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Summary: Background: Pre-exposure vaccination with MVA-BN has been widely used against mpox to contain the 2022 outbreak. Many countries have defined prioritized strategies, administering a single dose to those historically vaccinated for smallpox, to achieve quickly adequate coverage in front of low supplies. Using epidemiological models, real-life effectiveness was estimated at approximately 36%–86%, but no clinical trials were performed. Few data on MVA-BN immunogenicity are currently available, and there are no established correlates of protection. Immunological response in PLWH in the context of the 2022 outbreak was also poorly described. Methods: Blood samples were collected from participants eligible for pre-exposure MVA-BN vaccination before (T1) receiving a full course of vaccine (single-dose for vaccine-experienced or smallpox-primed and two-dose for smallpox vaccine-naïve or smallpox non-primed) and one month after the last dose (T2 and T3, respectively). MPXV-specific IgGs were measured by in-house immunofluorescence assay, using 1:20 as screening dilution, MPXV-specific nAbs by 50% plaque reduction neutralization test (PRNT50, starting dilution 1:10), and IFN-γ-producing specific T cells to MVA-BN vaccine, by ELISpot assay. Paired or unpaired t-test and Wilcoxon or Mann–Whitney test were used to analyse IgG and nAbs, and T-cell response, as appropriate. The probability of IgG and nAb response in vaccine-experienced vs. vaccine-naïve was estimated in participants not reactive at T1. The McNemar test was used to evaluate vaccination's effect on humoral response both overall and by smallpox vaccination history. In participants who were not reactive at T1, the proportion of becoming responders one month after full-cycle completion by exposure groups was compared by logistic regression and then analysed by HIV status strata (interaction test). The response was also examined in continuous, and the Average Treatment Effect (ATE) of the difference from baseline to schedule completion according to previous smallpox vaccination was estimated after weighting for HIV using a linear regression model. Self-reports of adverse effects following immunization (AEFIs) were prospectively collected after the first MVA-BN dose (T1). Systemic (S-AEFIs: fatigue, myalgia, headache, GI effects, chills) and local (L-AEFIs: redness, swelling, pain) AEFIs were graded as absent (grade 0), mild (1), moderate (2), or severe (3). The maximum level of severity for S-AEFIs and L-AEFIs ever experienced over the 30 days post-dose by vaccination exposure groups were analysed using a univariable multinomial logistic regression model and after adjusting for HIV status; for each of the symptoms, we also compared the mean duration by exposure group using an unpaired t-test. Findings: Among the 164 participants included, 90 (54.8%) were smallpox vaccine-experienced. Median age was 49 years (IQR 41–55). Among the 76 (46%) PLWH, 76% had a CD4 count >500 cells/μL. There was evidence that both the IgG and nAbs titers increased after administration of the MVA-BN vaccine. However, there was no evidence for a difference in the potential mean change in humoral response from baseline to the completion of a full cycle when comparing primed vs. non-primed participants. Similarly, there was no evidence for a difference in the seroconversion rate after full cycle vaccination in the subset of participants not reactive for nAbs at T1 (p = 1.00 by Fisher's exact test). In this same analysis and for the nAbs outcome, there was some evidence of negative effect modification by HIV (interaction p-value = 0.17) as primed people living with HIV (PLWH) showed a lower probability of seroconversion vs. non-primed, and the opposite was seen in PLWoH. When evaluating the response in continuous, we observed an increase in T-cell response after MVA-BN vaccination in both primed and non-primed. There was evidence for a larger increase when using the 2-dose vs. one-dose strategy with a mean difference of −2.01 log2 (p ≤ 0.0001), after controlling for HIV. No evidence for a difference in the risk of developing any AEFIs of any grade were observed by exposure group, except for the lower risk of grade 2 (moderate) fatigue, induration and local pain which was lower in primed vs. non-primed [OR 0.26 (0.08–0.92), p = 0.037; OR 0.30 (0.10–0.88), p = 0.029 and OR 0.19 (0.05–0.73), p = 0.015, respectively]. No evidence for a difference in symptom duration was also detected between the groups. Interpretation: The evaluation of the humoral and cellular response one month after the completion of the vaccination cycle suggested that MVA-BN is immunogenic and that the administration of a two-dose schedule is preferable regardless of the previous smallpox vaccination history, especially in PLWH, to maximize nAbs response. MVA-BN was safe as well tolerated, with grade 2 reactogenicity higher after the first administration in vaccine-naïve than in vaccine-experienced individuals, but with no evidence for a difference in the duration of these adverse effects. Further studies are needed to evaluate the long-term duration of immunity and to establish specific correlates of protection. Funding: The study was supported by the National Institute for Infectious Disease Lazzaro Spallanzani IRCCS “Advanced grant 5 × 1000, 2021” and by the Italian Ministry of Health “Ricerca Corrente Linea 2”.

