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This paper focuses on the linking potentials offered by the EpiLexO web-based front-end for creating and editing an ecosystem of digital resources for ancient languages, developed in the context of a project on the languages of fragmentary attestation of ancient Italy. The focus is particularly on mechanisms introduced for linking lexical information to other information bits either internally or externally, e.g., for creating attestations by linking lexical forms to their variants in relevant inscriptions, as well as for linking lexical data to external independent LOD datasets available on a remote endpoint. Finally, in the conclusions, we briefly introduce some future planned or desired enhancements as well as the final platform component, a parallel interface that constitutes the fruition application, which will be open to anyone on the web and will allow for browsing, searching, cross-querying and visualizing the created set of interlinked resources.

A mandioca apresenta ampla diversidade genética, podendo ser analisada por meio de marcadores moleculares. Dentre os disponíveis, estão os ISSR que são marcadores dominantes, universais e com alto índice de polimorfismo. Diante disso, esse estudo tem como objetivo avaliar a diversidade genética entre etnovariedades de mandioca cultivadas em assentamentos rurais no norte do estado de Mato Grosso, por meio de marcadores moleculares ISSR. Foram coletadas folhas de 30 etnovariedades cultivadas em três assentamentos rurais (São Paulo, Jacaminho e São Pedro) localizados em três municípios (Carlinda, Alta Floresta e Paranaíta) no norte do estado de Mato Grosso, Brazil. Para a extração do DNA total, seguiu-se o método CTAB. As amplificações foram realizadas via PCR utilizando 15 primers ISSR. Os primers ISSR amplificaram 190 fragmentos, dos quais 76,32% foram polimórficos. Os métodos de agrupamento formaram cinco grupos, demonstrando que há diversidade genética entre as etnovariedades de mandioca, com destaque para JAC09 (Cacau talo roxo) e SPA04 (Mandioca pão) como as mais divergentes dentro do acervo. Os assentamentos rurais são importantes locais para a conservação on farm da espécie.

Introduction: Nailfold video-capillaroscopy (NVC) is a non-invasive cost-effective technique involving the microscopic examination of small blood vessels of the distal nailfold with a magnification device. It provides valuable information regarding the microcirculation including anomalies such as tortuous or dilated capillaries, hemorrhages, and avascular areas, which can characterize connective tissue diseases. The utility of NVC in the diagnosis and monitoring of systemic sclerosis (SSc) has been investigated in numerous studies allowing the distinction of the specific microvascular pattern of scleroderma from different conditions other than scleroderma (non-scleroderma pattern). Sarcoidosis (SA) is a systemic inflammatory disease that can affect various organs, including the lungs, skin, and lymph nodes. The purpose of our review was to evaluate the current state of the art in the use of NVC in the diagnosis of SA, to understand the indications for its use and any consequent advantages in the management of the disease in different settings in terms of benefits for patients. Materials and Methods: We searched for the key terms “sarcoidosis” and “video-capillaroscopy” in a computerized search of Pub-Med, extending the search back in time without setting limits. We provided a critical overview of the literature, based on a precise evaluation. After our analysis, we examined the six yielded works looking for answers to our questions. Results: Few studies have evaluated that microcirculation is often compromised in SA, with alterations in blood flow and consequent tissue damage. Discussion: Basing on highlighted findings, NVC appears to be a useful tool in the initial evaluation of sarcoidosis patients. Furthermore, capillaroscopy is useful in the evaluation of the coexistence of sarcoidosis and scleroderma spectrum disorder or overlap syndromes. Conclusions: In conclusions, no specific pattern has been described for sarcoidosis, and further re-search is needed to fully understand the implications of nailfold capillaroscopy find-ings in this disease and to establish standardized guidelines for its use in clinical practice.

