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Study Objective: Non-physician practitioners, including nurse practitioners and physician assistants, increasingly practice in emergency departments, especially in rural areas, where they help mitigate physician shortages. However, little is known about non-physician practitioner durability and demographic trends in emergency departments. Our objective was to examine attrition rates and ages among non-physician practitioners in emergency medicine., Methods: We conducted a repeated cross-sectional analysis using the Medicare Data on Provider Practice and Specialty and Medicare Provider Utilization and Payment Data. The study included non-physician practitioners providing at least 25 independent evaluation and management services annually for Medicare beneficiaries between 2014 and 2021. Attrition rates, defined as the absence of emergency medicine clinical services in subsequent years, were stratified by gender, clinician type, and practice urbanicity., Results: The emergency medicine non-physician practitioner workforce grew from 14,559 to 17,679 between 2014 and 2021. Women non-physician practitioners comprised 64.6% of the workforce, and rural non-physician practitioners accounted for 15.7%. Across study years, the weighted annual attrition rate was 13.8%, rising from 12.1% in 2014 to 17.6% in 2019. Attrition rates were higher among physician assistants as well as women and rural non-physician practitioners, with median ages at attrition of 40.2 years for women and 45.9 years for men, and 38.6 years for urban non-physician practitioners versus 43.6 years for rural non-physician practitioners., Conclusion: The rate of non-physician practitioner attrition from the emergency medicine workforce is considerably higher and occurs at younger ages than prior work evaluating emergency physician attrition, with similar identified gender and geographic disparities. Targeted retention strategies are needed to support a more durable emergency medicine workforce and reduce disparities., (Copyright © 2024 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)

Mature and immature female swordfish show different gonadal expression patterns of melatonin synthesis-related and opsin genes, indicating that seasonality affects gonadal circadian genes, especially through opsin modulation. The high energy demands of reproduction may cause mature female swordfish to become more susceptible to environmental stressors/changes, potentially affecting their health post-reproduction. The modulation of melatonin and opsin expression may also influence swordfish biology, impacting basal metabolism and stress responses. This study aimed to investigate the hepatic expression patterns of genes involved in melatonin and opsins activity after the reproductive period, comparing mature and immature females. Liver samples of swordfish females, collected from the Central Adriatic Sea, were analyzed to evaluate the expression of a melatonin receptor ( mel1b ), acetylserotonin O-methyltransferase ( asmt ), opsins ( sws , VA opsin and opsin4 ), and stress response ( sod1 , sod2 and hsp4b ) genes, while histological analysis focused on hepatic melanomacrophages, melanomacrophage centers, and lipid content. The expression of all genes analyzed did not differ between mature and immature females except for sws , which was significantly downregulated in mature females. The overall health conditions of mature and immature females appeared comparable, as suggested by the histological analysis and the absence of significant differences in the expression of stress response genes. Although the study used a limited number of samples and lacked a comparison between the reproductive and non-reproductive periods, the preliminary results suggest that opsins may play a role in modulating physiological processes beyond reproduction.

Objectives: We aimed to evaluate ixekizumab (IXE) effectiveness, drug survival and clinical response predictors in moderate-severe psoriatic arthritis (PsA) patients in different clinical scenarios., Methods: This was a multicentre real-life observational study based on Gruppo Italiano Studio Early Arthritis (GISEA) registry of IXE treatment in PsA patients (January 2019-June 2023). Data were collected at baseline and every six months., Results: 223 PsA outpatients were included. Statistically significant improvement was observed after 6 (T6), 12 (T12) and 24 (T24) months of therapy for tender and swollen joint count (TJC and SJC), Visual Analogue Scale (VAS)-pain and Disease Activity in PSoriatic Arthritis (DAPSA) score. DAPSA remission was reached at T12 in 22% and at T24 in 18.5% of patients. At baseline, higher fibromyalgia and combination therapy with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) in females with respect to males and higher Psoriasis Area Severity Index (PASI) in males than in females were observed. Therapeutic effectiveness showed in males higher DAPSA and VAS-pain reduction, higher percentage of males in DAPSA remission/low disease activity (LDA) at T6, and higher ∆PASI at T6 and T12 than in female patients. At multivariate analysis, male sex was predictive for treatment response at T6 [p=0.02, odds ratio (OR) 2.49 (95% confidence interval 1.11-5.54)], while it lost significance at T12., Conclusions: IXE effectiveness was highlighted after 6 months at both joint and skin levels and lasted up to 24 months in different clinical scenarios, making IXE effective in the complexity of managing PsA in a real-life setting.

This research investigates the dynamics of contaminant exposure in European hake ( Merluccius merluccius , L. 1758) from the Adriatic Sea (Central Mediterranean Sea) by examining the levels of total mercury (THg) and polycyclic aromatic hydrocarbons (PAHs) in the muscle fish tissues. The study explores the correlations between these pollutants and somatic indexes to identify the early warning signals of pollution and ecological effects. The levels of pollutants are influenced by season and sex. Lipids appear to have a minimal effect on the PAH levels, whereas they exhibit a positive correlation with mercury levels in the muscle. No significant relationships between the pollutants and condition indexes were observed, except for a positive correlation between THg and the gonadosomatic index, indicating a potential impact on the reproductive health of fish. In contrast, PAHs showed no meaningful correlation with condition indexes. Differences in contaminant accumulations and lipid levels between sexes reflect variations in metabolic activity, reproductive costs, and adaptive strategies to seasonal changes and energy demands. This study highlights the importance of long-term monitoring to improve pollution management, environmental conservation, and the protection of marine organisms' health.

