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Vittorio Lenzo,1 Alberto Sardella,2 Alessandro Musetti,3 Maria Francesca Freda,4 Daniela Lemmo,4 Elena Vegni,5 Lidia Borghi,5 Giuseppe Plazzi,6,7 Laura Palagini,8,9 Gianluca Castelnuovo,10,11 Roberto Cattivelli,12 Rachele Mariani,13 Giovanni Michelini,14 Tommaso Manari,3 Emanuela Saita,10 Maria C Quattropani,15 Christian Franceschini16 1Department of Social and Educational Sciences of the Mediterranean Area, University for Foreigners “Dante Alighieri” of Reggio Calabria, Reggio, Calabria, Italy; 2Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy; 3Department of Humanities, Social Sciences and Cultural Industries, University of Parma, Parma, Italy; 4Department of Humanistic Studies, University of Naples Federico II, Naples, Italy; 5Department of Health Sciences, University of Milan, Milan, Italy; 6Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy; 7IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy; 8Department of Clinical and Experimental Medicine, Psychiatric Section, University of Pisa, Azienda Ospedaliera Universitaria Pisana (AUOP), Pisa, Italy; 9Department of Neuroscience and Rehabilitation, University of Ferrara, Ferrara, Italy; 10Department of Psychology, Catholic University of Milan, Milan, Italy; 11Istituto Auxologico Italiano IRCCS, Psychology Research Laboratory, Ospedale San Giuseppe, Verbania, Italy; 12Department of Psychology, University of Bologna, Bologna, Italy; 13Department of Dynamic and Clinical Psychology, University of Rome “La Sapienza”, Roma, Italy; 14Sigmund Freud University, Milano, Italy; 15Department of Educational Sciences, University of Catania, Catania, Italy; 16Department of Medicine and Surgery, University of Parma, Parma, ItalyCorrespondence: Vittorio LenzoDepartment of Social and Educational Sciences of the Mediterranean Area, University for Foreigners “Dante Alighieri” of Reggio Calabria, Via del Torrione 95, Reggio Calabria, 89125, ItalyEmail v.lenzo@unidarc.itPurpose: Previous studies showed poor sleep quality during the first Italian lockdown consequent to the quick spread of the virus. Poor sleep quality remained stable during the so-called “second wave”, which started in Autumn 2020. This study aimed to compare sleep quality between the two waves of contagions and to examine the effect of resilience, together with sociodemographic and COVID-related variables, on sleep quality during the second wave.Patients and Methods: A total of 648 participated in this longitudinal study through an online survey during the first lockdown consequent to the COVID-19 and during the second wave. The Medical Outcomes Study—Sleep Scale (MOS-SS) and the Resilience Scale (RS) were administered. Sociodemographic and COVID-related information were also collected.Results: The results showed sleep quality slightly increased in the second wave, even though with a small effect size. Correlational analysis showed that resilience is inversely correlated with sleep quality measured in the two waves. Sleep quality during the second wave was positively correlated with sleep quality in the first lockdown. Likewise, the results of multiple regression revealed that the sleep quality in the first lockdown and resilience were significant predictors of sleep quality during the second wave.Conclusion: These findings highlighted that the prevalence of poor sleepers remained high during the second wave. Together with the sleep quality in the first lockdown, resilience represents an important factor related to sleep quality during the second wave. Interventions to improve sleep quality among the general population should take into account these findings.Keywords: clinical psychology, health, sleep quality, resilience, longitudinal

The importance of computational thinking skills in mathematics has been recognized in educational research for a long time. More recently, this recognition has materialized in formal international recommendations (e.g., by PISA's 2022 Mathematics Framework) and in national or provincial curricular reforms (e.g., in France, Sweden, and Canada) that promote the incorporation of coding in mathematics classrooms. This has led to opportunities as well as challenges for mathematics teachers, and a pressing need for work on teacher training. To contribute to this emerging area, we report on a professional development experience in which 25 inservice teachers collaborated with 36 preservice teachers to plan, implement, and reflect on the implementation of coding-based mathematics activities (using Scratch or Python) with Gr. 5-9 school students. Teachers' reflections are shared as insights gained through the experience, which may be of interest to other teachers or policy makers engaged in the implementation of coding in school subjects such as mathematics. With other researchers and teacher educators in mind, participating teachers' reflections are also used as a springboard to evaluate the reported training approach, discuss the approach in the context of existing literature, and provide some perspectives for the future.