There is considerably greater variation in metabolic rates between men than between women, in terms of basal, activity and total (daily) energy expenditure (EE). One possible explanation is that EE is associated with male sexual characteristics (which are known to vary more than other traits) such as musculature and athletic capacity. Such traits might be predicted to be most prominent during periods of adolescence and young adulthood, when sexual behaviour develops and peaks. We tested this hypothesis on a large dataset by comparing the amount of male variation and female variation in total EE, activity EE and basal EE, at different life stages, along with several morphological traits: height, fat free mass and fat mass. Total EE, and to some degree also activity EE, exhibit considerable greater male variation (GMV) in young adults, and then a decreasing GMV in progressively older individuals. Arguably, basal EE, and also morphometrics, do not exhibit this pattern. These findings suggest that single male sexual characteristics may not exhibit peak GMV in young adulthood, however total and perhaps also activity EE, associated with many morphological and physiological traits combined, do exhibit GMV most prominently during the reproductive life stages.

Surface water can exhibit a range of colours beyond the expected blue or green. These anomalous colourations can be triggered by different factors, both natural and anthropogenic, and not always are signs of pollution. This note explores the phenomenon of water discolouration, focusing on natural causes and analysing how factors such as algal and bacterial blooms influence water colour. The study provides examples of specific events that occurred in the Emilia-Romagna region and documented by ARPAE and highlights the importance of monitoring these colouration events in order to provide valuable insights into the health of water bodies and the surrounding environment.

Purpose: To investigate the potential role of radiomics-based machine learning in differentiating small renal oncocytoma (RO) from clear cells carcinoma (ccRCC) on contrast-enhanced CT (CECT). Material and methods: Fifty-two patients with small renal masses who underwent CECT before surgery between January 2016 and December 2020 were retrospectively included in the study. At pathology examination 39 ccRCC and 13 RO were identified. All lesions were manually delineated unenhanced (B), arterial (A) and venous (V) phases. Radiomics features were extracted using three different fixed bin widths (bw) of 25 HU, 10 HU, and 5 HU from each phase (B, A, V), and with different combinations (B+A, B+V, B+A+V, A+V), leading to 21 different datasets. Montecarlo Cross Validation technique was used to quantify the estimator performance. The final model built using the hyperparameter selected with Optuna was trained again on the training set and the final performance evaluation was made on the test set. Results: The A+V bw 10 achieved the greater median (IQR) balanced accuracy considering all the models of 0.70 (0.64–0.75), while A bw 10 considering only the monophasic ones. The A bw 10 model achieved a median (IQR) sensitivity of 0.60 (0.40–0.60), specificity of 0.80 (0.73–0.87), AUC-ROC of 0.77 (0.66–0.84), accuracy of 0.75 (0.70–0.80), and a Phi Coefficient of 0.38 (0.20–0.47). None of the nine models with the lowest mean balanced accuracy values implemented features from A. Conclusion: The A bw 10 model was identified as the most efficient mono-phasic model in differentiating small RO from ccRCC.

Objectives In systemic sclerosis (SSc), gastrointestinal involvement is one of the earliest events. We compared the gut microbiota (GM), its short-chain fatty acids (SCFAs) and host-derived free fatty acids (FFAs) in patients with very early diagnosis of SSc (VEDOSS) and definite SSc.Methods Stool samples of 26 patients with SSc, 18 patients with VEDOSS and 20 healthy controls (HC) were collected. The GM was assessed through 16S rRNA sequencing, while SCFAs and FFAs were assessed by gas chromatography-mass spectrometry.Results In patients with VEDOSS, an increase in Bacteroidales and Oscillospirales orders and a decrease in Bacilli class, Blautia, Romboutsia, Streptococcus and Turicibacter genera was detected in comparison with HC. In patients with SSc, an elevated number of Acidaminococcaceae and Sutterellaceae families, along with a decrease of the Peptostreptococcaceae family and Anaerostipes, Blautia, Romboutsia and Turicibacter genera was found in comparison with HC. Patients with SSc and VEDOSS had a significantly lower butyrate and higher acetate with respect to HC. In VEDOSS, an increase in Oscillospiraceae family and Anaerostipes genus, and a decrease in Alphaproteobacteria class, and Lactobacillales order was identified with respect to SSc. Moreover, patients with VEDOSS exhibited higher acetate and lower valerate compared with definite SSc.Conclusion A GM dysbiosis with depletion of beneficial anti-inflammatory bacteria (especially butyrate-producing) and a significant decrease in faecal butyrate was identified in patients with VEDOSS. This early GM imbalance may foster the growth of inflammatory microbes, worsening intestinal dysbiosis and inflammation in early SSc stages. The potential butyrate administration in early disease phases might be considered as a novel therapeutic approach to mitigate gastrointestinal discomfort and progression preserving patient’s quality of life.

