Search

Traditional family norms often have persistent effects on household decisions. We question whether kinship ancestries of postmarital residence still affect household consumption sharing. We estimate a model of resource allocation using expenditure surveys for Ghana and Malawi, two countries in which patrilocal and matrilocal traditions coexist. Ancestral patrilocality coincides with a 10% lower resource share for women, contributing to a higher prevalence of poverty among women. Women's resource shares increase with age, a pattern more pronounced for matrilocal groups. These results indicate how a combination of cultural and demographic factors may be used to improve policies targeted at poor individuals. [ABSTRACT FROM AUTHOR]

Better employment quality can improve personal well-being, social cohesion, and inclusive growth and development. Yet good quality jobs – associated with greater well-being – are less accessible to women than men. While it is understood that policies balancing family and work lead to greater female labour participation, this paper investigates whether one such policy – increased childcare – improves the quality of jobs where mothers are employed. The context we analyse is a nationwide school reform in Chile that extended school schedules for primary school-aged children, providing childcare services. We combine administrative data of the phase-in of the policy with panel data of individual mothers' employment outcomes and socio-economic characteristics. We estimate a fixed-effects model that controls for mothers' unobserved heterogeneity and identifies the effect of the policy from plausibly exogenous temporal and spatial variations in access to schools with long schedules and exogenous exposure to the policy. We find a positive effect of childcare on several measures of employment quality and gender gaps within the couple. Our evidence suggests that the mechanism driving the impact is the implicit subsidy to the cost of childcare, affecting the opportunity cost of mothers' time. In addition, we find heterogeneous results by mothers' education level. Access to childcare through longer primary school schedules can increase household welfare and can play a role in reducing income and gender inequalities. [ABSTRACT FROM AUTHOR]

Myelodysplastic syndrome and acute myeloid leukemia (AML) belong to a continuous disease spectrum of myeloid malignancies with poor prognosis in the relapsed/refractory setting necessitating novel therapies. Natural killer (NK) cells from patients with myeloid malignancies display global dysfunction with impaired killing capacity, altered metabolism, and an exhausted phenotype at the single-cell transcriptomic and proteomic levels. In this study, we identified that this dysfunction was mediated through a cross-talk between NK cells and myeloid blasts necessitating cell-cell contact. NK cell dysfunction could be prevented by targeting the αvβ-integrin/TGF-β/SMAD pathway but, once established, was persistent because of profound epigenetic reprogramming. We identified BATF as a core transcription factor and the main mediator of this NK cell dysfunction in AML. Mechanistically, we found that BATF was directly regulated and induced by SMAD2/3 and, in turn, bound to key genes related to NK cell exhaustion, such as HAVCR2, LAG3, TIGIT, and CTLA4. BATF deletion enhanced NK cell function against AML in vitro and in vivo. Collectively, our findings reveal a previously unidentified mechanism of NK immune evasion in AML manifested by epigenetic rewiring and inactivation of NK cells by myeloid blasts. This work highlights the importance of using healthy allogeneic NK cells as an adoptive cell therapy to treat patients with myeloid malignancies combined with strategies aimed at preventing the dysfunction by targeting the TGF-β pathway or BATF. Editor's summary: Patients with myeloid malignancies, including myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), often relapse after standard of care. To improve outcomes, Kumar et al. have investigated the role of natural killer (NK) cells in antitumor immunity against myeloid blasts and have identified global dysfunction of NK cells in these patients. They identified BATF as responsible for this dysfunction, and by knocking out BATF downstream of the TGF-β canonical pathway in NK cells, they were able to enhance NK cell function against AML in vitro and in vivo. This has led to the initiation of a promising clinical trial using these TGFBR2 knockout NK cells against myeloid malignancies. —Dorothy Hallberg [ABSTRACT FROM AUTHOR]

The lysine-specific histone demethylase 1 A (LSD1) is involved in antitumor immunity; however, its role in shaping CD8 + T cell (CTL) differentiation and function remains largely unexplored. Here, we show that pharmacological inhibition of LSD1 (LSD1i) in CTL in the context of adoptive T cell therapy (ACT) elicits phenotypic and functional alterations, resulting in a robust antitumor immunity in preclinical models in female mice. In addition, the combination of anti-PDL1 treatment with LSD1i-based ACT eradicates the tumor and leads to long-lasting tumor-free survival in a melanoma model, complementing the limited efficacy of the immune or epigenetic therapy alone. Collectively, these results demonstrate that LSD1 modulation improves antitumoral responses generated by ACT and anti-PDL1 therapy, providing the foundation for their clinical evaluation.The lysine-specific histone demethylase 1 A (LSD1) can regulate cytotoxic CD8 T cell (CTL) responses and anti-tumor immunity. Here the authors show that ex vivo epigenetic reprogramming with a LSD1 inhibitor enhances cell persistence and anti-tumor activity of adoptively transferred CD8 T cells in preclinical tumor models. [ABSTRACT FROM AUTHOR]

Copyright of Annales Françaises de Médecine d'Urgence is the property of John Libbey Eurotext Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: The costs of disease-modifying therapies (DMTs) for multiple sclerosis (MS) have increased interest in generic alternatives. Methods: This prospective and observational study aims to investigate the safety, tolerability, and acceptance of switching from brand glatiramer acetate (GA) 40 mg/mL three times per week (Copaxone®) to generic GA 40 mg/mL three times per week (Glatiramyl®). Conducted at the Neurocenter of Southern Switzerland from September 2020 to September 2021, the study enrolled 27 patients; 21 completed the study. Participants reported on local and systemic side effects three months before and after the switch, and on switch acceptance by means of visual analogue scales (from 0 to 10). Results: Results indicated that those on generic GA experienced fewer local (81.0% vs. 96.3%) and systemic (33.3% vs. 59.3%) adverse events than with the brand drug. The median intensity of local adverse events was 8 (4–20) on generic GA vs. 16 (9–22) on brand GA, while the median intensity of systemic adverse events was similar between generic and brand GA [0 (0–27) vs. 0 (0–21.5), respectively]. Seventy-one percent of participants rated their acceptance of generic GA as 7/10 or higher. Conclusions: The results suggest that switching from brand to generic GA 40 mg/mL is safe, well-tolerated, and accepted by patients with MS. [ABSTRACT FROM AUTHOR]

