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Background Immune checkpoint inhibitors (ICIs), administered alone or combined with chemotherapy, are the standard of care in advanced non-oncogene addicted Non-Small Cell Lung Cancer (NSCLC). Despite these treatments' success, most long-term survival benefit is restricted to approximately 20% of patients, highlighting the need to identify novel biomarkers to optimize treatment strategies. In several solid tumors, immune soluble factors, the activatory CD137 + Tcells, and the immunosuppressive cell subsets Tregs and MDSCs (PMN(Lox1 + )-MDSC and M-MDSCs) correlated with responses to ICIs and clinical outcomes thus becoming appealing predictive and prognostic factors. This study investigated the role of distinct CD137 + Tcell subsets, Tregs, MDSCs, and immune-soluble factors in NSCLC patients as possible biomarkers. Methods The levels of T cells, MDSCs and soluble factors were evaluated in 89 metastatic NSCLC patients who underwent ICIs as first- or second-line treatment. T cell analysis was performed by cytoflurimetry evaluating Tregs and different CD137 + Tcell subsets also combined with CD3 + , CD8 + , PD1 + , and Ki67 + markers. Circulating cytokines and immune checkpoints were also evaluated by Luminex analysis. All these parameters were correlated with several clinical factors (age, sex, smoking status, PS and TPS), response to therapy, PFS , and OS . The analyses were conducted in the overall population and in patients treated with ICIs as first-line (naïve patients). Results In both groups of patients, high levels of circulating CD137 + and CD137 + PD1 + T cells (total, CD4 and CD8) and the soluble factor LAG3 positively correlated with response to therapy. In naïve patients, PMN(Lox1 + )-MDSCs negatively correlated with clinical response, and a high percentage of Tregs was associated with favorable survival. Moreover, the balance between Treg/CD137 + Tcells or PMN(Lox1 + )-MDSC/CD137 + Tcells was higher in non-responding patients and was associated with poor survival. CD137 + Tcells and Tregs resulted as two positive independent prognostic factors. Conclusion High levels of CD137 + , CD137 + PD1 + Tcells and sLAG3 could predict the response to ICIs in NSCLC patients independently by previous therapy. Combining the evaluation of CD137 + Tcells and Tregs also as Treg/CD137 + T cells ratio it is possible to identify naive patients with longer survival.

Background Over the past decade, the number of elderly cancer patients has increased, including those with NSCLCs, most of whom are over 60 years old. NSCLC patients receive anti-PD1-based therapies. These therapies directly target the immune system by activating T cells. However, older patients exhibit several baseline immune system changes compared to their younger counterparts, which could affect treatment effectiveness. This study aims to assess the immune systems of younger (<65) and older (≥65) NSCLC patients at baseline to determine whether immune aging may alter the efficacy of immune treatments. Methods Seventy-eight NSCLC patients were enrolled in this study and divided into two groups on an age basis: younger (26 pts, < 65 years; young-pts) and older (52 pts, ≥65 years; old-pts). The patient’s immune profile was assessed before therapy by evaluating circulating immune cell subsets and soluble immune mediators using flow cytometry and a Luminex assay, respectively. Immune populations and soluble factors were correlated with treatment response and survival outcomes. A cohort of 27 healthy donors (HDs) served as the control group. Results Cancer patients (CPs) exhibited higher levels of CD8 ( p  < 0.001), Ki67 ( p  < 0.001), effector ( p  < 0.0075), and regulatory T cells ( p  < 0.001) than HDs. These differences remained consistent across age groups, except for effector cells, which showed a slight increase ( p  = 0.0932) in young-CPs compared with young-HDs. Moreover, CD3 ( p  < 0.001), CD4 ( p  < 0.001), PD1 ( p  < 0.001), and naïve T cells ( p  = 0.0144) were significantly lower in CPs than in HDs, with a similar trend across age groups, except for naïve T cells ( p  = 0.0748). The OS data showed no differences between the young and old groups when analyzing the entire population and the responder patients (Rs). However, young non-responders (NRs) experienced longer survival than older NRs. Multivariate analysis identified PMN (Lox1 + )-MDSCs, Ki67, and response to therapy as independent predictors in NRs. The ROC curve established the cut-off for distinguishing the high-risk group, characterized by worse outcomes with elevated levels of PMN (Lox1 + )-MDSCs and Ki67 + T cells, from the low-risk group (log-rank p  = 0.0093). Moreover, old-NRs showed significantly higher levels of PMN (Lox1 + )-MDSCs than old-Rs, and a higher percentage of CD137 + PD1 + ( p  = 0.05) and central memory T cells ( p  = 0.09). Conclusion The combined index of PMN(Lox1 + )-MDSCs and Ki67 + T cells offers a practical tool for assessing immunological fitness in the NR setting, thereby enhancing patient stratification.

