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INTRODUCTION: Haematological reference values are very important for diagnostic orientation and treatment decision. The aim of this study was to establish haematological reference values for Malian healthy adults. METHODS: a cross-sectional study including 161 male Malians aged between 19 and 54 years old was performed. Median and reference ranges were calculated for haematological and biochemical parameters. Parametric student's t-test was used to determine any statistically significant differences by age, smoker status, body mass index (BMI) and occupation. Ranges were further compared with those reported for other African, Afro-American and Caucasian populations. RESULTS: increased levels of MCV, MCH, PLT and EOS were found in younger Malians who had abnormal BMI and altered platelets parameters. Notably, significantly lower eosinophil and monocyte counts were observed in Malians compared to Europeans The smoking status did not seem to directly affect RIs. CONCLUSION: this is the first study to determine normal laboratory parameters in Malian adult males. Our results underscore the necessity of establishing region-specific clinical reference ranges that would allow clinicians and practitioners to manage laboratory tests, diagnosis and therapies. These data are useful not only for the management of patients in Mali, but also to support European and American clinicians in the health management of asylum seekers and migrants from Mali.

Abstract Background Over the last two decades, tumor-derived RNA expression signatures have been developed for the two most commonly diagnosed tumors worldwide, namely prostate and breast tumors, in order to improve both outcome prediction and treatment decision-making. In this context, molecular signatures gained by main components of the tumor microenvironment, such as cancer-associated fibroblasts (CAFs), have been explored as prognostic and therapeutic tools. Nevertheless, a deeper understanding of the significance of CAFs-related gene signatures in breast and prostate cancers still remains to be disclosed. Methods RNA sequencing technology (RNA-seq) was employed to profile and compare the transcriptome of CAFs isolated from patients affected by breast and prostate tumors. The differentially expressed genes (DEGs) characterizing breast and prostate CAFs were intersected with data from public datasets derived from bulk RNA-seq profiles of breast and prostate tumor patients. Pathway enrichment analyses allowed us to appreciate the biological significance of the DEGs. K-means clustering was applied to construct CAFs-related gene signatures specific for breast and prostate cancer and to stratify independent cohorts of patients into high and low gene expression clusters. Kaplan-Meier survival curves and log-rank tests were employed to predict differences in the outcome parameters of the clusters of patients. Decision-tree analysis was used to validate the clustering results and boosting calculations were then employed to improve the results obtained by the decision-tree algorithm. Results Data obtained in breast CAFs allowed us to assess a signature that includes 8 genes (ITGA11, THBS1, FN1, EMP1, ITGA2, FYN, SPP1, and EMP2) belonging to pro-metastatic signaling routes, such as the focal adhesion pathway. Survival analyses indicated that the cluster of breast cancer patients showing a high expression of the aforementioned genes displays worse clinical outcomes. Next, we identified a prostate CAFs-related signature that includes 11 genes (IL13RA2, GDF7, IL33, CXCL1, TNFRSF19, CXCL6, LIFR, CXCL5, IL7, TSLP, and TNFSF15) associated with immune responses. A low expression of these genes was predictive of poor survival rates in prostate cancer patients. The results obtained were significantly validated through a two-step approach, based on unsupervised (clustering) and supervised (classification) learning techniques, showing a high prediction accuracy (≥ 90%) in independent RNA-seq cohorts. Conclusion We identified a huge heterogeneity in the transcriptional profile of CAFs derived from breast and prostate tumors. Of note, the two novel CAFs-related gene signatures might be considered as reliable prognostic indicators and valuable biomarkers for a better management of breast and prostate cancer patients.

