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Nello Tommasino, Matteo Megna, Sara Cacciapuoti, Alessia Villani, Fabrizio Martora, Angelo Ruggiero, Lucia Genco, Luca Potestio Section of Dermatology - Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, ItalyCorrespondence: Luca Potestio, Section of Dermatology - Department of Clinical Medicine and Surgery, University of Naples Federico II, Via Pansini 5, Napoli, 80131, Italy, Tel +39 - 081 – 7462457, Fax +39 - 081 – 7462442, Email potestioluca@gmail.comAbstract: Teledermatology may be defined as the application of telemedicine to dermatology. According to published data, teledermatology is more widespread in Europe and North America, probably where resources for health care are greater than in other areas of the world. Indeed, teledermatology requires advanced technology to be efficient, as high image quality is necessary to allow the dermatologist to make correct diagnoses. Thanks to the recent advances in this field, teledermatology is become routinary in daily clinical practice. However, its use has been improved over time, overcoming several challenges. The aim of this narrative review is to retrace the almost 30-year history of teledermatology, to address the new challenges posed by advancing technologies such as artificial intelligence and the implications it may have on healthcare.Keywords: teledermatology, artificial intelligence, dermatology

Luca Potestio,* Fabrizio Martora,* Sara Cacciapuoti, Matteo Megna, Alessia Villani, Angelo Ruggiero Section of Dermatology - Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy*These authors contributed equally to this workCorrespondence: Angelo Ruggiero, Section of Dermatology - Department of Clinical Medicine and Surgery, University of Naples Federico II, Via Pansini 5, Napoli, 80131, Italy, Tel +39 - 081 – 7462457, Fax +39 - 081 – 7462442, Email angeloruggiero1993@libero.itAbstract: COVID-19 pandemic completely changed every aspect of human life. Several measures were adopted to limit the spreading of the infection. Among these, vaccination was the main one. Globally, vaccination campaign was a success, showing to be efficient in controlling and preventing the SARS-Cov2 infection, reducing the risk of disease progression, hospitalization, and mortality. However, with the increasing number of vaccines administered, several cutaneous reactions were described, making dermatologists key players in their recognition and treatment. Among these, also viral reactivations have been described. In particular, cases of Pityriasis Rosea (PR) and PR-like reactivations have been collected. An early diagnosis is mandatory to avoid mistreatments. In this context, we conducted a review of the current literature investigating cases of PR following COVID-19 vaccination with the aim of understanding the possible pathogenetic mechanisms and causal correlation as well as to investigate the risk of this cutaneous eruption, to offer clinicians a wide perspective on the linkage between PR and COVID-19 vaccines.Keywords: COVID-19, vaccination, pityriasis rosea, safety

Background and Aims: Hypoalbuminemia, as defined by serum albumin (SA) levels ≤35 g/L, is associated to venous and arterial thrombosis in general population and in patients at risk of cardiovascular disease. It is unknown if SA ≤35 g/L is also associated to portal vein thrombosis (PVT) in cirrhosis. Methods: Cirrhotic patients enrolled in the Portal vein thrombosis Relevance On Liver cirrhosis: Italian Venous thrombotic Events Registry (PRO-LIVER) study (n = 753), were followed-up for 2 years to assess the risk of PVT, that was diagnosed by Doppler ultrasonography. Child-Pugh classes, Model for End-Stage Liver Disease score, presence of hepatocellular carcinoma and laboratory variables including SA, D-dimer, and high-sensitivity C-reactive protein (hs-CRP) were measured at baseline. Results: SA ≤35 g/L was detected in 52% of patients. A logistic multivariate regression analysis showed that higher Child-Pugh class, hepatocellular carcinoma and thrombocytopenia were significantly associated to SA ≤35 g/L. In a subgroup of patients where data regarding hs-CRP and D-dimer were available, SA ≤35 g/L was inversely associated with hs-CRP and D-dimer. During the follow-up, a total of 61 patients experienced PVT. A Kaplan Meier survival analysis showed SA ≤35 g/L was associated to increased risk of PVT compared to SA >35 g/L (P = .005). A multivariate Cox proportional hazards regression analysis showed that male sex, lower platelet count, and SA ≤35 g/L remained associated to PVT after adjusting for confounding factors. Conclusion: Cirrhotic patients with SA ≤35 g/L are at higher risk of experiencing PVT compared to those with SA >35 g/L and could be considered as potential candidates to anticoagulant prophylaxis for PVT prevention.

Luca Potestio, Matteo Megna, Alessia Villani, Sara Cacciapuoti, Massimiliano Scalvenzi, Fabrizio Martora Section of Dermatology - Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, ItalyCorrespondence: Luca Potestio, Section of Dermatology - Department of Clinical Medicine and Surgery, University of Naples Federico II, Via Pansini 5, Napoli, 80131, Italy, Tel +39 - 081 – 7462457, Fax +39 - 081 – 7462442, Email potestioluca@gmail.comAbstract: COVID-19 was a worldwide emergency, leading to a global health crisis, which completely revolutionized every aspect of human life. Several strategies were adopted to limit the spreading of the infection such as testing and contact tracing, quarantine and isolation, use of face mask, social distancing, lockdowns, travel restrictions, etc. Of these, vaccines were the most important measures to reduce the transmission of the virus and the severity of the infection, in order to overcome the pandemic. Fortunately, vaccination campaign was a success, showing to be efficient in controlling and preventing the COVID-19, reducing the risk of disease progression, hospitalization, and mortality. Monitoring and addressing vaccine-related adverse events have been essential for maintaining public confidence. Indeed, with the increasing number of vaccines administered, various cutaneous reactions have been reported, making dermatologists key players in their recognition and treatment. Particularly, several cutaneous diseases and cutaneous findings have been reported. Of note, also viral reactivations have been described following COVID-19 vaccination. Among these, varicella zoster virus (VZV) reactivation has been collected. Globally, an early diagnosis and an accurate treatment of herpes zoster (HZ) is mandatory to reduce possible complications. In this context, we conducted a review of the current literature investigating cases HZ following COVID-19 vaccination with the aim of understanding the possible causal correlation and underlying pathogenetic mechanisms to offer clinicians a wide perspective on VZV reactivation and COVID-19 vaccines.Keywords: COVID-19, vaccination, herpes zoster, safety