This paper introduces a database of 34 field-measured building occupant behavior datasets collected from 15 countries and 39 institutions across 10 climatic zones covering various building types in both commercial and residential sectors. This is a comprehensive global database about building occupant behavior. The database includes occupancy patterns (i.e., presence and people count) and occupant behaviors (i.e., interactions with devices, equipment, and technical systems in buildings). Brick schema models were developed to represent sensor and room metadata information. The database is publicly available, and a website was created for the public to access, query, and download specific datasets or the whole database interactively. The database can help to advance the knowledge and understanding of realistic occupancy patterns and human-building interactions with building systems (e.g., light switching, set-point changes on thermostats, fans on/off, etc.) and envelopes (e.g., window opening/closing). With these more realistic inputs of occupants' schedules and their interactions with buildings and systems, building designers, energy modelers, and consultants can improve the accuracy of building energy simulation and building load forecasting.

Background: Excessive student anxiety is a common problem that severely impairs short- and long-term academic functioning and increases teacher burden. Reducing student anxiety has been associated with improvement in educational functioning. Because anxiety manifests daily in the classroom, teachers are in an ideal position to identify and help students manage their anxiety. Unfortunately, teachers lack the knowledge and skills to support the learning of students with excessive anxiety. The Teacher Anxiety Program for Elementary Students (TAPES), a novel teacher-administered school-home collaborative intervention, was designed to address this gap. Methods: This manuscript describes the protocol for developing and evaluating TAPES. Specifically, we present a description of: (1) the intervention and theoretical model; and (2) methods for the proposed randomized controlled trial comparing TAPES to a standard professional development seminar focused on reducing student anxiety. Discussion: Primary aims examine the impact of the TAPES training on teacher knowledge and skill. Secondary aims examine the impact of TAPES on student outcomes. Exploratory aims will examine mediators based on our proposed theory of change. If effective, TAPES has the potential to directly benefit teachers (improving skills) and students (reducing anxiety and improving functioning).

Problematic anxiety in students impairs academic functioning. Teachers are often the first among school personnel to interact with these students, but they rarely receive training in evidence-based anxiety reduction strategies. This study assessed the feasibility of a brief teacher-administered school-home intervention (TAPES; Teacher Anxiety Program for Elementary Students) to reduce student anxiety symptoms. Eight elementary teachers completed a 1-day training and administered TAPES to 10 students with elevated symptoms of anxiety (M age: 8 years old; 50% female; 90% Caucasian). Feasibility of the intervention was assessed using several indicators, including training and intervention satisfaction as well as fidelity of implementation. Pre-post intervention student outcomes were collected from parents, students, and teachers. Results indicated that the majority of teachers were satisfied with the training and reported the intervention was feasible. Paired t-tests on pre-post outcome measures revealed significant reductions in student anxiety symptoms according to teachers and parents. Preliminary results suggest TAPES is feasible and helpful in reducing anxiety symptoms. Additional evaluation using a randomized controlled design is warranted.

Introduction: Coronavirus disease 2019 (COVID-19) is a significant and novel cause of acute respiratory distress syndrome (ARDS). During the COVID-19 pandemic, there has been an increase in the incidence of cases involving pneumothorax and pneumomediastinum. However, the risk factors associated with poor outcomes in these patients remain unclear. Methods: This observational study collected clinical and imaging data from COVID-19 patients with PTX and/or PNM across five tertiary hospitals in central Italy between 1 March 2020 and 1 March 2022. This study also calculated the incidence of PTX and PNM and utilized multivariable regression analysis and Kaplan–Meier curve analysis to identify predictor factors for 28-day mortality and 3-day orotracheal intubation after PTX/PNM. This study also considered the impact of the three main variants of concern (VoCs) (alfa, delta, and omicron) circulating during the study period. Results: During the study period, a total of 11,938 patients with COVID-19 were admitted. This study found several factors independently associated with a higher risk of death in COVID-19 patients within 28 days of pulmonary barotrauma. These factors included a SOFA score ≥ 4 (OR 3.22, p = 0.013), vasopressor/inotropic therapy (OR 11.8, p < 0.001), hypercapnia (OR 2.72, p = 0.021), PaO2/FiO2 ratio < 150 mmHg (OR 10.9, p < 0.001), and cardiovascular diseases (OR 7.9, p < 0.001). This study also found that a SOFA score ≥ 4 (OR 3.10, p = 0.015), PCO2 > 45 mmHg (OR 6.0, p = 0.003), and P/F ratio < 150 mmHg (OR 2.9, p < 0.042) were factors independently associated with a higher risk of orotracheal intubation (OTI) within 3 days from PTX/PNM in patients with non-invasive mechanical ventilation. SARS-CoV-2 VoCs were not associated with 28-day mortality or the risk of OTI. The estimated cumulative probability of OTI in patients after pneumothorax was 44.0% on the first day, 67.8% on the second day, and 68.9% on the third day, according to univariable survival analysis. In patients who had pneumomediastinum only, the estimated cumulative probability of OTI was 37.5%, 46.7%, and 57.7% on the first, second, and third days, respectively. The overall incidence of PTX/PNM among hospitalized COVID-19 patients was 1.42%, which increased up to 4.1% in patients receiving invasive mechanical ventilation. Conclusions: This study suggests that a high SOFA score (≥4), the need for vasopressor/inotropic therapy, hypercapnia, and PaO2/FiO2 ratio < 150 mmHg in COVID-19 patients with pulmonary barotrauma are associated with higher rates of intubation, ICU admission, and mortality. Identifying these risk factors early on can help healthcare providers anticipate and manage these patients more effectively and provide timely interventions with appropriate intensive care, ultimately improving their outcomes.