Tin halide perovskites represent the most suitable alternative to their lead-based counterparts for sustainable photovoltaics. One of the most important drawbacks of this class of materials is the intrinsic tendency of tin (II) to oxidize under certain conditions and as a consequence of aging. Here, we explore plasma processing to gently treat the surface of the tin perovskite films. As shown by chemical, optical, and morphological analyses, this treatment by generating transient active species on the surface of the material impacts its aging, inhibiting the tendency of tin (II) to oxidize. Plasma-treated stored devices show a power conversion efficiency slightly higher and narrower in the distribution than that of the reference devices. The positive impact of this noninvasive technique, which can be easily implemented in large-area manufacturing facilities, increases the potential of lead-free alternative perovskite photovoltaics.

Fisheries management requires improvement in scientific knowledge to ensure sustainable exploitation of important commercial species and population renewal. Within this context, this study focused on the reproductive biology of spot tail mantis shrimp, Squilla mantis , in the Central Mediterranean Sea, aiming to understand the reproductive pattern of this species and validate the macroscopic maturity scale through histological analysis. A multi-year sampling was performed from 2016 to 2020 by a commercial fishing fleet in the Northern Central Adriatic Sea (GSA 17), and a total of 2206 individuals were collected. The monthly average value of the total sex ratio of S. mantis was 0.524 ± 0.044 ( mean ± SEM ) in favor of females, which dominated the population from September to April. The proposed 5 stage macroscopic maturity scale was validated histologically through histological analysis, confirming synchronous ovarian development. The somatic indexes (GSI and K Fulton) and monthly incidence of macroscopic ovarian maturity stages highlighted a protracted reproductive season from winter to spring (January-May). Although the length-weight relationship showed a similar growth trend between genders, males reached a bigger size in terms of carapace length (C.L.) and dominated the population from 32 mm (C.L.). The macroscopic L50 estimated was 25.94 mm (C.L.).

Detecting RNA molecules within their natural environment inside intact arthropods has long been challenging, particularly in small organisms covered by a tanned and pigmented cuticle. Here, we have developed a methodology that enables high-resolution analysis of the spatial distribution of transcripts of interest without having to dissect tiny organs or tissues, thereby preserving their integrity. We have combined an in situ amplification approach based on hybridization chain reaction, which enhances the signal-to-noise ratio, and a clearing approach that allows the visualization of inner organs beneath the cuticle. We have implemented this methodology for the first time in Hemiptera, mapping two salivary aphid (Acyrthosiphon pisum) transcripts, the effector c002 and the salivary sheath protein SHP. With a multiplex approach, we could simultaneously detect different mRNAs in mounted pea aphid head-thorax samples and show that they were distributed in distinct secretory cells of salivary glands. RESEARCH HIGHLIGHTS: Combining hybridisation chain reaction and clearing allows the detection of transcripts in intact aphids heads. The transcripts of the two salivary proteins c002 and SHP are compartmentalized in distinct secretory cells of the principal glands., (© 2024 The Authors. Microscopy Research and Technique published by Wiley Periodicals LLC.)

Background: Exposure to environmental stressors like particulate matter (PM) and ultraviolet radiation (UV) induces cutaneous oxidative stress and inflammation and leads to skin barrier dysfunction and premature aging. Metals like iron or copper are abundant in PM and are known to contribute to reactive oxygen species (ROS) production., Aims: Although it has been suggested that topical antioxidants may be able to help in preventing and/or reducing outdoor skin damage, limited clinical evidence under real-life exposure conditions have been reported. The aim of the present study was to evaluate the ability of a topical serum containing 15% ascorbic acid, 0.5% ferulic acid, and 1% tocopherol (CF Mix) to prevent oxinflammatory skin damage and premature aging induced by PM + UV in a human clinical trial., Methods: A 4-day single-blinded, clinical study was conducted on the back of 15 females (18-40 years old). During the 4 consecutive days, the back test zones were treated daily with or without the CF Mix, followed by with/without 2 h of PM and 5 min of UV daily exposure., Results: Application of the CF Mix prevented PM + UV-induced skin barrier perturbation (Involucrin and Loricrin), lipid peroxidation (4HNE), inflammatory markers (COX2, NLRP1, and AhR), and MMP9 activation. In addition, CF Mix was able to prevent Type I Collagen loss., Conclusion: This is the first human study confirming multipollutant cutaneous damage and suggesting the utility of a daily antioxidant topical application to prevent pollution induced skin damage., (© 2024 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

