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Paolo Cameli,1 Maria Aliani,2 Elena Altieri,3 Pietro Bracciale,4 Luisa Brussino,5 Maria Filomena Caiaffa,6 Giorgio Walter Canonica,7,8 Cristiano Caruso,9 Stefano Centanni,10 Maria D’Amato,11 Fausto De Michele,12 Stefano Del Giacco,13 Fabiano Di Marco,14 Girolamo Pelaia,15 Paola Rogliani,16,17 Micaela Romagnoli,18 Pietro Schino,19 Jan Walter Schroeder,20 Gianenrico Senna,21 Alessandra Vultaggio,22 Marco Benci,23 Silvia Boarino,24 Francesco Menzella25 1Respiratory Diseases Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy; 2UO Pneumologia e Pneumologia Riabilitativa, ICS Maugeri, IRCCS Bari, Bari, Italy; 3Reparto di Pneumologia, P.O. Garbagnate Milanese, Garbagnate Milanese (MI), Italy; 4Reparto di Pneumologia, Ospedale Ostuni, Ostuni (BR), Italy; 5Dipartimento di Scienze Mediche, Università degli Studi di Torino; SCDU Immunologia e Allergologia, AO Ordine Mauriziano Umberto I, Torino, Italy; 6Cattedra e Scuola di Allergologia e Immunologia Clinica, Dipartimento di Scienze Mediche, Università di Foggia, Foggia, Italy; 7Department of Biomedical Sciences, Humanitas University, Pieve Emanuele (MI), Italy; 8Personalized Medicine Center: Asthma and Allergology, Humanitas Research Hospital, Rozzano (MI), Italy; 9Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico A. Gemelli, IRCCS, Università Cattolica del Sacro Cuore, Roma, Italy; 10Respiratory Unit ASST Santi Paolo e Carlo, Department of Health Sciences Universita’ degli Studi di Milano, Milano, Italy; 11UOSD Malattie Respiratorie “Federico II”, Ospedale Monaldi, AO Dei Colli, Napoli, Italy; 12UOC Pneumologia e Fisiopatologia Respiratoria, AORN A. Cardarelli, Napoli, Italy; 13Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy; 14Department of Health Sciences, Università Degli Studi Di Milano, Pneumologia, ASST Papa Giovanni XXIII, Bergamo, Italy; 15Dipartimento di Scienze della Salute, Università Magna Graecia, Catanzaro, Italy; 16Division of Respiratory Medicine, University Hospital “Tor Vergata”, Roma, Italy; 17Unit of Respiratory Medicine, Department of Experimental Medicine, University of Rome “Tor Vergata”, Roma, Italy; 18UOC Pneumologia, AULSS 2 Marca Trevigiana, Treviso, Italy; 19Fisiopatologia Respiratoria, Ospedale Generale Regionale, Ente Ecclesiastico “F. Miulli”, Acquaviva delle Fonti (BA), Italy; 20Allergy and Clinical Immunology, ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy; 21Allergy Unit and Asthma Center, Verona University Hospital, Verona, Italy; 22Dipartimento di Medicina Sperimentale e Clinica, Università degli Studi di Firenze, Firenze, Italy; 23Medical Affairs R&I, AstraZeneca, Milano, Italy; 24Medical Evidence R&I, AstraZeneca, Milano, Italy; 25Pulmonology Unit, Ospedale “S. Valentino”, AULSS 2 Marca Trevigiana, Montebelluna (TV), ItalyCorrespondence: Paolo Cameli, Respiratory Diseases Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy, Email paolo.cameli@unisi.itPurpose: Severe eosinophilic asthma (SEA) patients often present overlapping inflammatory features rendering them eligible for multiple biologic therapies; switching biologic treatment is a strategy adopted to optimize asthma control when patients show partial or no response to previous biologics.Patients and Methods: ANANKE is a retrospective, multicenter Italian study (NCT04272463). Here, we outline the characteristics and long-term clinical outcomes in naïve-to-biologics and biologics-experienced patients treated with benralizumab for up to 96 weeks. Bio-experienced patients were split into omalizumab and mepolizumab subsets according to the type of biologic previously used.Results: A total of 124 (76.5%) naïve and 38 (23.5%) bio-experienced patients were evaluated at index date; 13 patients (34.2%) switched from mepolizumab, 21 patients (55.3%) switched from omalizumab, and four patients (10.5%) received both biologics. The mepolizumab subset was characterized by the longest SEA duration (median of 4.6 years), the highest prevalence of chronic rhinosinusitis with nasal polyposis (CRSwNP) (76.5%), and the greatest oral corticosteroid (OCS) daily dosage (median of 25 mg prednisone equivalent). The omalizumab group showed the highest severe annual exacerbation rate (AER) (1.70). At 96 weeks, treatment with benralizumab reduced any and severe AER by more than 87% and 94%, respectively, across all groups. Lung function was overall preserved, with major improvements observed in the mepolizumab group, which also revealed a 100% drop of the median OCS dose. Asthma Control Test (ACT) score improved in the naïve group while its increment was more variable in bio-experienced patients; among these, a marked difference was noticed between omalizumab and mepolizumab subsets (median ACT score of 23.5 and 18, respectively).Conclusion: Benralizumab promotes durable and profound clinical benefits in naïve and bio-experienced groups, indicating that a nearly complete depletion of eosinophils is highly beneficial in the control of SEA, independently of previous biologic use.Keywords: benralizumab, asthma, eosinophils, switch, long-term