This research paper introduces an innovative approach to predicting failures in Local Area Network (LAN) switches, combining Double Exponential Smoothing (DES) with a suite of Machine Learning (ML) algorithms including Random Forest (RF), Logistic Regression (LR), Decision Trees (DT), and Support Vector Machines (SVM). The primary objective of this study is to enhance the accuracy and timeliness of LAN switch failure predictions, thereby facilitating more proactive and effective network management. Our methodology involves the integration of DES for trend analysis and forecasting in time-series data, with the advanced predictive capabilities of the aforementioned ML algorithms. This hybrid approach not only leverages the strengths of DES in identifying underlying patterns in failure data but also capitalizes on the diverse predictive models to handle various aspects of failure prediction more robustly. The paper details the process of data collection, preprocessing, and the specific application of DES and each ML algorithm to the dataset. A notable contribution of this research is the development of a framework that effectively combines the output of DES with ML models, leading to a significant improvement in predictive accuracy as compared to traditional methods. Through rigorous testing and validation; the proposed approach demonstrated a marked increase in the precision and reliability of failure predictions. The results indicate that the integration of DES with ML algorithms can substantially aid in preemptive maintenance and decision-making processes in LAN management. The implications of these findings are profound, suggesting that such a combined approach can greatly enhance network stability and efficiency. While the focus of this study is on LAN switches, the methodology has the potential for broader applications in various fields of network management and predictive maintenance.

Abstract Legal reserve areas (LRAs) are a fundamental part of the Brazilian conservation strategy, together with permanent preservation areas. The LRAs are intended to maintain biodiversity and can be managed sustainably. When these areas are home to ecosystems that depend on fire and grazing, such as native grasslands and savannas, management practices that are suitable for their conservation and for dealing with the effects of global climate change should be adopted. However, this subject is still poorly discussed in Brazil, and public policies are not clear on this matter. This review article describes the grassland and savanna ecosystems in Brazil, the legal aspects related to the management of LRAs, the current and future climate scenarios, and the relationship between climate and fire risk. It also presents a review about the use of fire and grazing in grassland and savanna ecosystems, the legal challenges related to their application in LRAs, and the use of geotechnologies to monitor these practices. The conclusion is that grazing and fire, as management tools, are adequate for LRA functions, as long as they are practiced in accordance with legal and scientifically based standards to avoid the negative effects of their incorrect use.