Literature supports the use of technological tools such as augmented reality, 3 D avatars and mobile devices to improve individuals with autism spectrum disorder skills. Possibilities of including these technological tools in intervention and the critical issues related to intervention design are essential research questions. The aim of the current work is to present an interdisciplinary research study on the design of an autism intervention considering these technologies. This study used qualitative evidence and thematic analysis to identify the main design guidelines. A semi-structured interview was administered to a total of twenty participants representing four stakeholder categories: ASD, clinicians, therapists and caregivers. Interviews focussed on three dimensions related to user, technology and environment since they represent a complex system within which the individual using technology is situated. Thematic analysis of the interviews identified a total of 10 themes considered central to the design of the technological intervention. Since the application of technology in autism intervention is a relatively new area, the guidelines related to the potential incentives and barriers of the proposed technology are helpful to inform future treatment studies. This study highlights the strengths and barriers associated with the use of smartphones and augmented reality in autism spectrum disorder interventions considering the dimensions within which the user using assistive technology is located. Strengths and major concerns that emerged are key points to consider during the development of the technological intervention. Considering these points can foster the use of technology within the intervention and promote its effectiveness. [ABSTRACT FROM AUTHOR]

Background: Currently approved vaccines are highly effective in protecting against hospitalization and severe COVID-19 infections. How pre-existing immunity responds to new variants with mutated antigens is crucial information for elucidating the functional interplay between antibodies and B and T cell responses during infection with new SARS-CoV-2 variants. Methods: In this study, we monitored the dynamics and persistence of the immune response versus different SARS-CoV-2 variants of concern that emerged during the pandemic period (2021–2022) in a cohort of vaccinated healthcare workers, who experienced breakthrough infection in the Pre-Delta, Delta, and Omicron waves. We evaluated both the humoral and cell-mediated responses after infection. We also evaluated the anti-SARS-CoV-2 antibodies levels produced by infection in comparison with those produced after vaccination. Results: Our results highlighted that the immune response against the Delta VOC mainly involved an adaptive humoral and switched memory B cells component, even 3 months after the last vaccine dose, conversely showing a high percentage of depleted adaptive T cells. Omicron infections triggered a consistent production of non-vaccine-associated anti-N antibodies, probably to balance the spike epitope immune escape mechanisms. Conclusion: Our results suggest a direct dependence between the VOC and different humoral and B and T cell balances in the post-infection period, despite the administration of a different number of vaccine doses and the elapsed time since the last vaccination. [ABSTRACT FROM AUTHOR]

The vast amount of available sequencing data allows the scientific community to explore different genetic alterations that may drive cancer or favor cancer progression. Software developers have proposed a myriad of predictive tools, allowing researchers and clinicians to compare and prioritize driver genes and mutations and their relative pathogenicity. However, there is little consensus on the computational approach or a golden standard for comparison. Hence, benchmarking the different tools depends highly on the input data, indicating that overfitting is still a massive problem. One of the solutions is to limit the scope and usage of specific tools. However, such limitations force researchers to walk on a tightrope between creating and using high-quality tools for a specific purpose and describing the complex alterations driving cancer. While the knowledge of cancer development increases daily, many bioinformatic pipelines rely on single nucleotide variants or alterations in a vacuum without accounting for cellular compartments, mutational burden or disease progression. Even within bioinformatics and computational cancer biology, the research fields work in silos, risking overlooking potential synergies or breakthroughs. Here, we provide an overview of databases and datasets for building or testing predictive cancer driver tools. Furthermore, we introduce predictive tools for driver genes, driver mutations, and the impact of these based on structural analysis. Additionally, we suggest and recommend directions in the field to avoid silo-research, moving towards integrative frameworks. [ABSTRACT FROM AUTHOR]

The RAS is a hormonal system playing a pivotal role in the control of blood pressure and electrolyte homeostasis, the alteration of which is associated with different pathologies, including acute respiratory distress syndrome (ARDS). As such, it is not surprising that a number of studies have attempted to elucidate the role and balance of the renin–angiotensin system (RAS) in COVID-19. In this review article, we will describe the evidence collected regarding the two main enzymes of the RAS (i.e., ACE and ACE2) and their principal molecular products (i.e., AngII and Ang1-7) in SARS-CoV-2 infection, with the overarching goal of drawing conclusions on their possible role as clinical markers in association with disease severity, progression, and outcome. Moreover, we will bring into the picture new experimental data regarding the systemic activity of ACE and ACE2 as well as the concentration of AngII and Ang1-7 in a cohort of 47 COVID-19 patients hospitalized at the IRCCS Sacro Cuore-Don Calabria Hospital (Negrar, Italy) between March and April 2020. Finally, we will discuss the possibility of considering this systemic pathway as a clinical marker for COVID-19. [ABSTRACT FROM AUTHOR]

Early diagnosis is crucial for Autism spectrum disorder (ASD) and is achieved through a screening of developmental indicators to recognise children who are at risk of autism. One of the most widely used instruments in clinical practice for assessing child development is the Griffiths Mental Development Scale (GMDS). We sought (a) to assess longitudinally whether children diagnosed with ASD, with a mean age of 33.50 months (SD 7.69 months), show a developmental delay of abilities measured by the GMDS over time and (b) to analyse which skills of the GMDS could be associate to the symptomatologic severity of ASD. Our results showed lower scores of General Quotient and all sub-quotients of GMDS from first (T0) to second assessment (T1), except for the Performance sub-quotient. Three sub-quotients (Personal-Social, Hearing and Language and Practical Reasoning) also associate symptom severity at the time when the diagnosis of ASD is made. [ABSTRACT FROM AUTHOR]

The availability of high-quality data of helminth genomes provided over the past two decades has supported and accelerated large-scale 'omics studies and, consequently, the achievement of a more in-depth molecular characterization of a number of pathogens. This has also involved Strongyloides spp. and since their genome was made available transcriptomics has been rather frequently applied to investigate gene expression regulation across their life cycle. Strongyloides proteomics characterization has instead been somehow neglected, with only a few reports performing high-throughput or targeted analyses associated with protein identification by tandem mass spectrometry. Such investigations are however necessary in order to discern important aspects associated with human strongyloidiasis, including understanding parasite biology and the mechanisms of host–parasite interaction, but also to identify novel diagnostic and therapeutic targets. In this review article, we will give an overview of the published proteomics studies investigating strongyloidiasis at different levels, spanning from the characterization of the somatic proteome and excretory/secretory products of different parasite stages to the investigation of potentially immunogenic proteins. Moreover, in the effort to try to start filling the current gap in host-proteomics, we will also present the first serum proteomics analysis in patients suffering from human strongyloidiasis. This article is part of the Theo Murphy meeting issue 'Strongyloides: omics to worm-free populations'. [ABSTRACT FROM AUTHOR]