Injection drug use represents an important contributor to hepatitis C virus (HCV) transmission, hence therapeutic communities (TCs) are promising points of care for the identification and treatment of HCV-infected persons who inject drugs (PWIDs). We evaluated the effectiveness and efficacy of an HCV micro-elimination program targeting PWIDs in the context of a drug-free TC; we applied the cascade of care (CoC) evaluation by calculating frequencies of infection diagnosis, confirmation, treatment and achievement of a sustained virological response (SVR). We also evaluated the risk of reinfection of PWIDs achieving HCV eradication by collecting follow-up virologic information of previously recovered individuals and eventual relapse in drug use, assuming the latter as a potential source of reinfection. We considered 811 PWIDs (aged 18+ years) residing in San Patrignano TC at the beginning of the observation period (January 2018–March 2022) or admitted thereafter, assessing for HCV and HIV serology and viral load by standard laboratory procedures. Ongoing infections were treated with direct-acting antivirals (DAA), according to the current national guidelines. Out of the 792 individuals tested on admission, 503 (63.5%) were found to be seropositive for antibodies against HCV. A total of 481 of these 503 individuals (95.6%) underwent HCV RNA testing. Out of the 331 participants positive for HCV RNA, 225 were ultimately prescribed a DAA treatment with a sustained viral response (SVR), which was achieved by 222 PWIDs (98.7%). Of the 222 PWIDs, 186 (83.8%) with SVR remained HCV-free on follow-up (with a median follow-up of 2.73 years after SVR ascertainment). The CoC model in our TC proved efficient in implementing HCV micro-elimination, as well as in preventing reinfection and promoting retention in the care of individuals, which aligns with the therapeutic goals of addiction treatment.

As buildings are one of the major contributors to greenhouse gas emissions and energy consumption, they have a key potential for energy efficiency and indoor environmental quality improvement. Therefore, the development of nearly Zero-Energy Buildings (nZEBs) is strategic to respond to these challenges and to design and retrofit sustainable highly performing buildings. Actually, the nZEB target can also be reached with highly insulated wooden technologies. However, they must be critically revised and adapted when taking into account the warm climate peculiarities. The paper contributes to this attempt by dealing with the implementation of a methodology specifically focused on the long-term assessment of the real building envelope performance. The methodology is applied to a recently built wooden nZEB detached single-story dwelling constructed in 2017 in central Italy. One year monitoring data were collected about the envelope in-field dynamic performance and the indoor microclimate and well-being conditions. The theoretical design-stage data and the monitored data were compared. The positive aspects as well as the critical issues of nZEB target in the Mediterranean climate context and the performance gap were underlined. Accordingly, the main aspects to be considered in the design of nZEBs envelope were highlighted.

"Gifted or talented" is a student exceptionality category that in many states requires a formal eligibility procedure to qualify for specialized school programming (Gallagher et al. 2014). Researchers agree that there is a historical overreliance on IQ in determining service eligibility; however, no brief parent rating scale appears in the empirical literature to support the decision-making of school evaluation teams. Items of the "Characteristics of Giftedness Scale" (Silverman 1993) were selected and expanded upon to create a brief 20-item instrument. Confirmatory factor analysis (CFA) revealed that the modified scale was best characterized as having a two-factor structure. Furthermore, group differences were found between students eligible for gifted school programming and those without gifted status at school. Taken together, present findings suggest that this modified scale may be a suitable evaluation tool for school-based use.

Objectives: A pre-exposure vaccination campaign to prevent the spread of the mpox virus was initiated in Italy in August 2022. We explore the possible factors affecting the trend of mpox cases in an Italian region (Lazio) with a rapid roll-out of the vaccination campaign. Methods: We estimated the impact of the communication and vaccination campaign by fitting a Poisson segmented regression model. Results By September 30, 2692, high-risk men who have sex with men had received at least one dose of vaccine, with a vaccination coverage of 37%. The analysis of surveillance data showed a significant decreasing trend in the number of mpox cases starting from the second week after vaccination (incidence rate ratio 0.452 [0.331-0.618]). Conclusion: The reported trend in mpox cases is likely to result from a combination of multiple social and public health factors combined with a vaccination campaign.

