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Background: Atrial fibrillation (AF) is the most common arrhythmia diagnosed at an older age. AF is associated with frailty, a condition possibly justifying the higher rate of complications and mortality in aged individuals. This study was aimed at describing the characteristics correlated to frailty in older AF subjects., Methods: After having excluded a < 3 months major surgery procedure, cancer or other conditions associated with activation of inflammation, and a life expectancy < 12 months, we consecutively enrolled patients ≥ 65 years with persistent AF. They underwent a Comprehensive Geriatric Assessment evaluation. In particular, Mini-Mental State Examination, 15-item Geriatric Depression Scale and Short-Physical Performance Battery (SPPB) described, respectively, cognitive profile, depressive symptoms and physical performance. A venous blood sample was collected to measure interleukin-6 (IL-6; marker of low-grade inflammation) and acylcarnitines, expression of mitochondrial dysfunction and abnormal energy production., Results: Overall, 49 patients (mean age: 76 ± 6 years; women 30.6 %) were studied. Cluster analysis described two different patterns; the second (N = 18, 36.7 %), when compared to the first one (N = 31, 63.3 %), was characterized by a worse phenotype, identified by the simultaneous presence of lower body mass index, higher CHA 2 DS 2 -VASc score (index of clinical complexity), worse SPPB functional performance, and high IL-6 levels. Second cluster patients had a higher concentration of 13 of the 35 acylcarnitines evaluated and increased 5-year mortality. All these features can outline a frail condition., Conclusions: Body size, clinical complexity, physical performance and low-grade inflammation seem to rapidly and adequately describe frailty., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Study Objectives: The umbrella term "Disorders of Arousal" (DoA), encompassing sleepwalking, confusional arousals, and sleep terrors, refers to parasomnias manifesting during non-rapid eye movement (NREM) sleep, commonly thought to arise from an aberrant arousal process. While previous studies have detailed EEG changes linked to DoA episodes, it remains uncertain how these alterations differ from a physiological arousal process. This study directly compared brain activity between DoA episodes and arousals associated with physiological movements (motor arousal) in individuals with DoA and healthy sleepers., Methods: Fifty-three adult patients with DoA (25 males, 32.2±15.5years) and 33 control subjects (14 males, 31.4±11.4years) underwent one or more home-EEG recordings. A semiparametric regression model was employed to elucidate the complex relationship between EEG activity across channels, within and across different groups, including motor arousals in DoA (n=169), parasomnia episodes in DoA (n=361), and motor arousals in healthy sleepers (n=137)., Results: Parasomnia episodes and motor arousals in both groups were preceded by a diffuse increase in slow-wave activity (SWA) and beta power, and a widespread decrease in sigma power. However, motor arousals in DoA displayed lower beta and central sigma than in healthy sleepers. Within DoA patients, episodes were preceded by lower beta, frontal sigma, and higher SWA than motor arousals., Conclusions: Our findings suggest that the arousal process is altered in DOA patients, and that specific EEG patterns are required for DOA episodes to emerge. These insights will help guide future research into the underlying circuits and objective markers of DOA., (© The Author(s) 2024. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

The study of evolutionary rates and patterns is the key to understand how natural selection shaped the current and past diversity of phenotypes. Phylogenetic comparative methods offer an array of solutions to undertake this challenging task, and help understanding phenotypic variation in full in most circumstances. However, complex, three-dimensional structures such as the skull and the brain serve disparate goals, and different portions of these phenotypes often fulfil different functions, making it hard to understand which parts truly were recruited by natural selection. In the recent past, we developed tools apt to chart evolutionary rate and patterns directly on three-dimensional shapes, according to their magnitude and direction. Here, we present further developments of these tools, which now allow to restitute the mapping of rates and patterns with full biological realism. The tools are condensed in a new R software package., (© 2024. The Author(s).)

