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Nicola Squillace,1 Elena Ricci,2 Barbara Menzaghi,3 Giuseppe Vittorio De Socio,4 Simone Passerini,5 Canio Martinelli,6 Maria Sabrina Mameli,7 Paolo Maggi,8 Katia Falasca,9 Laura Cordier,5 Benedetto Maurizio Celesia,10 Elena Salomoni,11 Antonio Di Biagio,12 Giovanni Francesco Pellicanò,13 Paolo Bonfanti1 On behalf of the CISAI Study Group1Infectious Diseases Unit ASST-MONZA, San Gerardo Hospital-University of Milano-Bicocca, Monza, Italy; 2“ASIA” Foundation ONLUS, Milan, Italy; 3Unit of Infectious Diseases, ASST della Valle Olona, Busto Arsizio, Italy; 4Department of Internal Medicine 2, Infectious Diseases Unit, “Santa Maria della Misericordia” General Hospital, Perugia, Italy; 5 1st Department of Infectious Diseases, ASST Fatebenefratelli Sacco, Milan, Italy; 6Infectious Diseases Unit, Careggi Hospital, Florence, Italy; 7Unit of Infectious Diseases, Department of Medical, Surgical and Experimental Sciences, University of Sassari, Sassari, Italy; 8University of Campania “Luigi Vanvitelli”, Napoli, Italy; 9Clinic of Infectious Diseases, Department of Medicine and Science of Aging, University “G. d’Annunzio” Chieti-Pescara, Chieti, Italy; 10Unit of Infectious Diseases, University of Catania, ARNAS Garibaldi, Catania, Italy; 11Infectious Diseases Unit, Santa Maria Annunziata Hospital, Usl centro, Florence, Italy; 12Infectious Diseases, San Martino Hospital Genoa, Genoa, Italy; 13Department of Human Pathology of the Adult and the Developmental Age “G. Barresi”, Unit of Infectious Diseases, University of Messina, Messina, ItalyCorrespondence: Nicola SquillaceInfectious Diseases Unit, Azienda Socio Sanitaria Territoriale di MONZA, San Gerardo Hospital-University of Milano-Bicocca, Via Pergolesi 33, Monza 20900, ItalyTel +390392339588Fax +390392339327Email nicolasquillace74@gmail.comObjective: We aimed to investigate the effect of switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) on the hepatic safety and metabolic profile.Methods: Consecutive HIV patients, enrolled in the Surveillance Cohort Long-term Toxicity Antiretrovirals/Antivirals (SCOLTA) project, switching from TDF to TAF were included. Changes from baseline (T0) to 6-month follow-up (T1) were evaluated using paired t-test and signed rank test.Results: A total of 190 patients switched from TDF to TAF and had one 6-month follow-up visit. They were 80% male, 74.2% at CDC stage A–B, 93.7% with undetectable HIV-viral load. Mean age was 46.7± 10.7 years, body mass index was 25.0± 3.9 kg/m2, median CD4 cell count was 634 cell/μL (interquartile range [IQR]=439– 900), aspartate aminotransferase (AST) was 23 (IQR=19– 30) IU/L, and alanine aminotransferase (ALT) was 24 (IQR=17– 34) IU/L. At T1, both AST (median=− 1, IQR=− 5– 2 IU/L, P=0.004) and ALT (median=− 2, IQR=− 7– 3 IU/L, P=0.0004) showed a significant decrease. Among 28 patients with ALT > 40 at baseline, reduction was significant both clinically (− 17, IQR=− 32–− 1) and statistically (P=0.0003). Total cholesterol levels (TC) increased (+13.4± 3.8 mg/dL, P=0.0006), as well as HDL-cholesterol (HDL-C) (+3.8± 1.2 mg/dL, P=0.02), LDL Cholesterol (LDL-C) (+7.6± 3.4, P=0.03) and glucose (+4.0± 1.8 mg/dL, P=0.02). D:A:D: and Framingham risk score did not change at 6 months after switch.Conclusion: A significant reduction of liver enzymes was observed after switching from TDF to TAF, especially in subjects with initial level of ALT > 40 IU/L. Glucose, TC, HDL-C, and LDL-C increased, with no effect on cardiovascular risk scores.Keywords: HIV, TDF, TAF, liver enzymes