Accurate river hydraulic characterization is fundamental to assess flood risk, parametrize flood forecasting models, and develop river maintenance workflows. River hydraulic roughness and riverbed/floodplain geometry are the main factors controlling inundation extent and water levels. However, gauging stations providing hydrometric observations are declining worldwide, and they provide point measurements only. To describe hydraulic processes, spatially distributed data are required. In situ surveys are costly and time-consuming, and they are sometimes limited by local accessibility conditions. Satellite earth observation (EO) techniques can be used to measure spatially distributed hydrometric variables, reducing the time and cost of traditional surveys. Satellite EO provides high temporal and spatial frequency, but it can only measure large rivers (wider than ca. 50 m) and only provides water surface elevation (WSE), water surface slope (WSS), and surface water width data. UAS hydrometry can provide WSE, WSS, water surface velocity and riverbed geometry at a high spatial resolution, making it suitable for rivers of all sizes. The use of UAS hydrometry can enhance river management, with cost-effective surveys offering large coverage and high-resolution data, which are fundamental in flood risk assessment, especially in areas that difficult to access. In this study, we proposed a combination of UAS hydrometry techniques to fully characterize the hydraulic parameters of a river. The land elevation adjacent to the river channel was measured with LiDAR, the riverbed elevation was measured with a sonar payload, and the WSE was measured with a UAS radar altimetry payload. The survey provided 57 river cross-sections with riverbed elevation, and 8 km of WSE and land elevation and took around 2 days of survey work in the field. Simulated WSE values were compared to radar altimetry observations to fit hydraulic roughness, which cannot be directly observed. The riverbed elevation cross-sections have an average error of 32 cm relative to RTK GNSS ground-truth measurements. This error was a consequence of the dense vegetation on land that prevents the LiDAR signal from reaching the ground and underwater vegetation, which has an impact on the quality of the sonar measurements and could be mitigated by performing surveys during winter, when submerged vegetation is less prevalent. Despite the error of the riverbed elevation cross-sections, the hydraulic model gave good estimates of the WSE, with an RMSE below 3 cm. The estimated roughness is also in good agreement with the values measured at a gauging station, with a Gauckler–Manning–Strickler coefficient of M = 16–17 m1/3/s. Hydraulic modeling results demonstrate that both bathymetry and roughness measurements are necessary to obtain a unique and robust hydraulic characterization of the river.

Background: Non-muscle invasive bladder cancer (NMIBC) patients are affected by a high risk of recurrence. The topography of collagen fibers represents a hallmark of the neoplastic extracellular microenvironment. Objective: Assess the topographic change associated with different stages of bladder cancer (from neoplastic lesions to bona fide tumor) and whether those changes favour the development of NMIBC. Design, Setting, and Participants: Seventy-one clinical samples of urothelial carcinoma at different stages were used. Topographic changes preceding tumor onset and progression were evaluated in the rat bladder cancer model induced by nitrosamine (BBN), a bladder-specific carcinogen. The preclinical model of actinic cystitis was also used in combination with BBN. Validated hematoxylin-eosin sections were used to assess the topography of collagen fibrils associated with pre-tumoral steps, NMIBC, and MIBC. Findings: Linearization of collagen fibers was higher in Cis and Ta vs. dysplastic urothelium, further increased in T1 and greatest in T2 tumors. In the BBN preclinical model, an increase in the linearization of collagen fibers was established since the beginning of inflammation, such as the onset of atypia of a non-univocal nature and dysplasia, and further increased in the presence of the tumor. Linearization of collagen fibers in the model of actinic cystitis was associated with earlier onset of BBN-induced tumor. Conclusions: The topographic modification of the extracellular microenvironment occurs during the inflammatory processes preceding and favoring the onset of bladder cancer. The topographic reconfiguration of the stroma could represent a marker for identifying and treating the non-neoplastic tissue susceptible to tumor recurrence.

Introduction Studies on the impacts of COVID-19 on patient safety are emerging. However, few studies have elicited the perspectives of front-line clinicians.Methods We interviewed clinicians from 16 US hospitals who worked in the emergency department, intensive care unit or inpatient unit during the COVID-19 pandemic. We asked about their experiences with both clinician well-being and patient care throughout the pandemic. We used a rigorous thematic analysis to code the interview transcripts. This study was part of a larger randomised control trial of an intervention to improve healthcare worker well-being during the COVID-19 pandemic; the findings described here draw from clinicians who spontaneously raised issues related to patient safety.Results 11 physicians and 16 nurses in our sample raised issues related to patient safety. We identified two primary themes: (1) compromised access to healthcare and (2) impaired care delivery. First, clinicians discussed how changes in access to healthcare early in the pandemic–including a shift to telehealth and deferred care–led to delays in accurate diagnosis and patients presenting later in their disease course. Second, clinicians discussed the effects of COVID-19 on care delivery related to staffing, equipment shortages and space constraints and how they deviated from the standard of care to manage these constraints. Clinicians noted how these issues led to patient safety events such as central line infections, patient falls and serious medication administration errors.Conclusions Several well-intentioned interventions implemented in the early weeks of the pandemic created a unique context that affected patient safety throughout the pandemic. Future pandemic preparedness should consider planning that incorporates a patient safety lens to mitigate further harm from occurring during a public health crisis.