Luca Potestio, Fabrizio Martora, Sara Cacciapuoti, Matteo Megna, Alessia Villani, Angelo Ruggiero Section of Dermatology - Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, ItalyCorrespondence: Angelo Ruggiero, Section of Dermatology - Department of Clinical Medicine and Surgery, University of Naples Federico II, Via Pansini 5, Napoli, 80131, Italy, Tel +39 - 081 – 7462457, Fax +39 - 081 - 7462442, Email angeloruggiero1993@libero.it

We propose the results of a research that combines the educational and psychological media approach, to verify the pedagogical potential of coding and robotics in the learning processes of 4-year-old children at the cognitive and socio-relational level.

This paper proposes to observe the linguistic forms by which it is possible to translate and interpret the fruition of audiovisual content in the domestic context, between linear broadcast schedule and on-demand streaming portals. In line with Louis Hjelmslev's linguistic theory, the two devices are observed through their syntagmatic and paradigmatic nature, emphasizing how they differently relate the content they convey by generating different forms of audiovisual discursiveness. Through this differentiation it will then be possible to account for the different valorization at play first in the schedule device - which prioritizes the linguistic/positional value - and then in the streaming portal - in which the phenomenological value proposed by A.J. Greimas comes into play. This comparative reading, in addition to returning to a formalization of the modes of viewing across devices, allows us to introduce a reading of the regimes of interaction that come into play at the time of the fruition of differentially conveyed and valorized content.

Fabrizio Martora, Matteo Megna,* Teresa Battista,* Luca Potestio,* Maria Carmela Annunziata, Claudio Marasca, Alessia Villani, Gabriella Fabbrocini Section of Dermatology - Department of Clinical Medicine and Surgery, University of Naples Federico II, Napoli, Italy*These authors contributed equally to this workCorrespondence: Fabrizio Martora, Section of Dermatology - Department of Clinical Medicine and Surgery, University of Naples Federico II, Via Pansini 5, Napoli, 80131, Italy, Tel +39 - 081 – 7462457, Fax +39 - 081 – 7462442, Email fabriziomartora92@libero.itAbstract: To date, adalimumab (ADA) is the only biotechnology drug approved for the management of hidradenitis suppurativa (HS), an inflammatory skin condition. However, it quickly became apparent that the efficacy of adalimumab in daily practice was highly variable. In our review, we highlighted the current evidence from literature on the use of biologics in HS in a real-life setting, particularly adalimumab, secukinumab and ustekinumab. Data on the effectiveness and safety of biologic drugs in HS management have been analyzed. Even if the results are promising, more studies are needed. In our opinion, the armamentarium of drugs for HS management is increasing, and treatment will be based on a tailored-tail approach, minimizing the risk of adverse events. In this context, we want to point out the reported effectiveness and safety data concerning adalimumab, ustekinumab and secukinumab as well as ixekizumab.Keywords: hidradenitis suppurativa, adalimumab, ustekinumab, secukinumab, ixekizumab, guselkumab, real life evidence

Angelo Ruggiero,1 Fabrizio Martora,1 Gabriella Fabbrocini,1 Alessia Villani,1 Claudio Marasca,1 Matteo Megna,1 Luigi Fornaro,1 Rosita Comune,2 Luca Potestio1 1Section of Dermatology, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy; 2Department of Precision Medicine, University of Campania Luigi Vanvitelli, Naples, ItalyCorrespondence: Angelo Ruggiero, Section of Dermatology, Department of Clinical Medicine and Surgery, University of Naples Federico II, Via Pansini, 5, Naples, 80131, Italy, Tel +39 - 081 - 7462457, Fax +39 - 081 - 7462442, Email Angeloruggiero1993@libero.itAbstract: Teledermatology represented one of the most important and useful tools during the COVID-19 pandemic era. Indeed, due to the severe restriction, and to reduce the spread of the infection, different measures were applied among different countries and hospitals to ensure a continuity of care for patients. In this scenario, teledermatology played a central role, especially in the management of patients suffering from chronic inflammatory skin diseases. The aim of this narrative review is to describe the role of teledermatology during the COVID-19 pandemic to analyze main strengths and limitations of this tool, as well as to provide future perspectives in clinical applications.Keywords: teledermatology, telemedicine, COVID-19, psoriasis, atopic dermatitis, hidradenitis suppurativa