Paola Bagella,1 Giuseppe VL De Socio,2 Elena Ricci,3 Barbara Menzaghi,4 Canio Martinelli,5 Nicola Squillace,6 Paolo Maggi,7 Giancarlo Orofino,8 Leonardo Calza,9 Laura Carenzi,3 Benedetto Maurizio Celesia,10 Giovanni Penco,11 Antonio Di Biagio,12 Laura Valsecchi,3 Francesca Vichi,13 Valeria Colombo,14 Giustino Parruti,15 Chiara Dentone,16 Katia Falasca,17 Paolo Bonfanti,18 Giordano Madeddu1 On behalf of the C.I.S.A.I. Study Group, Italy 1Unit of Infectious Diseases, Department of Medical, Surgical and Experimental Sciences, University of Sassari, Sassari, Italy; 2Infectious Diseases Unit, Department of Medicine, Azienda Ospedaliero-Universitaria di Perugia, Santa Maria Hospital, Perugia, Italy; 3Department of Infectious Diseases, ASST Fatebenefratelli Sacco, Milan, Italy; 4Unit of Infectious Diseases, ASST della Valle Olona, Busto Arsizio, Italy; 5Unit of Infectious and Tropical Diseases, Careggi Hospital Florence, Florence, Italy; 6Infectious Diseases Unit, San Gerardo Hospital, University of Milano-Bicocca, Monza, Italy; 7Infectious Diseases Clinic, University of Bari, Policlinico Consorziale, Bari, Italy; 8Amedeo di Savoia Hospital Unit of Infectious Diseases, Torino, Italy; 9University of Bologna, Department of Infectious Diseases, S. Orsola Malpighi Hospital, Bologna, Italy; 10Unit of Infectious Diseases, Garibaldi Hospital, Catania, Italy; 11Infectious Diseases Unit, Galliera Hospital, Genoa, Italy; 12Unit of Infectious Diseases, IRCCS San Martino Hospital – IST, Genoa, Italy; 13Infectious Diseases Unit, Santa Maria Annunziata Hospital, Florence, Italy; 14Infectious Diseases Unit, University of Milan, DIBIC Luigi Sacco, Milan, Italy; 15Unit of Infectious Diseases, Pescara Hospital, Pescara, Italy; 16Unit of Infectious Diseases, Sanremo Hospital, Sanremo, Italy; 17Infectious Diseases Unit, University of Chieti, Chieti, Italy; 18Unit of Infectious Diseases, A. Manzoni Hospital, Lecco, Italy Abstract: Rilpivirine is associated with a good efficacy and safety profile. However, data from real-life settings are scarce. Methods: We investigated the durability, safety and efficacy of Rilpivirine-based antiretroviral therapy in a prospective, observational, multicenter study. Results: We enrolled 499 HIV-infected patients, 360 (72.1%) males, mean age 43.4 ± 10.5 years, mean CD4 600 ± 327 cell/μL, mean HIV-RNA 3.80 ± 1.15 log10 cp/mL. After a median follow up of 16 months, 81 (16.2%) interruptions were reported, 36 (7.2%) of which for adverse events (16 of grade ≥3), most commonly neurological and gastrointestinal. We observed virological failures in only 8 (1.6%) patients. Naive patients showed a significant reduction in eGFR at week 24, 48 and 72 and in total cholesterol (TC)/HDL ratio at week 48 (p=0.007). In patients switching from PI we found a significant decrease at week 24 and 48 in TC and triglycerides at week 24, 48 and 72. eGFR showed a significant decrease at week 48 and 72. TC/HDL ratio showed a statistically significant decrease at week 24 (p=0.0008) and 72 (p=0.04). A significant increase at week 24 and 48 in AST and ALT values was observed. Patients switching from TDF/FTC/EFV showed a reduction in HDL, total cholesterol and triglycerides at week 24 and 48 and in eGFR at all follow up times. TC/HDL ratio showed a significant decrease at week 48 (p=0.01). CDC stage C and antiretroviral-experience (especially Protease Inhibitors) were associated with RPV discontinuation. Conclusion: In conclusion, our data confirm Rilpivirine efficacy, safety and tolerability with improvement in lipid profile. Although hepatic and renal events rarely caused discontinuation, liver and kidney parameters should be monitored. Keywords: HIV-1, combination antiretroviral therapy, NNRTI, cohort study, naive, experienced patients

Giovanni Cenderello,1 Caterina Fanizza,2 Simona Marenco,3 Laura Ambra Nicolini,4 Stefania Artioli,5 Isabella Baldissarro,3 Chiara Dentone,6 Pasqualina De Leo,7 Antonio Di Biagio4 1SC Malattie Infettive, EO Ospedali Galliera, 2Rete ligure HIV, 3SSD Epatologia, AOU S. Martino, 4Clinica Malattie Infettive, AOU S. Martino, Genoa, 5SC Malattie Infettive ASL5 La Spezia, 6SC Malattie Infettive, ASL‑1, Sanremo, 7SC Malattie Infettive ASL2, San Paolo, Savona, Italy Aims: Despite the remarkable efficacy shown in clinical practice, concerns have been raised about the costs associated with direct antiviral agent (DAA) therapy. This article presents the real-life costs for DAA treatment sustained by the Italian National Health Service in the Liguria Region (Northern Italy).Methods: A retrospective analysis of the cost per care sustained for DAA treatment, relating to the period from January 1 to December 31, 2015 in five centers in Liguria was performed. All patients undergoing DAA-based treatments for hepatitis C virus (HCV) infection were enrolled. On-treatment costs included: HCV treatment, laboratory test, outpatient services, attended visits, drugs used for the management of adverse events (erythropoietin, albumin or red blood cell packs) and inpatient service admissions.Results: In total, 327 patients were enrolled. No difference in terms of sustained virologic response (SVR) rate among different treatments was reported. The majority (85.0%) of patients did not report any side effects and only 15 (4.6%) required hospital admission. Forty-two patients (12.8%) required high-cost drugs for the management of adverse events. The overall cost sustained was €14,744,433. DAA±ribavirin (RBV) accounted for the wide majority of this cost (98.9%; €14,585,123). Genotype (GT) 1, the most commonly treated GT, was associated with an average cost of €43,445 per patient. Detailed analysis of the costs for GT 1 showed the treatment based on ritonavir boosted paritaprevir/ombitasvir + dasabuvir±RBV with an average cost of €24,978 (RBV+) and €25,448 (RBV−) per patient was the most cost-effective. The average cost per SVR was €48,184. Once again, the ritonavir boosted ­paritaprevir/ombitasvir + dasabuvir regimen was associated with the lowest cost/SVR (€25,448/SVR [GT 1b] and similar results for other GTs).Conclusion: Antiviral regimen is the major contributor to costs in the treatment of HCV infection. Appropriate regimen selection could result in a major cost saving, which can be reinvested to allow more patients to be treated. Keywords: HCV treatment, HCV costs, cost efficacy

