Showing papers by "University of Cagliari published in 2021"

EAACI Biologicals Guidelines—Recommendations for severe asthma

Abstract: Severe asthma imposes a significant burden on patients, families and healthcare systems. Management is difficult, due to disease heterogeneity, co-morbidities, complexity in care pathways and differences between national or regional healthcare systems. Better understanding of the mechanisms has enabled a stratified approach to the management of severe asthma, supporting the use of targeted treatments with biologicals. However, there are still many issues that require further clarification. These include selection of a certain biological (as they all target overlapping disease phenotypes), the definition of response, strategies to enhance the responder rate, the duration of treatment and its regimen (in the clinic or home-based) and its cost-effectiveness. The EAACI Guidelines on the use of biologicals in severe asthma follow the GRADE approach in formulating recommendations for each biological and each outcome. In addition, a management algorithm for the use of biologicals in the clinic is proposed, together with future approaches and research priorities.

Effect of SARS-CoV-2 mRNA Vaccination in MS Patients Treated With Disease Modifying Therapies

Abstract: Background: In patients with Multiple Sclerosis (pwMS) disease-modifying therapies (DMTs) are known to affect immune response to antigens and possibly to SARS-CoV2 vaccine. Therefore, post-vaccination serological assessments are needed to evaluate the effect of the vaccine on SARS-CoV-2 antibody response. Methods: We designed a prospective multicenter cohort study enrolling pwMS who were scheduled for SARS-Cov-2 vaccination with mRNA vaccines (BNT162b2, Pfizer/BioNTech, Inc or mRNA-1273, Moderna Tx, Inc). A blood collection for the measure of SARS-CoV-2 antibody before the first vaccine dose and 4 weeks after the second dose was planned, with a centralized serological assessment (electrochemiluminescence immunoassay, ECLIA, Roche Diagnostics). Findings: 780 pwMS (76% BNT162b2 and 24% mRNA-1273) had pre- and 4-week post-vaccination blood assessments. 87 (11·2%) were untreated, 154 (19·7%) on ocrelizumab, 25 (3·2%) on rituximab, 85 (10·9%) on fingolimod, 25 (3·2%) on cladribine and 404 (51·7%) on other DMTs. 677 patients (86·8%) had detectable post-vaccination SARS-CoV-2 antibodies. At multivariate analysis, the antibody levels of patients on ocrelizumab (178-fold decrease, p<0·001), fingolimod (26-fold decrease, p<0·001) and rituximab (17-fold decrease, p<0·001) were significantly reduced as compared to untreated patients. mRNA-1273 vaccine resulted in a systematically 3·5-fold higher antibody level than the BNT162b2 vaccine (p<0·001). Interpretation: In pwMS, therapy with anti-CD20 and fingolimod led to a reduced humoral response to SARS-CoV-2 vaccines. As mRNA-1273 elicits 3·5-higher antibody titers than BNT162b2, this vaccine may be preferentially considered for patients under anti-CD20 or fingolimod. Since it is still unknown the role of T-cells vaccine response, further information is required about the role of cellular immunity triggered by vaccination to better define the most appropriate strategy to vaccinate pwMS under specific DMTs. Funding Information: FISM [2021/Special-Multi/001]; the Italian Ministry of Health grant ‘Progetto Z844A 5x1000’. Declaration of Interests: MPS reports grants from Roche, during the conduct of the study; personal fees from Biogen, Merck, Roche, Sanofi, personal fees from Novartis, Medday, Geneuro, Celgene, Mylan, outside the submitted work; MI reports consulting fees from Roche, Merck-Serono, Novartis, Sanofi-Genzyme, Biogen; AL has received personal compensation from Novartis, Sanofi Genzyme, Biogen, Merck, and Roche for public speaking and advisory boards. AL received funding for research by Fondazione Italiana Sclerosi Multipla, the Italian Ministry of Health, and the Italian Ministry of University; CC reports personal fees from Novartis, personal fees from Biogen Idec, personal fees from Almirall, personal fees from Merck Serono, outside the submitted work; DL reports consulting fees Roche, Biogen, Teva, Mylan, Sanofi-Genzyme, fess for advisory boards from Bristol-Celgene, Merck, Novartis, JF reports consulting fees fromSanofi, Biogen, Admirall; ADS reports personal consulting fees from Biogen, Novartis, Genzyme; MS reports research support and personal consulting fees from Merk, Sanofi, Novartis, Biogen, Roche; AU has received personal compensation from Novartis, Biogen, Merck, Roche and Sanofi Genzyme for public speaking and advisory boards. AU received funding for research by Fondazione Italiana Sclerosi Multipla, the Italian Ministry of Health and the European Community. IS, LC, CL, GDR, CS, IG, TT, GP, PG, GPB, AM, MLS, MC, ES, MTF, LP, MU, FM, GC, RI, GL, AMR, FC, SC, MAB, DF, have nothing to dislcose. Ethics Approval Statement: The study is done in compliance with the principles of the Declaration of Helsinki. The protocol is approved by the regional (CER Liguria: 5/2021 - DB id 11169- 21/01/2021) and the centralized national ethical committee AIFA/Spallanzani (Parere n 351, 2020/21). Written informed consent was obtained from all participants before starting any study procedures.

