kits proved that crude, rapid, and simple methods are sufficient for obtaining DNA from single S. haematobium eggs, and that these extracts can be used with Sh-RPA in most cases. However, the observed incompatibility of specific kits with Sh-RPA highlights the need for each stage of a molecular diagnostic platform to be robustly tested prior to implementation. Graphical Abstract

Bullous pemphigoid (BP) is an autoimmune bullous disease, typically affecting the elderly, characterized by the production of autoantibodies directed against structural components of the dermal–epidermal junction. An association between BP and psoriasis has been described several times, but the mechanisms underlying this association have yet to be clearly defined. The pathophysiological mechanism underlying psoriasis may be implicated in the pathogenesis of BP, as psoriasis precedes BP in most cases; in particular, a promoting role has been hypothesized by biologic therapies, which may induce a switch from a T helper 1 (TH1)/TH17-dominant cytokine milieu, typical of patients with psoriasis, to a TH2-dominant one, typical of patients with BP. IL-17 inhibitors, in particular, have also been successfully used to treat BP in patients with psoriasis. The use of these drugs in these patients has been based on in vitro studies. However, cases of new-onset BP or relapses of BP already diagnosed in patients with psoriasis treated with biologic drugs have also been reported, and they occurred mainly in patients on anti-TNF drugs, yet very few cases with anti-IL-174 drugs have been described. We hereby describe two cases of new-onset BP in two patients treated with anti-IL-17 drugs for psoriasis.

ABSTRACT The human gut microbiota possesses the capacity to synthesize vitamins, especially B group vitamins, which are recognized as indispensable for various biological processes both among members of these bacterial communities and host cells. Accordingly, vitamin production by intestinal commensals has attracted significant interest. Nevertheless, our current understanding of bacterial vitamin synthesis is primarily based on individual genomic and monoculture investigations, therefore not providing an overall view of the biosynthetic potential of complex microbial communities. In the current study, we utilized over 100 bacterial genes known to be involved in the biosynthesis of B group and K vitamins to assess the corresponding vitamin biosynthetic potential of approximately 8,000 human gut microbiomes. Our analyses reveal that host-associated factors, such as age and geographical origin, appear to influence the diversity and abundance of vitamin biosynthetic pathways. Furthermore, we identify gut microbiota members that substantially contribute to these biosynthetic functions at each stage of human life. Interestingly, inference of microbial co-associations and network relationships uncovered the apparent key role played by folate and cobalamin in equilibrium establishment of the infant and adult gut microbial communities, respectively.IMPORTANCEOverall, this study expands our understanding of microbe-mediated vitamin biosynthesis in the human gut and may provide potential novel targets to improve availability of these essential micronutrients in the host.

ObjectiveThe aim of the present retrospective study was to compare the changes resulting from treatment using the MA and the TB with special regard to the oro-and naso-pharyngeal sagittal airway dimensions in subjects with dentoskeletal Class II malocclusions and positive history of Sleep Disorder Breathing (SDB) diagnosed through the Pediatric Sleep Questionnaire (PSQ).Materials and methodsThis retrospective study involved 2 groups of subjects: patients treated with Twin Block (TB group: n = 22, 10 males, 12 females; mean age 12.0 ± 1.3 years) and patients treated with Mandibular Advancement (MA group: n = 23, 11 males, 12 females; mean age 12.2 ± 1.1 years). Pretreatment (T1) and posttreatment (T2) lateral cephalograms were analyzed. All patients underwent the PSQ to diagnose SDB.ResultsIn both treated groups there was an increase in the airways dimensions and an improvement in symptoms related SDB. The statistical comparison of the changes between T1 and T2 in the TB group showed a significant increment in upper airway size (PNS-AD2, +1.50 mm + −3.30; McNamara's upper pharynx dimension, +2.21 + −4.21) after active treatment. The MA group showed similar results during active treatment with a significant increase in both upper (PNS-AD2, +2.72 + −2.65; McNamara's upper pharynx dimension, +2.97 + −3.07) and lower (PNS-AD1, +2.17 mm + −3.54) airway size.ConclusionsDespite the different structure of these two devices and the different advancement protocols, both appliances were valuable as a suitable treatment option for Class II patients with respiratory disorders, inducing an increase of upper and lower airway size and a significant reduction in diurnal symptoms.