Abstract Although once regarded as a unique human feature, tool-use is widespread in the animal kingdom. Some of the most proficient tool-users are our closest living relatives, chimpanzees. These repertoires however consist primarily of tool use, rather than tool manufacture (for later use). Furthermore, most populations of chimpanzees use organic materials, such as sticks and leaves, rather than stones as tools. This distinction may be partly ecological, but it is also important as chimpanzees are often used as models for the evolution of human material culture, the oldest traces of which consist of manufactured sharp stone tools (so-called “flakes”). Thus, examining the conditions (if any) under which chimpanzees may develop flake manufacture and use can provide insight into the drivers of these behaviours in our own lineage. Previous studies on non-human apes’ ability to make and use flakes focused on enculturated apes, giving them full demonstrations of the behaviour immediately, without providing social information on the task in a stepwise manner. Here we tested naïve, captive chimpanzees (N = 4; three potentially enculturated and one unenculturated subject) in a social learning experimental paradigm to investigate whether enculturated and/or unenculturated chimpanzees would develop flake making and use after social information of various degrees (including a human demonstration) was provided in a scaffolded manner. Even though social learning opportunities were provided, neither the unenculturated subject nor any of the potentially enculturated subjects made or used flakes, in stark contrast to previous studies with enculturated apes. These data suggest that flake manufacture and use is outside of our tested group of captive chimpanzees’ individual and social learning repertoires. It also suggests that high levels of enculturation alongside human demonstrations (and/or training) may be required before captive chimpanzees can develop this behaviour.

Digital solutions in the field of restorative neurology offer significant assistance, enabling patients to engage in rehabilitation activities remotely. This research introduces ReMoVES, an Internet of Medical Things (IoMT) system delivering telemedicine services specifically tailored for multiple sclerosis rehabilitation, within the overarching framework of the STORMS project. The ReMoVES platform facilitates the provision of a rehabilitative exercise protocol, seamlessly integrated into the Individual Rehabilitation Project, curated by a multidimensional medical team operating remotely. This manuscript delves into the second phase of the STORMS pilot feasibility study, elucidating the technology employed, the outcomes achieved, and the practical, professional, and academic implications. The STORMS initiative, as the genesis of digital telerehabilitation solutions, aims to enhance the quality of life for multiple sclerosis patients.

Background and Objectives: In patients with severe aortic stenosis (AS), left ventricular systolic dysfunction is one of the main predictors of adverse events after surgical aortic valve replacement (SAVR). However, more patients undergo surgery earlier, often with preserved systolic function. In these cases, global longitudinal strain (GLS) has been proposed as a marker of ventricular remodeling post-surgery. This study aims to evaluate GLS variation in patients undergoing SAVR and explore differences across the diastolic dysfunction classes. Methods: From June 2020 to March 2023, patients with AS and preserved ejection fraction (EF) requiring SAVR were enrolled. Echocardiographic evaluations were conducted preoperatively, seven days post-surgery, and twelve months after surgery. Patients were divided into two groups based on the severity of diastolic dysfunction: Group A (grade I) and Group B (grades II–III). Results: The final analysis included 108 patients (mean age 71.3 ± 7.2 years). Twenty-two patients (20.4%) also underwent coronary artery bypass grafting (CABG). The preoperative EF averaged 61.6 ± 6.03%, with no significant differences between groups. Preoperative GLS was 16 ± 4.3%, decreasing to 12.8 ± 3.4% postoperatively (p < 0.0001). GLS was comparable between the groups preoperatively (p = 0.185) and postoperatively (0.854). After twelve months, GLS improved in both groups (Group A: 17.7 ± 3.4%, Group B: 15.7 ± 3.2%, p < 0.0001), but only Group A showed significant improvement from preoperative values (p = 0.018). SAVR improved GLS regardless of CABG intervention. Conclusions: SAVR in patients with preserved LVEF results in an early reduction in GLS, regardless of diastolic dysfunction. After twelve months, GLS improved significantly, with significant recovery only in patients with mild dysfunction.