Abstract Background The cyclin D1-cyclin dependent kinases (CDK)4/6 inhibitor palbociclib in combination with endocrine therapy shows remarkable efficacy in the management of estrogen receptor (ER)-positive and HER2-negative advanced breast cancer (BC). Nevertheless, resistance to palbociclib frequently arises, highlighting the need to identify new targets toward more comprehensive therapeutic strategies in BC patients. Methods BC cell lines resistant to palbociclib were generated and used as a model system. Gene silencing techniques and overexpression experiments, real-time PCR, immunoblotting and chromatin immunoprecipitation studies as well as cell viability, colony and 3D spheroid formation assays served to evaluate the involvement of the G protein-coupled estrogen receptor (GPER) in the resistance to palbociclib in BC cells. Molecular docking simulations were also performed to investigate the potential interaction of palbociclib with GPER. Furthermore, BC cells co-cultured with cancer-associated fibroblasts (CAFs) isolated from mammary carcinoma, were used to investigate whether GPER signaling may contribute to functional cell interactions within the tumor microenvironment toward palbociclib resistance. Finally, by bioinformatics analyses and k-means clustering on clinical and expression data of large cohorts of BC patients, the clinical significance of novel mediators of palbociclib resistance was explored. Results Dissecting the molecular events that characterize ER-positive BC cells resistant to palbociclib, the down-regulation of ERα along with the up-regulation of GPER were found. To evaluate the molecular events involved in the up-regulation of GPER, we determined that the epidermal growth factor receptor (EGFR) interacts with the promoter region of GPER and stimulates its expression toward BC cells resistance to palbociclib treatment. Adding further cues to these data, we ascertained that palbociclib does induce pro-inflammatory transcriptional events via GPER signaling in CAFs. Of note, by performing co-culture assays we demonstrated that GPER contributes to the reduced sensitivity to palbociclib also facilitating the functional interaction between BC cells and main components of the tumor microenvironment named CAFs. Conclusions Overall, our results provide novel insights on the molecular events through which GPER may contribute to palbociclib resistance in BC cells. Additional investigations are warranted in order to assess whether targeting the GPER-mediated interactions between BC cells and CAFs may be useful in more comprehensive therapeutic approaches of BC resistant to palbociclib.

Abstract Extreme atmospheric-marine events, known as medicanes (short for “Mediterranean hurricanes”), have affected the Mediterranean basin in recent years, resulting in extensive coastal flooding and storm surges, and have occasionally been responsible for several casualties. Considering that the development mechanism of these events is similar to tropical cyclones, it is plausible that these phenomena are strongly affected by sea surface temperatures (SSTs) during their development period (winter and autumn seasons). In this study, we compared satellite data and the numerical reanalysis of SSTs from 1969 to 2023 with in situ data from dataloggers installed at different depths off the coast of southeastern Sicily as well as from data available on Argo floats on the Mediterranean basin. A spectral analysis was performed using a continuous wavelet transform (CWT) for each SST time series to highlight the changes in SSTs prior to the occurrence of Mediterranean Hurricanes as well as the energy content of the various frequencies of the SST signal. The results revealed that decreases in SST occurred prior to the formation of each Mediterranean hurricane, and that this thermal drop phenomenon was not observed in intense extra-tropical systems. The spectral analyses revealed that high CWT coefficients representing high SST energy contents were observed before the occurrence of a Mediterranean hurricane. This information may provide a useful fingerprint for distinguishing Mediterranean hurricanes from common seasonal storms at the onset of these events.

BackgroundTo identify a diagnostic blood transcriptomic signature that distinguishes multisystem inflammatory syndrome in children (MIS-C) from Kawasaki disease (KD), bacterial infections, and viral infections.MethodsChildren presenting with MIS-C to participating hospitals in the United Kingdom and the European Union between April 2020 and April 2021 were prospectively recruited. Whole-blood RNA Sequencing was performed, contrasting the transcriptomes of children with MIS-C (n = 38) to those from children with KD (n = 136), definite bacterial (DB; n = 188) and viral infections (DV; n = 138). Genes significantly differentially expressed (SDE) between MIS-C and comparator groups were identified. Feature selection was used to identify genes that optimally distinguish MIS-C from other diseases, which were subsequently translated into RT-qPCR assays and evaluated in an independent validation set comprising MIS-C (n = 37), KD (n = 19), DB (n = 56), DV (n = 43), and COVID-19 (n = 39).ResultsIn the discovery set, 5696 genes were SDE between MIS-C and combined comparator disease groups. Five genes were identified as potential MIS-C diagnostic biomarkers (HSPBAP1, VPS37C, TGFB1, MX2, and TRBV11-2), achieving an AUC of 96.8% (95% CI: 94.6%-98.9%) in the discovery set, and were translated into RT-qPCR assays. The RT-qPCR 5-gene signature achieved an AUC of 93.2% (95% CI: 88.3%-97.7%) in the independent validation set when distinguishing MIS-C from KD, DB, and DV.ConclusionsMIS-C can be distinguished from KD, DB, and DV groups using a 5-gene blood RNA expression signature. The small number of genes in the signature and good performance in both discovery and validation sets should enable the development of a diagnostic test for MIS-C.