Angelo Ruggiero,1 Matteo Megna,1 Alessia Villani,1 Rosita Comune,2 Gabriella Fabbrocini,1 Francesca di Vico1 1Section of Dermatology, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, 80131, Italy; 2Section of Radiology and Radiotherapy, Department of Precision Medicine, University of Campania Luigi Vanvitelli, Naples, 80138, ItalyCorrespondence: Angelo Ruggiero, Section of Dermatology, Department of Clinical Medicine and Surgery, University of Naples Federico II, Via Pansini 5, Napoli, 80131, Italy, Tel +39 081 7462457, Fax +39 081 7462442, Email angeloruggiero1993@libero.itAbstract: Bullous pemphigoid (BP) is the most frequent autoimmune bullous disease mainly affecting elderlies. Diagnosis usually results from clinical features, histological examination, and the quantification of circulating typical autoantibodies, due to its higher incidence in elderly patients, bullous pemphigoid treatment and management still represents a challenge due to the higher frequency of several comorbidities in this group of patients, which may also be linked to a reduced tolerance to BP treatments. Hence, an early diagnosis and a prompt correct treatment are mandatory to reach better clinical outcomes and improve as much as possible BP outcomes. Herein, we carried out a comprehensive literature review about the known clinical presentations, diagnosis, assessment and monitoring procedures used in daily clinical practice in patients with BP, to better define strategies to improve as much as possible BP clinical outcomes.Keywords: bullous pemphigoid, pemphigoid, review, monitoring, assessment, prognosis

The motivations for the National Research Project on the Short Wood Supply Chain stem from the recognition of the great importance of the wood-based bio-economy for the future carbon-free society. In addition to the essential ecological benefits provided by forests, natural wood resources are expected to play a significant role due to the increasing wood demand for structural and non-structural uses. However, in Italy most industrial wood products are made from imported timber, which results in poor attention to local forestry, loss of traditional silvicultural know-how and reduced forest employment in most mountain areas. The project specifically aims: (i) to assess the feasability and sustainability of wood short supply chains; (ii) to promote new models of environmental certification and energy efficiency analysis; (iii) to create innovative products for bio-building (CrossLam, laminated timber, wood panels) using wood assortments from sustainable forest management in Italy; (iv) to characterise the functionality of wood products (with attention paid to architectural issues), predict wood degradation rate and assess conservation methods. Attention is specifically devoted to most common forest species in Italy, such as beech, pines, chestnut, deciduous oaks and poplar and to test thermal and surface treatments with natural substances and nano-materials.

BackgroundThe heart is commonly involved in COVID-19, and rhythm disorders have been largely reported.ObjectiveTo evaluate the association of some non-cardiac and cardiac comorbidities and QT dispersion with arrhythmias and their impact on outcomes in hospitalized patients with COVID-19.MethodsEach patient underwent cardiac telemetry monitoring through the entire hospitalization period, laboratory analyses, 12-lead ECG, and lung imaging examination. Patients with arrhythmia were divided into three groups (bradyarrhythmias, tachyarrhythmias, and tachy- and bradyarrhythmias).ResultsTwo-hundred patients completed the study (males, 123; mean age, 70.1 years); of these, 80 patients (40%) exhibited rhythm disorders on telemetry. Patients with arrhythmia were older (p < 0.0001), had a greater number of comorbidities (p < 0.0001), higher values of creatinine (p = 0.007), B-type natriuretic peptide (p < 0.0001), troponin (p < 0.0001), C-reactive protein (p = 0.01), ferritin (p = 0.001), D-dimer (p < 0.0001), procalcitonin (p = 0.0008), QT interval (p = 0.002), QTc interval (p = 0.04), and QTc dispersion (p = 0.01), and lower values of sodium (p = 0.03), magnesium (p = 0.04), glomerular filtration rate (p < 0.0001), and hemoglobin (p = 0.008) as compared to patients without arrhythmia. By comparing the three subgroups of patients, no significant differences were found. At multivariate analysis, age [odds ratio (OR) = 1.14 (95% CI: 1.07–1.22); p = 0.0004], coronary artery disease [OR = 12.7 (95% CI: 2.38–68.01); p = 0.005], and circulating troponin [OR = 1.05 (95% CI: 1.003–1.10); p = 0.04] represented risk factors independently associated with arrhythmia. All-cause in-hospital mortality was ∼40-fold higher among patients with arrhythmia [OR = 39.66 (95% CI: 5.20–302.51); p = 0.0004].ConclusionArrhythmias are associated with aging, coronary artery disease, subtle myocardial injury, hyperinflammatory status, coagulative unbalance, and prolonged QTc dispersion in patients with COVID-19, and confer a worse in-hospital prognosis. Given its usefulness, routinary use of cardiac telemetry should be encouraged in COVID wards.