This study presents what we believe is the first extensive assessment of the water reflectance products from the German hyperspectral Environmental Mapping and Analysis Program (EnMAP). We evaluate EnMAP's standard normalized water leaving reflectance [ρ W ] N over 17 water sites in the first two years of the mission. The EnMAP [ρ W ] N standard product is generated by a dedicated water atmospheric correction (AC) called the Modular Inversion Program (MIP). The quality of the [ρ W ] N retrievals was assessed using in situ hyperspectral measurements and Aerosol Robotic Network - Ocean Colour (AERONET-OC) multispectral measurements. The results showed very good agreement between in situ hyperspectral match-ups and EnMAP [ρ W ] N , with an underestimation of EnMAP of -17.37% (bias, β) and an error ( ϵ ) of 23.75% at 418 - 797 nm. Two other AC processors were also investigated: the polynomial based algorithm applied to MERIS (Polymer) and the atmospheric correction for OLI lite (Acolite). The intercomparison exercise between the three AC methods applied to EnMAP data using the hyperspectral match-up dataset showed better statistical metrics for MIP ( ϵ =23 % , β =-17.37 % ) compared to Polymer ( ϵ =42.20 % , β =-2.43 % ) and Acolite ( ϵ =97 % , β =97 % ). The superior performance of MIP was further confirmed by the validation results obtained with the multispectral match-up dataset; MIP retrievals show good agreement with in situ measurements at the majority of study sites. Conversely, Polymer and Acolite retrievals tended to overestimate, especially in clearer waters as the Lampedusa study site.

Fostered by the top power conversion efficiencies (PCEs) of lab-scale devices, industrialization of perovskite solar cells is underway. Nevertheless, the intrinsically poor stability of these materials still represents a major concern. Herein, inspired by Nature, the use of β-carotene in perovskite solar cells is proposed to mimic its role as a protective pigment, as occurs in natural photosynthesis. Laser-mediated photostability (LMPS) assessment, Fourier-transform infrared spectra analysis acquired in attenuate total reflectance (ATR-FTIR), spectroscopy ellipsometry (SE), and time-resolved photoluminescence (TRPL) measurements under stress conditions prove that the inclusion of a thin β-carotene interlayer promotes a high improvement in the photostability of the perovskite films against photooxidation. Importantly, this is accompanied by an improvement of the solar cell PCE that approaches 20% efficiency with no hysteresis, which is among the highest values reported for a mixed halide (I-Br) perovskite with a band gap of 1.74 eV, relevant for coupling with silicon in tandem cells.

We use a distinctive methodology that leverages a fixed population of Twitter users located in France to gauge the mental health effects of repeated lockdown orders. To do so, we derive from our population a mental health indicator that measures the frequency of words expressing anger, anxiety and sadness. Our indicator did not reveal a statistically significant mental health response during the first lockdown, while the second lockdown triggered a sharp and persistent deterioration in all three emotions. Our estimates also show a more severe deterioration in mental health among women and younger users during the second lockdown. These results suggest that successive stay-at-home orders significantly worsen mental health across a large segment of the population. We also show that individuals who are closer to their social network were partially protected by this network during the first lockdown, but were no longer protected during the second, demonstrating the gravity of successive lockdowns for mental health., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The skin is the outermost layer of the body and, therefore, is exposed to a variety of stressors, such as environmental pollutants, known to cause oxinflammatory reactions involved in the exacerbation of several skin conditions. Today, inflammasomes are recognized as important modulators of the cutaneous inflammatory status in response to air pollutants and ultraviolet (UV) light exposure. In this study, human skin explants were exposed to the best-recognized air pollutants, such as microplastics (MP), cigarette smoke (CS), diesel engine exhaust (DEE), ozone (O 3 ), and UV, for 1 or 4 days, to explore how each pollutant can differently modulate markers of cutaneous oxinflammation. Exposure to environmental pollutants caused an altered oxidative stress response, accompanied by increased DNA damage and signs of premature skin aging. The effect of specific pollutants being able to exert different inflammasomes pathways (NLRP1, NLRP3, NLRP6, and NLRC4) was also investigated in terms of scaffold formation and cell pyroptosis. Among all environmental pollutants, O 3 , MP, and UV represented the main pollutants affecting cutaneous redox homeostasis; of note, the NLRP1 and NLRP6 inflammasomes were the main ones modulated by these outdoor stressors, suggesting their role as possible molecular targets in preventing skin disorders and the inflammaging events associated with environmental pollutant exposure.

In mature symbiotic root nodules, differentiated rhizobia fix atmospheric dinitrogen and provide ammonium to fulfill the plant nitrogen (N) demand. The plant enables this process by providing photosynthates to the nodules. The symbiosis is adjusted to the whole plant N demand thanks to systemic N signaling controlling nodule development. Symbiotic plants under N deficit stimulate nodule expansion and activate nodule senescence under N satiety. Besides, nodules are highly sensitive to drought. Here, we used split-root systems to characterize the systemic responses of symbiotic plants to a localized osmotic stress. We showed that polyéthylène glycol (PEG) application rapidly inhibited the symbiotic dinitrogen fixation activity of nodules locally exposed to the treatment, resulting to the N limitation of the plant supplied exclusively by symbiotic dinitrogen fixation. The localized PEG treatment triggered systemic signaling stimulating nodule development in the distant untreated roots. This response was associated with an enhancement of the sucrose allocation. Our analyses showed that transcriptomic reprogramming associated with PEG and N deficit systemic signaling(s) shared many targets transcripts. Altogether, our study suggests that systemic N signaling is a component of the adaptation of the symbiotic plant to the local variations of its edaphic environment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Martin, Pervent, Lambert, Colella, Tancelin, Severac, Clément, Tillard, Frugier and Lepetit.)