Giovanni Cenderello,1 Stefania Artioli,2 Claudio Viscoli,3 Ambra Pasa,4 Mauro Giacomini,5 Barbara Giannini,5 Chiara Dentone,6 Laura Ambra Nicolini,3 Giovanni Cassola,1 Antonio Di Biagio31Infectious Diseases Unit EO, Ospedali Galliera, Genoa, 2Infectious Diseases Unit, ASL-5 Spezzina, La Spezia, 3Infectious Diseases Unit, AOU San Martino, IST, Genoa University, Genoa, 4IT Unit, Ospedali Galliera, Genoa, 5Department of Informatics, Bioengineering, Robotics and System Engineering (DIBRIS), University of Genoa, Genova, 6Infectious Diseases Unit, ASL-1 Imperiese, Sanremo, Imperia, ItalyObjectives: Chronic hepatitis C virus (HCV) is a leading cause of hospitalization and death in populations coinfected with human immunodeficiency virus (HIV). Sofosbuvir (SOF) is a pan-genotypic drug that should be combined with other agents as an oral treatment for HCV. We performed a 5-year horizon budget impact analysis of SOF-based regimens for the management of HIV/HCV-coinfected patients.Methods: A multicenter, prospective evaluation was conducted, involving four Italian Infectious Diseases Departments (Galliera, San Martino, Sanremo, and La Spezia). All 1,005 genotype-coinfected patients (30% cirrhotics) under observation were considered (patients in all disease-stages were considered: chronic hepatitis C, cirrhosis, transplant, hepatocellular carcinoma). Disease stage costs per patient were collected; the expected disease progression in the absence of treatment and sustained virological response (SVR) success rate for SOF-based regimens were calculated based on the literature and expert opinion. Drug prices were based on what the National Health Service paid for them. The comparison of "no treatment" disease progression costs versus the economic impact of SOF-based regimens was investigated.Results: Over the following 5 years, the disease progression scenario resulted in direct costs of approximately €54 million. Assuming an SVR success rate of 90%, average SOF-based regimens cost up to €50,000 per person, resulting in a final cost of more than €56 million, so this option is not economically viable. At the average price of €12,000, SOF-based regimens, expense was €17 million, saving 68%. At this price level, the economic resources invested in treating mild to moderate fibrosis stage patients would be equal to the amount of direct costs of disease management in this stage, resulting in a valid return of investment in the short-term.Conclusion: Given the high rates of SVR, in the Italian Healthcare System, SOF-based regimens, price is a determinant and a predictor of the overall cost for the Hepatitis C patient's management. At the average price per therapy of €12,000 over the next 5 years, SOF-based regimens are becoming highly sustainable.Keywords: HCV treatment, sofosbuvir, HIV, budget impact, HIV/HCV coinfection, cirrhosis

Roberta Prinapori,1 Antonio Di Biagio2 1Infectious Diseases, University of Genoa, Genoa, Italy; 2Unit of Infectious Diseases, IRCCS AOU San Martino-IST, Genoa, Italy Abstract: The fixed-dose combination (FDC) elvitegravir/cobicistat/emtricitabine/tenofovir (EVG/c/FTC/TDF) is a once-daily, single-tablet regimen containing an integrase strand transfer inhibitor and a pharmacoenhancer (cobicistat) associated with two nucleos(t)ide reverse transcriptase inhibitors. It is approved as the preferred regimen and as the first-line combined antiretroviral therapy in treatment-naïve patients with HIV infection. Two large trials, 102-Study and 103-Study, demonstrated that EVG/c/FTC/TDF was not inferior to efavirenz/FTC/TDF and ritonavir-boosted atazanavir in association with FTC/TDF, in terms of virological suppression and immunological reconstitution through week 144. Also, simplification arms containing EVG/c/FTC/TDF reached noninferiority in comparison with a nonnucleoside reverse transcriptase inhibitor, or a protease inhibitor, or a raltegravir-based regimen. Furthermore, EVG/c/FTC/TDF exhibited an excellent tolerability profile, with a safer lipid profile, and despite the indication of its use in subjects with an estimated creatinine clearance >70 mL/min, recent data demonstrated that EVG/c/FTC/TDF determined a reduction in estimated glomerular filtration rate (GFR) but not a reduction of actual GFR. Moreover, in a cohort of naïve patients with pretreatment mild-to-moderate renal impairment, GFR decrease was noted as early at week 2, after which it generally stabilized and was nonprogressive through week 48. The FDC’s efficacy and good tolerability enable EVG/c/FTC/TDF to meet the patients’ needs, improving adherence and quality of life, which are among the most important factors affecting the therapeutic efficacy of an antiretroviral regimen. This paper describes the evidence making EVG/c/FTC/TDF a new therapeutic opportunity for different HIV-infected patients. Keywords: HIV, once daily, elvitegravir, single-tablet regimen, fixed-dose combination, adherence

Abstract Uncertainty in desert dust composition poses a big challenge to understanding Earth’s climate across different epochs. Of particular concern is hematite, an iron-oxide mineral dominating the solar absorption by dust particles, for which current estimates of absorption capacity vary by over two orders of magnitude. Here, we show that laboratory measurements of dust composition, absorption, and scattering provide valuable constraints on the absorption potential of hematite, substantially narrowing its range of plausible values. The success of this constraint is supported by results from an atmospheric transport model compared with station-based measurements. Additionally, we identify substantial bias in simulating hematite abundance in dust aerosols with current soil mineralogy descriptions, underscoring the necessity for improved data sources. Encouragingly, the next-generation imaging spectroscopy remote sensing data hold promise for capturing the spatial variability of hematite. These insights have implications for enhancing dust modeling, thus contributing to efforts in climate change mitigation and adaptation.