Pembrolizumab (an anti-PD1 antibody) alone or combined with chemotherapy represented the standard of care for advanced non-oncogene addicted non-small cell lung cancer (NSCLC) patients. These therapies induced early modifications of the immune response impacting the clinical outcome. Identifying early changes in the immune system was critical to directing the therapeutic choice and improving the clinical outcome. In this study, we aim to analyze the activating and inhibiting immune cells of NSCLC patients before and during therapy to identify patients who will benefit from immunotherapies. Forty-eight NSCLC patients were analyzed before (T0) and after the first cycle of immunotherapy (T1), evaluating several activating (CD137 + and PD1 + ), proliferating (Ki67 + ) and immunosuppressing immune subsets (Tregs: total, active, resting, and non-suppressive; MDSCs: PMN(Lox1 + )-MDSC and M-MDSCs) by cytofluorimetry. Concurrently, 14 soluble immune checkpoints were analyzed by Luminex assay. Immunotherapy significantly increased the levels of Ki67 + (total and CD8 + ) T cells, PMN(Lox1 + )-MDSCs, non-suppressive Tregs (nsTregs), and soluble PD1 from T0 to T1 in the entire NSCLC population, while decreased active Tregs. These changes were partially attributed to responding patients who showed an increase of Ki67 + and CD8 + T cells and nsTregs at T1. CD137 + (total, CD8 + , and CD4 + ) T cells and soluble LAG3 were predictor factors at T0 and T1. A low ratio of Tregs/CD137+ T cells and high levels of Ki67 + CD137 + T cells positively correlated with response to therapy at T0 and T1, respectively. Results highlighted that immunotherapy improved the immunological fitness of those patients who benefited from immunotherapy, changing the immunological balance towards immune activation.

During the COVID-19 pandemic, the most severe form of the disease was most often seen in male patients. The aim of this study was to identify any male predispositions that could be used to predict the outcome of the disease and enable early intervention. We investigated CAG polymorphism in the androgen receptor gene and serum levels of testosterone and LH, which were considered as probably responsible for this predisposition. The study involved 142 patients who had recovered from COVID-19 at least three months previously and were classified according to their disease severity using the World Health Organization (WHO) classification. We observed a significant increase in the number of CAG repeats with increasing disease severity: the percentage of patients with more than 23 repeats increased two-fold from Grade I to Grade IV. Furthermore, testosterone levels were significantly lower in patients with severe disease. Reduced androgenic signaling could predispose men to a more severe form: low testosterone levels and a reduced androgen receptor activity (CAG > 23) expose the host to an excessive inflammatory response, leading downstream to the multi-organ damage seen in severe COVID-19.

