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Inflammatory myofibroblastic tumor (IMT) is a mesenchymal tumor that can occur at any age. However, it is primarily seen in children, with the most common site being in the lung parenchyma, usually present with rare endobronchial lesions. This case reports the incidence in a 3-year-old girl diagnosed with pericardiac pneumonia treated with antibiotics with no clinical improvement. A chest computed tomography (CT) scan identified a 1.5-cm lesion in the left main bronchus. Bronchoscopy revealed complete obstruction of the left main stem bronchus. A left posterolateral thoracotomy was performed. Additionally, a left sleeve upper bronchial resection was conducted under fibroendoscopic control. Definitive histology confirmed IMT. After 2 years of endoscopic follow-up, there is no evidence of recurrence.

Knowledge about the aboveground biomass (AGB) and the diameters at breast height (DBH) distribution can lead to a precise estimation of carbon density and forest structure which can be very important for ecology studies especially for those concerning climate change. In this study, we propose to predict DBH and AGB of individual trees using tree height (H) and crown diameter (CD), and other metrics extracted from airborne laser scanning (ALS) data as input. In the proposed approach, regression methods, such us support vector machine for regression (SVR) and random forests (RF), were used to find a transformation or a transfer function that links the input parameters (H, CD, and other ALS metrics) with the output (DBH and AGB). The developed approach was tested on two datasets collected in southern Norway comprising 3970 and 9467 recorded trees, respectively. The results demonstrate that the developed approach provides better results compared to a state-of-the-art work (based on a linear model with the standard least-squares method) with RMSE equal to 81.4 kg and 92.0 kg, respectively (compared to 94.2 kg and 110.0 kg) for the prediction of AGB, and 5.16 cm and 4.93 cm, respectively (compared to 5.49 cm and 5.30 cm) for DBH.

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 Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory condition. Given patients with COPD continue to experience exacerbations despite the availability of effective therapies, anti-inflammatory treatments targeting novel pathways are needed. Kinases, notably the phosphoinositide 3-kinases (PI3K), are thought to be involved in chronic airway inflammation, with this pathway proposed as a critical regulator of inflammation and oxidative stress response in COPD. CHF6523 is an inhaled PI3Kδ inhibitor that has shown positive preclinical results. This manuscript reports the results of a study of CHF6523 in patients with stable COPD (chronic bronchitis phenotype), and who had evidence of type-2 inflammation. Methods This randomised, double-blind, placebo-controlled, two-way crossover study comprised two 28-day treatment periods separated by a 28-day washout. Patients (N = 44) inhaled CHF6523 in one period, and placebo in the other, both twice daily. The primary objective was to assess the safety and tolerability of CHF6523; the secondary objective was to assess CHF6523 pharmacokinetics. Exploratory endpoints included target engagement (the relative reduction in phosphatidylinositol (3,4,5)-trisphosphate [PIP3]), pharmacodynamic evaluations such as airflow obstruction, and hyperinflation, and to identify biomarker(s) of drug response using proteomics and transcriptomics. Results CHF6523 plasma pharmacokinetics were characterised by an early maximum concentration (Cmax), reached 15 and 10 min after dosing on Days 1 and 28, respectively, followed by a rapid decline. Systemic exposure on Day 28 showed limited accumulation, with ratios

This paper presents a model intercomparison study to improve the prediction and understanding of Mediterranean cyclone dynamics. It is based on a collective effort with five mesoscale models to look for a robust response among 10 numerical frameworks used in the community involved in the networking activity of the EU COST Action “MedCyclones”. The obtained multi-model, multi-physics ensemble is applied to the high-impact Medicane Ianos of September 2020 with a focus on the cyclogenesis phase, which was poorly forecast by numerical weather prediction systems. Models systematically perform better when initialised from operational IFS analysis data compared to the widely used ERA5 reanalysis. Reducing horizontal grid spacing from 10 km with parameterised convection to convection-permitting 2 km further improves the cyclone track and intensity. This highlights the critical role of deep convection during the early development stage. Higher resolution enhances convective activity, which improves the phasing of the cyclone with an upper-level jet and its subsequent intensification and evolution. This upscale impact of convection matches a conceptual model of upscale error growth in the midlatitudes, while it emphasises the crucial interplay between convective and baroclinic processes during medicane cyclogenesis. The 10 numerical frameworks show robust agreement but also reveal model specifics that should be taken into consideration, such as the need for a parameterisation of deep convection even at 2 km horizontal grid spacing in some models. While they require generalisation to other cases of Mediterranean cyclones, the results provide guidance for the next generation of global convection-permitting models in weather and climate.