Andrea De Giacomo,1 Francesco Craig,2,3 Silvia Medicamento,1 Federica Gradia,1,* Dario Sardella,1,* Angela Costabile,2 Emilia Matera,4 Marco Turi5,6 1Department of Translational Biomedicine and Neurosciences (DiBraiN), University Hospital, Bari, Italy; 2Department of Cultures, Education and Society, Calabria University, Rende (CS), Italy; 3Scientific Institute, IRCCS E. Medea, Unit for Severe Disabilities in Developmental Age and Young Adults, Brindisi, Italy; 4Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), University Hospital, Bari, Italy; 5Department of Human and Social Sciences, Salento University, Lecce, Italy; 6Fondazione Stella Maris Mediterraneo, Potenza, Italy*These authors contributed equally to this workCorrespondence: Andrea De Giacomo, Department of Translational Biomedicine and Neurosciences (DiBraiN), University Hospital, Piazza Giulio Cesare, 11, Bari, BA, 70124, Italy, Email andrea.degiacomo@uniba.itPurpose: Recent literature has focused attention on the presence of autistic-like symptoms in children with Attention Deficit/Hyperactivity Disorder (ADHD), who often exhibit social difficulties, posing challenges for a distinct clinical diagnosis. The current study aimed to identify the specific pattern of autistic symptoms in subjects with ADHD or Autistic Spectrum Disorder (ASD), examining similarities or differences at both the domain and individual item levels.Patients and Methods: In this study, we enrolled 43 school-age children divided into the following: the ADHD group (n=25) consisted of children initially referred for ASD symptoms but subsequently clinically diagnosed with ADHD, and the ASD group consisted of 18 children with ASD. We used the Autism Diagnostic Observation Schedule, 2nd edition (ADOS-2), to examine relative differences in the presence of symptoms such as deficits in communication and social interaction, and restricted and repetitive behaviors in these two groups. Comparison between groups was conducted to explore differences in IQ, age, ADOS-2 domains, and externalizing and internalizing problems among the groups.Results: We found significant differences between the groups when comparing summary scores of ADOS-2 domains (Social Affect, Restricted and Repetitive Behavior, and Total Score). Interestingly, at the individual item level, the ADHD group exhibited a similar level of atypical behaviors compared to the ASD group in two items related to the social-communication area: “Pointing” and “Gestures”. Additionally, the frequencies of “Stereotyped/idiosyncratic words or phrases”, “Mannerisms”, and “Repetitive interests and behaviors” also showed similarities between groups.Conclusion: These findings indicate the importance of exploring and developing potential transdiagnostic domains that could be targeted for treatments specifically designed for children with ADHD.Keywords: autistic spectrum disorders, attention deficit hyperactivity disorder, autism diagnostic observation schedule-2, autistic-like symptoms, social difficulties

Abstract Vulnerability evaluation plays a key role in risk assessment and reduction and is essential for defining strategies for climate change adaptation and mitigation. In dealing with the safeguarding of cultural heritage at risk, we are still far from adopting and applying an agreed methodology for vulnerability assessment. With the aim to support practitioners, heritage managers, and policy and decision makers to undertake actions that address the protection of cultural heritage at risk, the methodology set up in the framework of the Interreg Central Europe STRENCH is illustrated and discussed here. Based on three major requirements (susceptibility, exposure, and resilience) and a continuous consultation with local stakeholders, the proposed methodology is applicable for evaluating the vulnerability of built heritage and cultural landscape exposed to hydrometeorological hazards, such as heavy rains, floods, and droughts. The results obtained through its validation on 15 case studies from seven Central European regions are shown to underline the strengths and limitations of the methodological approach. Iterative consultation with local stakeholders was fundamental for the definition of the criteria/subcriteria and related values for the assessment of the requirements. Application to further sites in other contexts would surely contribute to strengthening the reliability of the methodological approach.