Gianenrico Senna,1,2 Maria Aliani,3 Elena Altieri,4 Pietro Bracciale,5 Luisa Brussino,6 Maria Filomena Caiaffa,7 Paolo Cameli,8 Giorgio Walter Canonica,9,10 Cristiano Caruso,11 Maria D’Amato,12 Fausto De Michele,13 Stefano Del Giacco,14 Fabiano Di Marco,15 Francesco Menzella,16 Girolamo Pelaia,17 Paola Rogliani,18,19 Micaela Romagnoli,20 Pietro Schino,21 Jan Walter Schroeder,22 Alessandra Vultaggio,23 Sara Rizzoli,24 Alessandro Zullo,24 Silvia Boarino,25 Marilena Palmisano,26 Alessandra Rossi,26 Gianfranco Vitiello,26 Stefano Centanni27 1Department of Medicine, University of Verona, Verona, Italy; 2Allergy Unit and Asthma Center, Verona University Hospital, Verona, Italy; 3UO Pneumologia e Pneumologia Riabilitativa, ICS Maugeri, IRCCS Bari, Bari, Italy; 4Reparto di Pneumologia, P.O., Garbagnate Milanese, Italy; 5Reparto di Pneumologia, Ospedale Ostuni, Ostuni, BR, Italy; 6Dipartimento di Scienze Mediche, SSDDU Allergologia e Immunologia Clinica, Università degli Studi di Torino, AO Ordine Mauriziano Umberto I, Torino, Italy; 7Cattedra e Scuola di Allergologia e Immunologia Clinica, Dipartimento di Scienze Mediche, Università di Foggia, Foggia, Italy; 8Respiratory Diseases and Lung Transplantation, Department of Medical and Surgical Sciences & Neurosciences, Siena University Hospital, Siena, Italy; 9Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, MI, Italy; 10Personalized Medicine Center: Asthma and Allergology, Humanitas Research Hospital, Rozzano, MI, Italy; 11Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico A. Gemelli, IRCCS, Università Cattolica del Sacro Cuore, Roma, Italy; 12UOSD Malattie Respiratorie “Federico II”, Ospedale Monaldi, AO Dei Colli, Napoli, Italy; 13UOC Pneumologia e Fisiopatologia Respiratoria, AORN A. Cardarelli, Napoli, Italy; 14Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy; 15Department of Health Sciences, Università Degli Studi Di Milano, Pneumologia, ASST Papa Giovanni XXIII, Bergamo, Italy; 16UOC Pneumologia, Ospedale “S. Valentino”, AULSS 2 Marca Trevigiana, Montebelluna, TV, Italy; 17Dipartimento di Scienze della Salute, Università Magna Graecia, Catanzaro, Italy; 18Division of Respiratory Medicine, University Hospital “Tor Vergata”, Roma, Italy; 19Unit of Respiratory Medicine, Department of Experimental Medicine, University of Rome “Tor Vergata”, Roma, Italy; 20UOC Pneumologia, ULSS 2 Marca Trevigiana, Treviso, Italy; 21Fisiopatologia Respiratoria, Ospedale Generale Regionale, Ente Ecclesiastico “F. Miulli”, Acquaviva delle Fonti, BA, Italy; 22Allergy and Clinical Immunology, ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy; 23Dipartimento di Medicina Sperimentale e Clinica, Università degli Studi di Firenze, Firenze, Italy; 24Medineos Observational Research - An IQVIA Company, Modena, Italy; 25Medical Evidence R&I, AstraZeneca, Milano, Italy; 26Medical Affairs R&I, AstraZeneca, Milano, Italy; 27Respiratory Unit, ASST Santi Paolo e Carlo, Department of Health Sciences, Università degli Studi di Milano, Milano, ItalyCorrespondence: Marilena Palmisano, Medical Affairs R&I, AstraZeneca, Milano, Italy, Email marilena.palmisano@astrazeneca.comPurpose: Benralizumab effectively reduces severe eosinophilic asthma (SEA) exacerbations in patients with a wide range of baseline blood eosinophil count (BEC). Patients included in real-world studies are often characterized by high mean/median BEC, while patients with BEC close to 300 cells/mm3 are poorly represented. This post hoc analysis from the Italian study ANANKE aims to define the clinical features and corroborate the efficacy of benralizumab in real world in the BEC 300– 450 cells/mm3 subset of patients.Patients and Methods: Post hoc analysis of the Italian, multicenter, observational, retrospective real-life study ANANKE (NCT04272463). Baseline clinical and laboratory characteristics were collected in the 12 months prior to benralizumab treatment and presented for a BEC 300– 450 cells/mm3 subgroup of patients. Change over time of BEC, annualized exacerbation rate (AER), asthma control (ACT), lung function and oral corticosteroid (OCS) use at 16, 24 and 48 weeks after benralizumab introduction were collected.Results: A total of 164 patients were analyzed, 34 of whom with a BEC of 300– 450 cells/mm3. This subgroup was more likely to be female (64.7%), with lower rates of severe exacerbations at baseline when compared to the total population (0.69 vs 1.01). After 48 weeks of benralizumab treatment, the BEC 300– 450 subset