IntroductionThere are no reports in LATAM related to longitudinal humoral and cellular response to adenovirus based COVID-19 vaccines in people with Multiple Sclerosis (pwMS) under different disease modifying therapies (DMTs) and neutralization of the Omicron and Wuhan variants of SARS-COV-2.MethodsIgG anti- SARS-COV-2 spike titer were measured in a cohort of 101 pwMS under fingolimod, dimethyl fumarate, cladribine and antiCD20, as well as 28 healthy controls (HC) were measured 6 weeks after vaccination with 2nd dose (Sputnik V or AZD1222) and 3nd dose (homologous or heterologous schedule). Neutralizing capacity was against Omicron (BA.1) and Wuhan (D614G) variants and pseudotyped particles and Cellular response were analyzed.ResultsMultivariate regression analysis showed anti-cd20 (β= -,349, 95% CI: -3655.6 - -369.01, p=0.017) and fingolimod (β=-,399, 95% CI: -3363.8 - -250.9, p=0.023) treatments as an independent factor associated with low antibody response (r2 adjusted=0.157). After the 2nd dose we found a correlation between total and neutralizing titers against D614G (rho=0.6; p

The significant advancements in breast cancer management have led to an increase in the prevalence of breast cancer survivors. Despite their efficacy, these treatments can cause a variable range of side effects, significantly deteriorating the patients’ quality of life.Sexual dysfunction, and in particular the genitourinary syndrome of menopause, represent one of the major causes of quality-of-life impairment among breast cancer patients, potentially affecting treatment adherence and compliance. If in the general population, hypoestrogenism-related symptoms are typically managed through systemic or topical estrogen administration, this approach is contraindicated in breast cancer patients for the potential increased risk of disease recurrence, urging the investigation of alternative measures.The aim of this review is to summarize the most up-to-date pharmacological and non-pharmacological interventions, as well as supportive measures, available for the management of sexual dysfunctions in breast cancer patients and survivors.

Summary: The emergence of next-generation sequencing technologies and computational advances have expanded our understanding of gene expression regulation (i.e., the transcriptome). This has also led to an increased interest in using transcriptomic biomarkers to improve disease diagnosis and stratification, to assess prognosis and predict the response to treatment. Significant progress in identifying transcriptomic signatures for various clinical needs has been made, with large discovery studies accounting for challenges such as patient variability, unwanted batch effects, and data complexities; however, obstacles related to the technical aspects of cross-platform implementation still hinder the successful integration of transcriptomic technologies into standard diagnostic workflows. In this article, we discuss the challenges associated with integrating transcriptomic signatures derived using high-throughput technologies (such as RNA-sequencing) into clinical diagnostic tools using nucleic acid amplification (NAA) techniques. The novelty of the proposed approach lies in our aim to embed constraints related to cross-platform implementation in the process of signature discovery. These constraints could include technical limitations of amplification platform and chemistry, the maximal number of targets imposed by the chosen multiplexing strategy, and the genomic context of identified RNA biomarkers. Finally, we propose to build a computational framework that would integrate these constraints in combination with existing statistical and machine learning models used for signature identification. We envision that this could accelerate the integration of RNA signatures discovered by high-throughput technologies into NAA-based approaches suitable for clinical applications.