In theory, comprehensive two-dimensional liquid chromatography (2D-LC) allows for significant enhanced peak capacity compared to one-dimensional high performance LC (1D-HPLC). However, reaching such a separation performance while also obtaining robust, easily implementable, and sensitive methods proves challenging. Because it can hinder the broader use of 2D-LC, there is a need for developing easier, more trouble-free approaches that feature the benefits of LCxLC while not compromising with what can be done with 1D-HPLC. Commercial 2D-LC interfaces are based on two-position multiport valves composed of two loops, which are alternatingly used either to collect the effluent from the first dimension ([.sup.1]D), or to inject their content to the second dimension ([.sup.2]D). This design implies that if large sampling volumes transferred to the second column need to be avoided, a comparatively (much) higher flow rate and broader column i.d. is required for the second column. However, doing so can lead to a loss in sensitivity because of dilution and impractical analytical chromatography as a result of the high flow rates involved. In most LCxLC column combinations, this problem is exacerbated thanks to the high eluotropic strength of transferred loop volumes. However, when the elution strength of the transferred solvent is very small, refocusing the analytes can be obtained, which allows the user to overcome such issues. For example, this is the case when a purely aqueous separation mode is combined with reversed-phase LC (RPLC) in the [.sup.1]D and [.sup.2]D, respectively. Temperature responsive LC (TRLC), which is an emerging LC mode requiring only water as the mobile phase and whereby retention is controlled via temperature only, is promising in this context. In this second installment about TRLC, we illustrate the unique benefits of the combination of this separation mode with RPLC in comprehensive 2D-LC . The potential of the approach is shown through the analysis of representative standard mixtures, active pharmaceutical ingredients, synthetic impurities and phenolics in natural products., Temperature-responsive liquid chromatography (TRLC) is a separation mode in LC that allows for reversedphase (RP)-type separations under purely aqueous conditions. As a result, retention is controlled through column temperature (gradients), [...]

RESUMO A Covid-19 é uma doença multissistêmica e consequências funcionais e tardias estão em estudo. Sequelas psicológicas e neurocognitivas podem comprometer a Capacidade para o Trabalho (CT) dos trabalhadores. Objetivou-se investigar a CT de pessoas previamente infectadas pelo Sars-CoV-2, correlacionando-a com avaliação da sonolência, ansiedade, depressão e fadiga. Estudo transversal, com trabalhadores diagnosticados com Covid-19 e em acompanhamento no Serviço de Neurologia da Universidade Estadual de Campinas (Unicamp). Aplicou-se o instrumento Índice de Capacidade para o Trabalho (ICT), um formulário com dados sociodemográficos e ocupacionais, bem como escalas de sonolência, ansiedade, depressão e fadiga. Dos 119 trabalhadores que participaram do estudo, mais da metade apresentaram comprometimento da CT (52,9%). Distúrbio emocional foi o agravo relatado mais frequente (31,9%). A regressão logística múltipla mostrou que a interação entre ansiedade e sonolência esteve associada ao comprometimento da CT (OR=4,50 com p=0,002). Ansiedade e sonolência foram alterações tardias da Covid-19 e associadas ao comprometimento da CT dos trabalhadores avaliados. Este estudo demonstra a necessidade de que todos os trabalhadores com teste positivo por Covid-19 tenham sua CT avaliada por ocasião do retorno ao trabalho. Ações de promoção à saúde, reabilitação funcional e adaptação do trabalho de acordo com as sequelas apresentadas pelos trabalhadores.