Abstract Background This study aimed to analyze the moderating role of emotional exhaustion in the relationships between longitudinal associations of depression, anxiety, and stress among healthcare workers assisting end-of-life cancer patients during the COVID-19 pandemic. Methods A longitudinal study involving a final sample of 122 healthcare workers (61.5% females, mean age = 39.09 ± 11.04 years) was conducted. These participants completed the Maslach Burnout Inventory (MBI) and the Depression Anxiety Stress Scales-21 (DASS-21). Results: Results of correlation analysis showed that emotional exhaustion was correlated with both T1 and T2 measures of depression, anxiety, and stress. Results of the moderation analysis indicated that emotional exhaustion moderated the relationships between consecutive measures of depression and anxiety. Each of the moderation models explained about half of the variance for depression and anxiety. When considering stress, results did not show a moderating role for emotional exhaustion. Conclusions Overall, the results of this study highlight that emotional exhaustion moderated depression and anxiety over time. Psychological interventions to promote psychological mental health among healthcare workers assisting patients with end-stage cancer should carefully consider these findings.

Abstract Aim A healthy diet could help to prevent both oral and systemic diseases, with dentists and nutritionists supplementing their skills. The dental setting, where patients periodically refer to seeking oral health care, represents a powerful opportunity for nutritional counselling. To the best of our knowledge, no study is available on patients’ attitudes towards dietary counselling in the dental setting. This cross-sectional study investigates patients’ attitude towards receiving nutritional support within the dental setting and it elucidates whether a transdisciplinary approach would be well accepted. Materials and Methods A questionnaire was administered to patients attending three different clinics: a private clinic, a hospital dental clinic of the national healthcare system and the private dental practice within the same hospital. Results Three hundred thirteen questionnaires were collected. Most dental patients acknowledged receiving nutritional advice from both dentists and nutritionists. The nutritionist within the dental setting was positively perceived, providing useful advice to prevent oral and systemic diseases and also drawing up a diet with periodic follow-ups. Discussion and conclusion These findings support the positive attitude of patients towards receiving nutritional counselling within the dental setting. The dental clinics can be pivotal in oral and systemic disease screening and prevention and a multidisciplinary approach is highly encouraged.

Allantoin represents a compound widely employed in pharmaceutical and cosmetic fields. Its safety has been acknowledged by regulatory bodies such as the US Food and Drug Administration, the European Commission for Cosmetics and Consumer and Health and European Directorate for the Quality of Medicines & HealthCare. This justifies its wide use in dermatological/cosmetic formulations and allows their safe use.Allantoin possesses an asymmetric carbon atom, resulting in two enantiomers, with the (S)-enantiomer predominating in plants, although racemization may potentially occur during manufacturing processes. Notably, literature currently lacks enantioselective LC methods for allantoin analysis.In this study, two zwitterionic Cinchona alkaloid-based chiral stationary phases (CSPs), commercially known as CHIRALPAK® ZWIX(+) (CSP1) and CHIRALPAK® ZWIX(-) (CSP2), were utilized for the enantioseparation of allantoin under polar-ionic conditions. By employing a mobile phase consisting of acetonitrile/methanol/water/acetic acid (96:2:2:0.1, v/v/v/v), nearly complete baseline separation (with α=1.08) of allantoin enantiomers was achieved in less than 15 min with both CSPs. Due to the “pseudo-enantiomeric” nature of the two chiral selectors (quinine-based in CSP1 and quinidine-based in CSP2), an inversion of the enantiomer elution order was observed with the two CSPs under identical experimental conditions. Remarkably, this represents a rare instance where these CSPs demonstrate the ability to enantioseparate a non-ionic, non-ionizable species.The application of a molecular dynamics in silico protocol proved useful in elucidating the retention mechanism in depth, casting light on the central role of the H-bond formation and the involvement of the anionic moiety of the CSP 1.