Long bone ecomorphology has proven effective for paleohabitat reconstructions across a wide range of mammalian clades. Still, there is no comprehensive framework to allow interpretation of long bone morphological variation within and between different monophyletic groups. Here, we investigated the use of humerus morphometry to classify living members of the orders Carnivora and ungulates based on their preferred habitats. Using geometric morphometrics, we extracted three different kinds of humerus shape data describing interspecific variation with and without accounting for evolutionary allometry and phylogenetic signal. The traditional a priori categorization of species in open, mixed, and closed habitats was employed in combination with selected subsets of shape variables to identify the best-predictive models for habitat adaptation. These were identified based on the statistical performance of phylogenetic and non-phylogenetic discriminant analyses and then applied to predict habitats on a subsample of fossil species. Size-free shape data combined with phylogenetic discriminant analyses showed the highest rate of accuracy in habitat classification for a combined sample of carnivorans and ungulates. Conversely, when the two groups were investigated separately, traditional shape data analyzed with phylogenetic discriminant function analyses provided models with the greatest predictive power. By combining carnivorans and ungulates within the same methodological framework we identified common adaptive features in closed habitat-adapted species that show compressed epiphyses, while open habitat-adapted species have expanded epiphyses. These morphologies evolved to allow significant degree of direction switches during locomotion in closed habitats compared to open habitat-adapted species whose forelimb joints evolved to stabilize articulations for increasing speed., (© 2024 The Author(s). The Anatomical Record published by Wiley Periodicals LLC on behalf of American Association for Anatomy.)

Introduction: SARS-CoV-2 pandemic still poses a significant burden on global health and economy, especially for symptoms persisting beyond the acute disease. COVID-19 manifests with various degrees of severity and the identification of early biomarkers capable of stratifying patient based on risk of progression could allow tailored treatments., Methods: We longitudinally analyzed 67 patients, classified according to a WHO ordinal scale as having Mild, Moderate, or Severe COVID-19. Peripheral blood samples were prospectively collected at hospital admission and during a 6-month follow-up after discharge. Several subsets and markers of the innate and adaptive immunity were monitored as putative factors associated with COVID-19 symptoms., Results: More than 50 immunological parameters were associated with disease severity. A decision tree including the main clinical, laboratory, and biological variables at admission identified low NK-cell precursors and CD14 + CD91 + monocytes, and high CD8 + Effector Memory T cell frequencies as the most robust immunological correlates of COVID-19 severity and reduced survival. Moreover, low regulatory B-cell frequency at one month was associated with the susceptibility to develop long COVID at six months, likely due to their immunomodulatory ability., Discussion: These results highlight the profound perturbation of the immune response during COVID-19. The evaluation of specific innate and adaptive immune-cell subsets allows to distinguish between different acute and persistent COVID-19 symptoms., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Noviello, De Lorenzo, Chimienti, Maugeri, De Lalla, Siracusano, Lorè, Rancoita, Cugnata, Tassi, Dispinseri, Abbati, Beretta, Ruggiero, Manfredi, Merolla, Cantarelli, Tresoldi, Pastori, Caccia, Sironi, Marzinotto, Saliu, Ghezzi, Lampasona, Vicenzi, Cinque, Manfredi, Scarlatti, Dellabona, Lopalco, Di Serio, Malnati, Ciceri, Rovere-Querini and Bonini.)

The global biodiversity crisis is generated by the combined effects of human-induced climate change and land conversion. Madagascar is one of the World's most renewed hotspots of biodiversity. Yet, its rich variety of plant and animal species is threatened by deforestation and climate change. Predicting the future of Madagascar's chameleons, in particular, is complicated by their ecological rarity, making it hard to tell which factor is the most menacing to their survival. By applying an extension of the ENphylo species distribution model algorithm to work with extremely rare species, we find that Madagascar chameleons will face intense species loss in the north-western sector of the island. Land conversion by humans will drive most of the loss, and will intersect in a complex, nonlinear manner with climate change. We find that some 30% of the Madagascar's chameleons may lose in the future nearly all their habitats, critically jeopardizing their chance for survival., (© 2024. The Author(s).)