Ilaria Laurenzana,1,* Stefania Trino,1,* Daniela Lamorte,1 Marco Girasole,2 Simone Dinarelli,2 Angelo De Stradis,3 Vitina Grieco,4 Maddalena Maietti,5 Antonio Traficante,5 Teodora Statuto,4 Oreste Villani,6 Pellegrino Musto,6 Alessandro Sgambato,7 Luciana De Luca,4,* Antonella Caivano4,* 1Laboratory of Preclinical and Translational Research, Centro di Riferimento Oncologico della Basilicata (IRCCS-CROB), Rionero in Vulture, PZ, Italy; 2Institute for the Study of the Structure of Matter, National Research Council (CNR), Rome, Italy; 3Institute for Sustainable Plant Protection, National Research Council (CNR), Bari, Italy; 4Laboratory of Clinical Research and Advanced Diagnostics, Centro di Riferimento Oncologico della Basilicata (IRCCS-CROB), Rionero in Vulture, PZ, Italy; 5Unit of Clinical Pathology, Centro di Riferimento Oncologico della Basilicata (IRCCS-CROB), Rionero in Vulture, PZ, Italy; 6Hematology and Stem Cell Transplantation Unit, Centro di Riferimento Oncologico della Basilicata (IRCCS-CROB), Rionero in Vulture, PZ, Italy; 7Scientific Direction, Centro di Riferimento Oncologico della Basilicata (IRCCS-CROB), Rionero in Vulture, PZ, Italy*These authors contributed equally to this workCorrespondence: Antonella CaivanoLaboratory of Clinical Research and Advanced Diagnostics, IRCCS CROB, Rionero in Vulture, 85028, Potenza, ItalyTel +39 0972 726395Fax +39 0972 726482Email antonella.caivano@crob.itIntroduction: Extracellular vesicles (EVs) are naturally secreted cellular lipid bilayer particles, which carry a selected molecular content. Owing to their systemic availability and their role in tumor pathogenesis, circulating EVs (cEVs) can be a valuable source of new biomarkers useful for tumor diagnosis, prognostication and monitoring. However, a precise approach for isolation and characterization of cEVs as tumor biomarkers, exportable in a clinical setting, has not been conclusively established.Methods: We developed a novel and laboratory-made procedure based on a bench centrifuge step which allows the isolation of serum cEVs suitable for subsequent characterization of their size, amount and phenotype by nanoparticle tracking analysis, microscopy and flow cytometry, and for nucleic acid assessment by digital PCR.Results: Applied to blood from healthy subjects (HSs) and tumor patients, our approach permitted from a small volume of serum (i) the isolation of a great amount of EVs enriched in small vesicles free from protein contaminants; (ii) a suitable and specific cell origin identification of EVs, and (iii) nucleic acid content assessment. In clonal plasma cell malignancy, like multiple myeloma (MM), our approach allowed us to identify specific MM EVs, and to characterize their size, concentration and microRNA content allowing significant discrimination between MM and HSs. Finally, EV associated biomarkers correlated with MM clinical parameters.Conclusion: Overall, our cEV based procedure can play an important role in malignancy biomarker discovery and then in real-time tumor monitoring using minimal invasive samples. From a practical point of view, it is smart (small sample volume), rapid (two hours), easy (no specific expertise required) and requirements are widely available in clinical laboratories.Keywords: extracellular vesicles, biomarkers, hematological malignancies, nanoparticle tracking analysis, flow cytometry, digital PCR

Pietro Persiani,1 Daniele De Meo,1 Elettra Giannini,1 Valeria Calogero,1 Tommaso Speziale Varsamis,1 Armando Ugo Cavallo,2 Lorena Martini,1 Gianluca Cera,1 Flaminia Coluzzi,3 Ciro Villani1 1Department of Orthopaedic and Traumatology, Policlinico Umberto I Hospital, Sapienza University of Rome, Rome, 00185, Italy; 2Department of Biomedicine and Prevention, Tor Vergata University, Rome, 00133, Italy; 3Department of Medical and Surgical Sciences and Biotechnologies, Sapienza University of Rome, Rome, 00185, ItalyCorrespondence: Daniele De MeoDepartment of Orthopaedic and Traumatology, Policlinico Umberto I Hospital, Sapienza University of Rome, Piazzale A. Moro 3, Rome, 00185, ItalyTel +39 3338745373Email daniele.demeo@uniroma1.itPurpose: Following the 2019 coronavirus (COVID-19) pandemic, many reports have investigated the psychosocial effects of the lockdown. The aim of our study was to investigate the effects of the lockdown on the daily life habits of orthopaedic patients.Patients and Methods: Around 30 days after the start of the Italian lockdown, from April 17th to the end of the containment measures on May 18th, the Sapienza University of Rome carried out a 19-item survey on the effects the lockdown caused in patients suffering from an orthopaedic pathology (with regard to changes in lifestyle, pain, treatment) by stratifying the sample by age, sex, profession, pain location, pathogenesis and prior surgeries.Results: A total of 292 subjects with orthopaedic pathologies took part in the survey. Taking into consideration the totality of the sample, physical activity was significantly reduced (p < 0.001). The increase of a sedentary lifestyle was statistically significant (p < 0.001), as well as an increase in pain (p < 0.001) and the need to adjust the pharmacological treatment (p < 0.001). The increase in pain was particularly significant in the 50– 70 age group, among workers, and in polyarthralgic patients. About 55.48% stated that the lockdown period worsened their underlying pathological condition and 53.77% expressed the need to undergo a new clinical evaluation at the end of the lockdown.Conclusion: The impact of the COVID-19 pandemic lockdown and resulting sudden changes in lifestyle led to a change in patient perception of orthopedic pathology including a worsening of musculoskeletal pain requiring an adjustment or change in pharmacological and physical therapy.Keywords: lockdown, musculoskeletal pain, orthopaedic pathology, SARS-CoV-2, pandemic