Purpose: This paper assesses the impact of this program on the rural women's employment opportunities using data from the 2015 round of the household's living standard survey (HLSS) of Côte d'Ivoire. Design/methodology/approach: In 2013, in order to improve the living conditions of the rural population, the Ivorian government launched the National Program for rural electrification (PRONER) to electrify all localities with more than 500 inhabitants. Findings: The results show that PRONER, while reducing the time allocated to performing household chores, increases women's employment through the reallocation of time to full-time paid work in the agricultural and non-agricultural sectors. The authors also find that the allocation of men's time is not affected by this programme. A possible mechanism that would explain such a pro-women effect is the labour-saving technology introduced to home production as an effect of the reform. Research limitations/implications: As a limitation, it is important to note that these results were obtained in the specific context of PRONER in Côte d'Ivoire and are not necessarily applicable to rural electrification programmes in other contexts. Furthermore, the choice of other indicators to measure women's empowerment is limited by the quality of the data available. It would be interesting for future research to extend this analysis to include other aspects of women's empowerment and household welfare. Originality/value: This paper is the first to the author's knowledge to apply a robust econometric method by combining an inverse probability weighted regression adjustment model with Heckman sample selection method to access a robust causal effect of the PRONER in Côte d'Ivoire. [ABSTRACT FROM AUTHOR]

While technological advancements and their deep integration in connected and automated vehicles is a central aspect in the evolving trend of automotive industry, they also depict a growing size attack surface for malicious actors: the latter ones typically aim at exploiting known and unknown security vulnerabilities, with potentially disastrous consequences on the safety of vehicles, people, and infrastructures. In recent years, remarkable efforts have been spent to mitigate security vulnerabilities in intelligent and connected vehicles, in particular in the inside of vehicles, the so-called intra-vehicle networks. Despite those efforts, securing intra-vehicle networks remains a non-trivial task due to their heterogeneous and increasingly complex context. Starting from the above remarks and motivated by the industrial research and innovation project EMERGE, in this paper we report on a novel cryptographic hardware-software solution that we have designed and developed for securing the intra-vehicle network of intelligent connected vehicles: the Crypto-Engine. The Crypto-Engine relies on a lightweight hybrid-key cryptographic scheme to provide confidentiality and authentication without compromising the normal communication performance. We tested the Crypto-Engine and demonstrated that, once configured according to application-defined performance requirements, it can authenticate parties and secure the communications with a negligible overhead. [ABSTRACT FROM AUTHOR]

Background: Disease-modifying treatments (DMTs) can increase the risk of infections in multiple sclerosis (MS). Aged individuals are usually excluded from clinical trials, and there is uncertainty regarding safety of immunosuppressive DMTs in these patients. Objective: To investigate the association of DMTs, ageing and other clinical variables with risk of infections in MS patients. Methods: Prospective single-centre observational study collecting information on occurrence, type and grade of infections in patients followed at the MS centre, Lugano (Switzerland). Associations with infection risk were tested using multivariable Poisson and Cox regressions. Results: A total of 503 patients were included (injectables/untreated, n = 127; orals, n = 139; monoclonal antibodies (MAB), n = 237) and 326 infections recorded over 12.6 (11.6–14.0) months. As compared to injectable DMTs/no treatment, MAB and oral DMTs were positively associated with infection incidence (IRR = 2.32, 95% confidence interval (CI) = 1.39–3.89, p = 0.001; IRR = 2.04, 95% CI = 1.19–3.49, p = 0.009, respectively). After excluding COVID-19, the effect of MAB was stronger among patients <50 years (IRR = 5.90, 95% CI = 2.80–12.45, p < 0.001) than >50 years (IRR = 1.95, 95% CI = 0.91–4.15, p = 0.084). Higher disability and male sex were the only variables associated with severe infections. Conclusion: Treatment with MAB and oral DMTs is associated with higher incidence of infections, with a stronger effect in young MS patients. Disability appears the main predictor of severe infections regardless of treatment. [ABSTRACT FROM AUTHOR]

Although the pharmacological therapy of ADHD has been widely studied, little has been done to compare the different therapeutic approaches (e.g., drug therapy vs. psychological treatments) and even less has been done to compare the outcome of the therapy between centers. This multicenter observational study aims to assess between-center variation in functional outcome of ADHD patients one year after the diagnosis, according to the treatment received. We used the Regional ADHD Registry data on 1429 patients enrolled in 16 ADHD centers in the 2011–2022 period. To evaluate the effectiveness of the therapy we used a generalized linear mixed model with the center as the random effect, including patient condition at diagnosis and center characteristics, weighting by the inverse of the propensity score of the treatment received by the patient. Between-center variation was expressed as the relative difference in odds-ratios between the observed and the expected number of patients whose condition improved, using the Clinical Global Impressions—Improvement Scale (CGI-I), and the relative 95% CI. Patients who received combined treatment were significantly more likely to improve compared to other treatment groups (65.5% vs 54.4% for methylphenidate alone, 53.4% for psychological treatment alone, or 40.5% for no therapy). Adjusted for patients and center characteristics, the log-odds ratio ranged from 0.85 (0.29–1.55 95% CI) to − 0.64 (− 1.17–− 0.18 95% CI). The mean expected probability of improvement after one year of therapy for an average patient with ADHD for each center was 47.7% in a center at the 25th percentile and 61.2% in a center at the 75th percentile of the outcome distribution after adjustments. The wide between-center variation in patient functional improvement one year after the diagnosis of ADHD could be largely explained by center-specific therapeutic approaches or attitudes. More careful and stringent work is needed to reduce differences in responses between centers, as could formal and periodic audit programs within and between centers. [ABSTRACT FROM AUTHOR]

Introduction: Obesity and eating disorders are considered to be part of a broad spectrum of disorders associated with weight issues and maladaptive eating styles. Several studies show that psychopathological and personality characteristics contribute to the development and maintenance of obesity and dysfunctional eating behaviors, showing a bidirectional relationship. The purpose of this study was to understand the role of psychopathological factors and personality dimensions on dysfunctional eating behaviors in a sample of individuals with obesity. Methods: The study was conducted with 96 individuals with obesity (31 males and 65 females) who underwent psychological assessment. The instruments administered included the Cognitive Behavioral Assessment 2.0 - Primary Scales, the Minnesota Multiphasic Personality Inventory-2, and the Eating Disorder Inventory. Relationships between dysfunctional eating behaviors and personality and psychopathological factors were explored through mediation analysis. Results and discussion: Our results showed that difficulties related to impulse control and behavior, along with negative and dysphoric emotions, may be associated with difficulties in eating behavior. Mediation analysis showed that the combination of depressive and obsessive-compulsive symptomatology may exacerbate or contribute to the occurrence of eating disorders. These psychopathological aspects should be taken into account during the assessment of patients who decide to undergo bariatric surgery and should be targets of specific psychological interventions. [ABSTRACT FROM AUTHOR]