Celiac disease (CD) is an autoimmune enteropathy resulting from an interaction between diet, genome, and immunity. Although many patients respond to a gluten-free diet, in a substantive number of individuals, the intestinal injury persists. Thus, other factors might amplify the ongoing inflammation. Candida albicans is a commensal fungus that is well adapted to the intestinal life. However, specific conditions increase Candida pathogenicity. The hypothesis that Candida may be a trigger in CD has been proposed after the observation of similarity between a fungal wall component and two CD-related gliadin T-cell epitopes. However, despite being implicated in intestinal disorders, Candida may also protect against immune pathologies highlighting a more intriguing role in the gut. Herein, we postulated that a state of chronic inflammation associated with microbial dysbiosis and leaky gut are favorable conditions that promote C. albicans pathogenicity eventually contributing to CD pathology via a mast cells (MC)-IL-9 axis. However, the restoration of immune and microbial homeostasis promotes a beneficial C. albicans -MC cross-talk favoring the attenuation of CD pathology to alleviate CD pathology and symptoms., (© 2024 Renga et al.)

Abstract: CPX-351, a liposomal combination of cytarabine plus daunorubicin, has been approved for the treatment of adults with newly diagnosed, therapy-related acute myeloid leukemia (AML) or AML with myelodysplasia-related changes, because it improves survival and outcome of patients who received hematopoietic stem cell transplant compared with the continuous infusion of cytarabine plus daunorubicin (referred to as "7 + 3" combination). Because gut dysbiosis occurring in patients with AML during induction chemotherapy heavily affects the subsequent phases of therapy, we have assessed whether the superior activity of CPX-351 vs "7 + 3" combination in the real-life setting implicates an action on and by the intestinal microbiota. To this purpose, we have evaluated the impact of CPX-351 and "7 + 3" combination on mucosal barrier function, gut microbial composition and function, and antifungal colonization resistance in preclinical models of intestinal damage in vitro and in vivo and fecal microbiota transplantation. We found that CPX-351, at variance with "7 + 3" combination, protected from gut dysbiosis, mucosal damage, and gut morbidity while increasing antifungal resistance. Mechanistically, the protective effect of CPX-351 occurred through pathways involving both the host and the intestinal microbiota, namely via the activation of the aryl hydrocarbon receptor-interleukin-22 (IL-22)-IL-10 host pathway and the production of immunomodulatory metabolites by anaerobes. This study reveals how the gut microbiota may contribute to the good safety profile, with a low infection-related mortality, of CPX-351 and highlights how a better understanding of the host-microbiota dialogue may contribute to pave the way for precision medicine in AML., (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Background : Mild-to-moderate knee osteoarthritis (KOA) can be successfully treated using intra-articular hyaluronic acid (IA-HA). The medial infrapatellar (MIP) approach and lateral infrapatellar (LIP) approach are two of the most used techniques for performing IA-HA, but it is still not clear which one is preferable. Objectives : The study aims to find the best knee injection technique between MIP and LIP approaches. Methods: In total, 161 patients were enrolled, divided into two groups (MIP or LIP). Each technique was performed once a week for three weeks. Patients were evaluated using the Numeric Rating Scale (NRS), Knee Injury and Osteoarthritis Outcome Score (KOOS) and Roles and Maudsley Score (RMS) at T0 (before the first injection), T1 (one week after the third injection) and T2 (six months after). Results : NRS, KOOS and RMS showed a statistically significant improvement in both groups at all the detection times, without significant differences. No differences were detected between the groups in terms of systemic effect effusions, while the MIP group presented a mildly higher number of bruises in comparison with the LIP group ( p = 0.034). Conclusions : Both the IA-HA techniques are equally effective in measured outcomes. The MIP approach seems to produce some local and transient side effects. So, the choice of the LIP or MIP approach depends on the operator's skill and experience.