Objective: Incidences of post-transurethral resection of the prostate (post-TURP) strictures are between 2.2% and 9.8%. Stricture commonly occurs within the first 6 months. Our objective was to assess the outcomes of patients with obliterative strictures post-TURP that underwent a double-face urethroplasty. Methods: This is a single-center prospective study of 17 patients with obliterative proximal bulbar stricture post-TURP who underwent double-face graft urethroplasty by two surgeons between January 2014 and January 2020. We defined post-TURP obliterative strictures as those patients who presented with complete or almost complete obstruction of the urethral lumen and who have had a history of acute urine retention. We have excluded patients with bladder neck contracture. Primary outcome was treatment success, defined as the no need for further treatments. Secondary outcome was post-urethroplasty continent rate. Results: Seventeen patients were included in the study with median age of 66 (interquartile range 40–77) years; median time of follow-up was 24 (interquartile range 12–84) months; median stricture length was 4 (interquartile range 2–6) cm. Of the 17 patients, 15 (88.2%) were successful. All patients were continent after urethroplasty. Conclusion: With mid-term follow-up, treatment of obliterative proximal bulbar strictures with double-face buccal mucosa graft is a safe and effective procedure. Obliterative proximal bulbar strictures merit double-face urethroplasty with high-rate success and functional outcomes.

Acute myeloid leukemia (AML) is an aggressive heterogeneous disease characterized by several alterations of the immune system prompting disease progression and treatment response. The therapies available for AML can affect lymphocyte function, limiting the efficacy of immunotherapy while hindering leukemia-specific immune reactions. Recently, the treatment based on Venetoclax (VEN), a specific B-cell lymphoma 2 (BCL-2) inhibitor, in combination with hypomethylating agents (HMAs) or low-dose cytarabine, has emerged as a promising clinical strategy in AML. To better understand the immunological effect of VEN treatment, we characterized the phenotype and immune checkpoint (IC) receptors’ expression on CD4+ and CD8+ T cells from AML patients after the first and second cycle of HMA in combination with VEN. HMA and VEN treatment significantly increased the percentage of naïve CD8+ T cells and TIM-3+ CD4+ and CD8+ T cells and reduced cytokine-secreting non-suppressive T regulatory cells (Tregs). Of note, a comparison between AML patients treated with HMA only and HMA in combination with VEN revealed the specific contribution of VEN in modulating the immune cell repertoire. Indeed, the reduction of cytokine-secreting non-suppressive Tregs, the increased TIM-3 expression on CD8+ T cells, and the reduced co-expression of PD-1 and TIM-3 on both CD4+ and CD8+ T cells are all VEN-specific. Collectively, our study shed light on immune modulation induced by VEN treatment, providing the rationale for a novel therapeutic combination of VEN and IC inhibitors in AML patients.

The impact of common and rare variants in COVID-19 host genetics has been widely studied. In particular, in Fallerini et al. (Human genetics, 2022, 141, 147–173), common and rare variants were used to define an interpretable machine learning model for predicting COVID-19 severity. First, variants were converted into sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. After that, the Boolean features, selected by these logistic models, were combined into an Integrated PolyGenic Score (IPGS), which offers a very simple description of the contribution of host genetics in COVID-19 severity.. IPGS leads to an accuracy of 55%–60% on different cohorts, and, after a logistic regression with both IPGS and age as inputs, it leads to an accuracy of 75%. The goal of this paper is to improve the previous results, using not only the most informative Boolean features with respect to the genetic bases of severity but also the information on host organs involved in the disease. In this study, we generalize the IPGS adding a statistical weight for each organ, through the transformation of Boolean features into “Boolean quantum features,” inspired by quantum mechanics. The organ coefficients were set via the application of the genetic algorithm PyGAD, and, after that, we defined two new integrated polygenic scores (IPGSph1 and IPGSph2). By applying a logistic regression with both IPGS, (IPGSph2 (or indifferently IPGSph1) and age as inputs, we reached an accuracy of 84%–86%, thus improving the results previously shown in Fallerini et al. (Human genetics, 2022, 141, 147–173) by a factor of 10%.