The beneficial effects of sardine consumption can be related to the presence of bioactive compounds, such as vitamin E and ω3 polyunsaturated fatty acids. In any case, the levels of these compounds in sardine fillet depend on different factors mainly related to the diet and reproductive cycle phase of the fish as well as the technological treatments carried out to cook the fillets. The aim of the present study is two-fold: first, to evaluate changes in the total fatty acid profile, lipid oxidation, and vitamin E content of raw fillets from sardine ( Sardina pilchardus ) at different reproductive cycle phases (pre-spawning, spawning, and post-spawning); and second, to highlight how these nutritional profiles are affected by three oven treatments (conventional, steam, and sous-vide). For this purpose, raw fish was grouped into pre-spawning, spawning, and post-spawning phases according to the mesenteric fat frequency and the gonadosomatic index evaluation, and submitted to conventional (CO), steam (SO), and sous-vide (SV) baking. The ratio of EPA/DHA and vitamin E increased from post-spawning to pre-spawning, to spawning. Considering the reproductive phases, baking affected the oxidative degree differently: a CO > SO ≥ SV impact was found in the worst scenario (post-spawning), mitigated by vitamin E, to CO ≥ SO > SV in the best scenario (spawning). SV was the best treatment with high values of vitamin E in pre-spawning individuals (110.1 mg/kg). This study shows how vitamin E is correlated to the combined effect of endogenous and exogenous factors.

The improvement of scientific knowledge about overexploited fishery resources allow us to provide scientific advice for their management and stock protection. By using a multidisciplinary approach, the aim of the study was to characterize, for the first time in the Central Mediterranean Sea (GSA 17), the reproductive biology of males of M. merluccius , currently highly exploited. A multi-year sampling from January 2017 to December 2019 was performed to exhaustively evaluate the sex ratio of the stock, while the 2018 annual sampling was selected to investigate the reproductive pattern of males. Individuals in spawning conditions were found every month, proving that M. merluccius is an asynchronous species, reproducing all year round, with a seasonal reproductive peak in spring/summer, as indicated by GSI. Five gonadal development stages were defined to fully describe the reproductive cycle of males. The macroscopic and histological L 50 , respectively 18.6 cm and 15.4 cm, were both below the Minimum Conservation Reference Size (MCRS). According to the mRNA levels, fsh and lh played a significant role during spermiation, whereas the gnrhr2a was involved at the beginning of sexual maturity. In the testis, fshr and lhr reached maximum expression levels before the spermiation. The hormonal stimuli of 11-ketotestosterone and its receptor were significantly higher when the specimen was in reproductive activity.

Introduction: The objective of this study was to assess the 10-year prevalence of latent tuberculosis infection (LTBI) among Apulian patients with rheumatic diseases (RDs). Secondary endpoint was to record new cases of active TB disease and LTBI among patients treated with biologic disease-modifying antirheumatic drugs (bDMARDs)., Methods: We analysed the results from the patients included in the BIOPURE registry from 2009 to 2018, who underwent QuantiFERON-TB Gold In-tube (QFT-GIT) test as screening before bDMARDs treatment. Demographic and clinical data were recorded at the time of the first QFT-GIT test. Administration of preventive therapy and bDMARD treatments were recorded for patients with positive QFT-GIT test. All new tuberculosis infections were recorded during the follow-up., Results: The final study population included 3028 patients (855 rheumatoid arthritis, 1001 psoriatic arthritis, 833 spondyloarthritis, 130 connective tissue diseases, 33 systemic vasculitis and 176 other inflammatory rheumatic conditions), more frequently female (67.2%), with a mean age of 52 ± 18 years. Patients with QFT-GIT-positive test were elderly people, predominantly male with higher prevalence of diabetes as comorbidity. The 10-year prevalence of LTBI was 10.8%. Of note, no cases of TB reactivation were recorded in patients who completed preventive therapy treatment. Three thousand and sixteen patients were followed over time (42.6 ± 30 months), and five (.2%) developed active TB, which corresponds to .47 cases per 1000 person-years., Conclusions: In the 10-year observation, the use of bDMARDs seems to be safe in rheumatologic patients with positive QFT-GIT test treated according to current recommendations. Nevertheless, cases of primary TB disease did occur during treatment with biologicals., (© 2022 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)

There is increasing interest in the role of metal halide perovskites for heterogeneous catalysis. Here, we report a Ge-based 2D perovskite material that shows intrinsic water stability realized through organic cation engineering. Incorporating 4-phenylbenzilammonium (PhBz) we demonstrate, by means of extended experimental and computational results, that PhBz 2 GeBr 4 and PhBz 2 GeI 4 can achieve relevant air and water stability. The creation of composites embedding graphitic carbon nitride (g-C 3 N 4 ) allows a proof of concept for light-induced hydrogen evolution in an aqueous environment by 2D Ge-based perovskites thanks to the effective charge transfer at the heterojunction between the two semiconductors., Competing Interests: The authors declare no competing interests., (© 2022 The Author(s).)