Abstract Background Autism spectrum disorder is a complex condition with wide variation in type and severity that involves persistent challenges in social interaction, speech and nonverbal communication, restricted/repetitive behaviours and adaptive behaviours. In recent years, research has deepened the study of the predictive factors of optimal outcome, intended as indicators of positive trajectory in children with a previous diagnosis of autism who, after a therapeutic path, show a significant reduction in the “core” symptoms of autism and a positive evolution in social, adaptive, affective, and relational skills. Methods The study included 40 children aged 21 to 66 months, enrolled between 2015 and 2016 for an autism spectrum disorder clinical suspicious. Children were re-evaluated after at least 2 years of therapy and they were divided into two groups: the ASD-ASD group included children with a confirmed diagnosis of ASD, and the ASD-OO comparison group included children who no longer met the criteria for an autism classification. The aim of this retrospective study was to investigate the presence of cognitive, emotional and relational predictors capable of predicting the presence of optimal outcome in with a diagnosis of autism; the predictors taken into consideration were the intelligence quotient, the play, the emotional contagion and the understanding of other’s intentions. In this way, it is possible to support clinicians in defining a more complete diagnostic framework of autism, using assessment tools that can be administered quickly and therefore suitable for short observation sessions in paediatric patients. Results The findings showed that 15 out of 40 children, after at least for 2 years, no longer fell into the diagnostic ASD category based on the ADOS-2, DSM-5 and clinical criteria. The children in the ASD-OO group initially had a higher IQ than those in the ASD-ASD group, lower severity of autistic symptoms, greater understanding of intentions, more emotional contagion, and better quality of play. The results suggest that the initial coexistence of skills in these areas at the time of the first diagnostic assessment may allow us to predict the possibility of achieving optimal outcome after 2 years of therapy. Conclusions The data of this study highlight the importance of considering, during assessment, intelligence quotient, play, emotional contagion, and understanding of the intentions of others as potential prognostic predictors that can become useful tools for clinicians and paediatricians. This allows us to focus attention, in both the diagnostic and prognostic phases, on emotional-relational variables that can support the clinician in defining a more complete diagnostic framework and in planning a more personalized therapeutic path.

Abstract Background Acute Cerebral Nervous System Infections (ACNS) may cause death or severe complications even to promptly treated children. The role of the immune system in influencing the course and the outcome of meningitis has been studied but it is not yet completely understood. The aim of the research is to ascertain whether children who experienced ACNS infection had a normal immune system. Methods Patients under 18 years of age admitted at Bambino Gesù Children from January 2006 till June 2016 for meningitis were asked to participate to the follow-up study. The immune status was evaluated both clinically and by laboratory investigations. Results Most of the patients over 3 years at follow up had at least one immunological alteration at follow-up evaluation (74%). Considering ACNS infection etiology, certain pathogens were almost exclusive of patients affected by some immunological alteration, regardless of their age. Discussion Our preliminary results indicate that sub-clinical immunological defects may be associated to ACNS pediatric infections. Moreover, to the best of our knowledges, this is the first study correlating pathogens to immune evaluation in ACNS infections. It is, however, important to underline the high frequency of persistent immunological alterations in the analyzed patients. Further studies are needed to confirm our conclusions. Conclusions We recommend an immunological assessment at follow up evaluation in children who experienced an ACNS infection.

Marie Costa,1,2 Florian Correard,3,4 Maeva Montaleytang,3,4 Karine Baumstarck,5 Sandrine Loubière,5 Kahena Amichi,6 Patrick Villani,7 Stephane Honore,3,4,8 Aurélie Daumas,7 Pierre Verger1,2 1ORS PACA, Southeastern Health Regional Observatory, Marseille, France; 2Aix Marseille Univ, IRD, AP-HM, SSA, VITROME, IHU-Méditerranée Infection, Marseille, France; 3AP-HM, Service Pharmacie, Hôpital de la Timone, Marseille 13385, France; 4Laboratoire de Pharmacie Clinique, faculté de pharmacie, Aix-Marseille Université, Marseille 13385, France; 5EA3279, Self-Perceived Health Assessment Research Unit, Aix-Marseille University, Marseille 13385, France; 6Direction de la Recherche Clinique et de l’Innovation (DRCI), AP-HM, Marseille 13354, France; 7Service de Médecine Interne Gériatrie et Thérapeutique, CHU Sainte Marguerite, Assistance Publique des Hôpitaux de Marseille (AP-HM), Marseille 13274, France; 8Service de Pharmacie Clinique, Faculté de Pharmacie Timone, Aix-Marseille Université, Marseille F-13000, FranceCorrespondence: Marie Costa Email Mariecosta1212@gmail.comPurpose: In France, polypharmacy among older people living in nursing homes (NH) is a major public health concern. In this context, the randomized controlled trial TEM-EHPAD was recently launched in various NH in southern France to evaluate the impact of implementing a novel telemedication review (TMR) on hospital admission rates of NH residents at high risk of iatrogenic disease. A qualitative study was integrated into the main trial study to assess general practitioners’ (GP) and other NH healthcare professionals’ (HP) acceptability of the proposed TMR before its implementation.Material and Methods: A qualitative study using face-to-face semi-structured interviews was conducted with 16 HP before the beginning of the intervention. A manual thematic analysis was performed on the transcribed interviews.Results: Four main themes emerged from the thematic analysis: HP perceptions of the TMR, difficulties related to medication management for NH residents, HP perceptions of the roles of different professionals, and facilitators of good practices. Most participants were favorable to the TMR, but some GP expressed fears about loss of control over their prescription writing.Conclusion: This study fulfilled its objective to assess pre-intervention acceptability by GP and other HP. Results provided important information about how to adapt the TMR intervention to make it more acceptable to HP who will be involved in TEM-EHPAD. One of the main recommendations is the importance of providing participating GP with the opportunity to take part in the process of reviewing prescriptions.Keywords: qualitative study, telemedicine, older adults, telemedication review, nursing home, acceptability study, satisfaction assessment

Debris flows and avalanches are dangerous natural phenomena, characterized by the gravity-driven motion of granular media immersed in a fluid. For an appropriate hazard assessment or disaster mitigation by scenario investigation, it is crucial to capture the underlying dynamics of the granular solid phase. For this purpose, a multilayer depth-averaged approach represents a promising and computationally efficient tool over fully three-dimensional models. Here we use a mathematically well-posed multilayer model, which implements the µ(I)-rheology and a dilatancy law depending on the inertial number, I, and compare the numerical results of the model with laboratory experiments of steady uniform chute flows over an erodible bed. The well-posedness of the model for any value of I, which is essential to get convergent numerical solutions, is achieved by considering an approximation of the in-plane stress gradients, directly emerging from the µ(I)-rheology. The predicted velocity profiles show a very good agreement with the experimental ones, measured by particle image velocimetry (PIV). The volume fraction profiles by the multilayer model are also in good qualitative agreement with those measured by using the stochastic-optical method (SOM), while they tend to overestimate the volume fraction measurements in the more dilute upper region, closer to the free surface.