BackgroundBrown tumors are rare bone manifestations of primary hyperparathyroidism (PHPT) that may occur at different sites either as single or multiple lesions and they can easily be mistaken for malignant lesions. Neither bone site nor morphological or functional imaging are useful to drive the differential diagnosis and biopsy is often the only conclusive procedure.Case descriptionWe report the case of a 53 years-old man referred to our outpatient clinic for severe symptomatic PHPT complicated by nephrolithiasis and osteoporosis. Neck ultrasound and computed tomography (CT) scan showed a large irregular lesion posterior to the lower pole of the right thyroid lobe consistent with an enlarged parathyroid gland. Moreover, two bone lytic lesions were described at the left scapula and the contiguous 7th rib that showed an increased uptake at total bone scintigraphy. Given the clinical and biochemical picture, the features of the parathyroid lesion and the presence of bone lytic lesions, the suspicion of metastatic parathyroid carcinoma (PC) was raised. However, a CT-guided biopsy performed on the left scapula revealed a brown tumor. The patient underwent en-bloc resection of the right inferior parathyroid grand with the ipsilateral thyroid gland lobe. Histopathology confirmed the diagnosis of PC. Post-surgical biochemical evaluations showed that the patient was cured. A repeated total body CT scan revealed an osteoblastic appearance of the bone lesions ascribed to the partial regression of the brown tumors following surgery.ConclusionsThe implication of a diagnosis of brown tumor or bone metastasis is widely different; in fact, the first tends to regress with the surgical treatment of PHPT, whereas the latter has limited cure option and negatively affects the prognosis of patients. Therefore, although brown tumors are extremely rarer than in the past, they must always be taken into consideration in the presence of bone lesions, even in cases of high suspicion of malignancy, to avoid unnecessary and harmful surgical interventions.

Several craniodental and postcranial Bovinae fossil remains coming from the early Middle Pleistocene Contrada Monticelli (CM) site (Castellana Grotte, BA) and preserved at the Museum of Earth Sciences at the University of Bari are here studied in detail for the first time. In addition to Bovinae, the fauna of CM includes several Galerian taxa such as: Canis mosbachensis Soergel, 1925, Palaeoloxodon antiquus (Falconer & Cautley, 1847), Stephanorhinus hundsheimensis Toula, 1902, Equus sp. and Dama cf. roberti Breda & Lister, 2013. Although the scarcity of the sample and the lack of skulls, horncores or metapodial remains should suggest caution, the detailed morphological and biometric analyses allow to refer these remains to a large form of bison, here provisionally classified as Bison cf. schoetensacki Freudenberg, 1914. The presence of this species in the CM site would represent the southernmost occurrence of this taxon in Europe, validating the biochronological attribution of the CM site to the Isernia Faunal Unit (ca. 0.6 Ma). The presence of this bovid, and other large mammals in the site, provides further clues for the reconstruction of the paleoenvironment of Mediterranean Europe during the early Middle Pleistocene.

The present paper aims to study the Wachau Valley in Austria as a representative Cultural Landscape under threat from extreme hydrometeorological hazards linked to climate change. The primary objective is to investigate the impacts and assess the vulnerability associated with the events of heavy rain and flooding. The methodology employed consists of an investigation of recorded past events impacting the Wachau; a vulnerability ranking system; a climate time series analysis based on earth observation products; and future hazard maps at territorial level, developed with outputs from regional and global climate models. The investigation we carried out provides a vulnerability assessment of two terraced areas with a surface of about 10,000 m2 in total, characterized by the presence of dry stone walls, with different state of conservation in the Municipality of Krems (Wachau). In addition, climate projections at territorial level for the extreme climate indices R20mm, R95pTOT, and R×5day—selected for investigating the likelihood of increases/decreases in events of heavy rain and large basin flooding—are provided, with a spatial resolution of ~12 km for the near and far future (2021–2050; 2071–2100) under stabilizing (RCP 4.5) and pessimistic (RCP 8.5) scenarios. The results indicate a general increase for the three indices in the studied areas during the far future under the pessimistic scenario, suggesting a heightened risk of heavy rain and flooding. These findings aim to inform policymakers and decision-makers in their development of strategies for safeguarding cultural heritage. Furthermore, they serve to assist local stakeholders in enhancing their understanding of prioritizing interventions related to preparedness, emergency response, and recovery.

Artificial intelligence (AI) has emerged as a fundamental component of global agricultural research that is poised to impact on many aspects of plant science. In digital phenomics, AI is capable of learning intricate structure and patterns in large datasets. We provide a perspective and primer on AI applications to phenome research. We propose a novel human-centric explainable AI (X-AI) system architecture consisting of data architecture, technology infrastructure, and AI architecture design. We clarify the difference between post hoc models and 'interpretable by design' models. We include guidance for effectively using an interpretable by design model in phenomic analysis. We also provide directions to sources of tools and resources for making data analytics increasingly accessible. This primer is accompanied by an interactive online tutorial.