Aims: To evaluate the relationship between SARS-CoV-2 infection and autoimmunity in type 1 diabetes (T1D) and SARS-CoV-2 antibodies frequency at diagnosis of T1D during pandemic. Methods: The presence of T1D-specific autoimmunity was evaluated in a cohort of 99 children and adolescents without diabetes that contracted SARS-CoV-2 infection. Moreover, the frequency of IgM- and IgG-SARS-CoV-2 antibodies was evaluated in 41 newly diagnosed T1D patients not yet vaccinated against SARS-CoV-2 disease, collected during the pandemic, compared to healthy subjects (CTRL). Results: None of the 99 patients that contracted SARS-CoV-2 infection during the pandemic period was found positive for T1D autoantibodies. The frequency of SARS-CoV-2 antibodies was not significantly different in patients newly diagnosed with T1D (12.2%), compared with CTRL (8.4%). Among SARS-CoV-2 antibody positive T1D patients, 80% were target of diabetes autoantibodies and 60% had another concomitant autoimmune disease. Among the CTRL subjects positive for SARS-CoV-2Abs (n = 10), none was found positive for T1D autoantibodies. Conclusions: The results of the present study do not confirm, at least in the short term, a role of COVID-19 as a potential trigger of T1D autoimmunity and do not provide evidence of an increased frequency of SARS-CoV-2 antibodies in newly diagnosed T1D patients in comparison with healthy population. [ABSTRACT FROM AUTHOR]

Background: Mechanisms of myocardial ischemia in obstructive and non-obstructive coronary artery disease (CAD), and the interplay between clinical, functional, biological and psycho-social features, are still far to be fully elucidated. Objectives: To develop a machine-learning (ML) model for the supervised prediction of obstructive versus non-obstructive CAD. Methods: From the EVA study, we analysed adults hospitalized for IHD undergoing conventional coronary angiography (CCA). Non-obstructive CAD was defined by a stenosis < 50% in one or more vessels. Baseline clinical and psycho-socio-cultural characteristics were used for computing a Rockwood and Mitnitski frailty index, and a gender score according to GENESIS-PRAXY methodology. Serum concentration of inflammatory cytokines was measured with a multiplex flow cytometry assay. Through an XGBoost classifier combined with an explainable artificial intelligence tool (SHAP), we identified the most influential features in discriminating obstructive versus non-obstructive CAD. Results: Among the overall EVA cohort (n = 509), 311 individuals (mean age 67 ± 11 years, 38% females; 67% obstructive CAD) with complete data were analysed. The ML-based model (83% accuracy and 87% precision) showed that while obstructive CAD was associated with higher frailty index, older age and a cytokine signature characterized by IL-1β, IL-12p70 and IL-33, non-obstructive CAD was associated with a higher gender score (i.e., social characteristics traditionally ascribed to women) and with a cytokine signature characterized by IL-18, IL-8, IL-23. Conclusions: Integrating clinical, biological, and psycho-social features, we have optimized a sex- and gender-unbiased model that discriminates obstructive and non-obstructive CAD. Further mechanistic studies will shed light on the biological plausibility of these associations. Clinical trial registration: NCT02737982. [ABSTRACT FROM AUTHOR]

Prediction of driver genes (tumor suppressors and oncogenes) is an essential step in understanding cancer development and discovering potential novel treatments. We recently proposed Moonlight as a bioinformatics framework to predict driver genes and analyze them in a system-biology-oriented manner based on -omics integration. Moonlight uses gene expression as a primary data source and combines it with patterns related to cancer hallmarks and regulatory networks to identify oncogenic mediators. Once the oncogenic mediators are identified, it is important to include extra levels of evidence, called mechanistic indicators, to identify driver genes and to link the observed gene expression changes to the underlying alteration that promotes them. Such a mechanistic indicator could be for example a mutation in the regulatory regions for the candidate gene. Here, we developed new functionalities and released Moonlight2 to provide the user with a mutation-based mechanistic indicator as a second layer of evidence. These functionalities analyze mutations in a cancer cohort to classify them into driver and passenger mutations. Those oncogenic mediators with at least one driver mutation are retained as the final set of driver genes. We applied Moonlight2 to the basal-like breast cancer subtype, lung adenocarcinoma and thyroid carcinoma using data from The Cancer Genome Atlas. For example, in basal-like breast cancer, we found four oncogenes (COPZ2 , SF3B4 , KRTCAP2 and POLR2J) and nine tumor suppressor genes (KIR2DL4 , KIF26B , ARL15 , ARHGAP25 , EMCN , GMFG , TPK1 , NR5A2 and TEK) containing a driver mutation in their promoter region, possibly explaining their deregulation. Moonlight2R is available at https://github.com/ELELAB/Moonlight2R. [ABSTRACT FROM AUTHOR]