Biogenic volatile organic compounds (BVOCs) are emitted by vegetation and react with other compounds to form ozone and secondary organic matter (OM). In regional air quality models, biogenic emissions are often calculated using a plant functional type approach, which depends on the land use category. However, over cities, the land use is urban, so trees and their emissions are not represented. Here, we develop a bottom-up inventory of urban tree biogenic emissions in which the location of trees and their characteristics are derived from the tree database of the Paris city combined with allometric equations. Biogenic emissions are then computed for each tree based on their leaf dry biomass, tree-species-dependent emission factors, and activity factors representing the effects of light and temperature. Emissions are integrated in WRF-CHIMERE air quality simulations performed over June–July 2022. Over Paris city, the urban tree emissions have a significant impact on OM, inducing an average increase in the OM of about 5 %, reaching 14 % locally during the heatwaves. Ozone concentrations increase by 1.0 % on average and by 2.4 % during heatwaves, with a local increase of up to 6 %. The concentration increase remains spatially localized over Paris, extending to the Paris suburbs in the case of ozone during heatwaves. The inclusion of urban tree emissions improves the estimation of OM concentrations compared to in situ measurements, but they are still underestimated as trees are still missing from the inventory. OM concentrations are sensitive to terpene emissions, highlighting the importance of favoring urban tree species with low-terpene emissions.

The composition of soil dust aerosols derives from the mineral abundances in the parent soils that vary across dust source regions. Nonetheless, Earth system models (ESMs) have traditionally represented mineral dust as a globally homogeneous species. The growing interest in modeling dust mineralogy, facilitated by the recognized sensitivity of the dust climate impacts to composition, has motivated state-of-the-art ESMs to incorporate the mineral speciation of dust along with its effect upon the dust direct radiative effect (DRE). In this work, we enable the NASA Goddard Institute for Space Studies ModelE2.1 to calculate the shortwave (SW) DRE accounting for the regionally varying soil mineralogy. Mineral–radiation interaction at solar wavelengths is calculated according to two alternative coupling schemes: (1) external mixing of three mineral components that are optically distinguished, one of which contains embedded iron oxides; (2) a single internal mixture of all dust minerals with a dynamic fraction of iron oxides that varies regionally and temporally. We link dust absorption to the fractional mass of iron oxides based on recent chamber measurements using natural dust aerosol samples. We show that coupled mineralogy overall enhances the scattering by dust, and thus the global cooling, compared to our control run with globally uniform composition. According to the external mixing scheme, the SW DRE at the top of atmosphere (TOA) changes from −0.25 to -0.30Wm-2, corresponding to a change in the net DRE, including the longwave effect, from −0.08 to -0.12Wm-2. The cooling increase is accentuated when the internal mixing scheme is configured: the SW DRE at the TOA becomes -0.34Wm-2 with a net DRE of -0.15Wm-2. The varying composition modifies the regional distribution of single scattering albedo (SSA), whose variations in specific regions can be remarkable (above 0.03) and significantly modify the regional SW DRE. Evaluation against the AErosol RObotic NETwork (AERONET) shows that explicit representation of soil mineralogy and its regional variations reduces the low bias of model dust SSA while improving the range of variability across stations and calendar months. Despite these improvements, the moderate spatiotemporal correlation with AERONET reveals remaining modeling challenges and the need for more accurate measurements of mineral fractions in soils.

Summary: Background: Severe and prolonged mpox courses have been described during the 2022–2023 outbreak. Identifying predictors of severe evolution is crucial for improving management and therapeutic strategies. We explored the predictors of mpox severity and tested the association between mpox severity and viral load in biological fluids. We also analysed the predictors of disease duration and kinetics of inflammatory markers and described the viral presence and duration of shedding in biological fluids. Methods: This multicentre historical cohort study included adults diagnosed with laboratory-confirmed mpox diagnosis between May 2022 and September 2023 at 15 Italian centres. Patients were followed up from the day of diagnosis until clinical recovery. Biological fluids (blood, urine, saliva, and oropharyngeal and rectal swabs) were collected from each subgroup during the course of the disease and after healing. The primary outcomes were disease severity (presence of mucosal involvement, extended rash, or need for hospitalisation) and its association with the cycle threshold value (Ct-value, surrogate of viral load) in biological fluids, using standard linear and linear mixed-effect logistic regression models. Among the secondary outcomes, predictors of disease duration were assessed using a linear regression model. Findings: A total of 541 patients were enrolled, including four (0.74%) women, with a median age of 38 years (IQR 33–44). Among the 235 people living with HIV (PLWH) (43.44%), 22 (4.07%) had a CD4 count lower than 350 cells/μL. Severe mpox was reported in 215 patients (39.74%). No patient died. Multivariable analysis showed that, severe mpox was more likely among Caucasians (OR 1.82; 95% CI 1.14–2.90, p = 0.012) and patients who had an onset of fever (1.95; 1.27–2.99, p = 0.002), lymphadenopathy (2.30; 1.52–3.48, p