The common sole, Solea solea , is one the most important commercial species in Europe and, within the Mediterranean, the Adriatic basin is the most crucial area for its production. Although the species is overexploited in the basin, data on its trophic ecology are fragmentary, even though this is one of the most important features within the Ecosystem Approach to Fishery. Here, we analysed temporal variations in the feeding ecology of the species by using an integrated approach of stomach contents and stable isotope analyses coupled with the analysis of some condition indices such as the gonadosomatic and the hepatosomatic indices. Changes in diet and trophic level across the years in adult females were clearly linked to the different energetic requirements facing reproduction. Temporal changes throughout the year were mainly related to changes in food availability. This study confirms the opportunistic behaviour of this benthophagous species and its role as a mesopredator, opening new perspectives for further investigations on the effects of the overexploitation of this important fishery resource on the marine trophic web.

Background: In patients with interstitial lung diseases (ILD), histopathological input is often required to obtain a diagnosis. Surgical lung biopsy (SLB) is considered the reference standard, but many patients are clinically unfit to undergo this invasive procedure, and adverse events, length of hospitalisation and costs are considerable. This European Respiratory Society (ERS) guideline provides evidence-based clinical practice recommendations for the role of transbronchial lung cryobiopsy (TBLC) in obtaining tissue-based diagnosis in patients with undiagnosed ILD., Methods: The ERS Task Force consisted of clinical experts in the field of ILD and/or TBLC and methodological experts. Four PICO (Patient, Intervention, Comparator, Outcomes) questions and two narrative questions were formulated. Systematic literature searches were performed in MEDLINE and Embase (up to June 2021). GRADE (Grading, Recommendation, Assessment, Development and Evaluation) methodology was applied., Results: In patients with undiagnosed ILD and an indication to obtain histopathological data: 1) TBLC is suggested as a replacement test in patients considered eligible to undergo SLB, 2) TBLC is suggested in patients not considered eligible to undergo SLB, 3) SLB is suggested as an add-on test in patients with a non-informative TBLC, 4) no recommendation is made for or against a second TBLC in patients with a non-informative TBLC and 5) TBLC operators should undergo training, but no recommendation is made for the type of training required., Conclusions: TBLC provides important diagnostic information in patients with undiagnosed ILD. Diagnostic yield is lower compared to SLB, at reduced serious adverse events and length of hospitalisation. Certainty of the evidence is mostly "very low"., Competing Interests: Conflict of interest: L. Hagmeyer has received honoraria for lectures and presentations from Boehringer Ingelheim and Roche, and participated in advisory boards for Boehringer Ingelheim and Roche. J. Hetzel has received honoraria for lectures and presentations from Erbe and GlaxoSmithKline, and research support from Boehringer Ingelheim and AstraZeneca. A. Morais has received honoraria for presentations from Boehringer Ingelheim, Roche, Pfizer, AstraZeneca and Sanofi, and research grants from Roche, Boehringer Ingelheim and GlaxoSmithKline. S. Tomassetti has received honoraria for presentations from Roche and Boehringer Ingelheim. L.K. Troy has received honoraria for presentations from Boehringer Ingelheim, has been a member of an advisory board for Roche, and has received research support from Erbe. A.U. Wells has received personal fees from Roche and Boehringer Ingelheim. T. Tonia acts as an ERS methodologist. V. Poletti has received honoraria for lectures and presentations from Boehringer Ingelheim, Roche and Erbe, and participated in advisory boards for Boehringer Ingelheim, Roche and Ambu. The remaining authors have nothing to disclose., (Copyright ©The authors 2022. For reproduction rights and permissions contact permissions@ersnet.org.)

Purpose of the present paper is to point out the design, development and deployment of the AutoInflammatory Disease Alliance (AIDA) International Registry dedicated to pediatric and adult patients with Behçet's disease (BD). The Registry is a clinical physician-driven non-population- and electronic-based instrument implemented for the retrospective and prospective collection of real-life data about demographics, clinical, therapeutic, laboratory, instrumental and socioeconomic information from BD patients; the Registry is based on the Research Electronic Data Capture (REDCap) tool, which is thought to collect standardised information for clinical real-life research, and has been realised to change over time according to future scientific acquisitions and potentially communicate with other existing and future Registries dedicated to BD. Starting from January 31st, 2021, to February 7th, 2022, 110 centres from 23 countries in 4 continents have been involved. Fifty-four of these have already obtained the approval from their local Ethics Committees. Currently, the platform counts 290 users (111 Principal Investigators, 175 Site Investigators, 2 Lead Investigators, and 2 data managers). The Registry collects baseline and follow-up data using 5993 fields organised into 16 instruments, including patient's demographics, history, clinical manifestations and symptoms, trigger/risk factors, therapies and healthcare access. The development of the AIDA International Registry for BD patients will facilitate the collection of standardised data leading to real-world evidence, enabling international multicentre collaborative research through data sharing, international consultation, dissemination of knowledge, inclusion of patients and families, and ultimately optimisation of scientific efforts and implementation of standardised care.Trial registration NCT05200715 in 21/01/2022., (© 2022. The Author(s).)