showed similar reductions in AER (− 94.8% vs − 92.2%) and OCS use (median dose reduction of 100% in both groups), as well as improvement in ACT score (median scores 22.5 vs 22) and lung function (pre-BD FEV1: +200 mL vs +300 mL) when compared to the total population. No discontinuations for safety reasons were registered.Conclusion: At baseline, apart from lower severe exacerbation rate, the BEC 300– 450 cells/mm3 subset of patients is comparable to the total population prescribed with benralizumab. In this real-life study, benralizumab is as effective in BEC 300– 450 patients as in the total population.Keywords: severe eosinophilic asthma, blood eosinophil count, benralizumab, observational, real-world evidence, real-life

The paper presents the development and implementation of a Web-Based Vehicle Monitoring System at Mindanao State University-Lanao del Norte Agricultural College (MSU-LNAC). The current manual system, characterized by pen-and-logbook entries, is inefficient, prone to errors, and time-consuming. The proposed solution leverages QR code technology and SMS notifications to automate and streamline the monitoring process, enhancing both accuracy and efficiency. The system's development follows the Software Development Life Cycle (SDLC) using the waterfall model, ensuring a structured approach from requirement gathering to deployment. Key objectives include optimizing operations, improving data accuracy, reducing processing time, and enhancing security measures. The system's effectiveness and user satisfaction were evaluated through questionnaires, yielding high satisfaction scores among users. This research underscores the significance of integrating technology into campus security and administrative processes, offering a scalable solution for similar institutional environments. The study concludes with recommendations for future improvements, such as integrating the system with mobile platforms and enhancing database normalization and security features. [ABSTRACT FROM AUTHOR]

Michele Vitacca,1 Alberto Malovini,2 Bruno Balbi,3 Maria Aliani,4 Serena Cirio,5 Antonio Spanevello,6,7 Claudio Fracchia,8 Mauro Maniscalco,9 Giacomo Corica,10 Nicolino Ambrosino,8 Mara Paneroni1 1Istituti Clinici Scientifici Maugeri IRCCS, Respiratory Rehabilitation Unit of the Institute of Lumezzane, Brescia, Italy; 2Istituti Clinici Scientifici Maugeri IRCCS, Laboratory of Informatics and Systems Engineering for Clinical Research of the Institute of Pavia, Pavia, Italy; 3Istituti Clinici Scientifici Maugeri IRCCS, Respiratory Rehabilitation Unit of the Institute of Veruno, Novara, Italy; 4Istituti Clinici Scientifici Maugeri IRCCS, Respiratory Rehabilitation Unit of the Institute of Cassano Delle Murge, Bari, Italy; 5Istituti Clinici Scientifici Maugeri IRCCS, Respiratory Rehabilitation Unit of the Institute of Pavia, Pavia, Italy; 6Istituti Clinici Scientifici Maugeri IRCCS, Respiratory Rehabilitation Unit of the Institute of Tradate, Varese, Italy; 7University of Insubria, MACRO, Varese, Italy; 8Istituti Clinici Scientifici Maugeri IRCCS, Respiratory Rehabilitation Unit of the Institute of Montescano, Pavia, Italy; 9Istituti Clinici Scientifici Maugeri IRCCS, Respiratory Rehabilitation Unit of the Institute of Telese, Benevento, Italy; 10Istituti Clinici Scientifici Maugeri IRCCS, Health Directorate of the Institute of Lumezzane, Brescia, ItalyCorrespondence: Michele VitaccaIstituti Clinici Scientifici Maugeri IRCCS, Via Salvatore Maugeri, 4, Pavia 27100, ItalyEmail michele.vitacca@icsmaugeri.itBackground: The Barthel Index dyspnea (BId) is responsive to physiological changes and pulmonary rehabilitation in patients with chronic obstructive pulmonary disease (COPD). However, the minimum clinically important difference (MCID) has not been established yet.Aim: To identify the MCID of BId in patients with COPD stratified according to the presence of chronic respiratory failure (CRF) or not.Materials and Methods: Using the Medical Research Council (MRC) score as an anchor, receiver operating characteristic curves and quantile regression were retrospectively evaluated before and after pulmonary rehabilitation in 2327 patients with COPD (1151 of them with CRF).Results: The median post-rehabilitation changes in BId for all patients were − 10 (interquartile range = − 17 to − 3, p< 0.001), correlating significantly with changes in MRC (r = 0.57, 95% CI = 0.53 to 0.59, p< 0.001). Comparing different methods of assessment, the MCID ranged from − 6.5 to − 9 points for patients without and − 7.5 to − 12 points for patients with CRF.Conclusion: The most conservative estimate of the MCID is − 9 points in patients with COPD, without and − 12 in those with CRF. This estimate may be useful in the clinical interpretation of data, particularly in response to intervention studies.Keywords: activities of daily life, breathlessness, dyspnea, chronic respiratory failure, exercise training, health related quality of life, rehabilitation