Blood and tissue protozoan infections are responsible for an enormous burden in tropical and subtropical regions, even though they can also affect people living in high-income countries, mainly as a consequence of migration and travel. These pathologies are responsible for heavy socio-economic issues in endemic countries, where the lack of proper therapeutic interventions and effective vaccine strategies is still hampering their control. Moreover, the pathophysiological mechanisms associated with the establishment, progression and outcome of these infectious diseases are yet to be fully described. Among all the players, extracellular vesicles (EVs) have raised significant interest during the last decades due to their capacity to modulate inter–parasite and host–parasite interactions. In the present manuscript, we will review the state of the art of circulating host-derived EVs in clinical samples or in experimental models of human blood and tissue protozoan diseases (i.e., malaria, leishmaniasis, Chagas disease, human African trypanosomiasis and toxoplasmosis) to gain novel insights into the mechanisms of pathology underlying these conditions and to identify novel potential diagnostic markers. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to observe the effect of different finger rest positions on the muscular activity of the hand, forearm, arm, shoulder, thorax, and neck, as well as on the angular deviation from the neutral position of the neck, trunk, upper arm, and forearm on the working side during pre-clinical procedures. Methods: An experimental laboratory study was performed. Response variables were muscle activation of the abductor pollicis, brachioradialis, biceps brachii, deltoid, pectoralis major, and right sternocleidomastoid muscles and angular deviation from the neutral position of the neck, trunk, arm, and forearm during simulated clinical procedures. Independent variable was finger-rest position during cavity preparation (no finger rest, usual rest, and ergonomic rest). Class I cavity preparations (N = 120) were performed on artificial first molars (16, 26, 36, and 46) (N = 120). Muscular activation was assessed by surface electromyography and angular deviations using Software for Postural Assessment (SAPO) version 0.69. One-way analysis of variance and Tukey's or Games-Howell's post-hoc tests were performed (a = 0.05). Results: For the sternocleidomastoid muscle, there was no statistically significant difference between the different rest positions. For the deltoid muscle, work with no finger rest resulted in greater muscle activation (p < 0.001) during work on tooth 36. Regarding the pectoralis major and right brachioradialis muscles, we observed that for both teeth 16 and 26, working with ergonomic rest showed less muscle activation. Muscle activation of the right biceps brachii was higher for work with no rest in both the upper and lower arches, differing significantly only from the usual rest in tooth 16 (p < 0.001), usual rest and ergonomic rest in teeth 26 and 46 (p < 0.001), and only ergonomic rest in tooth 36 (p = 0.044). In the right abductor pollicis muscle, work with ergonomic rest resulted in less muscle activation for cavity preparation in teeth 16, 26, and 36, which was significantly different from work with no rest (p = 0.029, p < 0.001, and p = 0.013, respectively). Regarding angular deviation, it was observed that for tooth 16, there was a greater angular deviation of the arm when performing cavity preparations with no finger rest. For teeth 26 and 46, the ergonomic finger rest provided lower angular deviation from the neutral position of the right arm. For tooth 36, ergonomic rest provided less angular deviation from the neutral neck position. Conclusion: In general, the use of non-active finger rest during simulated cavity preparations, regardless of the type of rest, provided less muscle activation and angular deviation from the neutral position of the body's upper extremity when performing pre-clinical procedures. [ABSTRACT FROM AUTHOR]

The prompt identification of faults responsible for moderate‐to‐large earthquakes is fundamental for understanding the likelihood of further, potentially damaging events. This is increasingly challenging when the activated fault is an offshore buried thrust, where neither coseismic surface ruptures nor GPS/InSAR deformation data are available after an earthquake. We show that on 9 November 2022, an Mw 5.5 earthquake offshore Pesaro ruptured a portion of the buried Northern Apennines thrust front (the Cornelia thrust system [CTS]). By post‐processing and interpreting the seismic reflection profiles crossing this thrust system, we determined that the activated fault (CTS) is an arcuate 30‐km‐long, NW‐SE striking, SW dipping thrust and that older structures at its footwall possibly influenced its position and geometry. The activation of adjacent segments of the thrust system is a plausible scenario that deserves to be further investigated to understand the full earthquake potential of this offshore seismogenic source. Plain Language Summary: The Northern Apennines chain is characterized by thrust faults running from the Po Plain to the Adriatic Sea on the northeastern side of peninsular Italy. These thrusts are buried below ≈2,000 m cover of Plio‐Pleistocene deposits. Controversies arose about these thrust faults' activity and earthquake potential based on their hidden geological signature and the scanty seismicity that could be associated with them. The earthquake (magnitude 5.5) that occurred on 9 November 2022, offshore Pesaro revived this argument. In this work, we analyze the geological structure of the crustal volume affected by the seismic sequence, exploiting seismic reflection profiles and well‐log data to identify the earthquake causative fault. Our results demonstrate that the earthquake ruptured a well‐known fault of the Northern Apennines' buried thrust front, supporting that it is indeed active and seismogenic. The size and architecture of this thrust front suggest that it could generate even larger earthquakes (Mw > 6.5). This type of geological study is instrumental to understanding the geometry of earthquake faults, particularly in offshore areas, because they constitute reliable inputs for earthquake hazard models and, when done promptly after an earthquake, provide key elements for other studies on the seismic source and the unfolding of the ongoing seismic sequence. Key Points: 9 November 2022, earthquake consistent with activity of the Cornelia thrust, a fault system running off the central Adriatic coastThe seismic reflection profiles in the area allowed for delineating the thrust and its earthquake potential with a much finer resolutionThe properties of the causative fault suggest that the activation of adjacent segments is a plausible scenario that deserves consideration [ABSTRACT FROM AUTHOR]

NK cells represent key players capable of driving antitumor immune responses. However, the potent immunosuppressive activity of the tumor microenvironment (TME) may impair their effector function. Here, we strengthen the importance of metabolic interactions between NK cells and TME and propose metabolic dysfunction as one of the major mechanisms behind NK failure in cancer treatment. In particular, we described that TME has a direct negative impact on NK cell function by disrupting their mitochondrial integrity and function in pediatric and adult patients with primary and metastatic cancer. Our results will help to design new strategies aimed at increasing the NK cell antitumor efficacy by their metabolic reprogramming. In this regard, we reveal an unprecedented role of IL15 in the metabolic reprogramming of NK cells enhancing their antitumor functions. IL15 prevents the inhibitory effect of soluble factors present in TME and restores both the metabolic characteristics and the effector function of NK cells inhibited by exposure to malignant pleural fluid. Thus, we propose here that IL15 may be exploited as a new strategy to metabolically reprogram NK cells with the aim of increasing the efficacy of NK‐based immunotherapy in a wide range of currently refractory adult and pediatric solid tumors. What's new The tumor microenvironment may hamper the functional activities of tumor‐infiltrating immune effector cells by affecting both their antitumor cytotoxicity and metabolic fitness. This study shows that the tumor microenvironment exerts a direct negative impact on NK cells in pediatric and adult patients with primary and metastatic cancer by disrupting the integrity and function of NK cell mitochondria. The findings suggest that metabolic disruption is one of the key mechanisms driving NK cell exhaustion and support therapeutic interventions that exploit IL‐15 to reprogram NK cell metabolism and thereby increase the efficacy of NK cell‐based tumor immunotherapy. [ABSTRACT FROM AUTHOR]