Psychometric evaluation of three versions of the Italian Perceived Stress Scale

Abstract: Stress is measured through the use of tools that allow detection in large samples, and the search effort is directed to validating tools to ensure that they are predictable. The Perceived Stress Scale (PSS) is one of the three most commonly used tools to measure perceived stress. The three versions of the PSS have never been evaluated for use with Italian workers. Therefore, the overall aims of this study are to translate and clarify the psychometric properties of the Italian versions, known as IPSS-14, IPSS-10, and IPSS-4 for use with Italian precarious workers. A sample of 649 precarious workers (mean age = 39.6, SD = 10.1) participated in this study, which consisted of 393 males and 256 females. The sample was randomly split into two for exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) to investigate the PSS structure. The two-factor models for the three Italian versions of PSS showed a better fit than the single-factor models. The reliability was high for IPSS-14 and IPSS-10. The results suggest that the psychometric properties of IPSS-10 are greater than those of IPSS-14 and IPSS-4. Therefore, IPSS-10 can be reliably used to measure perceived stress and is a suitable tool to incorporate the support/intervention programs for Italian precarious workers.

Common-red-signal analysis with 24-yr high-precision timing of the European Pulsar Timing Array: Inferences in the stochastic gravitational-wave background search

Abstract: We present results from the search for a stochastic gravitational-wave background (GWB) as predicted by the theory of General Relativity using six radio millisecond pulsars from the Data Release 2 (DR2) of the European Pulsar Timing Array (EPTA) covering a timespan up to 24 years. A GWB manifests itself as a long-term low-frequency stochastic signal common to all pulsars, a common red signal (CRS), with the characteristic Hellings-Downs (HD) spatial correlation. Our analysis is performed with two independent pipelines, \eprise and \tn+\ftwo, which produce consistent results. A search for a CRS with simultaneous estimation of its spatial correlations yields spectral properties compatible with theoretical GWB predictions, but does not result in the required measurement of the HD correlation, as required for GWB detection. Further Bayesian model comparison between different types of CRSs, including a GWB, finds the most favoured model to be the common uncorrelated red noise described by a power-law with $A = 5.13_{-2.73}^{+4.20} \times 10^{-15}$ and $\gamma = 3.78_{-0.59}^{+0.69}$ (95% credible regions). Fixing the spectral index to $\gamma=13/3$ as expected from the GWB by circular, inspiralling supermassive black-hole binaries results in an amplitude of $A =2.95_{-0.72}^{+0.89} \times 10^{-15}$. We implement three different models, BAYESEPHEM, LINIMOSS and EPHEMGP, to address possible Solar-system ephemeris (SSE) systematics and conclude that our results may only marginally depend on these effects. This work builds on the methods and models from the studies on the EPTA DR1. We show that under the same analysis framework the results remain consistent after the data set extension.