Elena Bozzola,1 Giulia Spina,1 Alberto Eugenio Tozzi,2 Alberto Villani1 1Pediatric Unit, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy; 2Multifactorial and Complex Diseases Research Area, Predictive and Preventive Medicine Unit, Bambino Gesù Children’s Hospital, IRCCS, Rome, ItalyCorrespondence: Elena BozzolaBambino Gesù Children Hospital, Piazza S Onofrio 4, Rome 00165, ItalyTel +39(0)668592744Email elena.bozzola@opbg.netAbstract: A safe vaccine against measles has been available and globally recommended since 1974. The World Health Organization established measles elimination as a goal for 2020 but, unfortunately, this objective has not been achieved yet and outbreaks still occur. Herd immunity, ie, a population immunity higher than 95%, is required to stop the measles virus transmission. Communication plays a crucial role in immunization strategy to obtain high coverage levels, as it helps to fight barriers against vaccination. Delay and refusal of measles vaccination have become widespread due to misinformation, fake news and barriers to effective communication. This phenomenon has been defined as “vaccine hesitancy” and is considered as one of the top ten risks for global health. The alleged association between measles vaccination and autism has caused a sharp decline in vaccination rates. In this current situation, mass communication integrated into public health policies is fundamental to sway people’s positive attitudes toward vaccination. Digital communication strategies based on social media and other internet platforms may represent useful tools to promote immunization and discourage skepticism and complement information provided by health-care professionals who have been considered as the most credible source on risk/benefits on vaccines for families. Digital communication strategies that may help supporting the measles elimination strategy include monitoring information needs online, integrating digital communication into immunization programs, involving a multidisciplinary group in communication, developing content that balances facts with positive messaging, using multiple communication channels. Further research activities should be promoted in the field of effective communication for immunization.Keywords: measles, children, vaccination, health

Anne-Laure Couderc,1,2 Celia Boisseranc,3 Dominique Rey,1 Emilie Nouguerede,1 Laurent Greillier,4,5 Fabrice Barlesi,4,5 Florence Duffaud,4,6 Jean-Laurent Deville,6 Stéphane Honoré,3,4 Patrick Villani,1,2 Florian Correard3,4 1Internal Medicine, Geriatry and Therapeutic Unit, AP-HM, Marseille, France;Coordination Unit for Geriatric Oncology (UCOG), PACA West, Marseille, France; 2Aix-Marseille Université, CNRS, EFS, ADES, Marseille, France; 3Pharmacology Department, AP-HM, Marseille, France; 4Aix-Marseille University, Marseille, France; 5Multidisciplinary Oncology and Therapeutic Innovations Unit, AP-HM, Marseille, France; 6Oncology Unit, AP-HM, Marseille, FranceCorrespondence: Anne-Laure CoudercCoordination Unit for Geriatric Oncology (UCOG), PACA West, University Hospital of Marseille (AP-HM), 270 Boulevard De Sainte Marguerite, Marseille 13009, FranceTel +33 491744530Fax +33 491744833Email anne-laure.couderc@ap-hm.frBackground: Polymorbidity induces polypharmacy in older patients may lead to potential drug–drug interactions (DDI) which can modify the tolerance and safety of oncological treatments and alter the intended therapeutic effect. The objective of our study was to describe the decision-making process for oncological treatment and related outcomes, in a population of older adults undergoing a comprehensive geriatric assessment (CGA) associated to a comprehensive medication reconciliation (CMR) prior to initiating oncological treatment.Methods: ChimioAge is a prospective observational study conducted between 01/2017 and 07/2018 at Marseille University Hospital and approved by the French National Ethics Committee. It comprised all consecutive patients aged 70 years and over who were referred for a CGA as part of CMR, before initiating systemic treatment.Results: One hundred and seventy-one cancer patients were included. Mean age was 79.2 years, over half had metastatic cancers, 75% had an ECOG performance status zero or one, and two-thirds were independent in daily activities. Two-thirds of the patients had polypharmacy and the CMR identified potential DDI with systemic treatment in 43.3% of patients. Following the CGA, the CMR and the hospital oncologists decision, 30% of the patients received adapted systemic treatment with reduced doses at initiation. They presented fewer toxicities – irrespective of grade and type – than patients who received standard treatment (p< 0.001) and had comparable overall survival (Log rank p=0.21).Conclusion: This is one of the first studies to highlight the value in conducting CMR and a CGA simultaneously before initiating systemic treatment in older patients with cancer. These two evaluations could give oncologists decisive information to personalize cancer treatment of older patients and optimize treatment dose to offer the best efficacy and minimize toxicity.Keywords: aged, antineoplastic protocols, geriatric assessment, medication reconciliation, treatment failure