Concrete elements are frequently subjected to partially loaded areas; a typical example is represented by precast tunnel segments. In fact, during the excavation process, the hydraulic jacks of the boring machine exert, on the last assembled ring, high forces concentrated on small areas with respect to the size of ring joint. Similarly, when lining is embedded in ground, high hooping forces are transmitted through longitudinal joints, which present a contact zone smaller than the segment cross section. In both cases, spreading these loads into tunnel segments result in tensile transverse stresses which may cause splitting cracks. In the last decades, the growing desire to find more economic and sustainable solutions has driven enormous efforts in the tunnel industry to find new design solution such those based on Fiber Reinforced Concrete (FRC) or a combination of FRC and traditionally steel rebars. Research studies have already demonstrated the ability of fibers in controlling splitting crack phenomena. However, there is a lack of knowledge on reliable analytical approaches to quantify these benefits. The main aim of this paper is to develop a new model for determining the bearing capacity of FRC elements under partially loaded areas when splitting failure occurs. The analytical model herein reported allows a good prediction of the maximum loads exhibited by FRC prisms tested under high concentrated loads, whose data were selected from the literature. [ABSTRACT FROM AUTHOR]

Background Strongyloidiasis is a neglected tropical disease afecting an estimated 600 million people, particularly in resource-limited settings. The infection can persist lifelong due to unusual auto-infective cycle of Strongyloides stercoralis. The lack of a diagnostic gold standard and limited knowledge of the mechanisms underpinning this chronic infection are key issues in disease management. To date, only a few proteomics studies have been conducted to elucidate the molecular mechanisms associated with Strongyloides parasitism or to highlight novel immunological markers, with the result that our knowledge of S. stercoralis proteome remains limited. This study aims at expanding the characterization of S. stercoralis infective larvae (iL3) in order to further explore the mechanisms of parasitism and to highlight possible novel targets for serodiagnosis. Methods iL3 obtained from an infected subject were analysed by high-throughput tandem mass spectrometry. To achieve a more comprehensive characterization of the iL3 proteome we analysed the experimental dataset using an automatic search strategy combined with manual annotation, which included gene ontology (GO) analysis, InterPro annotation, assessment of the homology with Homo sapiens and other pathogens of clinical importance and B-cell epitope prediction. Results Our pipeline identifed 430 S. stercoralis proteins, 187 (43%) of which were uncharacterized. Oxidoreductases and peptidases were amongst the most represented protein categories, as highlighted by molecular function GO analyses, while membrane and mitochondrial proteins were the most represented cellular component GO categories. A high proportion of proteins bearing the CAP, SCP or thioredoxin domain or belonging to cysteine-rich secretory, transthyretin-like or peptidase protein families were also identifed. Additionally, we highlighted nine proteins displaying low homology with H. sapiens or other related pathogens and bearing amino acid sequences with immunogenic properties. Conclusions Our comprehensive description and annotation of the S. stercoralis iL3 proteome contribute to expanding the ‘omics characterization of this parasite and provide experimental evidence on the most represented proteins associated with S. stercoralis parasitism, as inferred from genomic and transcriptomic data. Moreover, novel candidate immunogenic proteins to be evaluated as novel serological diagnostic markers are highlighted. [ABSTRACT FROM AUTHOR]

We report a dataset of known and published occurrence records of Italian taxa from species (and subspecies) to family rank of the phylum Rotifera; we considered only Bdelloidea, Monogononta, and Seisonacea, and did not include Acanthocephala. The dataset includes 15,525 records (12,015 of which with georeferenced coordinates) of 584 valid species and subspecies names and other taxa at family level, gathered from 332 published papers. The published literature spans the period from 1838 to 2022, with the lowest number of papers published during the first half of the twentieth century, followed by an increasing number of papers, from 20 to more than 60 in each decade. The Italian regions with the highest number of records and species are Emilia-Romagna, Lombardy, and Piedmont, whereas no records are known for Molise. The number of species known from each region mostly mirrors sampling efforts, measured as the number of publications per region. The dataset is available through the Open Science Framework (OSF), and all the georeferenced occurrence data have been uploaded to the Global Biodiversity Information Facility (GBIF). [ABSTRACT FROM AUTHOR]

Reliable prediction of free energy changes upon amino acid substitutions (ΔΔGs) is crucial to investigate their impact on protein stability and protein–protein interaction. Advances in experimental mutational scans allow high‐throughput studies thanks to multiplex techniques. On the other hand, genomics initiatives provide a large amount of data on disease‐related variants that can benefit from analyses with structure‐based methods. Therefore, the computational field should keep the same pace and provide new tools for fast and accurate high‐throughput ΔΔG calculations. In this context, the Rosetta modeling suite implements effective approaches to predict folding/unfolding ΔΔGs in a protein monomer upon amino acid substitutions and calculate the changes in binding free energy in protein complexes. However, their application can be challenging to users without extensive experience with Rosetta. Furthermore, Rosetta protocols for ΔΔG prediction are designed considering one variant at a time, making the setup of high‐throughput screenings cumbersome. For these reasons, we devised RosettaDDGPrediction, a customizable Python wrapper designed to run free energy calculations on a set of amino acid substitutions using Rosetta protocols with little intervention from the user. Moreover, RosettaDDGPrediction assists with checking completed runs and aggregates raw data for multiple variants, as well as generates publication‐ready graphics. We showed the potential of the tool in four case studies, including variants of uncertain significance in childhood cancer, proteins with known experimental unfolding ΔΔGs values, interactions between target proteins and disordered motifs, and phosphomimetics. RosettaDDGPrediction is available, free of charge and under GNU General Public License v3.0, at https://github.com/ELELAB/RosettaDDGPrediction. [ABSTRACT FROM AUTHOR]

Adding steel fibers to concrete improves the post-cracking tensile strength of the composite material due to fibers bridging the cracks. The residual performance of the material is influenced by fiber type, content and orientation with respect to the crack plane. The latter is a main issue in fiber-reinforced concrete elements, since it significantly influences the structural behavior. The aim of this research is to develop a tailor-made composite material and casting method to orient fibers in order to optimize the performance of the material for structural applications. To this aim, a mechanized concreting device that induces such preferred fiber orientation is designed and fabricated. It uses vibration and a series of narrow channels to guide and orient fibers. A composite with oriented fibers is produced using a hybrid system of macro and micro fibers and high-performance concrete. From the same concrete batch, specimens are cast both with and without the fiber orientation device, obtaining different levels of fiber orientation. Three-point bending tests are performed to measure and compare the residual tensile strength capacities with standard specimens cast according to EN 14651. Elements with favorable fiber orientation show a significant increase in residual tensile strength with respect to the standard beams. Finally, computed tomography and an electromagnetic induction method are employed to better assess the orientation and distribution of fibers in the beams. Their results are in good agreement and enable to link the residual tensile strength parameters with fiber orientation. [ABSTRACT FROM AUTHOR]