IntroductionThe learning process goes beyond the acquisition of curricular cognitive elements to include extracurricular skills. This extended concept has attracted renewed attention through the European Council Recommendation (2018) on skills development for lifelong learning in schools. The Organization for Economic Cooperation and Development has also highlighted the relevance of socio-emotional skills for learning and life chances. The official uptake of extracurricular skills in curricula poses schools and educators the challenge of finding ways to conceptualize, teach, and assess them. To this end, co-operative learning and peer-to-peer education hold a prominent place among educational strategies alternative to conventional teaching practices. Both actively engage students and have a positive impact on achievement in curricular disciplines and on the development of lifelong learning skills and social and emotional competences. The present study presents a case study in which collaborative learning was supported via a digital platform.MethodsWe analyzed the qualitative data collected in Italian schools taking part in the Kids4alll, a Horizon 2020 project. The project’s aim is to improve lifelong learning skills directly and other skills indirectly through collaborative learning based on the “buddy method” (pairs or groups of peers working together).Results and discussionOur findings reveal the potential benefit of peer-to-peer approaches. This potential extends to the development of co-operative skills used in school context and transferable to other areas, along with the acquisition of character-building skills. However, a criticality in the application of peer learning interventions is that many teachers are often ill prepared to implement cooperative learning in classroom practice or lack sufficient training in matching peer-to-peer work and pedagogical needs.

Background: The last years have seen unprecedented improvement in breast cancer (BC) survival rates. However, this entirely apply to female BC patients, since gender minorities (male, transgender/gender-diverse) are neglected in BC phase III registration clinical trials. Methods: We conducted a scoping review of phase III clinical trials of agents with a current positioning within the therapeutic algorithms of BC. Results: We selected 51 phase III trials. Men enrollment was allowed in 35.3% of trials. In none of the trial inclusion/exclusion criteria referred to transgender/gender-diverse people. A numerical higher rate of enrolled men was observed in the contemporary as compared to historical group.We found a statistically significant association between the drug class and the possibility of including men: 100%, 80%, 50%, 33.3%, 25%, 10% and 9.1% of trials testing ICI/PARP-i, ADCs, PI3K/AKT/mTOR-i, anti-HER2 therapy, CDK4/6-i, ET alone, and CT alone.Overall, 77409 patients were enrolled, including 112 men (0.2%). None of the trial reported transgender/gender-diverse people proportion. Studies investigating PARP-i were significantly associated with the highest rate of enrolled men (1.42%), while the lowest rates were observed for trials of CT (0.13%), ET alone (0.10%), and CDK 4/6-I (0.08%), p

Abstract Several warm‐core cyclones in the Mediterranean, which were analyzed in the literature, are studied using ERA5 reanalysis, to identify the environment where they develop and distinguish tropical‐like cyclones from non‐tropical warm‐core cyclones. Initially, the cyclone phase space is analyzed to distinguish the cyclones that have a symmetrical deep warm core. Subsequently, the temporal evolution of several parameters is considered, including the distance between the area of maximum tangential wind speed and the cyclone center. Some differences are observed between the cyclones analyzed: one category of cyclones develops in areas of moderate‐low baroclinicity and intense convective processes, as occurs in tropical cyclones. Another group of cyclones develops in a strongly baroclinic environment with weak convective processes and intense vertical wind shear, as occurs in warm seclusions. Two cyclones, showing similarities with polar lows, are also identified.

On 31 December 2019, the Municipal Health Commission of Wuhan, China, reported a cluster of atypical pneumonia cases. On 5 January 2020, the WHO publicly released a Disease Outbreak News (DON) report, providing information about the pneumonia cases, implemented response interventions, and WHO’s risk assessment and advice on public health and social measures. Following 9 additional DON reports and 209 daily situation reports, on 17 August 2020, WHO published the first edition of the COVID-19 Weekly Epidemiological Update (WEU). On 1 September 2023, the 158th edition of the WEU was published on WHO’s website, marking its final issue. Since then, the WEU has been replaced by comprehensive global epidemiological updates on COVID-19 released every 4 weeks. During the span of its publication, the webpage that hosts the WEU and the COVID-19 Operational Updates was accessed annually over 1.4 million times on average, with visits originating from more than 100 countries. This article provides an in-depth analysis of the WEU process, from data collection to publication, focusing on the scope, technical details, main features, underlying methods, impact and limitations. We also discuss WHO’s experience in disseminating epidemiological information on the COVID-19 pandemic at the global level and provide recommendations for enhancing collaboration and information sharing to support future health emergency responses.