Cancer cachexia in adult patients: ESMO Clinical Practice Guidelines ☆

Abstract: • This ESMO Clinical Practice Guideline provides key recommendations for managing cancer-related cachexia. • It covers screening, assessment and multimodal management of cancer cachexia. • All recommendations were compiled by a multidisciplinary group of experts. • Recommendations are based on available scientific data and the author's expert opinion.

Gut microbiota markers associated with obesity and overweight in Italian adults.

Abstract: In the present study, we characterized the distinctive signatures of the gut microbiota (GM) from overweight/obese patients (OB), and normal-weight controls (NW), both of Sardinian origin. Fecal bacterial composition of 46 OB patients (BMI = 36.6 ± 6.0; F/M = 40/6) was analyzed and compared to that of 46 NW subjects (BMI = 21.6 ± 2.1; F/M = 41/5), matched for sex, age and smoking status, by using 16S rRNA gene sequencing on MiSeq Illumina platform. The gut microbial community of OB patients exhibited a significant decrease in the relative abundance of several Bacteroidetes taxa (i.e. Flavobacteriaceae, Porphyromonadaceae, Sphingobacteriaceae, Flavobacterium, Rikenella spp., Pedobacter spp., Parabacteroides spp., Bacteroides spp.) when compared to NW; instead, several Firmicutes taxa were significantly increased in the same subjects (Lachnospiraceae, Gemellaceae, Paenibacillaceae, Streptococcaceae, Thermicanaceae, Gemella, Mitsuokella, Streptococcus, Acidaminococcus spp., Eubacterium spp., Ruminococcus spp., Megamonas spp., Streptococcus, Thermicanus, Megasphaera spp. and Veillonella spp.). Correlation analysis indicated that body fatness and waist circumference negatively correlated with Bacteroidetes taxa, while Firmicutes taxa positively correlated with body fat and negatively with muscle mass and/or physical activity level. Furthermore, the relative abundance of several bacterial taxa belonging to Enterobacteriaceae family, known to exhibit endotoxic activity, was increased in the OB group compared to NW. The results extend our knowledge on the GM profiles in Italian OB, identifying novel taxa linking obesity and intestine.

Electrolyte-gated transistors for enhanced performance bioelectronics

Abstract: Electrolyte-gated transistors (EGTs), capable of transducing biological and biochemical inputs into amplified electronic signals and stably operating in aqueous environments, have emerged as fundamental building blocks in bioelectronics. In this Primer, the different EGT architectures are described with the fundamental mechanisms underpinning their functional operation, providing insight into key experiments including necessary data analysis and validation. Several organic and inorganic materials used in the EGT structures and the different fabrication approaches for an optimal experimental design are presented and compared. The functional bio-layers and/or biosystems integrated into or interfaced to EGTs, including self-organization and self-assembly strategies, are reviewed. Relevant and promising applications are discussed, including two-dimensional and three-dimensional cell monitoring, ultra-sensitive biosensors, electrophysiology, synaptic and neuromorphic bio-interfaces, prosthetics and robotics. Advantages, limitations and possible optimizations are also surveyed. Finally, current issues and future directions for further developments and applications are discussed. Electrolyte-gated transistors (EGTs) are fundamental building blocks of bioelectronics, which transduce biological inputs to electrical signals. This Primer examines the different architectures of EGTs, their mechanism of operation and practical considerations related to their wide range of applications.

Common variants in Alzheimer's disease and risk stratification by polygenic risk scores

Abstract: Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease.

Multidimensional Impact of Mediterranean Diet on IBD Patients.