Background: OSAS and COPD are often associated with day-time hypoxemia. Overlap Syndrome (OS), the association between both diseases, increases the risk of day-time hypoxemia. The aim of this study was to investigate the mechanisms which could justify the low oxygen level and the effect of CPAP. Methods: We performed a retrospective analysis in all patients referred to our institutes for suspected OSAS and who also underwent spirometry and blood gas analysis during our evaluation. Thus, 720 patients were selected. According to pulmonary function test parameters they were divided into 3 groups: OSAS (N = 466,65%); OS (N = 168,23%) and COPD (N = 86,12%). In order to evaluate the differences between the three groups, ANOVA analyses were carried out, whereas a multivariate analysis was performed in order to evaluate which factors determine the diurnal PaO2. In 90 patients we also have the data on blood gas analysis after one year of CPAP treatment, so we evaluate the PaO2 improvement in accordance with compliance to treatment in these patient subgroups. Results: The OS group showed a lower level of daytime PaO2 compared with OSAS patients and T90 was higher in OS compared with OSAS. A multivariate analysis showed that in the OS diurnal PaO2 correlated with age (β = 0.20) and moreover with FEV1 (β = 0.31) and T90 (β = 0.37), while in the OSAS a correlation was found with FEV1 (β = 0.11) and mostly with BMI (bZ0.25), age and T90. In all patients with good compliance to CPAP day-time PaO2 improved. Conclusions: Our data suggest that day-time hypoxemia in OSA patients is largely determined by the increase of body weight and severity of nocturnal hypoxia. However, CPAP therapy has been shown to improve daytime PaO2 values both in OSAS and in OS. [ABSTRACT FROM AUTHOR]

CO 2 is produced by many microorganisms present in cheese and it can affect cheese quality both during processing and storage. The knowledge of the extent of CO 2 production by cheese microorganism (CO 2 production rate coefficients) may be used to predict gas exchange in cheese/packaging systems, helping dairy industries in the right choice of the packaging (higher/lower gas permeability) and mastering of cheese ripening. However very few coefficients for CO 2 production rate have been published and the ones assessed in vitro (not inside real food) may not well describe the activity of the microorganisms in situ. We have therefore developed a methodology for the in situ assessment of CO 2 production rate and applied it to cheese with propionic acid fermentation. The proposed methodology is based on infra-red measurement of CO 2 and it allows measuring its accumulation up to 1% with 0.001% resolution, while monitoring the level of oxygen. The method showed a good repeatability, with a low coefficient of variation within samples (6.6%) and between samples (8.4%) compared to 10–30% between samples found in literature. The method was compared with a gas chromatography based method, which is also described. [ABSTRACT FROM AUTHOR]

Background: Diets including pulses are associated with better cardiovascular profiles, including lipid, glycemia, and hemodynamics; however, evidence is lacking regarding the contributions of individual pulse varieties., Objectives: This randomized, controlled trial examined the effects of beans or peas individually, relative to rice, on LDL-cholesterol levels (primary outcome) and other indices of cardiovascular disease risk (secondary outcomes) at 6 wk in adults with mild hypercholesterolemia., Methods: This randomized, controlled, single-blind, 3-arm parallel-group study was conducted in 2 Canadian cities (Edmonton, Alberta; Winnipeg, Manitoba). Participants (n = 60 per group) were randomly assigned to 6 wk of regular consumption of foods containing either 120 g (∼0.75 cups) of beans (mixture of black, great northern, navy, and pinto) or 120 g (∼0.75 cups) peas (mixture of yellow and green), or identical foods containing white, parboiled rice (control foods). LDL-cholesterol (primary outcome) and indices of lipid metabolism, glycemia, and hemodynamics (secondary outcomes) were assessed., Results: Mean LDL-cholesterol was lower in the bean group (-0.21; 95% CI: -0.39, -0.03) but not the pea group (-0.11; 95% CI: -0.29, 0.07) relative to rice after 6 wk. Non-HDL-cholesterol (-0.20; 95% CI: -0.40, -0.002) and total cholesterol (-0.28; 95% CI: -0.49, -0.06) were also lower in the bean compared with rice groups. No changes were noted in triglycerides (-0.07; 95% CI: -0.28, 0.14), glucose (0.02; 95% CI: -0.17, 0.14), insulin (4.94; 95% CI: -5.51, 11.38), or blood pressure (systolic: -1.39; 95% CI: -5.18, 2.40; diastolic: -1.89; 95% CI: -4.65, 0.88). Dietary fiber intake (grams per day or grams per 1000 kcal) was not correlated with LDL-cholesterol (grams per day: r 2 = 0.209, P = 0.142; grams per 1000 kcal: r 2 =0.126, P = 0.379) in the bean group. Gastrointestinal effects were transient and most often not related to the study foods., Conclusions: Beans, but not peas, lowered LDL-cholesterol, relative to rice, in adults with mild hypercholesterolemia. Fiber may not be responsible for the effect of beans, suggesting other phytochemicals may be the active component(s). Strategies incorporating 120 g of pulses in a meal are feasible for managing some cardiometabolic risk factors. This trial was registered at clinicaltrials.gov as NCT01661543., Competing Interests: Conflict of interest The authors report no conflicts of interest., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Introduction: Patients with chronic obstructive pulmonary disease (COPD) frequently have cardiovascular comorbidities, increasing the risk of hospitalised COPD exacerbations (H-ECOPDs) or death. This pragmatic study examined the effects of adding an inhaled corticosteroid (ICS) to long-acting bronchodilator(s) (LABDs) in patients with COPD and cardiac comorbidities who had a recent H-ECOPD., Methods: Patients >60 years of age with COPD and ≥1 cardiac comorbidity, within 6 months after discharge following an H-ECOPD, were randomised to receive LABD(s) with or without ICS, and were followed for 1 year. The primary outcome was the time to first rehospitalisation and/or all-cause death., Results: The planned number of patients was not recruited (803/1032), limiting the strength of the conclusions. In the intention-to-treat population, 89/403 patients (22.1 %) were rehospitalised or died in the LABD group (probability 0.257 [95 % confidence interval 0.206, 0.318]), vs 85/400 (21.3 %) in the LABD+ICS group (0.249 [0.198, 0.310]), with no difference between groups in time-to-event (hazard ratio 1.116 [0.827, 1.504]; p = 0.473). All-cause and cardiovascular mortality were lower in patients receiving LABD(s)+ICS, with relative reductions of 19.7 % and 27.4 %, respectively (9.8 % vs 12.2 % and 4.5 % vs 6.2 %), although the groups were not formally statistically compared for these endpoints. Fewer patients had adverse events in the LABD+ICS group (43.0 % vs 50.4 %; p = 0.013), with 4.9 % vs 5.4 % reporting pneumonia adverse events., Conclusions: Results suggest addition of ICS to LABDs did not reduce the time-to-combined rehospitalisation/death, although it decreased all-cause and cardiovascular mortality. ICS use was not associated with an increased risk of adverse events, particularly pneumonia., Competing Interests: Declaration of competing interest In addition to the medical writing support disclosed below, the authors have the following conflicts of interest. Alberto Papi reports grants to his institution from Chiesi, AstraZeneca, GlaxoSmithKline and Sanofi, consulting fees from Chiesi, AstraZeneca, GlaxoSmithKline, Novartis, Sanofi, Iqvia, Avillion, Elpen Pharmaceuticals, Moderna, and Roche, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Chiesi, AstraZeneca, GlaxoSmithKline, Menarini, Zambon, Mundipharma, Sanofi, Edmond Pharma, Iqvia, Avillion, Sanofi, and Regeneron, and participation on advisory boards for Chiesi, AstraZeneca, GlaxoSmithKline, Novartis, Sanofi, Iqvia, Avillion, Elpen Pharmaceuticals, and Moderna. All are outside the scope of the current manuscript. Giacomo Forini has no other conflicts to disclose. Mauro Maniscalco declares grants or contracts (with payments to Istituti Clinici Scientifici Maugeri IRCCS) from GlaxoSmithKline and AstraZeneca, and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from GlaxoSmithKline, AstraZeneca, and Chiesi. All are outside the scope of the current manuscript. Elena Bargagli has no other conflicts to disclose. Claudia Crimi received honoraria for lectures from Fisher & Paykel, ResMed, AstraZeneca, Sanofi, GlaxoSmithKline, and Vitalaire. All are outside the scope of the current manuscript. Pierachille Santus declares research grants from AstraZeneca, Edmondpharma, GlaxoSmithKline, and Novartis (payments were made to the Department of Biomedical and Clinical Sciences of University of Milan), consulting fees from GlaxoSmithKline, Sanofi, Edmondpharma, Dompè, Valeas, and Neopharmed, and honoraria for lectures from AstraZeneca, Sanofi, GlaxoSmithKline, Berlin Chemie, Edmondpharma, and Zambon Brasil. All are outside the scope of the current manuscript. Antonio Molino has no other conflicts to disclose. Valeria Bandiera is an employee of Alira Health SrI, which received funding from the Università degli Studi di Ferrara to provide biometrics services to the study. Federico