Summary: Brown adipose tissue (BAT) is mitochondria rich, enabling high oxidative metabolism for non-shivering thermogenesis. The release of large/small extracellular vesicles (EVs) containing mitochondria or mitochondrial fragments, termed mito-EVs, may support mitochondrial quality control or intercellular communication. We present a protocol to isolate and characterize mito-EVs. We detail steps for BAT processing, cell debris removal, differential centrifugation (dC), and mito-EV analysis by flow cytometry and immunoblotting assays.For complete details on the use and execution of this protocol, please refer to Rosina et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Giorgio L Colombo1,2, Vincenzo Colangeli3, Antonio Di Biagio4, Sergio Di Matteo2, Claudio Viscoli4, Pierluigi Viale31School of Pharmacy, University of Pavia, Pavia, Italy; 2SAVE - Studi Analisi Valutazioni Economiche, Milan, Italy; 3Clinica Malattie Infettive, Azienda Ospedaliera Sant'Orsola Malpighi Bologna, Alma Mater Studiorum, University of Bologna, Bologna, Italy; 4Clinica Malattie Infettive dell'Ospedale San Martino di Genova, University of Genova, Genova, ItalyIntroduction: Since the mid-1990s, highly active antiretroviral therapy (HAART) has modified the clinical course of human immunodeficiency virus (HIV) infection, reducing the rate of disease progression, the incidence of opportunistic infections, and mortality. The authors of this paper performed an economic analysis to estimate the cost-effectiveness of the HAART regimens in Italy for managing HIV-infected patients according to national guidelines.Patients and methods: The incremental cost-effectiveness analysis was carried out by means of a Markov model, which through a decision-analytic approach, made it possible to compare the studied antiretroviral regimens. The population considered in the model consisted of adult subjects with HIV who received antiretroviral HAART treatment for the first time. The population considered in the analysis reflects the patients’ characteristics according to one of the regional surveillance systems HIV/AIDS infection report currently operating in Italy. The analysis was carried out from the point of view of the Italian health care system. The considered outcome measures were quality-adjusted life years (QALYs) and direct health costs calculated for the year 2010. Both the outcomes (QALYs) and the costs were discounted by 3.5%. The time horizon adopted in the model was 10 years.Results: The model shows, in terms of cost per gained QALY, single tablet regimen (STR) appeared to be the most cost-effective therapeutic choice (€22,017), followed by tenofovir (TDF) + lamivudine + efavirenz (EFV) (€24,526), and TDF/emtricitabine (FTC) + nevirapine (€26,416), and TDF + FTC + EFV (€26,558); the remaining strategies have an incremental costeffectiveness ratio (ICER) value varying from €28,000 to €41,000 per QALY. The sensitivity analysis on the main variables confirmed the validity of the base case scenario.Conclusion: STR is the most cost-effective treatment strategy, compared with the other therapeutic regimens recommended by the Italian guidelines. All the ICER values of the various regimens considered by the Italian guidelines were lower than the threshold value of €50,000 commonly accepted at the international level. The model developed represents a tool for policy makers and health care professionals to make short- and long-term cost projections and thus evaluate their impact on the available budgets for HIV patients.Keywords: antiretroviral therapy regimens, single tablet regimens, STR, Markov model, quality-adjusted life years, QALYs, HAART

Abstract. In this study, we developed a novel algorithm based on the collocatedModerate Resolution Imaging Spectroradiometer (MODIS) thermal infrared (TIR)observations and dust vertical profiles from the Cloud–Aerosol Lidar withOrthogonal Polarization (CALIOP) to simultaneously retrieve dust aerosoloptical depth at 10 µm (DAOD10 µm) and the coarse-mode dusteffective diameter (Deff) over global oceans. The accuracy of theDeff retrieval is assessed by comparing the dust lognormal volumeparticle size distribution (PSD) corresponding to retrieved Deff withthe in situ-measured dust PSDs from the AERosol Properties – Dust(AER-D), Saharan Mineral Dust Experiment (SAMUM-2), and Saharan Aerosol Long-Range Transport and Aerosol–Cloud-InteractionExperiment (SALTRACE) fieldcampaigns through case studies. The new DAOD10 µm retrievals wereevaluated first through comparisons with the collocated DAOD10.6 µmretrieved from the combined Imaging Infrared Radiometer (IIR) and CALIOPobservations from our previous study (Zheng et al., 2022). The pixel-to-pixelcomparison of the two DAOD retrievals indicates a good agreement(R∼0.7) and a significant reduction in (∼50 %) retrieval uncertainties largely thanks to the better constraint ondust size. In a climatological comparison, the seasonal and regional(2∘×5∘) mean DAOD10 µm retrievals basedon our combined MODIS and CALIOP method are in good agreement with the twoindependent Infrared Atmospheric Sounding Interferometer (IASI) productsover three dust transport regions (i.e., North Atlantic (NA; R=0.9),Indian Ocean (IO; R=0.8) and North Pacific (NP; R=0.7)). Using the new retrievals from 2013 to 2017, we performed a climatologicalanalysis of coarse-mode dust Deff over global oceans. We found thatdust Deff over IO and NP is up to 20 % smaller than that over NA.Over NA in summer, we found a ∼50 % reduction in the numberof retrievals with Deff>5 µm from 15 to35∘ W and a stable trend of Deff average at 4.4 µm from35∘ W throughout the Caribbean Sea (90∘ W). Over NP inspring, only ∼5 % of retrieved pixels with Deff>5 µm are found from 150 to 180∘ E, whilethe mean Deff remains stable at 4.0 µm throughout eastern NP. To the best of our knowledge, this study is the first to retrieve both DAOD andcoarse-mode dust particle size over global oceans for multiple years. Thisretrieval dataset provides insightful information for evaluating dustlongwave radiative effects and coarse-mode dust particle size in models.

The impact of common and rare variants in COVID-19 host genetics has been widely studied. In particular, in Fallerini et al. (Human genetics, 2022, 141, 147–173), common and rare variants were used to define an interpretable machine learning model for predicting COVID-19 severity. First, variants were converted into sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. After that, the Boolean features, selected by these logistic models, were combined into an Integrated PolyGenic Score (IPGS), which offers a very simple description of the contribution of host genetics in COVID-19 severity.. IPGS leads to an accuracy of 55%–60% on different cohorts, and, after a logistic regression with both IPGS and age as inputs, it leads to an accuracy of 75%. The goal of this paper is to improve the previous results, using not only the most informative Boolean features with respect to the genetic bases of severity but also the information on host organs involved in the disease. In this study, we generalize the IPGS adding a statistical weight for each organ, through the transformation of Boolean features into “Boolean quantum features,” inspired by quantum mechanics. The organ coefficients were set via the application of the genetic algorithm PyGAD, and, after that, we defined two new integrated polygenic scores (IPGSph1 and IPGSph2). By applying a logistic regression with both IPGS, (IPGSph2 (or indifferently IPGSph1) and age as inputs, we reached an accuracy of 84%–86%, thus improving the results previously shown in Fallerini et al. (Human genetics, 2022, 141, 147–173) by a factor of 10%.