The effects of the COVID-19 lockdown on deposition and surface water chemistry were investigated in an area south of the Alps. Long-term data provided by the monitoring networks revealed that the deposition of sulfur and nitrogen compounds in this area has stabilized since around 2010; in 2020, however, both concentrations and deposition were significantly below the average values of the previous decade for SO4 and NO3. Less evident changes were observed for NH4 and base cation. The estimated decrease of deposition in 2020 with respect to the previous decade was on average − 54% and − 46% for SO4 and NO3, respectively. The lower deposition of SO4 and NO3 recorded in 2020 was caused by the sharp decrease of SO2 and particularly of NOx air concentrations mainly due to the mobility restrictions consequent to the COVID-19 lockdown. The limited effects on NH4 deposition can be explained by the fact that NH3 emission was not affected by the lockdown, being mainly related to agricultural activities. A widespread response to the decreased deposition of S and N compounds was observed in a group of pristine freshwater sites, with NO3 concentrations in 2020 clearly below the long-term average. The rapid chemical recovery observed at freshwater sites in response to the sharp decrease of deposition put in evidence the high resilience potential of freshwater ecosystems in pristine regions and demonstrated the great potential of emission reduction policy in producing further substantial ameliorations of the water quality at sensitive sites. [ABSTRACT FROM AUTHOR]

Introduced fish are a widespread ecological threat in originally fishless high mountain lakes. However, basic distribution data are largely missing for most high mountain regions.Using time‐consuming standard methods (e.g. Nordic standard fishing nets) to assess fish distribution and relative densities at a relevant spatial scale can be impracticable, because of the large number of high mountain lakes. To overcome this problem, alternative rapid monitoring methods would be helpful.Visual encounter survey (VES) is a candidate method that enables observing fish from the shoreline. It takes only minutes to implement and is already widely used for amphibian monitoring in high mountain lakes and ponds. VES was evaluated as a method for monitoring introduced salmonids and cyprinids (the most widespread fish families) in 52 high mountain lakes.The probability of detecting both families by VES rapidly approaches 100% as the relative densities of fish increase, and false absences are restricted to populations living at low relative densities. VES also provides simple indications about fish relative densities, distinguishing between high‐density and low‐density populations.As VES usually does not enable fish species identifications, we propose VES as a useful method to describe large fish distribution inventories, not needing high taxonomic detail, but necessary for planning large‐scale conservation measures. [ABSTRACT FROM AUTHOR]

Small fish species such as minnows (Phoxinus sp.) are introduced into mountain lakes by anglers that use them as live bait for fishing salmonids that were previously introduced in these naturally fishless habitats. Introduced fish severely impact native biota but minnows are nevertheless released believing to provide forage for game fish, i.e., salmonids. However, our results indicate that minnows negatively interact with game fish, reducing their relative densities. On some occasions, minnows can remain the only present fish following trout extinction. We believe that this information should be urgently disseminated among anglers as a pragmatic argument to also convince anglers less sensitive to conservation issues that carrying minnows to the mountains is not a good idea whatever the main interest is, e.g., nature conservation or outdoor recreation. [ABSTRACT FROM AUTHOR]

Antibodies (Abs) against intracellular epitopes of the tyrosine-phosphatase 2 (IA-2) are detected in type 1 diabetes. Abs directed against the IA-2(256-760) portion, with both intra- and extracellular epitopes, are present in people with latent autoimmune diabetes in adults (LADA) and in obese subjects with normal glucose tolerance (NGT). We aim to characterize distribution and clinical features of intra- and extra-cellular IA-2(256-760) immunoreactivities in people with LADA compared to obese people with NGT. The intracellular immunoreactivity represented by immune response against two intracellular IA-2 constructs (IA-2JM(601-630) and IA-2IC(605-979)) was analyzed and related to clinical and biochemical features in 101 people with LADA and in 20 NGT obese subjects, all testing positive for IA-2(256-760) Abs. IA-2 intracellular immunoreactivity showed a frequency of 40.6% in LADA while it was not detected among NGT obese (p<0.001). Amongst LADA, the presence of immunoreactivity against the IA-2 intracellular domains was associated with lower BMI, waist circumference, higher HDL cholesterol and lower triglycerides, lower prevalence of hypertension and higher prevalence of other autoimmune disorders. Immunoreactivity against IA-2 does not involve intracellular domains in the majority of LADA and in obese people with NGT. This study shows that there is heterogeneity in the IA-2 epitopes, associated with different clinical features. [ABSTRACT FROM AUTHOR]

Mutations, which result in amino acid substitutions, influence the stability of proteins and their binding to biomolecules. A molecular understanding of the effects of protein mutations is both of biotechnological and medical relevance. Empirical free energy functions that quickly estimate the free energy change upon mutation (ΔΔ G) can be exploited for systematic screenings of proteins and protein complexes. In silico saturation mutagenesis can guide the design of new experiments or rationalize the consequences of known mutations. Often software such as FoldX, while fast and reliable, lack the necessary automation features to apply them in a high-throughput manner. We introduce MutateX, a software to automate the prediction of ΔΔ G s associated with the systematic mutation of each residue within a protein, or protein complex to all other possible residue types, using the FoldX energy function. MutateX also supports ΔΔ G calculations over protein ensembles, upon post-translational modifications and in multimeric assemblies. At the heart of MutateX lies an automated pipeline engine that handles input preparation, parallelization and outputs publication-ready figures. We illustrate the MutateX protocol applied to different case studies. The results of the high-throughput scan provided by our tools can help in different applications, such as the analysis of disease-associated mutations, to complement experimental deep mutational scans, or assist the design of variants for industrial applications. MutateX is a collection of Python tools that relies on open-source libraries. It is available free of charge under the GNU General Public License from https://github.com/ELELAB/mutatex. [ABSTRACT FROM AUTHOR]