Baraldi received a short-term research fellowship from the European Respiratory Society, outside the scope of the current manuscript Silvestro Ennio D'Anna has no other conflicts to disclose. Mauro Carone received honoraria as speaker from GlaxoSmithKline and AstraZeneca, and honoraria for participation in speaker bureaus from Boehringer Ingelheim, support for attending meetings and travel from the Associazione Italiana Pneumologi Ospedalieri – Italian Thoracic Society (AIPO-ITS/ETS), and an unpaid role as the National President of the AIPO-ITS/ETS. All are outside the scope of the current manuscript. Maurizio Marvisi has no other conflicts to disclose. Corrado Pelaia received honoraria for lectures from AstraZeneca, GlaxoSmithKline, and Sanofi, all outside the scope of the current manuscript. Giulia Scioscia has no other conflicts to disclose. Vincenzo Patella has no other conflicts to disclose. Maria Aliani has no other conflicts to disclose. Leonardo M Fabbri received consulting fees from Alfasigma, AstraZeneca, Chiesi, GlaxoSmithKline, ICON, Menarini, Novartis, and Verona Pharma, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Chiesi, GlaxoSmithKline, Glenmark, Lusofama, and Novartis, support for attending meetings and/or travel from the Italian Society of Allergy, Asthma and Clinical Immunology and the Menarini Foundation, and participated in a data safety monitoring board or advisory board for Novartis, Chiesi, and ICON. All are outside the scope of the current manuscript., (Copyright © 2024 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Obstructive sleep apnoea syndrome (OSAS) is a prevalent sleep-related breathing disorder that has been extensively studied for its effects on cognitive functions. However, little attention has been given to investigating Mind Reading (MR) skills in patients with OSAS. In this study, we employed a neuropsychological approach to thoroughly assess various facets of MR skills in patients with OSAS. Forty-two patients with untreated moderate or severe OSAS (AHI ≥15; 30 men, 12 women) and 16 healthy controls (7 men and 9 women), matched by age, were enrolled. To assess MR skills, we used: (i) The Story-based Empathy Task (SET), which includes three experimental conditions: identifying intentions (SET-IA), emotional states (SET-EA), and a control condition for inferring causality reactions (SET-CI); (ii) the Ekman 60 Faces Test (Ek60), which measures emotion recognition from facial expressions. Our findings revealed that patients with OSAS exhibit deficits in emotion-related MR skills, while their ability to make inferences about the cognitive states of social partners remains largely preserved. This finding corroborates previous evidence indicating that social cognition, particularly MR skills, may be one of the cognitive domains affected by OSAS. It emphasizes the significance of investigating social cognition and the relationship between MR skills and social functioning as a new and intriguing area of research in patients with OSAS., (© 2024 The British Psychological Society.)

Metabolic syndrome (MetS) is a combination of metabolic disorders that concurrently act as factors promoting systemic pathologies such as atherosclerosis or diabetes mellitus. It is now believed to encompass six main interacting conditions: visceral fat, imbalance of lipids (dyslipidemia), hypertension, insulin resistance (with or without impairing both glucose tolerance and fasting blood sugar), and inflammation. In the last 10 years, there has been a progressive interest through scientific research investigations conducted in the field of metabolomics, confirming a trend to evaluate the role of the metabolome, particularly the intestinal one. The intestinal microbiota (IM) is crucial due to the diversity of microorganisms and their abundance. Consequently, IM dysbiosis and its derivate toxic metabolites have been correlated with MetS. By intervening in these two factors (dysbiosis and consequently the metabolome), we can potentially prevent or slow down the clinical effects of the MetS process. This, in turn, may mitigate dysregulations of intestinal microbiota axes, such as the lung axis, thereby potentially alleviating the negative impact on respiratory pathology, such as the chronic obstructive pulmonary disease. However, the biomolecular mechanisms through which the IM influences the host's metabolism via a dysbiosis metabolome in both normal and pathological conditions are still unclear. In this study, we seek to provide a description of the knowledge to date of the IM and its metabolome and the factors that influence it. Furthermore, we analyze the interactions between the functions of the IM and the pathophysiology of major metabolic diseases via local and systemic metabolome's relate endotoxemia.