Abstract This study describes the effects on the skeletal phenotype of two pivotal factors, density and water volume, don the hatchery (larval) phase of gilthead seabream (Sparus aurata) larvae previoulsy described for two model species (Danio rerio and Oryzias latipes) and sub‐adult (pre‐ongrowing) gilthead seabream (Sparus aurata). The experimental trial was conducted using single conditions in a pilot study, starting with a total of 615,385 eggs from the same batch. Three densities (LD low density: 25 larvae/L; MD medium density: 125 larvae/L; and HD high density: 250 larvae/L) and two water volumes (500 and 1000 L) were tested from spawning up to 60 days post‐hatching (dph) (average standard length: 1.79 cm; average dry weight: 27.11 mg). On the final samples, morphometric, anatomical, and histological data were collected for data pertinent to meristic counts and skeletal anomalies. The results (analyzed by means of multivariate analyses) indicated that the LD‐reared larvae were significantly longer and heavier than HD‐reared fish. Furthermore, LD‐reared gilthead seabream exhibited a significant reduction in the frequency of individuals with anomalies of jaws, vertebral body shape, and vertebral arches than the MD and HD conditions, which is in agreement with previous experiments carried out on model species and gilthead seabream sub‐adults.

Background: Contamination and transmission of different Listeria monocytogenes strains along food chain are a serious threat to public health and food safety. Understanding the distribution of diseases in time and space-time is fundamental in the epidemiological study and in preventive medicine programs. The aim of this study is to estimate listeriosis incidence along 10-years period and to perform space-time cluster analysis of listeriosis cases in Marche Region, Italy. Methods: The number of observed listeriosis cases/year was derived from regional data of surveillance of notifiable diseases and hospital discharge form. The capture and recapture method (C-R method) was applied to estimate the real incidence of listeriosis cases in Marche Region and the space-time scan statistics analysis was performed to detect clusters of space-time of listeriosis cases and add precision to the conventional epidemiological analysis. Results: The C-R method estimation of listeriosis cases was 119 in the 10- year period (2010–2019), with an average of 31.93 % of unobserved cases (lost cases). The estimated mean annual incidence of listeriosis was 0.77 per 100,000 inhabitants (95 %CI 0.65–0.92), accounting for 6.07 % of additional listeriosis cases per year than observed cases. Using the scan statistic, the two most likely clusters were identified, one of these was statistically significant (p

The Mediterranean Forecasting System produces operational analyses and reanalyses and 10 d forecasts for many essential ocean variables (EOVs), from currents, temperature, salinity, and sea level to wind waves and pelagic biogeochemistry. The products are available at a horizontal resolution of 1/24∘ (approximately 4 km) and with 141 unevenly spaced vertical levels. The core of the Mediterranean Forecasting System is constituted by the physical (PHY), the biogeochemical (BIO), and the wave (WAV) components, consisting of both numerical models and data assimilation modules. The three components together constitute the so-called Mediterranean Monitoring and Forecasting Center (Med-MFC) of the Copernicus Marine Service. Daily 10 d forecasts and analyses are produced by the PHY, BIO, and WAV operational systems, while reanalyses are produced every ∼ 3 years for the past 30 years and are extended (yearly). The modelling systems, their coupling strategy, and their evolutions are illustrated in detail. For the first time, the quality of the products is documented in terms of skill metrics evaluated over a common 3-year period (2018–2020), giving the first complete assessment of uncertainties for all the Mediterranean environmental variable analyses.

The aerosol optical depth (AOD) is a derived measurement useful to investigate the aerosol load and its distribution at different spatio-temporal scales. In this work we use long-term (2000–2021) MAIAC (Multi-Angle Implementation of Atmospheric Correction) retrievals with 1 km resolution to investigate the climatological AOD variability and trends at different scales in Europe: a continental (30–60∘ N, 20∘ W–40∘ E), a regional (100 × 100 km2) and an urban–local scale (3 × 3 km2). The AOD climatology at the continental scale shows the highest values during summer (JJA) and the lowest during winter (DJF) seasons. Regional and urban–local scales are investigated for 21 cities in Europe, including capitals and large urban agglomerations. Analyses show AOD average (550 nm) values between 0.06 and 0.16 at the urban–local scale while also displaying a strong north–south gradient. This gradient corresponds to a similar one in the European background, with higher AOD being located over the Po Valley, the Mediterranean Basin and eastern Europe. Average enhancements of the local with respect to regional AOD of 57 %, 55 %, 39 % and 32 % are found for large metropolitan centers such as Barcelona, Lisbon, Paris and Athens, respectively, suggesting a non-negligible enhancement of the aerosol burden through local emissions. Negative average deviations are observed for other cities, such as Amsterdam (−17 %) and Brussels (−6 %), indicating higher regional background signal and suggesting a heterogeneous aerosol spatial distribution that conceals the urban–local signal. Finally, negative statistically significant AOD trends for the entire European continent are observed. A stronger decrease rate at the regional scale with respect to the local scale occurs for most of the cities under investigation.

Men who have sex with men (MSM) are disproportionately impacted by sexually transmitted infections (STIs), including HIV and those preventable through vaccination such as mpox, HPV, HAV, and HBV. A retrospective cohort study was conducted to evaluate the effectiveness of counseling provided during mpox vaccination on the uptake of other recommended vaccines (HPV, HAV, and HBV) and to identify associated factors. Relevant covariates such as nationality, age, HIV status, and use of PrEP were retrieved from electronic medical records. Vaccination status data were retrieved from the regional vaccination registry. Of the 330 participants, 98.8% were males and the mean age was 40.6 years (SD: 11.2). Following consultation, a statistically significant increase for both HPV (from 25.8% to 39.1%) and HAV (from 26.7% to 36.1%) was observed (p < 0.001). The multivariate analysis showed a significant negative association between the uptake of HPV and HBV vaccines and foreign nationality (aOR 0.25 (95%CI 0.08–0.69), p = 0.012; and aOR 0.31 (95%CI 0.11–0.81), p = 0.021). The HBV vaccine uptake was negatively associated with increasing age. Our results suggest that tailored counseling can effectively bridge the gap in vaccine acceptance among vulnerable populations, thereby improving overall public health outcomes.