Abstract: BACKGROUND & AIMS Malnutrition with the accumulation of fat tissue and nonalcoholic fatty liver disease (NAFLD) are conditions associated with inflammatory bowel disease (IBD). Visceral fat and NAFLD-related liver dysfunction can both worsen intestinal inflammation. Because the Mediterranean diet (Md) has been shown to ameliorate both obesity and NAFLD, the aim of this study was to analyze the impact of Md on the nutritional state, liver steatosis, clinical disease activity, and quality of life (QoL) in IBD patients. METHODS Patients with IBD, both Crohn's disease (CD) and ulcerative colitis (UC), followed Md for 6 months. Their body mass index (BMI), body tissue composition, liver steatosis and function, serum lipid profile, clinical disease activity, and inflammatory biomarkers (C-reactive protein and fecal calprotectin) were collected at baseline (T0) and compared with those obtained after 6 months (T180) to evaluate the impact of Md. RESULTS One hundred forty-two IBD patients, 84 UC and 58 CD, followed Md for 6 months. At T180, diet-adherent CD and UC improved BMI (UC -0.42, P = 0.002; CD -0.48, P = 0.032) and waist circumference (UC -1.25 cm, P = 0.037; CD -1.37 cm, P = 0.041). Additionally, the number of patients affected by liver steatosis of any grade was significantly reduced in both groups (UC T0 31 of 84 [36.9%] vs T180 18 of 84 [21.4%], P = 0.0016; CD T0 27 of 58 [46.6%] vs T180 18 of 58 [31.0%], P < 0.001) after dietary intervention. Finally, after 6 months of the diet, fewer UC and CD patients with stable therapy had active disease (UC T0 14 of 59 [23.7%] vs T180 4 of 59 [6.8%], P = 0.004; CD T0 9 of 51 [17.6%] vs T180 2 of 51 [3.0%], P = 0.011) and elevated inflammatory biomarkers. Mediterranean diet improved QoL in both UC and CD, but neither serum lipid profile nor liver function were modified by the diet. CONCLUSIONS A significant reduction of malnutrition-related parameters and liver steatosis was observed in both CD and UC patients after short-term dietary intervention based on the adoption of Md, and this was associated with a spontaneous improvement of disease activity and inflammatory markers.

AT-527, a Double Prodrug of a Guanosine Nucleotide Analog, Is a Potent Inhibitor of SARS-CoV-2 In Vitro and a Promising Oral Antiviral for Treatment of COVID-19.

Abstract: The impact of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of COVID-19, is global and unprecedented. Although remdesivir has recently been approved by the FDA to treat SARS-CoV-2 infection, no oral antiviral is available for outpatient treatment. AT-527, an orally administered double prodrug of a guanosine nucleotide analog, was previously shown to be highly efficacious and well tolerated in hepatitis C virus (HCV)-infected subjects. Here, we report the potent in vitro activity of AT-511, the free base of AT-527, against several coronaviruses, including SARS-CoV-2. In normal human airway epithelial cells, the concentration of AT-511 required to inhibit replication of SARS-CoV-2 by 90% (EC90) was 0.47 µM, very similar to its EC90 against human coronavirus (HCoV)-229E, HCoV-OC43, and SARS-CoV in Huh-7 cells. Little to no cytotoxicity was observed for AT-511 at concentrations up to 100 µM. Substantial levels of the active triphosphate metabolite AT-9010 were formed in normal human bronchial and nasal epithelial cells incubated with 10 µM AT-511 (698 ± 15 and 236 ± 14 µM, respectively), with a half-life of at least 38 h. Results from steady-state pharmacokinetic and tissue distribution studies of nonhuman primates administered oral doses of AT-527, as well as pharmacokinetic data from subjects given daily oral doses of AT-527, predict that twice daily oral doses of 550 mg AT-527 will produce AT-9010 trough concentrations in human lung that exceed the EC90 observed for the prodrug against SARS-CoV-2 replication. This suggests that AT-527 may be an effective treatment option for COVID-19.

EAACI statement on the diagnosis, management and prevention of severe allergic reactions to COVID-19 vaccines.

Abstract: The first approved COVID-19 vaccines include Pfizer/BioNTech BNT162B2, Moderna mRNA-1273 and AstraZeneca recombinant adenoviral ChAdOx1-S. Soon after approval, severe allergic reactions to the mRNA-based vaccines that resolved after treatment were reported. Regulatory agencies from the European Union, Unites States and the United Kingdom agree that vaccinations are contraindicated only when there is an allergy to one of the vaccine components or if there was a severe allergic reaction to the first dose. This position paper of the European Academy of Allergy and Clinical Immunology (EAACI) agrees with these recommendations and clarifies that there is no contraindication to administer these vaccines to allergic patients who do not have a history of an allergic reaction to any of the vaccine components. Importantly, as is the case for any medication, anaphylaxis may occur after vaccination in the absence of a history of allergic disease. Therefore, we provide a simplified algorithm of prevention, diagnosis and treatment of severe allergic reactions and a list of recommended medications and equipment for vaccine centres. We also describe potentially allergenic/immunogenic components of the approved vaccines and propose a workup to identify the responsible allergen. Close collaboration between academia, regulatory agencies and vaccine producers will facilitate approaches for patients at risks, such as incremental dosing of the second injection or desensitisation. Finally, we identify unmet research needs and propose a concerted international roadmap towards precision diagnosis and management to minimise the risk of allergic reactions to COVID-19 vaccines and to facilitate their broader and safer use.