Introduction: Although pulses are nutritious foods containing high amounts of protein, fiber and phytochemicals, their consumption and use in the food industry have been limited due to the formation of unappealing flavors/aromas described as beany, green, and grassy. Lipoxygenase (LOX) enzymes are prevalent among pulse seeds, and their activity can lead to the formation of specific volatile organic compounds (VOCs) from certain polyunsaturated fatty acids (PUFAs). As a widespread issue in legumes, including soybean, these VOCs have been linked to certain unappealing taste perception of foods containing processed pulse seeds., Methods: To address this problem in pea and as proof of principle to promote the wider use of pulses, a Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) construct was designed to create null alleles (knockouts) of PsLOX2 which had been implicated in the generation of VOCs in peas., Results and Discussion: Successful CRISPR/Cas9-mediated LOX gene editing of stable transgenic pea lines (TGP) was confirmed by DNA sequencing of the wild type (WT) and TGP pslox2 mutant lines. These lines were also assessed for LOX activity, PUFA levels, and VOCs. Compared to WT peas, the TGP lines showed a significant reduction (p < 0.05) in LOX activity and in the concentration of key VOCs, including hexanal, 2-hexenal, heptanal, (E)-2-heptenal, (E,E)-2,4-heptadienal, 1-octen-3-ol, octanal, (E)-2-octenal (E,E)-2,4-nonadienal and furan-2-pentyl. The content of two essential PUFAs, linoleic and α-linolenic acids, the known substrates of LOX in plants, was higher in TGP flours, indicating the efficacy of the CRISPR-mediated gene editing in minimizing their oxidation and the further modification of PUFAs and their products. The collection of VOCs from the headspace of ground pea seeds, using a portable eNose also distinguished the TGP and WT lines. Multiple regression analysis showed that LOX activity correlated with the two VOCs, heptanal and (E,E)-2,4-heptadienal in pea flours. Partial Least Squares Regression (PLS-R) plot for selected PUFAs, VOCs, and sensor responses in WT and TGP lines showed distinct clusters for WT and TGP lines. Together this data demonstrates the utility of CRISPR mediated mutagenesis of PsLOX2 to quickly improve aroma and fatty acid (FA) profiles of pea seeds of an elite Canadian variety., 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 His Majesty the King in Right of Canada.)

Summary: Background. Asthma affects millions of people worldwide, with a subgroup suffering from severe asthma (SA). Biologics have revolutionized SA treatment, but challenges remain in managing different patient traits. This study analyzed data from the Italian Registry on Severe Asthma (IRSA) to investigate changes in SA characteristics and effectiveness of treatments after one year of follow-up, and to identify factors associated with response to treatments in a real-world setting. Methods. Data on SA patients with one year of follow-up were extracted from IRSA. Asthma control, exacerbations, lung function, and treatments, were assessed at follow-up and analyzed against baseline characteristics. Results. After one year of follow-up, notable improvements were observed in all the outcomes of SA of the included patients (n = 570). The effectiveness of biologic therapies was particularly evident, as they contributed significantly to these positive outcomes. Additionally, certain factors were found to be associated with improvement, namely T2 phenotype, baseline eosinophil count (BEC), and area of residence. On the other hand, comorbidities (obesity, gastro-esophageal reflux disease) and poor lung function were risk factors. Notably, poor-responders to biologics exhibited lower level of education, BEC, and exacerbations, and higher frequency of atopy and ACT score ≥ 20. Conclusions. The findings demonstrate the effectiveness of biologics in asthma management, when implemented as part of a planned follow-up strategy aimed at optimizing and fine-tuning the therapy. Moreover, the study highlights the importance of considering key traits such as the T2 phenotype, BEC, education, and comorbidities when tailoring SA treatment. Overall, this study contributes to enhancing our understanding of SA management and guiding the development of personalized treatment approaches for patients with SA.