Abstract Super‐coarse dust particles (diameters >10 μm) are evidenced to be more abundant in the atmosphere than model estimates and contribute significantly to the dust climate impacts. Since super‐coarse dust accounts for less dust extinction in the visible‐to‐near‐infrared (VIS‐NIR) than in the thermal infrared (TIR) spectral regime, they are suspected to be underestimated by remote sensing instruments operates only in VIS‐NIR, including Aerosol Robotic Networks (AERONET), a widely used data set for dust model validation. In this study, we perform a radiative closure assessment using the AERONET‐retrieved size distribution in comparison with the collocated Atmospheric Infrared Sounder (AIRS) TIR observations with comprehensive uncertainty analysis. The consistently warm bias in the comparisons suggests a potential underestimation of super‐coarse dust in the AERONET retrievals due to the limited VIS‐NIR sensitivity. An extra super‐coarse mode included in the AERONET‐retrieved size distribution helps improve the TIR closure without deteriorating the retrieval accuracy in the VIS‐NIR.

Purpose The PRESTIGIO Registry was established in 2017 to collect clinical, virological and immunological monitoring data from people living with HIV (PLWH) with documented four-class drug resistance (4DR). Key research purposes include the evaluation of residual susceptibility to specific antiretrovirals and the validation of treatment and monitoring strategies in this population.Participants The PRESTIGIO Registry collects annual plasma and peripheral blood mononuclear cell samples and demographic, clinical, virological, treatment and laboratory data from PLWH followed at 39 Italian clinical centres and characterised by intermediate-to-high genotypic resistance to ≥1 nucleoside reverse transcriptase inhibitors, ≥1 non-nucleoside reverse transcriptase inhibitors, ≥1 protease inhibitors, plus either intermediate-to-high genotypic resistance to ≥1 integrase strand transfer inhibitors (INSTIs) or history of virological failure to an INSTI-containing regimen. To date, 229 people have been recorded in the cohort. Most of the data are collected from the date of the first evidence of 4DR (baseline), with some prebaseline information obtained retrospectively. Samples are collected from the date of enrollment in the registry.Findings to date The open-ended cohort has been used to assess (1) prognosis in terms of survival or development of AIDS-related or non-AIDS-related clinical events; (2) long-term efficacy and safety of different antiretroviral regimens and (3) virological and immunological factors predictive of clinical outcome and treatment efficacy, especially through analysis of plasma and cell samples.Future plans The registry can provide new knowledge on how to implement an integrated approach to study PLWH with documented resistance to the four main antiretroviral classes, a population with a limited number of individuals characterised by a high degree of frailty and complexity in therapeutic management. Given the scheduled annual updates of PLWH data, the researchers who collaborate in the registry can send study proposals at any time to the steering committee of the registry, which evaluates every 3 months whether the research studies can be conducted on data and biosamples from the registry and whether they are aimed at a better understanding of a specific health condition, the emergence of comorbidities or the effect of potential treatments or experimental drugs that may have an impact on disease progression and quality of life. Finally, the research studies should aim to be inclusive, innovative and in touch with the communities and society as a whole.Trial registration number NCT04098315.

Summary: Severe COVID-19 outcomes have been reported in people living with HIV (PLWH), yet the underlying pathogenetic factors are largely unknown. We therefore aimed to assess SARS-CoV-2 RNAemia and plasma cytokines in PLWH hospitalized for COVID-19 pneumonia, exploring associations with magnitude and functionality of SARS-CoV-2-specific immune responses.Eighteen unvaccinated PLWH (16/18 on cART; median CD4 T cell count 361.5/μL; HIV-RNA

Abstract. The role of mineral dust aerosol in the global radiative energy budget is oftenquantified by the dust direct radiative effect (DRE). The dust DRE stronglydepends on dust aerosol optical depth (DAOD), therefore, DRE efficiency(DREE = DRE / DAOD) is widely compared across different studies to eliminatedifferences due to the various dust loads. Nevertheless, DREE is stillinfluenced by the uncertainties associated with dust particle sizedistribution (PSD) and optical properties. In this study, we derive a globalclear-sky size-resolved DREE dataset in both shortwave (SW) and longwave (LW) at top ofthe atmosphere (TOA) and surface based on satellite observations (i.e.,satellite-retrieved dust extinction spatial and vertical distributions). Inthe DREE dataset, dust geometric diameter from 0.1 to 100 µmis divided into 10 bins and the corresponding monthly mean DREE (withrespect to DAOD at 532 nm) for each size bin is derived by using the RapidRadiative Transfer Model (RRTM). Three sets of state of the art dustrefractive indices (RI) and two sets of dust shape models (sphere vs. spheroid) are adopted to investigate the sensitivity of dust DREE to dustabsorption and shape. As a result, the size-resolved dust DREE datasetcontains globally distributed monthly mean dust DREE at TOA and surface foreach of 10 size bins with 5∘ (longitude) ×2∘(latitude) resolution as well as for each dust RI and shape combination. Thesize-resolved dust DREE dataset can be used to readily calculate global dustDRE for any DAOD and dust PSD, including the uncertainty in the DRE inducedby dust microphysical properties, (e.g., dust PSD, RI and shape). Bycalculating dust DRE based on DAOD climatology retrieved from differentsatellite sensors and based on different dust PSD, we find that uncertaintyin the spatial pattern of DAOD induces more than 10 % of the uncertaintyin SW dust DRE at TOA. The observation-based dust PSD induces around15–20 % uncertainty in dust DRE at TOA and in theatmosphere. The sensitivity assessments of dust DRE to dust RI and shapefurther suggest that dust nonsphericity induces a negligible effect on dustDRE estimations, while dust RI turns out to be the most important factor indetermining dust DRE, particularly in SW.