Cytosolic delivery of nucleic acids: The case of ionizable lipid nanoparticles.

Abstract: Ionizable lipid nanoparticles (LNPs) are the most clinically advanced nano-delivery system for therapeutic nucleic acids. The great effort put in the development of ionizable lipids with increased in vivo potency brought LNPs from the laboratory benches to the FDA approval of patisiran in 2018 and the ongoing clinical trials for mRNA-based vaccines against SARS-CoV-2. Despite these success stories, several challenges remain in RNA delivery, including what is known as "endosomal escape." Reaching the cytosol is mandatory for unleashing the therapeutic activity of RNA molecules, as their accumulation in other intracellular compartments would simply result in efficacy loss. In LNPs, the ability of ionizable lipids to form destabilizing non-bilayer structures at acidic pH is recognized as the key for endosomal escape and RNA cytosolic delivery. This is motivating a surge in studies aiming at designing novel ionizable lipids with improved biodegradation and safety profiles. In this work, we describe the journey of RNA-loaded LNPs across multiple intracellular barriers, from the extracellular space to the cytosol. In silico molecular dynamics modeling, in vitro high-resolution microscopy analyses, and in vivo imaging data are systematically reviewed to distill out the regulating mechanisms underlying the endosomal escape of RNA. Finally, a comparison with strategies employed by enveloped viruses to deliver their genetic material into cells is also presented. The combination of a multidisciplinary analytical toolkit for endosomal escape quantification and a nature-inspired design could foster the development of future LNPs with improved cytosolic delivery of nucleic acids.

Biomarkers of conversion to α-synucleinopathy in isolated rapid-eye-movement sleep behaviour disorder

Abstract: Patients with isolated rapid-eye-movement sleep behaviour disorder (RBD) are commonly regarded as being in the early stages of a progressive neurodegenerative disease involving α-synuclein pathology, such as Parkinson's disease, dementia with Lewy bodies, or multiple system atrophy. Abnormal α-synuclein deposition occurs early in the neurodegenerative process across the central and peripheral nervous systems and might precede the appearance of motor symptoms and cognitive decline by several decades. These findings provide the rationale to develop reliable biomarkers that can better predict conversion to clinically manifest α-synucleinopathies. In addition, biomarkers of disease progression will be essential to monitor treatment response once disease-modifying therapies become available, and biomarkers of disease subtype will be essential to enable prediction of which subtype of α-synucleinopathy patients with isolated RBD might develop.

Quercetin and its derivates as antiviral potentials: A comprehensive review.

Abstract: Quercetin, widely distributed in fruits and vegetables, is a flavonoid known for its antioxidant, antiviral, antimicrobial, and antiinflammatory properties. Several studies highlight the potential use of quercetin as an antiviral, due to its ability to inhibit the initial stages of virus infection, to be able to interact with proteases important for viral replication, and to reduce inflammation caused by infection. Quercetin could also be useful in combination with other drugs to potentially enhance the effects or synergistically interact with them, in order to reduce their side effects and related toxicity. Since there is no comprehensive compilation about antiviral activities of quercetin and derivates, the aim of this review is providing a summary of their antiviral activities on a set of human viral infections along with mechanisms of action. Thus, the following family of viruses are examined: Flaviviridae, Herpesviridae, Orthomyxoviridae, Coronaviridae, Hepadnaviridae, Retroviridae, Picornaviridae, Pneumoviridae, and Filoviridae.