In recent years, research has emerged to quantitatively and qualitatively understand occupants' interactions with buildings. However, there has been surprisingly little research on building interfaces and how their design, context (e.g., location), and underlying logic impact their usability and occupants’ perceived control, as well as the resulting comfort and energy performance. Research is needed to better understand how occupants interact with building interfaces in both commercial and residential applications; both applications are important to address as there are many differences in interface types, level of control and understanding, and even expectations of engagement. This paper provides a cursory review and discussion of select common building interfaces: windows, window shades/blinds, thermostats, and lighting controls. The goal of this paper is to review literature related to these human-building interfaces to explore interface characteristics, current design and use challenges, and relationships between building interfaces and occupants. Human-building interface interactions are complex, more research is needed to understand design, use, and characteristics. Common themes emerged throughout the literature review to explain occupant interactions (or lack of interactions) with building interfaces, which included thermal and visual comfort, ease and access of control, interface/control placement, poor interface/control design, lack of understanding, and social-behavioral dynamics.

In recent years, research has emerged to quantitatively and qualitatively understand occupants' interactions with buildings. However, there has been surprisingly little research on building interfaces and how their design, context (e.g., location), and underlying logic impact their usability and occupants’ perceived control, as well as the resulting comfort and energy performance. Research is needed to better understand how occupants interact with building interfaces in both commercial and residential applications; both applications are important to address as there are many differences in interface types, level of control and understanding, and even expectations of engagement. This paper provides a cursory review and discussion of select common building interfaces: windows, window shades/blinds, thermostats, and lighting controls. The goal of this paper is to review literature related to these human-building interfaces to explore interface characteristics, current design and use challenges, and relationships between building interfaces and occupants. Human-building interface interactions are complex, more research is needed to understand design, use, and characteristics. Common themes emerged throughout the literature review to explain occupant interactions (or lack of interactions) with building interfaces, which included thermal and visual comfort, ease and access of control, interface/control placement, poor interface/control design, lack of understanding, and social-behavioral dynamics.

An extensive, representative, and, multi-country tailored survey questionnaire eliciting social practices with heat as an energy service and the relative perceptions about heating devices was submitted to a randomized sample of more than 6,000 potential end-users in Europe within the framework of the Horizon 2020 project SWS-HEATING. The project is developing an innovative seasonal thermal energy storage unit for residential use. Moreover, within the project, the role of occupancy variability and use conditions in the performance of the proposed system is assessed. The present study focuses on tailor-made user-building interaction models to be implemented into dynamic simulation for the assessment of the proposed and similar systems starting from the sociological assessment of such large-scale survey results. These models take advantage from the knowledge raised by the findings of the social survey to frame for the first time occupants’ behavior scenarios representative of South, central, and North European countries. In this way, the influence of cultural context and demographic factors and their relation to heating practices are considered when developing these tailored occupant behavior models. Results show the non-negligible influence (up to 43% in the coldest climate) of implementing these models on predicted building heating energy needs, as quantitative demonstration of the role of societal-related variables on final energy use estimation.

Background: we aim to investigate attitudes toward vaccination by analyzing empirical factors associated with vaccine acceptance in the Lazio region mpox vaccination (MpoxVax) campaign in Italy. Methods: all subjects who accessed MpoxVax and signed the informed consent were prospectively enrolled in the MPOX-VAC Study and were asked to fill out an anonymous survey. Two endpoints were selected: ‘delayed acceptance’ and ‘early acceptance’, defined as access for vaccination >60 and ≤30 days from the vaccination campaign starting (VCS), respectively. Results: over the study period, 1717 individuals underwent vaccination: 129 (7%) > 60 [1588 (92.5%) ≤ 60] and 676 (60%) ≤ 30 days from VCS. A bisexual orientation, a lower education level and a worse perceived physical and mental health were associated with delayed access to vaccination. Being pre-exposure prophylaxis (PrEP) users and, marginally, HIV positive; having a high perceived risk for mpox infection; and reporting high-risk behaviors like the use of recreational drugs/chems, sex under the influence of drugs and/or alcohol and having a higher number of principal sexual partners, were associated with early access to vaccination. Conclusions: according to our data, risk awareness was a major determinant of early MpoxVax acceptance. Conversely, worse perceived health status and a low educational level were critical factors associated with delayed vaccination.