Teodora Statuto,1,* Fiorella D’Auria,2,* Luigi Del Vecchio3,4,†, Giovanna Rosaria Mansueto,5 Oreste Villani,5 Anna Vittoria Lalinga6,†, Luciana Possidente,6 Filomena Nozza,1 Gabriella Vona,1 Luciana Rago,7 Giovanni Storto,8 Vanessa Rebecca Gasparini,9 Renato Zambello,10 Giovanni D’Arena,5,* Luciana Valvano1,* 1Laboratory of Clinical Research and Advanced Diagnostics, Centro Di Riferimento Oncologico Della Basilicata (IRCCS-CROB), Rionero in Vulture, Pz, Italy; 2Unit of Clinical Pathology, Centro Di Riferimento Oncologico Della Basilicata (IRCCS-CROB), Rionero in Vulture, Pz, Italy; 3CEINGE Biotecnologie Avanzate S.c.a.r.l, Federico II University, Naples, Italy; 4Department of Molecular Medicine and Medical Biotechnology (DMMBM), Federico II University, Naples, Italy; 5Hematology Department of Basilicata, Centro Di Riferimento Oncologico Della Basilicata (IRCCS-CROB), Rionero in Vulture, Pz, Italy; 6Pathology Unit, Centro Di Riferimento Oncologico Della Basilicata (IRCCS-CROB), Rionero in Vulture, Pz, Italy; 7Radiotherapy Unit, Centro Di Riferimento Oncologico Della Basilicata (IRCCS-CROB), Rionero in Vulture, Pz, Italy; 8Department of Nuclear Medicine, Centro Di Riferimento Oncologico Della Basilicata (IRCCS-CROB), Rionero in Vulture, Pz, Italy; 9Department of Medicine, University of Padova - Veneto Institute of Molecular Medicine, VIMM, Padova, PD, Italy; 10Hematology and Clinical Immunology, Department of Medicine, Padua School of Medicine, Padova, PD, Italy†Anna Vittoria Lalinga passed away on January 26, 2020 and Luigi Del Vecchio passed away on August 16, 2018*These authors contributed equally to this workCorrespondence: Luciana ValvanoLaboratory of Clinical Research and Advanced Diagnostics, Centro Di Riferimento Oncologico Della Basilicata (IRCCS-CROB), Rionero in Vulture, Pz, ItalyTel +39 0972 726395Fax +39 0972 723509Email luciana.valvano@crob.itAbstract: Lymphoproliferative disorders are a heterogeneous group of malignant clonal proliferations of lymphocytes whose diagnosis remains challenging, despite diagnostic criteria are now well established, due to their heterogeneity in clinical presentation and immunophenotypic profile. Lymphoid T-cell disorders are more rarely seen than B-cell entities and more difficult to diagnose for the absence of a specific immunophenotypic signature. Flow cytometry is a useful tool in diagnosing T-cell lymphoproliferative disorders since it is not only able to better characterize T-cell neoplasms but also to resolve some very complicated cases, in particular those in which a small size population of neoplastic cells is available for the analysis. Here, we report three patients with mature T-cell neoplasms with atypical clinical and biological features in which analysis of peripheral blood and bone marrow specimens by means of multicolor flow cytometry was very useful to identify and characterize three rare T-cell lymphoproliferative disorders, such as angioimmunoblastic T-cell lymphoma, peripheral T-cell lymphoma not otherwise specified and T-cell prolymphocytic leukemia. The aim of this case series report is not only to describe three rare cases of lymphoproliferative neoplasms but also to raise awareness that a fast, highly sensitive, and reproducible procedure, such as flow cytometry immunophenotyping, can have a determinant diagnostic role in these patients.Keywords: flow cytometry, immunophenotype, angioimmunoblastic T-cell lymphoma, peripheral T-cell lymphoma not otherwise specified, T-cell prolymphocytic leukemia, diagnosis

BackgroundSeveral models have been developed to predict mortality in patients with COVID-19 pneumonia, but only a few have demonstrated enough discriminatory capacity. Machine learning algorithms represent a novel approach for the data-driven prediction of clinical outcomes with advantages over statistical modeling. ObjectiveWe aimed to develop a machine learning–based score—the Piacenza score—for 30-day mortality prediction in patients with COVID-19 pneumonia. MethodsThe study comprised 852 patients with COVID-19 pneumonia, admitted to the Guglielmo da Saliceto Hospital in Italy from February to November 2020. Patients’ medical history, demographics, and clinical data were collected using an electronic health record. The overall patient data set was randomly split into derivation and test cohorts. The score was obtained through the naïve Bayes classifier and externally validated on 86 patients admitted to Centro Cardiologico Monzino (Italy) in February 2020. Using a forward-search algorithm, 6 features were identified: age, mean corpuscular hemoglobin concentration, PaO2/FiO2 ratio, temperature, previous stroke, and gender. The Brier index was used to evaluate the ability of the machine learning model to stratify and predict the observed outcomes. A user-friendly website was designed and developed to enable fast and easy use of the tool by physicians. Regarding the customization properties of the Piacenza score, we added a tailored version of the algorithm to the website, which enables an optimized computation of the mortality risk score for a patient when some of the variables used by the Piacenza score are not available. In this case, the naïve Bayes classifier is retrained over the same derivation cohort but using a different set of patient characteristics. We also compared the Piacenza score with the 4C score and with a naïve Bayes algorithm with 14 features chosen a priori. ResultsThe Piacenza score exhibited an area under the receiver operating characteristic curve (AUC) of 0.78 (95% CI 0.74-0.84, Brier score=0.19) in the internal validation cohort and 0.79 (95% CI 0.68-0.89, Brier score=0.16) in the external validation cohort, showing a comparable accuracy with respect to the 4C score and to the naïve Bayes model with a priori chosen features; this achieved an AUC of 0.78 (95% CI 0.73-0.83, Brier score=0.26) and 0.80 (95% CI 0.75-0.86, Brier score=0.17), respectively. ConclusionsOur findings demonstrated that a customizable machine learning–based score with a purely data-driven selection of features is feasible and effective for the prediction of mortality among patients with COVID-19 pneumonia.