Adenosine deaminase (ADA) deficiency leads to severe combined immunodeficiency (SCID). Previous clinical trials showed that autologous CD34 + cell gene therapy (GT) following busulfan reduced-intensity conditioning is a promising therapeutic approach for ADA-SCID, but long-term data are warranted. Here we report an analysis on long-term safety and efficacy data of 43 patients with ADA-SCID who received retroviral ex vivo bone marrow-derived hematopoietic stem cell GT. Twenty-two individuals (median follow-up 15.4 years) were treated in the context of clinical development or named patient program. Nineteen patients were treated post-marketing authorization (median follow-up 3.2 years), and two additional patients received mobilized peripheral blood CD34 + cell GT. At data cutoff, all 43 patients were alive, with a median follow-up of 5.0 years (interquartile range 2.4-15.4) and 2 years intervention-free survival (no need for long-term enzyme replacement therapy or allogeneic hematopoietic stem cell transplantation) of 88% (95% confidence interval 78.7-98.4%). Most adverse events/reactions were related to disease background, busulfan conditioning or immune reconstitution; the safety profile of the real world experience was in line with premarketing cohort. One patient from the named patient program developed a T cell leukemia related to treatment 4.7 years after GT and is currently in remission. Long-term persistence of multilineage gene-corrected cells, metabolic detoxification, immune reconstitution and decreased infection rates were observed. Estimated mixed-effects models showed that higher dose of CD34 + cells infused and younger age at GT affected positively the plateau of CD3 + transduced cells, lymphocytes and CD4 + CD45RA + naive T cells, whereas the cell dose positively influenced the final plateau of CD15 + transduced cells. These long-term data suggest that the risk-benefit of GT in ADA remains favorable and warrant for continuing long-term safety monitoring. Clinical trial registration: NCT00598481 , NCT03478670 ., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Although CO2 field-flooding was first used during cardiac surgery more than 60 years ago, its efficacy is still disputed. The invisible nature of the gas and the difficulty in determining the "safe" quantity to protect the patient are two of the main obstacles to overcome for its validation. Moreover, CO2 concentration in the chest cavity is highly sensitive to procedural aspects, such suction and hand movements. Based on our review of the existing literature, we identified four major factors that influence the intra-cavity CO2 concentration during open-heart surgery: type of delivery device (diffuser), delivery CO2 flow rate, diffuser position around the wound cavity, and its orientation inside the cavity. In this initial study, only steady state conditions were considered to establish a basic understanding on the effect of the four above-mentioned factors. Transient factors, such as suction or hand movements, will be reported separately., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Puthettu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Atrial fibrillation (AF) is associated with chronic inflammation, a hallmark of ageing process. The aim of this study was to determine interleukin-6 (IL-6)-associated variables, also exploring acylcarnitines, expression of mitochondrial abnormalities., Methods: We evaluated 22 controls and 50 patients with persistent AF. IL-6 and acylcarnitines were measured with ELISA kits and mass spectrometry techniques., Results: IL-6 concentration (mean: 3.9 ± 3.1 pg/mL) was lower in controls and increased in AF patients, especially with heart failure. The CHA 2 DS 2 -VASc, the MMSE and the SPPB scores were 3.8 ± 1.6, 28 ± 2 and 9.4 ± 2.1. Thirteen acylcanitines correlated with IL-6. At multivariable analysis, IL-6 was directly associated with C4-OH-a short-chain acylcarnitine, fibrinogen and alanine aminotransferase values, and with hyperuricemia. An inverse association existed with calcium concentration and SPPB score., Conclusions: In older AF patients, IL-6 correlated with acylcarnitines and lower physical performance. Alterations in energy production, reduced physical function and inflammation could contribute to frailty development., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Whether clinical practice guidelines have a significant impact on practice is unclear. The effect of guideline recommendations on clinical practice often a lags behind the date of publication. We evaluated by means of a data-driven approach if and when the guidelines on red blood cell transfusions (RBCTs) issued by Swiss Smarter Medicine in 2016 had an impact on RBCTs practice within a hospital network, where awareness of guidelines was promoted mainly among internal medicine specialties. Data on RBCTs performed in a Swiss hospital network from January 2014 to April 2021 were analyzed by hospital site and specialty to assess whether guidelines led to a decrease in inappropriate RBCTs. RBCTs were defined as "inappropriate" if patients had a hemoglobin level ≥ 70 g/L without or ≥ 80 g/L with significant cardiovascular comorbidities. Changes in the rate of inappropriate transfusions were analyzed with an advanced statistical approach that included generalized additive models. Overall prior to March 2017 there were more inappropriate than appropriate RBCTs, but after October 2017 the opposite could be observed. A change-point in the time trend was estimated from transfusion data to occur in the time interval between March and October 2017. This change was mainly driven by practice changes in the medical wards, while no significant change was observed in the critical care, surgical and oncology wards. Change in practice varied by hospital site. In conclusion, our results show that a significant change in the RBCTs practice at the hospital level occurred approximately 18 months after national guidelines were issued., (© 2023. The Author(s).)