Measurement(s) room temperature ambient air • room relative humidity • outdoor weather • window status • door status • fan status • HVAC measurement • lighting status • occupancy measurement • plug load • shade status Technology Type(s) Temperature Sensor Device • relative humidity sensor • weather station • window status sensor • door status sensor • fan status sensor • HVAC measurement sensors • lighting sensor • occupancy sensor • power sensor • shade status sensor

Kidney transplant (KT) recipients are known to be at risk of developing several cancer types; however, cancer mortality in this population is underinvestigated. Our study aimed to assess the risk of cancer death among Italian KT recipients compared to the corresponding general population. A cohort study was conducted among 7373 individuals who underwent KT between 2003 and 2020 in 17 Italian centers. Date and cause of death were retrieved until 31 December 2020. Indirect standardization was used to estimate standardized mortality ratios (SMRs) and corresponding 95% confidence intervals (CIs). Cancer was the most common cause of death among the 7373 KT recipients, constituting 32.4% of all deaths. A 1.8-fold excess mortality (95% CI: 1.59-2.09) was observed for all cancers combined. Lymphomas (SMR = 6.17, 95% CI: 3.81-9.25), kidney cancer (SMR = 5.44, 95% CI: 2.97-8.88) and skin melanoma (SMR = 3.19, 95% CI: 1.03-6.98) showed the highest excess death risks. In addition, SMRs were increased about 1.6 to 3.0 times for cancers of lung, breast, bladder and other hematopoietic and lymphoid tissues. As compared to the general population, relative cancer mortality risk remained significantly elevated in all age groups though it decreased with increasing age. A linear temporal increase in SMR over time was documented for all cancers combined (P < .01). Our study documented significantly higher risks of cancer death in KT recipients than in the corresponding general population. Such results support further investigation into the prevention and early detection of cancer in KT recipients., (© 2023 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Abstract Background Several biomarkers have been identified to predict the outcome of COVID-19 severity, but few data are available regarding sex differences in their predictive role. Aim of this study was to identify sex-specific biomarkers of severity and progression of acute respiratory distress syndrome (ARDS) in COVID-19. Methods Plasma levels of sex hormones (testosterone and 17β-estradiol), sex-hormone dependent circulating molecules (ACE2 and Angiotensin1-7) and other known biomarkers for COVID-19 severity were measured in male and female COVID-19 patients at admission to hospital. The association of plasma biomarker levels with ARDS severity at admission and with the occurrence of respiratory deterioration during hospitalization was analysed in aggregated and sex disaggregated form. Results Our data show that some biomarkers could be predictive both for males and female patients and others only for one sex. Angiotensin1-7 plasma levels and neutrophil count predicted the outcome of ARDS only in females, whereas testosterone plasma levels and lymphocytes counts only in males. Conclusions Sex is a biological variable affecting the choice of the correct biomarker that might predict worsening of COVID-19 to severe respiratory failure. The definition of sex specific biomarkers can be useful to alert patients to be safely discharged versus those who need respiratory monitoring.

Abstract Background The Social Responsiveness Scale (SRS) is a 65‐item measure yielding a continuous score capturing autism‐related traits. Scores based on SRS item subsets have been analytically examined but administration of shortened versions has not been evaluated prospectively. Objective The goal of this study was to compare psychometric properties of two shortened versions of the SRS to the full 65‐item SRS, in young children from both a clinical and general population setting. Methods Study participants (aged 3–5 years) were drawn from the AJ Drexel Autism Institute clinic (n = 154) and Kaiser Permanente Northern California (n = 201) and block randomized to receive either the 16‐item short SRS, a newly developed computer adaptive testing‐SRS, or the published full‐length SRS. Total scores across the three SRS administration methods were scaled to facilitate comparisons. Scores were plotted to assess distributional properties, while Receiver Operating Characteristic analysis was used to estimate Area Under the Curve (AUC) and address predictive ability. Results Overall, distributional properties of the three administration methods were highly comparable, with shortened measures demonstrating similar ability to capture the range of the distribution and case non‐case separation as the full SRS. In addition, AUC values were high (0.91–0.97) and comparable across the administration methods, though there was evidence of difference in predictive ability across measures for females (AUC for full SRS = 0.99 vs. 0.84 for short). Within individual comparisons of short versus full scores (available only for participants at the general population site) suggested underestimation of actual full SRS scores with the CAT‐SRS. Conclusions Our findings broadly support the construct validity and performance of shortened SRS versions examined here, though the full measure may be needed to more accurately assess traits consistent with ASD diagnosis in females. This work suggests opportunities for collection of ASD‐related phenotype in settings where participant burden or feasibility considerations may have otherwise prohibited such measurement.