Several materials and techniques have been described for the procedure of chest wall reconstruction: the choice of using a technique or a material over another relies mainly on the surgeon's experience as well as thoracic defect localization and dimension, local availability of materials, and costs. From a technical point of view, autologous and alloplastic reconstruction are available, and, in both cases, rigid and non-rigid prostheses are found. Each material has its peculiarities, with advantages and disadvantages; thus, it is mandatory to be confident when planning the intervention to foresee possible complications and minimize them. We have reviewed the literature on chest wall reconstruction in chest wall tumors (both malignant and non malignant) with non-rigid prosthetic materials, focusing on safety outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 Colella, Brandimarte, Marra, Marinari, D'Incecco, Di Genesio Pagliuca, De Vico, Crisci and Divisi.)

The proper use of statistical modeling in NGS data analysis requires an advanced level of expertise. There has recently been a growing consensus on using generalized linear models for differential analysis of RNA-Seq data and the advantage of mixture models to perform co-expression analysis. To offer a managed setting to use these modeling approaches, we developed DiCoExpress that provides a standardized R pipeline to perform an RNA-Seq analysis. Without any particular knowledge in statistics or R programming, beginners can perform a complete RNA-Seq analysis from quality controls to co-expression through differential analysis based on contrasts inside a generalized linear model. An enrichment analysis is proposed both on the lists of differentially expressed genes, and the co-expressed gene clusters. This video tutorial is conceived as a step-by-step protocol to help users take full advantage of DiCoExpress and its potential in empowering the biological interpretation of an RNA-Seq experiment.

Objective: Aim of this paper is to illustrate the methodology, design, and development of the AutoInflammatory Disease Alliance (AIDA) International Registry dedicated to patients with the Periodic Fever, Aphthous stomatitis, Pharyngitis, and cervical Adenitis (PFAPA) syndrome., Methods: This is a physician-driven, non-population- and electronic-based registry proposed to gather real-world demographics, clinical, laboratory, instrumental and socioeconomic data from PFAPA patients. Data recruitment is realized through the on-line Research Electronic Data Capture (REDCap) tool. This registry is thought to collect standardized information for clinical research leading to solid real-life evidence. The international scope and the flexibility of the registry will facilitate the realization of cutting-edge study projects through the constant updating of variables and the possible merging and transfer of data between current and future PFAPA registries., Results: A total of 112 centers have already been involved from 23 countries and 4 continents starting from August 24th, 2021, to April 6th, 2022. In total 56/112 have already obtained the formal approval from their local Ethics Committees. The platform counts 321 users (113 principal investigators, 203 site investigators, two lead investigators, and three data managers). The registry collects retrospective and prospective data using 3,856 fields organized into 25 instruments, including PFAPA patient's demographics, medical histories, symptoms, triggers/risk factors, therapies, and impact on the healthcare systems., Conclusions: The development of the AIDA International Registry for PFAPA patients will enable the on-line collection of standardized data prompting real-life studies through the connection of worldwide groups of physicians and researchers. This project can be found on https://clinicaltrials.gov NCT05200715., (Copyright © 2022 Della Casa, Vitale, Cattalini, La Torre, Capozio, Del Giudice, Maggio, Conti, Alessio, Ogunjimi, Ragab, Emmi, Aragona, Giani, Lopalco, Parronchi, Shahram, Verrecchia, Ricci, Cardinale, Di Noi, Nuzzolese, Lubrano, Patroniti, Naddei, Sabato, Hussein, Dotta, Mastrorilli, Gentileschi, Tufan, Caggiano, Hegazy, Sota, Almaghlouth, Ibrahim, Wiȩsik-Szewczyk, Ozkiziltas, Grosso, Frassi, Tarsia, Pereira, Taymour, Gaggiano, Colella, Fabiani, Morrone, Ruscitti, Frediani, Spedicato, Giardini, Balistreri, Rigante and Cantarini.)

Background: Psoriatic Arthritis (PsA) is a multifactorial disease, and predicting remission is challenging. Machine learning (ML) is a promising tool for building multi-parametric models to predict clinical outcomes. We aimed at developing a ML algorithm to predict the probability of remission in PsA patients on treatment with Secukinumab (SEC)., Methods: PsA patients undergoing SEC treatment between September 2017 and September 2020 were retrospectively analyzed. At baseline and 12-month follow-up, we retrieved demographic and clinical characteristics, including Body Mass Index (BMI), disease phenotypes, Disease Activity in PsA (DAPSA), Leeds Enthesitis Index (LEI) and presence/absence of comorbidities, including fibromyalgia and metabolic syndrome. Two random feature elimination wrappers, based on an eXtreme Gradient Boosting (XGBoost) and Logistic Regression (LR), were trained and validated with 10-fold cross-validation for predicting 12-month DAPSA remission with an attribute core set with the least number of predictors. The performance of each algorithm was assessed in terms of accuracy, precision, recall and area under receiver operating characteristic curve (AUROC)., Results: One-hundred-nineteen patients were selected. At 12 months, 20 out of 119 patients (25.21%) achieved DAPSA remission. Accuracy and AUROC of XGBoost was of 0.97 ± 0.06 and 0.97 ± 0.07, overtaking LR (accuracy 0.73 ± 0.09, AUROC 0.78 ± 0.14). Baseline DAPSA, fibromyalgia and axial disease were the most important attributes for the algorithm and were negatively associated with 12-month DAPSA remission., Conclusions: A ML approach may identify SEC good responders. Patients with a high disease burden and axial disease with comorbid fibromyalgia seem challenging to treat., Competing Interests: FI and GL received speaker honoraria from Novartis. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Venerito, Lopalco, Abbruzzese, Colella, Morrone, Tangaro and Iannone.)