A full understanding of the characteristics of Covid-19 patients with a better chance of experiencing poor vital outcomes is critical for implementing accurate and precise treatments. In this paper, two different advanced data-driven statistical approaches along with standard statistical methods have been implemented to identify groups of patients most at-risk for death or severity of respiratory distress. First, the tree-based analysis allowed to identify profiles of patients with different risk of in-hospital death (by Survival Tree-ST analysis) and severity of respiratory distress (by Classification and Regression Tree-CART analysis), and to unravel the role on risk stratification of highly dependent covariates (i.e., demographic characteristics, admission values and comorbidities). The ST analysis identified as the most at-risk group for in-hospital death the patients with age > 65 years, creatinine [Formula: see text] 1.2 mg/dL, CRP [Formula: see text] 25 mg/L and anti-hypertensive treatment. Based on the CART analysis, the subgroups most at-risk of severity of respiratory distress were defined by patients with creatinine level [Formula: see text] 1.2 mg/dL. Furthermore, to investigate the multivariate dependence structure among the demographic characteristics, the admission values, the comorbidities and the severity of respiratory distress, the Bayesian Network analysis was applied. This analysis confirmed the influence of creatinine and CRP on the severity of respiratory distress., (© 2023. The Author(s).)

Acute myeloid leukemia may be characterized by a fraction of leukemia stem cells (LSCs) that sustain disease propagation eventually leading to relapse. Yet, the contribution of LSCs to early therapy resistance and AML regeneration remains controversial. We prospectively identify LSCs in AML patients and xenografts by single-cell RNA sequencing coupled with functional validation by a microRNA-126 reporter enriching for LSCs. Through nucleophosmin 1 (NPM1) mutation calling or chromosomal monosomy detection in single-cell transcriptomes, we discriminate LSCs from regenerating hematopoiesis, and assess their longitudinal response to chemotherapy. Chemotherapy induced a generalized inflammatory and senescence-associated response. Moreover, we observe heterogeneity within progenitor AML cells, some of which proliferate and differentiate with expression of oxidative-phosphorylation (OxPhos) signatures, while others are OxPhos (low) miR-126 (high) and display enforced stemness and quiescence features. miR-126 (high) LSCs are enriched at diagnosis in chemotherapy-refractory AML and at relapse, and their transcriptional signature robustly stratifies patients for survival in large AML cohorts., (© 2023. The Author(s).)