Background and aimCOVID-19, the infectious disease caused by SARS-CoV-2 virus that has been causing a severe pandemic worldwide for more than 2 years, is characterized by a high heterogeneity of clinical presentations and evolution and, particularly, by a varying severity of respiratory involvement. This study aimed to analyze the diversity and taxonomic composition of the gut microbiota at hospital admission, in order to evaluate its association with COVID-19 outcome. In particular, the association between gut microbiota and a combination of several clinical covariates was analyzed in order to characterize the bacterial signature associate to mild or severe symptoms during the SARS-CoV-2 infection.Materials and methodsV3–V4 hypervariable region of 16S rRNA gene sequencing of 97 rectal swabs from a retrospective cohort of COVID-19 hospitalized patients was employed to study the gut microbiota composition. Patients were divided in two groups according to their outcome considering the respiratory supports they needed during hospital stay: (i) group “mild,” including 47 patients with a good prognosis and (ii) group “severe,” including 50 patients who experienced a more severe disease due to severe respiratory distress that required non-invasive or invasive ventilation. Identification of the clusters of bacterial population between patients with mild or severe outcome was assessed by PEnalized LOgistic Regression Analysis (PELORA).ResultsAlthough no changes for Chao1 and Shannon index were observed between the two groups a significant greater proportion of Campylobacterota and Actinobacteriota at phylum level was found in patients affected by SARS-CoV-2 infection who developed a more severe disease characterized by respiratory distress requiring invasive or non-invasive ventilation. Clusters have been identified with a useful early potential prognostic marker of the disease evolution.DiscussionMicroorganisms residing within the gut of the patients at hospital admission, were able to significantly discriminate the clinical evolution of COVID-19 patients, in particular who will develop mild or severe respiratory involvement. Our data show that patients affected by SARS-CoV-2 with mild or severe symptoms display different gut microbiota profiles which can be exploited as potential prognostic biomarkers paving also the way to new integrative therapeutic approaches.

Abstract Background Hepatitis C virus (HCV) infection represents a global health issue with severe implications on morbidity and mortality. This study aimed to evaluate the impact of HCV infection on all-cause, liver-related, and non-liver-related mortality in a population living in an area with a high prevalence of HCV infection before the advent of Direct-Acting Antiviral (DAA) therapies, and to identify factors associated with cause-specific mortality among HCV-infected individuals. Methods We conducted a cohort study on 4492 individuals enrolled between 2003 and 2006 in a population-based seroprevalence survey on viral hepatitis infections in the province of Naples, southern Italy. Study participants provided serum for antibodies to HCV (anti-HCV) and HCV RNA testing. Information on vital status to December 2017 and cause of death were retrieved through record-linkage with the mortality database. Hazard ratios (HRs) for cause-specific mortality and 95% confidence intervals (CIs) were estimated using Fine-Grey regression models. Results Out of 626 deceased people, 20 (3.2%) died from non-natural causes, 56 (8.9%) from liver-related conditions, 550 (87.9%) from non-liver-related causes. Anti-HCV positive people were at higher risk of death from all causes (HR = 1.38, 95% CI: 1.12–1.70) and liver-related causes (HR = 5.90, 95% CI: 3.00–11.59) than anti-HCV negative ones. Individuals with chronic HCV infection reported an elevated risk of death due to liver-related conditions (HR = 6.61, 95% CI: 3.29–13.27) and to any cause (HR = 1.51, 95% CI: 1.18–1.94). The death risk of anti-HCV seropositive people with negative HCV RNA was similar to that of anti-HCV seronegative ones. Among anti-HCV positive people, liver-related mortality was associated with a high FIB-4 index score (HR = 39.96, 95% CI: 4.73–337.54). Conclusions These findings show the detrimental impact of HCV infection on all-cause mortality and, particularly, liver-related mortality. This effect emerged among individuals with chronic infection while those with cleared infection had the same risk of uninfected ones. These results underline the need to identify through screening all people with chronic HCV infection notably in areas with a high prevalence of HCV infection, and promptly provide them with DAAs treatment to achieve progressive HCV elimination and reduce HCV-related mortality.

Optical imaging of objects at the nanometric scale is limited by light diffraction, and for this reason several sub-diffractive optical microscopy techniques have been developed in the last decades. In this article we present an optical laser microscope specifically designed for detection of nano-materials exploiting the Mie scattering between the evanescent wave generated by a laser beam travelling in a transparent substrate through total internal reflection and the nano-objects deposited on the substrate itself. The setup, including the laser source, can be fully integrated inside an optical microscope requiring only a geometric alignment with the substrate thus reducing the complexity and the cost. We also report two possible applications: quantitative detection of Au nanoparticles in the 20-100 nm size range and semi-quantitative detection of virions immobilized on the substrate through bioreceptor / antigen binding, including, but not limited to, SARS-CoV-2. A minimum virus amount of ≈105 in the reaction volume is observed. The results presented here open the route towards unprecedent applications in molecular biology or molecular diagnostics.