Bifidobacteria are well known as common and abundant colonizers of the human gut and are able to exert multiple beneficial effects on their host, although the cooperative and competitive relationships that may occur among bifidobacterial strains are still poorly investigated. Therefore, to dissect possible molecular interactions among bifidobacterial species that typically colonize the human gut, three previously identified bifidobacterial prototypes, i.e., B. bifidum PRL2010, B. breve PRL2012, and B. longum PRL2022 were cultivated individually as well as in bi- and tri-association in a human gut-simulating medium. Transcriptomic analyses of these co-associations revealed up-regulation of genes predicted to be involved in the production of extracellular structures including pili (i.e., flp pilus assembly TadE protein gene), exopolysaccharides (i.e., GtrA family protein gene) and teichoic acids (i.e., ABC transporter permease), along with carbohydrate, amino acid and vitamin metabolism-related genes (i.e., exo-alpha-sialidase; beta-galactosidase and pyridoxamine kinase), suggesting that co-cultivation of bifidobacteria induces a response, in individual bifidobacterial strains, aimed at enhancing their proliferation and survival, as well as their ability to cooperate with their host to promote their persistence. Furthermore, exposure of the selected prototypes to human cell line monolayers unveiled the ability of the bifidobacterial tri-association to communicate with their host by increasing the expression of genes involved in adherence to/interaction with intestinal human cells. Lastly, bifidobacterial tri-association promoted the transcriptional upregulation of genes responsible for maintaining the integrity and homeostasis of the intestinal epithelial barrier.

In this review we focus on the role of in-car sound, specifically the artificial engine sounds, on drivers’ speed perception and control, a topic that has received little attention so far. Previous studies indicate that removing or reducing engine sound leads drivers to underestimate speed and, consequently, to drive faster. Furthermore, evidence suggests that specific sound frequencies could play a role in this process, highlighting the importance of in-car sound features. First, we show that the amount of research in the field is scarce and rather outdated, and that this is largely due to the fact that industrial research is subject to very few publications. Then, we examine benefits and limitations of different research paradigms used and we propose a protocol to investigate systematically the phenomenon. In particular, we argue for the benefits of a wider use of psychophysical methods in speed perception, a field that has been typically explored by means of driving simulation. Finally, we highlight some methodological and statistical limitations that might impact the interpretation of the evidence considered. Our methodological considerations could be particularly useful for researchers aiming to investigate the impact of sound on speed perception and control, as well as for those involved in the design of in-car sounds. These are particularly relevant for the design of electric vehicles, which represent a challenge but also the ideal testing ground to advance the knowledge in the field.

Aim: the aim of the present study was to assess the prevalence of dental caries in a population of schoolchildren in Rome (Italy) with different age ranges. Materials and Method: the study involved n.1033 subjects, between 6 and 14 years of age, attending public schools in Rome (Italy). All the subjects included in the study were divided into three different age groups: 6 to 8 years (Group A), 9 to 11 years (Group B) and 12 to 14 years (Group C), respectively. The Group A consisted of n. 385 patients (197 M, 188 F) with a mean age of 6.9±0.8 years; the Group B consisted of n. 355 patients (188 M; 167 F) with a mean age of 10.5±1.2 years; the Group C consisted of n. 293 patients (157 M; 136 F) with a mean age of 12.6±0.9 years. The subjects selected for the study were analyzed about the oral conditions by six expert examiners and the prevalence of dental caries on deciduous or permanent were calculated in each group. The Pearson Chi test was used to perform the statistical analysis. The level of significance was set at P < 0.05. Results: in Group A, most participants were caries free (255 subjects). In children with caries (160 subjects), 126 presented caries on deciduous teeth and 34 on permanent teeth. Similarly, more than half of the students of Group B were caries free (226 patients) and 129 students showed caries on primary (82 patients) and permanent teeth (47 patients). Dental caries on permanent teeth was present in most of the subjects of Group C (35 subjects) and only 10 participants showed caries on primary teeth. In the same group, a good number of participants (248 subjects) were caries free. Conclusions: dental caries is still a major public health concern in the schoolchildren population in Rome. The Results of the current study highlighted that dental screening plays an important role to improve public oral health conditions and involving the school structure means motivating teachers and parents for a good oral hygiene habit. A proper oral hygiene, especially if established at an early age, can translate into benefits in the permanent teeth that can last a lifetime if cared for properly. This underlines the importance of communication with families, which is also one of the main goals of this work.