IntroductionPrimary hyperparathyroidism (PHPT) is a common endocrine disorder in which surgery is the only curative therapy. Ectopic parathyroid adenoma in the pyriform sinus resulting from a pathological migration of parathyroid glands along the embryological development is a rare cause of PHPT. We describe a case of a persistent primary hyperparathyroidism after previous unsuccessful surgery due to an ectopic parathyroid adenoma within the pyriform sinus and we review the previous reports on this issue.Case presentationA 62-year-old woman was referred for persistent hypercalcemia following unsuccessful cervical exploratory surgery. Cervical ultrasound did not detect any parathyroid abnormalities. At variance, 99mTc-sestamibi SPECT/CT and CT scan of the neck identified a parathyroid adenoma in the left pyriform sinus, which was confirmed by endoscopy. The patient was successfully treated by transoral robotic resection and the pathology confirmed a parathyroid adenoma.ConclusionsThe ectopic parathyroid adenoma in the pyriform sinus is so uncommon that only fourteen cases have been reported. However, the pyriform sinus should be considered a possible location of ectopic parathyroid glands, especially in the setting of persistent or recurrent PHPT after parathyroid surgery.

Abstract Effective antiviral treatments for coronavirus disease 2019 (COVID‐19) are needed to reduce the morbidity and mortality associated with severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2) infection, particularly in patients with risk factors for severe disease. Molnupiravir (MK‐4482, EIDD‐2801) is an orally administered, ribonucleoside prodrug of β‐D‐N4‐hydroxycytidine (NHC) with submicromolar potency against SARS‐CoV‐2. A population pharmacokinetic (PopPK) analysis for molnupiravir exposure was conducted using 4202 NHC plasma concentrations collected in 1207 individuals from a phase I trial in healthy participants, a phase IIa trial in non‐hospitalized participants with COVID‐19, a phase II trial in hospitalized participants with COVID‐19, and a phase II/III trial in non‐hospitalized participants with COVID‐19. Molnupiravir pharmacokinetics (PK) was best described by a two‐compartment model with a transit‐compartment absorption model and linear elimination. Molnupiravir apparent elimination clearance increased with body weight less‐than‐proportionally (power 0.412) and was estimated as 70.6 L/h in 80‐kg individuals with a moderate interindividual variability (43.4% coefficient of variation). Additionally, effects of sex and body mass index on apparent central volume and food status and formulation on the absorption mean transit time were identified as statistically significant descriptors of variability in these PK parameters. However, none of the identified covariate effects caused clinically relevant changes in the area under the NHC concentration versus time curve between doses, the exposure metric most closely related to clinical response. Overall, the PopPK model indicates that molnupiravir can be administered in adults without dose adjustment based on age, sex, body size, food, and mild‐to‐moderate renal or mild hepatic impairment.

Ficus spp. are often used as food and in traditional medicine, and their biological activities as anti-inflammatory and diuretic, for wound healing, and as antimicrobial agents have been largely reviewed. The aim of this work was to investigate the polyphenol content and the antioxidant and anti-tyrosinase properties of the extracts from F. rubiginosa, a very poorly explored Ficus species. For this purpose, F. rubiginosa leaves were collected at three different maturity stages (H1, H2, and H3), and the environmentally sustainable methanolic extracts were evaluated for the total phenolic content (TPC), total flavonoid content (TFC), and total catechins content (TCC). The polyphenolic profile was studied using HPLC-UV/DAD and UHPLC-MS, and the antioxidant activity was determined in vitro using DPPH, FRAP, and ABTS assays. The study showed that the H2 extract had higher TPC and TFC values (113.50 mg GA/g and 43.27 mg QE/g, respectively) and significant antioxidant activity. Therefore, the H2 extract was selected to study the anti-tyrosinase activity. The results also showed that H2 was able to bind and inhibit tyrosinase, with rutin being the compound responsible for the measured activity on the enzyme.