There is controversy around the mechanisms that guided the change in brain shape during the evolution of modern humans. It has long been held that different cortical areas evolved independently from each other to develop their unique functional specializations. However, some recent studies suggest that high integration between different cortical areas could facilitate the emergence of equally extreme, highly specialized brain functions. Here, we analyse the evolution of brain shape in primates using three-dimensional geometric morphometrics of endocasts. We aim to determine, firstly, whether modern humans present unique developmental patterns of covariation between brain cortical areas; and secondly, whether hominins experienced unusually high rates of evolution in brain covariation as compared to other primates. On the basis of analyses including modern humans and other extant great apes at different developmental stages, we first demonstrate that, unlike our closest living relatives, Homo sapiens retain high levels of covariation between cortical areas into adulthood. Among the other great apes, high levels of covariation are only found in immature individuals. Secondly, at the macro-evolutionary level, our analysis of 400 endocasts, representing 148 extant primate species and 6 fossil hominins, shows that strong covariation between different areas of the brain in H. sapiens and Homo neanderthalensis evolved under distinctly higher evolutionary rates than in any other primate, suggesting that natural selection favoured a greatly integrated brain in both species. These results hold when extinct species are excluded and allometric effects are accounted for. Our findings demonstrate that high covariation in the brain may have played a critical role in the evolution of unique cognitive capacities and complex behaviours in both modern humans and Neanderthals., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

This paper is based on a retrospective longitudinal study on people living with HIV under antiretroviral treatment (ART) where allelic variants (either heterozygous CT genotype or homozygous CC genotype) have been evaluated at position -168 of the promoter region of the protein kinase R (-168/PKR). In general, antiviral effects of interferon are partially mediated by a RNA-dependent protein kinase (PKR) that, once activated, inhibits protein synthesis. Indeed, activation of PKR response can inhibit HIV replication. To explore the role of allelic variants in shaping dynamics of commonly monitored HIV biomarkers, CD4 cells, CD8 cells and HIV-load were modelled within a latent class mixed model (LCMM) to account for participants' heterogeneity over time. The estimated models identified two sub-groups from CD4 and HIV-load dynamics, revealing better outcomes for subgroups of participants with the heterozygous CT genotype. Heterozygous CT subjects in one of the two identified subgroups exhibited higher increase of CD4 cells and more marked decrease of HIV-load, over time, with respect to the homozygous CC subjects assigned to the same group., (© 2022. The Author(s).)

Competing Interests: Conflict of interest: None declared.

Background and Objectives: Data on the clinical efficacy of EUS-guided ablation using the HybridTherm-Probe (EUS-HTP) in locally advanced pancreatic ductal adenocarcinoma (LA-PDAC) are lacking. The aim of the study was to assess the impact of EUS-HTP added to chemotherapy (CT) on overall survival (OS) and progression-free survival (PFS) of LA-PDAC patients with local disease progression (DP) after first-line therapy, compared to CT alone in controls., Methods: LA-PDAC cases, prospectively treated by EUS-HTP, were retrospectively compared to matched controls (1:2) receiving standard treatment. Study endpoints were the OS and PFS from local DP after first-line therapy, compared through log-rank test calculating hazard ratios and differences in restricted mean OS/PFS time (RMOST/RMPFST) within prespecified time points (4, 6, and 12 months)., Results: Thirteen cases and 26 controls were included. Clinical, tumor, and therapy features before and after first-line therapy were case-control balanced. The median OS and PFS were not significantly improved in cases over controls (months: 7 vs. 5 and 5 vs. 3, respectively). At 4 and 6 months, the RMPFST difference was in favor of cases (P = 0.0001 and P = 0.003, respectively). In cases and controls not candidate to further CT (N = 5 and N = 9), the median OS and PFS were not significantly improved in cases over controls (months: 6 vs. 3 and 4 vs. 2, respectively), but the RMPFST difference was in favor of cases at 4 months (P = 0.002)., Conclusions: In locally progressive PDAC patients experiencing failure of first-line therapy, EUS-HTP achieves a significantly better RMPFST up to 6 months compared to standard treatment, although without a significant impact on OS., Competing Interests: None