Objective: This paper points out the design, development and deployment of the AutoInflammatory Disease Alliance (AIDA) International Registry dedicated to pediatric and adult patients affected by Undifferentiated Systemic AutoInflammatory Diseases (USAIDs)., Methods: This is an electronic registry employed for real-world data collection about demographics, clinical, laboratory, instrumental and socioeconomic data of USAIDs patients. Data recruitment, based on the Research Electronic Data Capture (REDCap) tool, is designed to obtain standardized information for real-life research. The instrument is endowed with flexibility, and it could change over time according to the scientific acquisitions and potentially communicate with other similar tools; this platform ensures security, data quality and data governance., Results: The focus of the AIDA project is connecting physicians and researchers from all over the world to shed a new light on heterogeneous rare diseases. Since its birth, 110 centers from 23 countries and 4 continents have joined the AIDA project. Fifty-four centers have already obtained the approval from their local Ethics Committees. Currently, the platform counts 290 users (111 Principal Investigators, 179 Site Investigators, 2 Lead Investigators, and 2 data managers). The Registry is collecting baseline and follow-up data using 3,769 fields organized into 23 instruments, which include demographics, history, symptoms, trigger/risk factors, therapies, and healthcare information access for USAIDs patients., Conclusions: The development of the AIDA International Registry for USAIDs patients will facilitate the online collection of real standardized data, connecting a worldwide group of researchers: the Registry constitutes an international multicentre observational groundwork aimed at increasing the patient cohort of USAIDs in order to improve our knowledge of this peculiar cluster of autoinflammatory diseases. NCT05200715 available at https://clinicaltrials.gov/., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Della Casa, Vitale, Lopalco, Ruscitti, Ciccia, Emmi, Cattalini, Wiesik-Szewczyk, Maggio, Ogunjimi, Sfikakis, Tufan, Al-Mayouf, Del Giudice, Aragona, La Torre, Sota, Colella, Di Cola, Iacono, Mattioli, Jahnz-Rózyk, Joos, Laskari, Gaggiano, Abbruzzese, Cipriani, Rozza, AlSaleem, Yildirim, Tarsia, Ragab, Ricci, Cardinale, Korzeniowska, Frassi, Caggiano, Saad, Pereira, Berlengiero, Gentileschi, Guerriero, Giani, Gelardi, Iannone, Giardini, Almaghlouth, Kardas, Ait-Idir, Frediani, Balistreri, Fabiani, Rigante and Cantarini.)

COVID-19 lockdown brought to a drastic reduction of anthropic impacts on the environment worldwide, including the marine-coastal system. Earth-Observation (EO) data have the potential to monitor and diagnose the effects of the lockdown in terms of water quality. Here we connect the dots among some coastal environmental changes that occurred during the Italian COVID-19 lockdown by using EO data, also seeking to assess connectivity between inland and marine systems. We present a holistic analysis of spatial and temporal variability of environmental parameters in the North Adriatic Sea, Mediterranean basin, exploiting the synergy of different satellite sensors, as well as hydrologic data from in situ observations. Our analysis indicates a favourable interplay of environmental variability that resulted in negative anomalies of Chlorophyll-a concentration, with respect to the climatologic values. Peculiar meteo-oceanographic and hydrological conditions made hard to disentangle potential anthropogenic effects. However, a multi-year hierarchical cluster analysis of riverine remote sensing reflectances groups together the optical properties of inland waters during the lockdown. This emergent cluster highlights the possibility of a second-order, anthropogenic effect that, superimposed to the (first-order) environmental natural causes, may have enhanced water quality during the lockdown., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: Aim of this paper is to present the design, construction, and modalities of dissemination of the AutoInflammatory Disease Alliance (AIDA) International Registry for patients with systemic juvenile idiopathic arthritis (sJIA) and adult-onset Still's disease (AOSD), which are the pediatric and adult forms of the same autoinflammatory disorder., Methods: This Registry is a clinical, physician-driven, population- and electronic-based instrument implemented for the retrospective and prospective collection of real-world data. The collection of data is based on the Research Electronic Data Capture (REDCap) tool and is intended to obtain evidence drawn from routine patients' management. The collection of standardized data is thought to bring knowledge about real-life clinical research and potentially communicate with other existing and future Registries dedicated to Still's disease. Moreover, it has been conceived to be flexible enough to easily change according to future scientific acquisitions., Results: Starting from June 30th to February 7th, 2022, 110 Centers from 23 Countries in 4 continents have been involved. Fifty-four of these have already obtained the approval from their local Ethics Committees. Currently, the platform counts 290 users (111 Principal Investigators, 175 Site Investigators, 2 Lead Investigators, and 2 data managers). The Registry collects baseline and follow-up data using 4449 fields organized into 14 instruments, including patient's demographics, history, clinical manifestations and symptoms, trigger/risk factors, therapies and healthcare access., Conclusions: This international Registry for patients with Still's disease will allow a robust clinical research through collection of standardized data, international consultation, dissemination of knowledge, and implementation of observational studies based on wide cohorts of patients followed-up for very long periods. Solid evidence drawn from "real-life" data represents the ultimate goal of this Registry, which has been implemented to significantly improve the overall management of patients with Still's disease. NCT05200715 available at https://clinicaltrials.gov/., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Vitale, Della Casa, Lopalco, Pereira, Ruscitti, Giacomelli, Ragab, La Torre, Bartoloni, Del Giudice, Lomater, Emmi, Govoni, Maggio, Maier, Makowska, Ogunjimi, Sfikakis, Sfriso, Gaggiano, Iannone, Dagostin, Di Cola, Navarini, Ahmed Mahmoud, Cardinale, Riccucci, Paroli, Marucco, Mattioli, Sota, Abbruzzese, Antonelli, Cipriani, Tufan, Fabiani, Ramadan, Cattalini, Kardas, Sebastiani, Giardini, Hernández-Rodríguez, Mastrorilli, Więsik-Szewczyk, Frassi, Caggiano, Telesca, Giordano, Guadalupi, Giani, Renieri, Colella, Cataldi, Gentile, Fabbiani, Al-Maghlouth, Frediani, Balistreri, Rigante and Cantarini.)