This study examined how well people can recognize and relate to animated pedagogical agents of varying ethnicities/races and genders. For both Study 1 (realistic-style agents) and Study 2 (cartoon-style agents), participants viewed brief video clips of virtual agents of varying racial/ethnic categories and gender types and then identified their race/ethnicity and gender and rated how human-like and likable the agent appeared. Participants were highly accurate in identifying Black and White agents but were less accurate for Asian, Indian, and Hispanic agents. Participants were accurate in recognizing gender differences. Participants rated all types of agents as moderately human-like, except for White agents. Likability ratings were lowest for White and male agents. The same pattern of results was obtained across two independent studies with different participants and different onscreen agents, which indicates that the results are not solely due to one specific set of agents. Consistent with the Media Equation Hypothesis and the Alliance Hypothesis, this work shows that people are sensitive to the race/ethnicity and gender of onscreen agents and relate to them differently. These findings have implications for how to design animated pedagogical agents for improved multimedia learning environments in the future and serve as a crucial first step in highlighting the possibility and feasibility of incorporating diverse onscreen virtual agents into educational computer software.

In this paperwe address the need to design adaptive interacting systems for advanced industrial production machines. Modern production systems have become highly complex and include many subsidiary functionalities, thus making it difficult for least skilled human operators interact with them. In this regard, adapting the behavior of the machine and of the operator interface to the characteristics of the user allows a more effective interaction process, with a positive impact on manufacturing efficiency and user’s satisfaction. To this end, it is crucial to understandwhich are the user’s capabilities that influence the interaction and, hence, should be measured to provide the correct amount of adaptation.Moving along these lines, in this paper we identify groups of users that, despite having different individual capabilities and features, have common needs and response to the interaction with complex production systems. As a consequence,we define clusters of users that have the same need for adaptation. Then, adaptation rules can be defined by considering such users’ clusters, rather than addressing specific individual user’s needs.

This article focuses on ethical issues raised by increasing levels of autonomy for surgical robots. These ethical issues are explored mainly by reference to state-ofart case studies and imminent advances in Minimally Invasive Surgery (MIS) and Microsurgery. In both area, surgicalworkspace is limited and the required precision is high. For this reason, increasing levels of robotic autonomy can make a significant difference there, and ethically justified control sharing between humans and robots must be introduced. In particular, from a responsibility and accountability perspective suitable policies for theMeaningfulHuman Control (MHC) of increasingly autonomous surgical robots are proposed. It is highlighted how MHC should be modulated in accordance with various levels of autonomy for MIS and Microsurgery robots. Moreover, finer MHC distinctions are introduced to deal with contextual conditions concerning e.g. soft or rigid anatomical environments.

The seventh iteration of the reference genome assembly for Rattus norvegicus-mRatBN7.2-corrects numerous misplaced segments and reduces base-level errors by approximately 9-fold and increases contiguity by 290-fold compared with its predecessor. Gene annotations are now more complete, improving the mapping precision of genomic, transcriptomic, and proteomics datasets. We jointly analyzed 163 short-read whole-genome sequencing datasets representing 120 laboratory rat strains and substrains using mRatBN7.2. We defined ∼20.0 million sequence variations, of which 18,700 are predicted to potentially impact the function of 6,677 genes. We also generated a new rat genetic map from 1,893 heterogeneous stock rats and annotated transcription start sites and alternative polyadenylation sites. The mRatBN7.2 assembly, along with the extensive analysis of genomic variations among rat strains, enhances our understanding of the rat genome, providing researchers with an expanded resource for studies involving rats.

Assessing the information provided by coproduced climate services is a timely challenge, given the continuously evolving scientific knowledge and its increasing translation to address societal needs. Here, we propose a joint evaluation and verification framework to assess prototype services that provide seasonal forecast information based on the experience from the Horizon 2020 (H2020) Climate forecasts enabled knowledge services (CLARA) project. The quality and value of the forecasts generated by CLARA services were first assessed for five climate services utilizing the Copernicus Climate Change Service seasonal forecasts and responding to knowledge needs from the water resources management, agriculture, and energy production sectors. This joint forecast verification and service evaluation highlights various skills and values across physical variables, services, and sectors, as well as a need to bridge the gap between verification and user-oriented evaluation. We provide lessons learned based on the service developers' and users' experience and recommendations to consortia that may want to deploy such verification and evaluation exercises. Last, we formalize a framework for joint verification and evaluation in service development, following a transdisciplinary (from data purveyors to service users) and interdisciplinary chain (climate, hydrology, economics, and decision analysis). SIGNIFICANCE STATEMENT: Tools to communicate climate-related information to users, typically dam managers, irrigation consortia, or energy producers, are fast evolving to answer societal needs. It is crucial to estimate the quality of the provided information, along with economic, environmental, and/or societal gains. Here, we exemplify how to assess information quality and potential gains in five services that provide data and information for hydropower, solar power, irrigation, and water reservoirs in Europe and South America. Based on this work, we recommend 1) service developers to well anticipate such quality and value assessments, due to the number of actors to be involved; 2) flexibility when screening how to quantify quality and gain to account for decision contexts; and 3) sustained funding or collaborating platforms to ensure the iterative coevaluation process. KEYWORDS: Forecast verification/skill; Seasonal forecasting; Climate services; Economic value, 1. Introduction Climate and water services convey climate-relevant knowledge and information (processed, structured, and well-communicated data interpreted for decision-making contexts) for horizons ranging from weeks to decades ahead. Climate services, [...]