Purpose: To develop and validate an effective and user-friendly AI platform based on a few unbiased clinical variables integrated with advanced CT automatic analysis for COVID-19 patients' risk stratification., Material and Methods: In total, 1575 consecutive COVID-19 adults admitted to 16 hospitals during wave 1 (February 16-April 29, 2020), submitted to chest CT within 72 h from admission, were retrospectively enrolled. In total, 107 variables were initially collected; 64 extracted from CT. The outcome was survival. A rigorous AI model selection framework was adopted for models selection and automatic CT data extraction. Model performances were compared in terms of AUC. A web-mobile interface was developed using Microsoft PowerApps environment. The platform was externally validated on 213 COVID-19 adults prospectively enrolled during wave 2 (October 14-December 31, 2020)., Results: The final cohort included 1125 patients (292 non-survivors, 26%) and 24 variables. Logistic showed the best performance on the complete set of variables (AUC = 0.839 ± 0.009) as in models including a limited set of 13 and 5 variables (AUC = 0.840 ± 0.0093 and AUC = 0.834 ± 0.007). For non-inferior performance, the 5 variables model (age, sex, saturation, well-aerated lung parenchyma and cardiothoracic vascular calcium) was selected as the final model and the extraction of CT-derived parameters was fully automatized. The fully automatic model showed AUC = 0.842 (95% CI: 0.816-0.867) on wave 1 and was used to build a 0-100 scale risk score (AI-SCoRE). The predictive performance was confirmed on wave 2 (AUC 0.808; 95% CI: 0.7402-0.8766)., Conclusions: AI-SCoRE is an effective and reliable platform for automatic risk stratification of COVID-19 patients based on a few unbiased clinical data and CT automatic analysis., (© 2022. The Author(s).)

This work analyzes nitrogen dioxide (NO 2 ) pollution over a set of cities in the Po Valley in northern Italy, using satellite and in situ observations. The cities include Milan, Bergamo, and Brescia, the first area of the COVID-19 outbreak and diffusion in Italy, with a higher mortality rate than in other parts of Italy and Europe. The analysis was performed for three years, from May 2018 to April 2021, including the period of first-wave diffusion of COVID-19 over the Po Valley, that is, January 2020-April 2020. The study aimed at giving a more general picture of the NO 2 temporal and spatial variation, possibly due to the lockdown adopted for the pandemic crisis containment and other factors, such as the meteorological conditions and the seasonal cycle. We have mainly investigated two effects: first, the correlation of NO 2 pollution with atmospheric parameters such as air and dew point temperature, and second the possible correlation between air quality and COVID-19 deaths, which could explain the high mortality rate. We have found a good relationship between air quality and temperature. In light of this relationship, we can conclude that the air quality improvement in March 2020 was primarily because of the lockdown adopted to prevent and limit virus diffusion. We also report a good correlation between NO 2 pollution and COVID-19 deaths, which is not seen when considering a reference city in the South of Italy. The critical factor in explaining the difference is the persistence of air pollution in the Po Valley in wintertime. We found that NO 2 pollution shows a seasonal cycle, yielding a non-causal correlation with the COVID-19 deaths. However, causality comes in once we read the correlation in the context of current and recent epidemiological evidence and leads us to conclude that air pollution may have acted as a significant risk factor in boosting COVID-19 fatalities., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s).)