INTRODUCTION: The postnatal activation of the hypothalamic-pituitary-gonadal (HPG) axis is usually known as 'minipuberty'. There are still open questions about its biological function and significance depending on sex, gestational age (GA) and birth weight (BW) with few available longitudinal data. METHODS: A single-centre, longitudinal study to quantify urinary follicle stimulating hormone (uFSH), luteinizing hormone (uLH) and testosterone (uTs) in male neonates. Neonates were enrolled and stratified into three subgroups: full-term boys appropriate for GA (FT AGA); FT boys with BW ≤3rd centile [FT small for gestational age (SGA)]; and preterm (PT) boys ≤33 weeks of GA. Urinary hormones were correlated to simultaneous auxological parameters, linear growth and external genitalia at scheduled time-points. RESULTS: Forty-six boys were recruited, with subgroup sizes FT AGA n=23, FT SGA n=11 and PT n=12. PT boys display a pulsatile pattern of urinary gonadotropins (uGns) with higher levels of uLH and a gradual increase of uTs. Testicular descent started from 29-32 weeks with the peak of uTs. During the first 12-months post-term age (PTA), FT AGA boys displayed a better linear growth (p

The approach to skeletal dysmorphisms in the maxillofacial area usually requires an orthodontic treatment by means of fixed appliances, both before and after the surgical phase. Since its introduction, Invisalign system has become a popular treatment choice for the clinicians because of the aesthetics and comfort of the removable clear aligners compared with the traditional appliances. Therefore, the aim of the present report was to illustrate the management of a malocclusion by means of clear aligners associated with the traditional surgical technique. The present paper shows a case of a 18-year-old female patient characterized by a Class III malocclusion with lateral deviation of the mandible. Clear aligners were used during the pre- and postsurgical phases rather than fixed appliances. The posttreatment cephalometric analysis emphasized the stability of the dental and skeletal symmetry corrections, occlusion and functional balance, over a 4-year follow-up. The results achieved at the end of the treatment showed how clear aligners can be effective in the management of the orthodontic phases in orthognathic surgery. The follow-up after 4 years emphasizes the stability of the treatment over time.

In the last year a new virus (SARS-CoV-2) and the disease caused by it (COVID-19) has quickly spread around the world, leading the World Health Organization to declare a public health emergency and, then, a global pandemic status. The strategies adopted by many countries to reduce the impact of the pandemic were mainly based on social distancing rules and on stay-at-home measures or lockdowns. These strategies had severe disruptive consequences on many sectors, including all levels of education. While the "traditional" (face-to-face) Higher Education (HE) system was unprepared for the lockdown (e.g., no plans for a massive shift to online teaching were available/ready), it reacted in an extremely quick and effective way, replacing face-to-face teaching with online teaching. While COVID-19 has been extremely challenging for education, the experience has undoubtedly provided positive inputs for the digitalization of the HE system. The question is however, if whether after the COVID-19 emergency everything will go back to the previous situation or instead if the pandemic has irreversibly changed HE. While we are still in the middle of the crisis, it is in our view beneficial to start to reflect on the challenges and open issues that emerged during this period and the lessons learned for the "new normal" (as it is often referred to). In this conceptual paper we seek to start this discussion by focusing on the following relevant aspects that should be considered to succeed in the digital transformation: broadband network infrastructure and hardware devices; e-learning software; organization of teaching activities; pedagogical issues; diversity and inclusivity; and a number of other issues. We conclude that the COVID-19 pandemic will irreversibly change HE and probably for the better.

BackgroundAlthough telemedicine has been proven to have significant potential for improving care for patients with cardiac problems, there remains a substantial risk of introducing disparities linked to the use of digital technology, especially for older or socially vulnerable subgroups. ObjectiveWe investigated factors influencing adherence to a telemedicine-delivered health education intervention in patients with ischemia, emphasizing demographic and socioeconomic considerations. MethodsWe conducted a descriptive, observational, prospective cohort study in consecutive patients referred to our cardiology center for acute coronary syndrome, from February 2022 to January 2023. Patients were invited to join a web-based health educational meeting (WHEM) after hospital discharge, as part of a secondary prevention program. The WHEM sessions were scheduled monthly and used a teleconference software program for remote synchronous videoconferencing, accessible through a standard computer, tablet, or smartphone based on patient preference or availability. ResultsOut of the 252 patients (median age 70, IQR 61.0-77.3 years; n=189, 75% male), 98 (38.8%) declined the invitation to participate in the WHEM. The reasons for nonacceptance were mainly challenges in handling digital technology (70/98, 71.4%), followed by a lack of confidence in telemedicine as an integrative tool for managing their medical condition (45/98, 45.9%), and a lack of internet-connected devices (43/98, 43.8%). Out of the 154 patients who agreed to participate in the WHEM, 40 (25.9%) were unable to attend. Univariable logistic regression analysis showed that the presence of a caregiver with digital proficiency and a higher education level was associated with an increased likelihood of attendance to the WHEM, while the converse was true for increasing age and female sex. After multivariable adjustment, higher education level (odds ratio [OR] 2.26, 95% CI 1.53-3.32; P