Effects of COVID-19 lockdown on eating disorders and obesity: A systematic review and meta-analysis.

Abstract: OBJECTIVE: This systematic review and meta-analysis aimed to examine: the pooled prevalence of symptomatic behaviours and mental health deterioration amongst individuals with eating disorders (EDs) and obesity during the COVID-19 confinement. Moreover, we examined changes in EDs and distress before and during the confinement, and the association between psychosocial factors and EDs symptoms. METHOD: A systematic search was carried out in biomedical databases from January 2020 to January 2021. Both cross-sectional and longitudinal studies that used quantitative measures of ED symptoms and psychological distress during and after the COVID-19 confinement were included. RESULTS: A total of 26 studies met inclusion criteria (n = 3399, 85.7% female). The pooled prevalence of symptomatic deterioration in EDs was 65% (95% CI[48,81], k = 10). The pooled prevalence of increased weight in obesity was 52% (95% CI[25,78], k = 4). More than half of the participants experienced depression and anxiety. Moreover, at least 75% of the individuals with EDs reported shape and eating concerns, and increased thinking about exercising. However, the pooled analyses of longitudinal studies showed no significant differences from pre-pandemic levels to the first lockdown phase in Body Mass Index and ED symptoms, whereas only few studies suggested increased distress, particularly among individuals with anorexia nervosa. CONCLUSIONS: The majority of individuals with EDs and obesity reported symptomatic worsening during the lockdown. However, further longitudinal studies are needed to identify vulnerable groups, as well as the long-term consequences of COVID-19.

COVID-19 pandemic: Practical considerations on the organization of an allergy clinic - an EAACI/ARIA Position Paper.

Abstract: Background The Coronavirus disease 2019 (COVID-19) has evolved as a pandemic infectious disease transmitted by the severe acute respiratory syndrome coronavirus (SARS-CoV-)2. Allergists and other health care providers (HCPs) in the field of allergies and associated airway diseases are in the front line, taking care of patients potentially infected with SARS-CoV-2. Hence, strategies and practices to minimize risks of infection for both HCPs and treated patients have to be developed and followed by allergy clinics. Method The scientific information on COVID-19 was analyzed by a literature search in Medline, Pubmed, national and international guidelines from the European Academy of Allergy and Clinical Immunology (EAACI), the Cochrane Library and the Internet. Results Based on diagnostic and treatment standards developed by EAACI, on international information regarding COVID-19, on guidelines of the World Health Organization (WHO) and other international organizations as well as on previous experience, a panel of experts including clinicians, psychologists, IT experts and basic scientists along with EAACI and the "Allergic Rhinitis and its Impact on Asthma (ARIA)" inititiative have developed recommendations for the optimal management of allergy clinics during the current COVID-19 pandemic. These recommendations are grouped into nine sections on different relevant aspects for the care of patients with allergies. Conclusions This international Position Paper provides recommendations on operational plans and procedures to maintain high standards in the daily clinical care of allergic patients whilst ensuring necessary safety in the current COVID-19 pandemic.

Evidence for a 'window of opportunity' in hidradenitis suppurativa treated with adalimumab: a retrospective, real-life multicentre cohort study.

Abstract: BACKGROUND The anti-tumour necrosis factor (TNF)-α adalimumab is the only licenced biologic for moderate-to-severe hidradenitis suppurativa (HS). No predictors of response have been identified so far. OBJECTIVES To identify clinical parameters predicting response to adalimumab and confirm its efficacy/safety. METHODS The data of 389 patients with HS treated with adalimumab in 21 Italian centres were reviewed. Sex, age at onset/diagnosis/baseline, body mass index, smoking, phenotype, previous treatments, concomitant antibiotics and 'therapeutic delay', defined as the time from HS onset to adalimumab initiation, were assessed. Response to adalimumab and its impact on quality of life (QoL) were evaluated using the Hidradenitis Suppurativa Clinical Response (HiSCR) and the Dermatology Life Quality Index (DLQI) or the Visual Analogue Scale for pain (VAS pain), respectively. Logistic regression analysis was performed. RESULTS The therapeutic delay correlated to lack of response to adalimumab at week 16 [odds ratio (OR) 1·92 for therapeutic delay > 10 years; 95% confidence interval (CI) 1·28-2·89; P = 0·0016). HiSCR was achieved in 43·7% and 53·9% patients at week 16 and 52, respectively. Significant reductions in both DLQI and VAS pain were found between week 16 vs. baseline (P < 0·0001 for both) and week 52 vs. baseline (P < 0·0001 for both). Previous immunosuppressants inversely correlated to HiSCR at week 52 (OR = 1·74, 95% CI 1·04-2·91, P = 0·0342). CONCLUSIONS Inverse correlation between therapeutic delay and clinical response was found, supporting early adalimumab use and providing evidence for a 'window of opportunity' in HS treatment. Adalimumab efficacy and safety were confirmed, along with patients' QoL improvement. Immunosuppressants could negatively influence the response to adalimumab inducing a switch to non-TNF-α-driven pathways.