The release of organic compounds from roots is a key process influencing soil carbon (C) dynamics and nutrient availability in terrestrial ecosystems. Through this process, plants stimulate microbial activity and soil organic matter (SOM) mineralization thus releasing nitrogen (N) that sustains gross and net primary production (GPP and NPP, respectively). Root inputs also contribute to SOM formation. In this study, we quantified the annual net root-derived C input to soil (Net-Croot) across six high fertility forests using an in-growth core isotope technique. On the basis of Net-Croot, wood and coarse root biomass changes, and eddy covariance data, we quantified net belowground C sequestration. Belowground C accumulation and GPP were inversely related to soil C:N, but not to climate or stand age. Soil C content and C:N were also related to soil texture. At these high fertility sites, biomass growth did not change with soil C:N; however, biomass growth-to-GPP ratio significantly increased with increasing soil C:N. This was true for both our six forest sites and for another 23 high fertility sites selected at a global scale. We suggest that, at high fertility sites, plant N demand interacts with soil C:N stoichiometry and microbial activity, resulting in higher allocation of C to above ground tree biomass with increasing soil C:N ratio. When C:N is high, microbes have a low C use efficiency, respire more of the fresh C inputs by roots and prime SOM decomposition, thereby increasing N availability for tree uptake. Soil C sequestration would therefore decrease, whereas the extra N released during SOM decomposition can promote tree growth and ecosystem C sink allocation in aboveground biomass. Conversely, C is sequestered in soil when low soil C:N promotes microbial C use efficiency and new SOM formation and stabilization on clay particles.

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.

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.

Abstract Leveraging the Copernicus high‐resolution multi‐year Mediterranean Sea Surface Temperature (SST) dataset, 15 selected tropical‐like cyclones (TLCs) are analyzed with the objective of elucidating the anomalies of SST at the time of cyclogenesis and the connection between the change in SST during the cyclone lifetime and its characteristics. The long‐term SST increase associated with climate change is identified by comparing detrended and original anomalies. Detrending removes the effect of the intensification of SST anomaly over time, revealing that no significant anomalies generally emerge in the early stages of the TLC lifetimes. Conversely, winter events exhibit early‐stage positive SST anomalies. Also, high SST values were observed during the intensification of the most intense cyclones. A cold SST anomaly is left after the passage of the cyclones, due to the intense sea surface fluxes extracting heat from the sea.

Resumen: El objetivo de este trabajo fue evaluar los factores explicativos de la respuesta inmune humoral en adultos mayores de establecimientos de estancia prolongada de Buenos Aires, Argentina, hasta 180 días post vacunación. Se utilizó un diseño de cohorte abierta, prospectiva, multicéntrica, con voluntarios que recibieron dos dosis de vacunas Sputnik V, Sinopharm o AZD1222. Se analizaron muestras de plasma en los tiempos 0, 21 días post primera dosis, 21 días post segunda dosis, 120 y 180 días post primera dosis. Se ajustaron modelos lineales marginales y aditivos generalizados mixtos para evaluar el comportamiento de la concentración de anticuerpos IgG anti-Spike en el tiempo según grupo de exposición (naïve/no-naïve) y vacuna. Las covariables analizadas fueron: ocurrencia de brote de COVID-19 en establecimientos de estancia prolongada y comorbilidades. Se incluyeron en el análisis 773 participantes con una mediana de edad de 83 años (RIQ: 76-89). Al final del estudio, los niveles de anticuerpos del grupo naïve: Sinopharm fueron significativamente menores que el resto de los grupos (p < 0,05); los del no-naïve: Sinopharm resultaron similares a los naïve que recibieron AZD1222 (p = 0,945) o Sputnik V (p = 1). Los participantes expuestos a brotes en establecimientos de estancia prolongada presentaron niveles de anticuerpos significativamente mayores, independientemente del grupo de exposición y la vacuna (p < 0,001). Concluimos que la exposición previa a COVID-19, el tipo de vacuna y la pertenencia a un establecimiento de estancia prolongada con antecedente de brote son factores a considerar frente a futuros eventos epidémicos con dinámicas de transmisión y mecanismos inmunológicos similares al COVID-19, en poblaciones similares a la analizada en este trabajo.