Introduction: This article points out the design, methods, development and deployment of the international registry promoted by the AutoInflammatory Disease Alliance (AIDA) Network with the aim to define and assess paediatric and adult patients with immune-mediated scleritis., Methods: This registry collects both retrospective and prospective real-world data from patients with non-infectious scleritis through the Research Electronic Data Capture (REDCap) tool and aims to promote knowledge and real-life evidence from patients enrolled worldwide; the registry also allows the collection of standardised data, ensuring the highest levels of security and anonymity of patients' data and flexibility to change according to scientific acquisitions over time. The communication with other similar registries has been also ensured in order to pursue the sustainability of the project with respect to the adaptation of collected data to the most diverse research projects., Results: Since the launch of the registry, 99 centres have been involved from 20 countries and four continents. Forty-eight of the centres have already obtained a formal approval from their local ethics committees. At present, the platform counts 259 users (95 principal investigators, 160 site investigators, 2 lead investigators, and 2 data managers); the platform collects baseline and follow-up data using 3683 fields organised into 13 instruments, including patient's demographics, history, symptoms, trigger or risk factors, therapies and healthcare utilization., Conclusions: The development of the AIDA International Registry for patients with non-infectious scleritis will allow solid research on this rare condition. Real-world evidence resulting from standardised real-life data will lead to the optimisation of routine clinical and therapeutic management, which are currently limited by the rarity of this ocular inflammatory condition., (© 2022. The Author(s).)

In this study we analysed total mercury (THg) levels in European hake (Merluccius merluccius) - an ecologically and commercially important species throughout the Mediterranean - caught in the northern and central Adriatic Sea. To the best of our knowledge, this is the first study evaluating THg levels in hake fillets in relation to ecological (season) and biological (body size, sex, sexual maturity, lipid content) parameters. THg levels in muscle showed no sex-related differences; in contrast, significant season-related differences were found in females, with higher levels in spring-summer compared with autumn-winter. No season-related differences were seen in males. A significant sex effect was found for body size and sexual maturity. Females showed a correlation between THg level and length, THg being significantly higher in mature compared with immature specimens. No significant sex effect was found for muscle lipid content, because a correlation between THg concentration and tissue lipids was found in both sexes. Since the mean THg concentration found in M. merluccius fillets (0.64 ± 0.29 mg kg -1 dry weight; range, 0.20-1.53) was consistently under the level set by EU regulations, this study demonstrates that European hake caught in the northern and central Adriatic is safe for human consumption., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Several cardiovascular (CV) risk algorithms are available to predict CV events in the general population. However, their performance in patients with rheumatoid arthritis (RA) might differ from the general population. This cross-sectional multicentre study aimed to estimate the 10-year CV risk using two different algorithms in a large RA cohort and in patients with osteoarthritis (OA)., Methods: In a consecutive series of RA patients and matched OA controls without prior CV events, clinical and serologic data and traditional CV risk factors were recorded. The 10-year CV risk was assessed with the Systematic COronary Risk Evaluation (SCORE) and the "Progetto Cuore" algorithms., Results: 1,467 RA patients and 342 OA subjects were included. RA patients were more frequently diabetic (9.9% vs 6.4%; p=0.04) and smokers (20.4% vs 12.5%; p=0.002) but had lower prevalence of obesity (15% vs 21%; p=0.003). Dyslipidaemia was more prevalent in OA (32.5% vs 21.7%; p<0.0001). The 10-year estimated CV risk was 1.6% (95%CI 1.3-1.9) in RA and 1.4% (95%CI 1.3-1.6) in OA (p=0.002) according to SCORE and 6.5% (95%CI 6.1-6.9) in RA and 4.4% (95%CI 3.9-5.1) in OA (p<0.001) according to "Progetto Cuore". Regardless of the score used, RA patients had a 3- to-4-fold increased 10-year risk of CV events compared to OA subjects., Conclusion: RA patients have a significantly higher 10-year risk of CV events than OA subjects. In addition to effective disease control and joint damage prevention, specific protective measures targeting modifiable traditional CV risk factors should be implemented in RA., (Copyright © 2021. Published by Elsevier B.V.)