Connecting user and item perspectives in popularity debiasing for collaborative recommendation

Abstract: Recommender systems learn from historical users’ feedback that is often non-uniformly distributed across items. As a consequence, these systems may end up suggesting popular items more than niche items progressively, even when the latter would be of interest for users. This can hamper several core qualities of the recommended lists (e.g., novelty, coverage, diversity), impacting on the future success of the underlying platform itself. In this paper, we formalize two novel metrics that quantify how much a recommender system equally treats items along the popularity tail. The first one encourages equal probability of being recommended across items, while the second one encourages true positive rates for items to be equal. We characterize the recommendations of representative algorithms by means of the proposed metrics, and we show that the item probability of being recommended and the item true positive rate are biased against the item popularity. To promote a more equal treatment of items along the popularity tail, we propose an in-processing approach aimed at minimizing the biased correlation between user-item relevance and item popularity. Extensive experiments show that, with small losses in accuracy, our popularity-mitigation approach leads to important gains in beyond-accuracy recommendation quality.

Advances in applied supramolecular technologies

Abstract: Supramolecular chemistry is a comparatively young field that to date has mainly been focused on building a foundation of fundamental understanding. With much progress in this area, researchers are seeking to apply this knowledge to the development of commercially viable products. In this review we seek to outline historical and recent developments within the field of supramolecular chemistry that have made the transition from laboratory to market, and to bring to light those technologies that we believe have commercial potential. In doing so we hope we may illuminate pathways to market for research currently being conducted.

Factors Associated With Real-Life Functioning in Persons With Schizophrenia in a 4-Year Follow-up Study of the Italian Network for Research on Psychoses.

Abstract: Importance The goal of schizophrenia treatment has shifted from symptom reduction and relapse prevention to functional recovery; however, recovery rates remain low. Prospective identification of variables associated with real-life functioning domains is essential for personalized and integrated treatment programs. Objective To assess whether baseline illness-related variables, personal resources, and context-related factors are associated with work skills, interpersonal relationships, and everyday life skills at 4-year follow-up. Design, Setting, and Participants This multicenter prospective cohort study was conducted across 24 Italian university psychiatric clinics or mental health departments in which 921 patients enrolled in a cross-sectional study were contacted after 4 years for reassessment. Recruitment of community-dwelling, clinically stable persons with schizophrenia was conducted from March 2016 to December 2017, and data were analyzed from January to May 2020. Main Outcomes and Measures Psychopathology, social and nonsocial cognition, functional capacity, personal resources, and context-related factors were assessed, with real-life functioning as the main outcome. Structural equation modeling, multiple regression analyses, and latent change score modeling were used to identify variables that were associated with real-life functioning domains at follow-up and with changes from baseline in these domains. Results In total, 618 participants (427 male [69.1%]; mean [SD] age, 45.1 [10.5] years) were included. Five baseline variables were directly associated with real-life functioning at follow-up: neurocognition with everyday life (β, 0.274; 95% CI, 0.207-0.341;P Conclusions and Relevance Findings of this large prospective study suggested that baseline variables associated with functional outcome at follow-up included domains not routinely assessed and targeted by intervention programs in community mental health services. The key roles of social and nonsocial cognition and of baseline everyday life skills support the adoption in routine mental health care of cognitive training programs combined with personalized psychosocial interventions aimed to promote independent living.