Respiratory syncytial virus (RSV) infection is the most common cause of hospitalization in young children. In the last 2 years, public health measures aimed at controlling the spread of SARS-CoV-2 have affected the epidemiology and seasonality of RSV worldwide. The aim of this descriptive retrospective observational study was to describe the characteristics of children hospitalized with RSV in an academic tertiary care hospital in Southern Italy in 2021. We also investigate the seasonal trends of RSV from 2017 to 2021. The demographic characteristics, comorbidities, clinical data, and coinfections were retrospectively evaluated. Compared with previous seasons, the 2021 outbreak of RSV was characterized by an increased number of patients, with a delayed peak observed in November. Overall, 179 children, including 128 (71.5%) aged <12 months, were hospitalized for RSV infection between August and December 2021. Ten children (5.6%) were admitted to the intensive care unit (ICU), all aged <5 months. One patient (0.5%) aged <1 month with severe comorbidities died. The severity of symptoms was significantly associated with younger age, underlying chronic disease, and the length of hospital stay (p < 0.05 each). History of prematurity was not significantly associated with the presence of coinfections. Because of the high burden of RSV infection and the expected larger RSV epidemics resulting from a greater number of RSV-naïve children, systematic epidemiological and virological surveillance is needed. Appropriate pathways for access to RSV prevention in all infants should also be introduced.

Background: The COVID-19 pandemic has accelerated the adoption of digital tools to support individuals struggling with their mental health. The use of a digital intervention plus human coaching ("dual" intervention) is gaining momentum in increasing overall engagement in digital cognitive behavioral interventions (dCBIs). However, there is limited insight into the methodologies and coaching models used by those deploying dual interventions. To achieve a deeper understanding, we need to identify and promote effective engagement that leads to clinical outcomes versus simply monitoring engagement metrics. Motivational interviewing (MI) is a collaborative, goal-oriented communication approach that pays particular attention to the language of change and is an effective engagement approach to help people manage mental health issues. However, this approach has been traditionally used for in-person or telephonic interventions, and less is known about the application of MI to digital interventions., Objective: We sought to provide a dual intervention approach and address multiple factors across two levels of engagement to operationalize a dCBI that combined cognitive behavioral therapy-based techniques and MI-based interactions between the digital health coach (DHC) and user., Methods: We reviewed hundreds of digital exchanges between DHCs and users to identify and improve training and quality assurance activities for digital interventions., Results: We tested five hypotheses and found that: (1) users of a dual digital behavioral health intervention had greater engagement levels than users of a noncoached intervention (P<.001); (2) DHCs with a demonstrated competency in applying MI to digital messages had more engaged users, as measured by the DHC-to-user message exchange ratio (P<.001); (3) the DHC-to-user message exchange ratio was correlated with more engagement in app activities (r=0.28, 95% CI 0.23-0.33); (4) DHCs with demonstrated MI proficiency elicited a greater amount of "change talk" from users than did DHCs without MI proficiency (H=25.12, P<.001); and (5) users who were engaged by DHCs with MI proficiency had better clinical outcomes compared to users engaged by DHCs without MI proficiency (P=.02)., Conclusions: To our knowledge, this pilot was the first of its kind to test the application of MI to digital coaching protocols, and it demonstrated the value of MI proficiency in digital health coaching for enhanced engagement and health improvement. Further research is needed to establish coaching models in dCBIs that incorporate MI to promote effective engagement and optimize positive behavioral outcomes., (©Catherine Serio, Amanda Gabarda, Fatma Uyar-Morency, Valerie Silfee, Justin Ludwig, Eva Szigethy, Susan Butterworth. Originally published in JMIR Formative Research (https://formative.jmir.org), 11.05.2022.)

The COVID-19 pandemic cast a dramatic spotlight on the use of data as a fundamental component of good decision-making. Evaluating and comparing alternative policies required information on concurrent infection rates and insightful analysis to project them into the future. Statisticians in Israel were involved in these processes early in the pandemic in some silos as an ad-hoc unorganized effort. Informal discussions within the statistical community culminated in a roundtable, organized by three past presidents of the Israel Statistical Association, and hosted by the Samuel Neaman Institute in April 2021. The meeting was designed to provide a forum for exchange of views on the profession's role during the COVID-19 pandemic, and more generally, on its influence in promoting evidence-based public policy. This paper builds on the insights and discussions that emerged during the roundtable meeting and presents a general framework, with recommendations, for involving statisticians and statistics in decision-making., (© 2022. The Author(s).)