As the urgency to mitigate climate change intensifies, the achievement of zero carbon targets in the built environment has become a critical objective. Building retrofitting plays a vital role in reducing energy consumption and carbon emissions in existing buildings. This paper presents an approach that combines Building Information Modeling (BIM) with multiple domains to strive for zero carbon targets in building retrofit projects. The proposed approach is based on a dynamic multi-parameter analysis that integrates indoor comfort, energy savings, CO2eq reduction, and the social cost of carbon while considering investment costs. Renewable energy technologies, such as photovoltaic panels and solar thermal systems, are emphasized to achieve the desired zero-carbon outcomes. Real-time monitoring mechanisms enable continuous performance evaluation and adaptive retrofit strategies for further energy savings. This approach is validated through a case study of an existing thermal bath building, known as “Terme Lucane”, located in southern Italy. The results of the study demonstrate significant reductions in energy consumption and carbon emissions, highlighting the potential of the proposed approach to achieve zero carbon targets through the integration of multi-data BIM implementation. These findings offer a promising pathway for building retrofit projects aiming for zero carbon targets through multi-data BIM modeling.

Background: Limited data are available about the predictors and outcomes associated with prolonged SARS-CoV-2 RNA shedding (VS). Methods: A retrospective study including COVID-19 patients admitted to an Italian hospital between March 1 and July 1, 2020. Predictors of viral clearance (VC) and prolonged VS from the upper respiratory tract were assessed by Poisson regression and logistic regression analyses. The causal relation between VS and clinical outcomes was evaluated through an inverse probability weighted Cox model. Results: The study included 536 subjects. The median duration of VS from symptoms onset was 18 days. The estimated 30-day probability of VC was 70.2%. Patients with comorbidities, lymphopenia at hospital admission, or moderate/severe respiratory disease had a lower chance of VC. The development of moderate/severe respiratory failure, delayed hospital admission after symptoms onset, baseline comorbidities, or D-dimer >1000 ng/mL at admission independently predicted prolonged VS. The achievement of VC doubled the chance of clinical recovery and reduced the probability of death/mechanical ventilation. Conclusions: Respiratory disease severity, comorbidities, delayed hospital admission and inflammatory markers negatively predicted VC, which resulted to be associated with better clinical outcomes. These findings highlight the importance of prompt hospitalization of symptomatic patients, especially where signs of severity or comorbidities are present.

Liver transplanted (LT) patients for hepatocellular carcinoma (LT-HCC) or for other causes (LT-no-HCC) may develop post-transplantation malignancies. Although immune activation and senescence are frequently implicated in cancer development, no data is available on their possible role as biomarkers predictive of tumor onset in this setting. A total of 116 patients were investigated: the 45 LT-HCC patients were older than the 71 LT-non-HCC (p=0.011), but comparable for sex, HCV, HBV infection and immunosuppressive treatment. At baseline, the numbers of activated and senescent-like circulating cells were significantly higher in LT-HCC patients than in LT-no-HCC ones. After a median follow-up of 26.8 months, 6 post-transplant malignancies (PTM) occurred: 4 in LT-HCC (8.9%) and 2 in LT-no-HCC (2.8%) patients. Overall, subjects with high percentages of activated and exhausted T and B cells at baseline were at higher risk of PTM. Notably, within the LT-HCC group, a higher percentage of senescence-like T cells was also associated with cancer development. Moreover, patients with PTM had higher telomere erosion and higher levels of circulating PAMPs (16S rDNA) and DAMPs (mtDNA) when compared with matched patients without PTM. Overall, these findings suggest that immune activation and exhaustion may be useful to predict the risk of PTM occurrence, regardless of the cause of transplantation. In LT-HCC, T-cell senescence represents an additional risk factor for tumor onset.

ObjectivesComparative analysis between different monoclonal antibodies (mAbs) against SARS-CoV-2 are lacking. We present an emulation trial from observational data to compare effectiveness of Bamlanivimab/Etesevimab (BAM/ETE) and Casirivimab/Imdevimab (CAS/IMD) in outpatients with early mild-to-moderate COVID-19 in a real-world scenario of variants of concern (VoCs) from Alpha to Delta.MethodsAllocation to treatment was subject to mAbs availability, and the measured factors were not used to determine which combination to use. Patients were followed through day 30. Viral load was measured by cycle threshold (CT) on D1 (baseline) and D7.Primary outcome was time to COVID-19-related hospitalization or death from any cause over days 0-30. Weighted pooled logistic regression and marginal structural Cox model by inverse probability weights were used to compare BAM/ETE vs. CAS/IMD. ANCOVA was used to compare mean D7 CT values by intervention. Models were adjusted for calendar month, MASS score and VoCs. We evaluated effect measure modification by VoCs, vaccination, D1 CT levels and enrolment period.ResultsCOVID19-related hospitalization or death from any cause occurred in 15 of 237 patients in the BAM/ETE group (6.3%) and in 4 of 196 patients in the CAS/IMD group (2.0%) (relative risk reduction [1 minus the relative risk] 72%; p=0.024). Subset analysis carried no evidence that the effect of the intervention was different across stratification factors. There was no evidence in viral load reduction from baseline through day 7 across the two groups (+0.17, 95% -1.41;+1.74, p=0.83). Among patients who experienced primary outcome, none showed a negative RT-PCR test in nasopharyngeal swab (p=0.009) and 82.4% showed still high viral load (p