Welfare analyses conducted by policy practitioners around the world usually rely on equivalised or per capita expenditures and ignore the extent of within-household inequality. Recent advances in the estimation of collective models suggest ways to retrieve the complete sharing process within families using homogeneity assumptions (typically preference stability upon exclusive goods across individuals or household types) and the observation of exclusive goods. So far, the prediction of these models has not been validated, essentially because intrahousehold allocation is seldom observed. We provide such a validation by leveraging a unique dataset from Bangladesh, which contains information on the fully individualised expenditures of each family member. We also test the core assumption (efficiency) and homogeneity assumptions used for identification. It turns out that the collective model predicts individual resources reasonably well when using clothing, i.e. one of the rare goods commonly assignable to males, females and children in standard expenditure surveys. It also allows for identifying poor individuals in non-poor households, while the traditional approach understates poverty among the poorest individuals. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the safety and clinical efficacy of tirofiban during primary percutaneous coronary interventions (pPCI).Background: Gp IIb/IIIa inhibitors (GPI) use during pPCI has declined over years, mainly for the increased hemorrhagic risk associated to their use and for the availability of potent, fast-acting oral antiplatelet drugs. However, several pharmacodynamic studies showed suboptimal platelet inhibition with P2Y12-blockers, such as prasugrel or ticagrelor.Methods: Patients with ST-segment elevation myocardial infarction (STEMI) undergoing pPCI were prospectively enrolled in a multicenter registry conducted in high-volume centers in Italy. All patients received intraprocedural tirofiban. The primary safety endpoint was the occurrence of in-hospital bleedings according to the Bleeding Academic Research Consortium definition. In-hospital major adverse coronary events (MACE, defined as death, reinfarction, stent thrombosis, and target vessel revascularization), final TIMI flow, myocardial blush grade, and ST-segment resolution were also evaluated.Results: A total of 472 patients (mean age 61 ± 11 years, 83% males) were enrolled in 16 Italian centers from October 2015 to June 2018. Mean basal thrombus grade score was 3.47 ± 1.25. PCI was performed by transradial approach in 88% of patients. We observed a very low rate of 30 days BARC bleedings (2.1%) and MACE (0.8%). Complete (>70%) ST-segment resolution was observed in 67% of patients.Conclusions: In the FASTER registry, the use of tirofiban during primary PCI, performed with a transradial approach in most cases, in patients with high thrombus burden was associated with high rates of complete ST-segment resolution and low rates of in-hospital bleeding and MACE. [ABSTRACT FROM AUTHOR]

Most youths in developing countries leave school with only a general academic education level, slowing down their transition to the labour market. We analyse whether work experience during school can ease youth transition to first job in Benin. Using data from the 2014 School‐to‐Work Transition Survey (SWTS), we estimate a three‐equation model to control for endogenous treatment assignment and sample selection and a hazard frailty model. We find that working while studying eases transition from school to first job. However, these findings were significant only for men and youth who left school with at least a secondary education. [ABSTRACT FROM AUTHOR]

This paper uses a large database of surveys of household incomes to characterize income underreporting in household surveys in low- and middle-income countries. The objective is to document (a) the extent of this underreporting, and (b) whether and how it varies systematically with respondent, household, income, and survey design features. Drawing on rural household data from 20 developing and transition countries, and using consumption expenditure as a benchmark, results indicate that the observed income/consumption ratios are very small, being on average around 0.76. Results suggest that income underreporting is systematically associated with household and survey characteristics. In particular, the degree of underreporting is strongly associated with the income source, with agricultural income being the component suffering more than any other components from underreporting. The analysis also provides evidence supporting the well-established proposition that underreporting tends to increase with household welfare: richer households appear to underreport income more. Implications for survey design and for future research are drawn. [ABSTRACT FROM AUTHOR]

While there is growing awareness of the issue of food losses at the political level, official post-harvest loss data for informing policymaking and reporting on SDG Indicator 12.3.1. (a) Food Loss Index is scarce. Representative sample-based surveys are necessary to obtain information on on-farm losses at the country level, but due to the issue's complexity, a loss module covering several key questions is needed. One main strategy proposed by the 50x2030 Initiative for optimizing data collection is sub-sampling for some of the survey modules. This paper examines whether modelling approaches can be combined with sub-sampling to improve harvest and post-harvest loss estimates and allow for further sample and cost reduction. The paper first presents the loss models generated on four selected surveys conducted in Malawi, Zimbabwe, and Nigeria, which were built using the Classification and Regression Tree (CART) method. The performance of each model is assessed for different sizes of sub-samples to improve the sample-based estimates, either by model-based estimates or by model-based imputation. The research concludes that the model-based estimates improve the loss estimates of the sub-samples due to post-stratification implied in the CART method, whereby they can constitute a cost-effective complement to sub-sampling strategies, while model-based imputations should only be used on a reduced number of missing observations. The models perform best when the survey invests in obtaining more detailed on-farm loss data and considers some key variables identified as relevant for on-farm loss models. Sub-sampling allows for investment in more detailed questionnaires and some considerations are derived for its design. [ABSTRACT FROM AUTHOR]

Background: The host immune response has a prominent role in the progression and outcome of SARS-CoV-2 infection. Lymphopenia has been described as an important feature of SARS-CoV-2 infection and has been associated with severe disease manifestation. Lymphocyte dysregulation and hyper-inflammation have been shown to be associated with a more severe clinical course; however, a T cell subpopulation whose dysfunction correlate with disease progression has yet to be identify. Methods: We performed an immuno-phenotypic analysis of T cell sub-populations in peripheral blood from patients affected by different severity of COVID-19 (n=60) and undergoing a different clinical evolution. Clinical severity was established based on a modified WHO score considering both ventilation support and respiratory capacity (PaO2/FiO2 ratio). The ability of circulating cells at baseline to predict the probability of clinical aggravation was explored through multivariate regression analyses. Results: The immuno-phenotypic analysis performed by multi-colour flow cytometry confirmed that patients suffering from severe COVID-19 harboured significantly reduced circulating T cell subsets, especially for CD4+ T, Th1, and regulatory T cells. Peripheral T cells also correlated with parameters associated with disease severity, i.e., PaO2/FiO2 ratio and inflammation markers. CD4+ T cell subsets showed an important significant association with clinical evolution, with patients presenting markedly decreased regulatory T cells at baseline having a significantly higher risk of aggravation. Importantly, the combination of gender and regulatory T cells allowed distinguishing between improved and worsened patients with an area under the ROC curve (AUC) of 82%. Conclusions: The present study demonstrates the association between CD4+ T cell dysregulation and COVID-19 severity and progression. Our results support the importance of analysing baseline regulatory T cell levels, since they were revealed able to predict the clinical worsening during hospitalization. Regulatory T cells assessment soon after hospital admission could thus allow a better clinical stratification and patient management. [ABSTRACT FROM AUTHOR]