This study investigated whether existential quest, a relatively new construct defining individual willingness to reflect on existential issues such as the meaning of life and death, was negatively associated with generalized prejudice through the mediation with personal values of universalism and conservation (conformity, security, and tradition). A structural equation model was performed on a convenience sample of 1136 Italian adults. Results confirmed a negative indirect relationship with generalized prejudice mediated by universalism. Findings support the argument that engagement with existential issues is associated with the value of universalism, which in turn is associated with lower levels of generalized prejudice. The present study contributes to the scholarly literature to explain the concept of existential quest.

Abstract Electronic traceability (e-traceability) is a growing trend in the agri-food industry, offering improved transparency, accountability, and reduced risk of foodborne illnesses through the use of electronic systems to trace products throughout the entire supply chain. E-traceability drivers in the agri-food supply chain encompass diverse factors motivating companies to adopt electronic systems for product tracking, aiming to enhance visibility, minimize risk, ensure compliance, and promote safety, sustainability, and efficiency through clear and verifiable records of product origins, quality, and sustainability, building consumer trust and loyalty. By identifying the main drivers of e-traceability, this research aims to shed light on the factors that motivate companies to implement electronic systems for tracking and monitoring products. For solving this problem of multi-criteria decision-making (MCDM), this study proposes a hybrid MCDM model. The model combines “Factor Relationship” (FARE) and “Axial Distance-based Aggregated Measurement” (ADAM) methods in the fuzzy environment. The results indicate that the most important drivers are supply chain efficiency, technology development and sustainability. These drivers are critical and they significantly impact the successful implementation and adoption of e-traceability strategies in the agri-food sector.

Mediterranean hurricanes, also known as medicanes, can cause significant damage to coastal communities. Consequently, they have been the subject of intense study in recent decades. Geographic Information Systems (GISs) and Web-GIS applications are essential for processing and analyzing geographic data from various sources, particularly in the field of spatial planning. Due to their ability to integrate heterogeneous information, these tools can provide experts with a comprehensive overview of relevant geospatial data. Here, we present ARCHIMEDE, a relational geodatabase connected to an open-source Web-GIS platform focused on Mediterranean hurricanes that contains data from recent research on these extreme weather phenomena. These datasets comprise climatic and oceanographic data obtained from remote sensing techniques as well as seismic and geomorphological data obtained from field observations. Consequently, this Web-GIS platform can enhance our understanding of Mediterranean cyclones by relating the physical properties of these natural phenomena with their impacts on coastal regions. ARCHIMEDE is an innovative tool for the dissemination of geographic information to stakeholders, researchers, and decision-makers, offering valuable support for the development of robust coastal management strategies aimed at mitigating the challenges posed by Mediterranean hurricanes.

WHO works, on a daily basis, with countries globally to detect, prepare for and respond to acute public health events. A vital component of a health response is the dissemination of accurate, reliable and authoritative information. The Disease Outbreak News (DON) reports are a key mechanism through which WHO communicates on acute public health events to the public. The decision to produce a DON report is taken on a case-by-case basis after evaluating key criteria, and the subsequent process of producing a DON report is highly standardised to ensure the robustness of information. DON reports have been published since 1996, and up to 2022 over 3000 reports have been published. Between 2018 and 2022, the most frequently published DON reports relate to Ebola virus disease, Middle East respiratory syndrome, yellow fever, polio and cholera. The DON web page is highly visited with a readership of over 2.6 million visits per year, on average. The DON report structure has evolved over time, from a single paragraph in 1996 to a detailed report with seven sections currently. WHO regularly reviews the DON report process and structure for improvements. In the last 25 years, DON reports have played a unique role in rapidly disseminating information on acute public health events to health actors and the public globally. They have become a key information source for the global public health response to the benefit of individuals and communities.