Abstract Advancing knowledge of the mineralogical composition of dust is key for understanding and predicting its climate and environmental impacts. The variability of dust mineralogy from one source to another and its evolution during atmospheric transport is not measured at large scale. In this study we use laboratory measurements to demonstrate that the extinction signature of suspended dust aerosols in the 740 − 1250 cm−1 atmospheric window can be used to derive dust mineralogy in terms of the main infrared − active minerals, namely quartz, clays, feldspars and calcite. Various spectral signatures in dust extinction enable to distinguish between multiple global sources with changing composition, whereas modifications of the dust extinction spectra with time inform on size − dependent particles mineralogy changes during transport. The present study confirms that spectral and hyperspectral infrared remote sensing observations offer great potential for elucidating the size − segregated mineralogy of airborne dust at regional and global scales.

In this study, we developed a novel algorithm based on the collocated Moderate Resolution Imaging Spectroradiometer (MODIS) thermal infrared (TIR) observations and dust vertical profiles from the Cloud–Aerosol Lidar with Orthogonal Polarization (CALIOP) to simultaneously retrieve dust aerosol optical depth at 10 µm (DAOD10 µm) and the coarse-mode dust effective diameter (Deff) over global oceans. The accuracy of the Deff retrieval is assessed by comparing the dust lognormal volume particle size distribution (PSD) corresponding to retrieved Deff with the in situ-measured dust PSDs from the AERosol Properties – Dust (AER-D), Saharan Mineral Dust Experiment (SAMUM-2), and Saharan Aerosol Long-Range Transport and Aerosol–Cloud-Interaction Experiment (SALTRACE) field campaigns through case studies. The new DAOD10 µm retrievals were evaluated first through comparisons with the collocated DAOD10.6 µm retrieved from the combined Imaging Infrared Radiometer (IIR) and CALIOP observations from our previous study (Zheng et al., 2022). The pixel-to-pixel comparison of the two DAOD retrievals indicates a good agreement (R∼0.7) and a significant reduction in (∼50 %) retrieval uncertainties largely thanks to the better constraint on dust size. In a climatological comparison, the seasonal and regional (2∘×5∘) mean DAOD10 µm retrievals based on our combined MODIS and CALIOP method are in good agreement with the two independent Infrared Atmospheric Sounding Interferometer (IASI) products over three dust transport regions (i.e., North Atlantic (NA; R=0.9), Indian Ocean (IO; R=0.8) and North Pacific (NP; R=0.7)). Using the new retrievals from 2013 to 2017, we performed a climatological analysis of coarse-mode dust Deff over global oceans. We found that dust Deff over IO and NP is up to 20 % smaller than that over NA. Over NA in summer, we found a ∼50 % reduction in the number of retrievals with Deff>5 µm from 15 to 35∘ W and a stable trend of Deff average at 4.4 µm from 35∘ W throughout the Caribbean Sea (90∘ W). Over NP in spring, only ∼5 % of retrieved pixels with Deff>5 µm are found from 150 to 180∘ E, while the mean Deff remains stable at 4.0 µm throughout eastern NP. To the best of our knowledge, this study is the first to retrieve both DAOD and coarse-mode dust particle size over global oceans for multiple years. This retrieval dataset provides insightful information for evaluating dust longwave radiative effects and coarse-mode dust particle size in models.

Icelandic dust can impact the radiative budget in high-latitude regions directly by affecting light absorption and scattering and indirectly by changing the surface albedo after dust deposition. This tends to produce a positive radiative forcing. However, the limited knowledge of the spectral optical properties of Icelandic dust prevents an accurate assessment of these radiative effects. Here, the spectral single scattering albedo (SSA) and the complex refractive index (m=n-ik) of Icelandic dust from five major emission hotspots were retrieved between 370–950 nm using online measurements of size distribution and spectral absorption (βabs) and scattering (βsca) coefficients of particles suspended in a large-scale atmospheric simulation chamber. The SSA(λ) estimated from the measured βabs and βsca increased from 0.90–0.94 at 370 nm to 0.94–0.96 at 950 nm in Icelandic dust from the different hotspots, which falls within the range of mineral dust from northern Africa and eastern Asia. The spectral complex refractive index was retrieved by minimizing the differences between the measured βabs and βsca and those computed using the Mie theory for spherical and internally homogeneous particles, using the size distribution data as input. The real part of the complex refractive index (n(λ)) was found to be 1.60–1.61 in the different samples and be independent of wavelength. The imaginary part (k(λ)) was almost constant with wavelength and was found to be around 0.004 at 370 nm and 0.002–0.003 at 950 nm. The estimated complex refractive index was close to the initial estimates based on the mineralogical composition, also suggesting that the high magnetite content observed in Icelandic dust may contribute to its high absorption capacity in the shortwave part of the spectrum. The k(λ) values retrieved for Icelandic dust are at the upper end of the reported range for low-latitude dust (e.g., from the Sahel). Furthermore, Icelandic dust tends to be more absorbing towards the near-infrared. In Icelandic dust, k(λ) between 660–950 nm was 2–8 times higher than most of the dust samples sourced in northern Africa and eastern Asia. This suggests that Icelandic dust may have a stronger positive direct radiative forcing on climate that has not been accounted for in climate predictions.