The damage observed during past earthquakes demonstrated the need for the seismic vulnerability assessment of industrial plants to reduce the risk of major accidents and to develop detailing for risk mitigation. If damaged by a seismic event, industrial plants might be affected by a domino effect with the consequent interruption of plant serviceability and severe economic losses; at the same time, toxic substances could be released due to the damage of pipelines and tanks, causing environmental damages and loss of lives. This preliminary study investigates the influence of the dynamic properties of pressurised tanks on the industrial plant seismic vulnerability, focusing on the possible issues to which the pipelines connecting the tanks are prone. To this purpose, numerical analyses are conducted aimed at identifying the most critical conditions in terms of displacements and stress state to which the pipelines are subjected. At the same time, a framework for the definition of fragility functions including the damage states related to piping connections, is also presented.

Will Mediterranean terrestrial ecosystems be affected by the expected changes in precipitation regimes? If so, by how much and in which direction? These questions are at the basis of the research performed in context of the EU MIND project, whose key objectives were: i) to investigate the potential effects of increasing drought on Mediterranean terrestrial ecosystems at the process, ecosystem and regional scales and ii) to assess ecosystem vulnerability to changes in rainfall patterns. A network of experimental study sites has been created in Portugal, Spain, France and Italy, where field manipulations alter the amount of water available to the ecosystem. The most up-to-date methods of ecophysiology, micrometeorology, soil ecology and remote sensing have been used to elucidate the mechanisms that regulate the response of vegetation and soil to changes in water availability. This information is providing the basis for the implementation and validation of simulation models capable of predicting the drought response of Mediterranean terrestrial ecosystems, and their vulnerability to future climate change, on a larger scale. The out-coming results are elucidating how water availability affects plant ecophysiological processes, the dynamics of soil carbon and the overall exchange of mass and energy between the land and the atmosphere. This paper focuses on some of the important, yet preliminary, results on C and energy fluxes that have been obtained at the large scale troughfall manipulation experiment (Tolfa, Italy), in a forest dominated by Arbutus unedo L.

The mechanisms involved in carbon exchange between terrestrial ecosystems and the atmosphee are mostly well known. Reliable estimates of CO exchange can be done using biological simulation models at plant, plot and, with lower accuracy, at ecosystem scale. Direct measurement of such exchange is of outmost importance to verify models and the hypothesis on which they rare based, and also to investigate, verify and model new and poorly known processes. Until today scientific research has been provided with reliable tecniques to measure carbon exchange at leaf and plant level (chambers), and ecosystem level (eddy covariance), while difficulties exist into up scaling these figures to the regional and the global scales. The advent of compact instruments and data systems has recently allowed small research aircraft to measure mass, momentum, and energy fluxes at the regional scale with the eddy covariance tecnique. This paper describes the aerial platform and the application of micrometeorological methods from moving platforms. A methodology, applied within international research projects, aimed at quantifying the regional annual carbon balance is described, based on the computation of mean daily fluxes for ecosystem type. The advanteges and the limitations of using such approach to derive regional fluxes are discussed, while potential improvements based on the integration of direct flux measurements with multispectral remote sensing are highlighted.

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.

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

A reply to the letter by Mollicone and Federici, published in the current issue of this journal, and a restatement of the transparent objectives and expected results from the CarboItaly project.