Ensuring transparency and traceability of food local products: A blockchain application to a Smart Tourism Region

Abstract: This article proposes a blockchain oriented platform to guarantee the origin and provenance of food items in a Smart Tourism Region context. Local food and beverage, in fact, can become a good combination to attract tourist and to promote the area provided that their provenance is clearly certified. We designed and developed a blockchain‐based system to manage an agri‐food supply chain for tracking food items. By using smart contracts the platform guarantees transparency, efficiency and trustworthiness. Our system is particularly suitable to manage cold chain since the system interfaces with IoT network devices providing detailed information about data monitoring food such as storage temperature, environment humidity, and GPS data. All involved actors can share data and information in a more efficient, transparent, and tamper proof way than traditional systems. The final consumer can access with transparency to all the agri‐food chain of the purchased product and verify provenance by retrieving all detailed information registered in the blockchain public ledger. The proposed system has been designed according to the ABCDE method, an agile development process recently conceived, to obtain a higher software quality to design a general blockchain system by means software engineering practices. A real case study applied to local products from Sardinia, Italy, is proposed at the end of the article.

Real-life experience on effectiveness and safety of dupilumab in adult patients with moderate-to-severe atopic dermatitis

Abstract: Background: Dupilumab, a fully human monoclonal antibody targeting the alpha subunit of IL-4 was recently approved for the treatment of moderate-to-severe atopic dermatitis (AD) in adult patients. Objective: To assess dupilumab effectiveness and safety in adults with moderate-to-severe AD in a real-life Italian multicentre retrospective cohort. Methods: Adult moderate-to-severe AD patients, referring to 39 Italian centers, received dupilumab in the context of a national patient access program. Disease assessment was performed at baseline, after 4 and 16 weeks of treatment using Eczema-Area-and-Severity-Index (EASI) score, itch and sleep numerical-rating-score (itch-NRS, sleep-NRS) and Dermatology-Life-Quality-Index (DLQI). Results: A total of 109 (71 M/38F) patients was studied. There was a significant reduction in EASI score, itch-NRS, sleep-NRS and DLQI from baseline to week 4 and a further significant decline to week 16. EASI 50, EASI75 and EASI90 were achieved by 59.6%, 28.4% and 9.3% of patients at 4 weeks and by 87.2%, 60.6% and 32.4% of them at 16 weeks, respectively. Adverse events were experienced by 19.2% (21/109) of the patients and they were all mild in intensity, being conjunctivitis the most common side effect. Conclusions: Dupilumab significantly improved disease severity, pruritus, sleep loss and quality of life with an acceptable safety profile.

A multi-layer and multi-ensemble stock trader using deep learning and deep reinforcement learning

Abstract: The adoption of computer-aided stock trading methods is gaining popularity in recent years, mainly because of their ability to process efficiently past information through machine learning to predict future market behavior. Several approaches have been proposed to this task, with the most effective ones using fusion of a pile of classifiers decisions to predict future stock values. However, using prices information in single supervised classifiers has proven to lead to poor results, mainly because market history is not enough to be an indicative of future market behavior. In this paper, we propose to tackle this issue by proposing a multi-layer and multi-ensemble stock trader. Our method starts by pre-processing data with hundreds of deep neural networks. Then, a reward-based classifier acts as a meta-learner to maximize profit and generate stock signals through different iterations. Finally, several metalearner trading decisions are fused in order to get a more robust trading strategy, using several trading agents to take a final decision. We validate the effectiveness of the approach in a real-world trading scenario, by extensively testing it on the Standard & Poor’s 500 future market and the J.P. Morgan and Microsoft stocks. Experimental results show that the proposed method clearly outperforms all the considered baselines (which still performs very well in the analysed period), and even the conventional Buy-and-Hold strategy, which replicates the market behaviour.

Red list of threatened vascular plants in Italy

Abstract: Italy has a rich natural heritage, which is dangerously under pressure. In recent years, there is an increased awareness of the crucial role of plants in ecosystem functioning and in providing ecos...