Background: The efficacy of benralizumab has been broadly demonstrated in severe eosinophilic asthma (SEA), but only few real-life studies evaluated its long-term effects. Here we present novel data from the ANANKE study in which a large cohort of SEA patients was treated for up to 96 weeks., Methods: ANANKE (NCT04272463) is an observational retrospective Italian study investigating the key characteristics of SEA patients (collected during the 12 months prior to benralizumab initiation) and the clinical outcomes during benralizumab treatment (annual exacerbation rate [AER], lung function, asthma control, OCS use, healthcare resource utilization). A post hoc analysis was also conducted in groups of patients based on history of previous biologic therapy (bio-experienced versus naïve patients). Analyses were descriptive only., Results: Before benralizumab initiation, evaluable SEA patients (N = 162, 61.1% females, mean age 56.0 ± 12.7) showed a median blood eosinophil count (BEC) of 600 cells/mm 3 (IQR: 430-890). Patients experienced frequent exacerbations (annualized exacerbation rate [AER]: 4.10, severe AER: 0.98), with impaired lung function and poor asthma control (median ACT score: 14) despite 25.3% reported oral corticosteroid (OCS) use. Nasal polyposis was present in 53.1% patients; 47.5% patients were atopic. After 96 weeks since the start of benralizumab, nearly 90% patients were still on treatment; benralizumab dramatically decreased exacerbations (AER: - 94.9%; severe AER: - 96.9%), improved respiratory parameters (median increase in pre-bronchodilator forced expiratory volume [pre-BD FEV1]: + 400 mL) and asthma control (median ACT score: 23) while eliminating OCS in 60% patients. Importantly, benralizumab effects were either maintained or progressively improved over time, accompanied by a nearly complete depletion of BEC. Benralizumab reduced AER both in naïve (any AER: - 95.9%; severe AER: - 97.5%) and bio-experienced patients (any AER: - 92.4%; severe AER: - 94.0%)., Conclusions: Profound and sustained improvements in all asthma outcomes were observed with benralizumab. The correct identification of patients' eosinophilic-driven asthma phenotype was essential to ensure the achievement of such remarkable results., Trial Registration: ClinicalTrials.gov Identifier: NCT04272463., (© 2023. The Author(s).)

The ‘no-reflow’ phenomenon (NRP) after primary percutaneous coronary intervention (PCI) is a serious complication among acute ST-segment elevation myocardial infarction (STEMI) patients. Herein, a comprehensive lipidomics approach was used to quantify over 300 distinct molecular species in circulating plasma from 126 patients with STEMI before and after primary PCI. Our analysis showed that three lipid classes: phosphatidylcholine (PC), alkylphosphatidylcholine (PC(O)), and sphingomyelin (SM), were significantly elevated (p < 0.05) in no-reflow patients before primary PCI. The levels of individual fatty acids and total fatty acid levels were significantly lower (p < 0.05) in no-reflow subjects after PCI. The grouping of patients based on ECG ST-segment resolution (STR) also demonstrated the same trend, confirming the possible role of these differential lipids in the setting of no-reflow. Sphingomyelin species, SM 41:1 and SM 41:2, was invariably positively correlated with corrected TIMI frame count (CTFC) at pre-PCI and post-PCI. The plasma levels of SM 42:1 exhibited an inverse association (p < 0.05) consistently with tumor necrosis factor-alpha (TNF-α) at pre-PCI and post-PCI. In conclusion, we identified plasma lipid profiles that distinguish individuals at risk of no-reflow and provided novel insights into how dyslipidemia may contribute to NRP after primary PCI.

(1) Background: We investigated the differences in the neuropsychological profile as well as the pneumological and motor functions in two groups of patients admitted to rehabilitation who received different respiratory support during their COVID-19 infection. (2) Methods: Group-1 ( n = 18; 15 male, median age 67.5) consisted of patients who received non-invasive mechanical ventilation; Group-2 ( n = 19; 16 male, median age 63) consisted of patients who received invasive mechanical ventilation. All patients underwent a neuropsychological assessment including Mini-Mental State Examination (MMSE), Frontal Assessment Battery (FAB), and the Repeatable Battery for the Assessment of Neuropsychological Status (R-BANS) to evaluate the patients' cognition. Depression and anxiety were also measured at admission and discharge to rehabilitation. (3) Results: At admission, patients impaired at MMSE were 44% in Group-1 and 5% in Group-2, while patients impaired at FAB were 88% in Group-1 and 26% in Group-2. Wilcoxon's effect size revealed meaningful differences between groups for FAB, R-BANS global score, immediate and delayed memory, and attention-coding task, with Group-2 performing better than Group-1 across all measures. At discharge, 52% of the 25 patients re-assessed still had mild to moderate cognitive deficits, while 19% had depression and 35% had anxiety. (4) Conclusions: Patients who received oxygen therapy experienced higher levels of acute and chronic stress compared to those who benefitted from invasive mechanical ventilation. Despite patients showing a meaningful improvement at discharge, cognitive impairment persisted in a great number of patients; therefore, long-term neuropsychological follow-up and treatment for COVID-19 patients are recommended.