The frequent finding of thrombocytopenia in patients with severe SARS-CoV-2 infection (COVID-19) and previous evidence that several viruses enter platelets suggest that SARS-CoV-2 might be internalized by platelets of COVID-19. Aim of our study was to assess the presence of SARS-CoV-2 RNA in platelets from hospitalized patients with aconfirmed diagnosis of COVID-19. RNA was extracted from platelets, leukocytes and serum from 24 COVID-19 patients and 3 healthy controls, real-time PCR and ddPCR for viral genes were carried out. SARS-CoV-2 RNA was not detected in any of the samples analyzed nor in healthy controls, by either RT-PCR or ddPCR, while RNA samples from nasopharyngeal swabs of COVID-19 patients were correctly identified. Viral RNA was not detected independently of viral load, of positive nasopharyngeal swabs, or viremia, the last detected in only one patient (4.1%). SARS-CoV-2 entry in platelets is not acommon phenomenon in COVID-19 patients, differently from other viral infections.

This cohort study examined 25-year variations in cancer incidence among 11,418 Italian recipients of kidney transplantation (KT) from 17 Italian centers. Cancer incidence was examined over three periods (1997–2004; 2005–2012; and 2013–2021) by internal (Incidence rate ratio-IRR) and external (standardized incidence ratios-SIR) comparisons. Poisson regression was used to assess trends. Overall, 1646 post-transplant cancers were diagnosed, with incidence rates/1000 person-years ranging from 15.5 in 1997–2004 to 21.0 in 2013–2021. Adjusted IRRs showed a significant reduction in incidence rates across periods for all cancers combined after exclusion of nonmelanoma skin cancers (IRR = 0.90, 95% confidence interval-CI: 0.76–1.07 in 2005–2012; IRR = 0.72, 95% CI: 0.60–0.87 in 2013–2021 vs. 1997–2004; Ptrend < 0.01). In site-specific analyses, however, significant changes in incidence rates were observed only for Kaposi’s sarcoma (KS; IRR = 0.37, 95% CI: 0.24–0.57 in 2005–2012; IRR = 0.09, 95% CI: 0.04–0.18 in 2013–2021; Ptrend < 0.01). As compared to the general population, the overall post-transplant cancer risk in KT recipients was elevated, with a decreasing magnitude over time (SIR = 2.54, 95% CI: 2.26–2.85 in 1997–2004; SIR = 1.99, 95% CI: 1.83–2.16 in 2013–2021; Ptrend < 0.01). A decline in SIRs was observed specifically for non-Hodgkin lymphoma and KS, though only the KS trend retained statistical significance after adjustment. In conclusion, apart from KS, no changes in the incidence of other cancers over time were observed among Italian KT recipients.

Except for specific vaccines and monoclonal antibodies, effective prophylactic or post-exposure therapeutic treatments are currently limited for COVID-19. Propolis, a honeybee’s product, has been suggested as a potential candidate for treatment of COVID-19 for its immunomodulatory properties and for its powerful activity against various types of viruses, including common coronaviruses. However, direct evidence regarding the antiviral activities of this product still remains poorly documented. VERO E6 and CALU3 cell lines were infected with SARS-CoV-2 and cultured in the presence of 12.5 or 25 μg/ml of a standardized Hydroalcoholic Extract acronym (sHEP) of Eurasian poplar type propolis and analyzed for viral RNA transcription, for cell damage by optical and electron microscopy, and for virus infectivity by viral titration at 2, 24, 48, and 72 h post-infection. The three main components of sHEP, caffeic acid phenethyl ester, galangin, and pinocembrin, were tested for the antiviral power, either alone or in combination. On both cell lines, sHEP showed significant effects mainly on CALU3 up to 48 h, i.e., some protection from cytopathic effects and consistent reduction of infected cell number, fewer viral particles inside cellular vesicles, reduction of viral titration in supernatants, dramatic drop of N gene negative sense RNA synthesis, and lower concentration of E gene RNA in cell extracts. Interestingly, pre-treatment of cells with sHEP before virus inoculation induced these same effects described previously and was not able to block virus entry. When used in combination, the three main constituents of sHEP showed antiviral activity at the same levels of sHEP. sHEP has a remarkable ability to hinder the replication of SARS-CoV-2, to limit new cycles of infection, and to protect host cells against the cytopathic effect, albeit with rather variable results. However, sHEP do not block the virus entry into the cells. The antiviral activity observed with the three main components of sHEP used in combination highlights that the mechanism underlying the antiviral activity of sHEP is probably the result of a synergistic effect. These data add further emphasis on the possible therapeutic role of this special honeybee’s product as an adjuvant to official treatments of COVID-19 patients for its direct antiviral activity.