The evaluation of morpho-functional sperm characteristics alone is not enough to explain infertility or to predict the outcome of Assisted Reproductive Technologies (ART): more sensitive diagnostic tools are needed in clinical practice. The aim of the present study was to analyze Sperm DNA Fragmentation (SDF) and sperm-borne miR-34c-5p and miR-449b-5p levels in men of couples undergoing ART, in order to investigate any correlations with fertilization rate, embryo quality and development. Male partners (n = 106) were recruited. Semen analysis, SDF evaluation and molecular profiling analysis of miR-34c-5p and miR-449b-5p (in 38 subjects) were performed. Sperm DNA Fragmentation evaluation- a positive correlation between SDF post sperm selection and the percentage of low-quality embryos and a negative correlation with viable embryo were found. SDF > 2.9% increased the risk of obtaining a non-viable embryo by almost 4-fold. Sperm miRNAs profile—we found an association with both miRNAs and sperm concentration, while miR-449b-5p is positively associated with SDF. Moreover, the two miRNAs are positively correlated. Higher levels of miR-34c-5p compared to miR-449b-5p increases by 14-fold the probability of obtaining viable embryos. This study shows that SDF, sperm miR-34c-5p, and miR-449b-5p have a promising role as biomarkers of semen quality and ART outcome.

Among the cancer types that commonly affect men of reproductive age there are leukemias. In literature, little is known about the correlation between semen quality and acute leukemia. It could be assumed that the disease may evoke a systemic response mediated by cytokines secreted by tumor cells, which may have an impact on semen parameters. Significant advances in survival rates due to new therapeutic strategies have focused attention on fatherhood and fertility preservation. The aim of this study was to evaluate semen quality of patients with acute leukemia before chemotherapy. We also evaluated semen parameters after therapy in a subgroup of patients and we collected fertility information. Finally, we collected information about the feasibility of the semen cryopreservation and evaluated any shifts in the approach to fertility preservation in these patients. A retrospective study was conducted, and it included the collection of data related to: semen analysis, information related to paternity desire and childbearing, number of cryopreservations performed over the years and the feasibility of the procedure. The median semen characteristics of these patients were above the 25° percentile, before cancer treatment. After therapies, an increase of the percentage of azoospermic at one year of follow-up can be observed. Four patients succeeded in achieving fatherhood through at least one cycle of assisted reproductive technology. These results allow us to recommend increased awareness among onco-hematologists about cryopreservation of semen for acute leukemia patients to ensure that they can become parents in the future and face the treatment course with greater confidence.

Background/Objectives: Aberrant DNA methylation of imprinted genes and increased sperm DNA fragmentation (SDF) have been implicated in male infertility. However, their impact on assisted reproductive technology (ART) outcomes remains unclear. This pilot study aimed to investigate SDF and methylation status of H19, IGF2, and PEG1/MEST in relation to fertilisation and embryo development following intracytoplasmic sperm injection (ICSI). Methods: Twenty male partners of women undergoing ICSI were recruited and classified according to ART outcome into viable embryos (VEs, n = 7), non-viable embryos (NVEs, n = 7), and no fertilisation (NF, n = 6). Before sperm selection, an aliquot of each seminal sample was used for semen analysis according to WHO, 2021, SDF assessment (TUNEL assay), and sperm DNA methylation analysis of H19, IGF2, and PEG1/MEST (pyrosequencing). Results: Semen parameters were above the fifth percentile. SDF was significantly lower in the VE group compared with the other groups. H19 CpG1 methylation correlated positively with viable embryos (p = 0.016), while H19 CpG2 island showed a positive correlation with sperm concentration (p = 0.028). In male/couple infertility cases, total H19 methylation correlated negatively with SDF (p = 0.050). IGF2 CpG3 island methylation correlated positively with viable embryos (p = 0.027). Total PEG1/MEST methylation was positively correlated with fertilisation events (p = 0.002) and viable embryos (p = 0.011). PEG1/MEST CpG2 island also positively correlated with sperm motility (p = 0.034), while CpG3 and CpG4 showed significant correlations with fertilisation (p < 0.001; p = 0.004). Conclusions: This pilot study shows that SDF and sperm methylation levels of H19, IGF2, and PEG1/MEST are related to ICSI outcomes, supporting that sperm molecular and epigenetic features may influence fertilisation and embryo development.

In patients with advanced breast cancer, switching to camizestrant with a CDK4/6 inhibitor after ESR1 -mutation detection (and before disease progression) led to significantly longer progression-free survival.

Background: Atherosclerotic disease is the leading global cause of death, driven by progressive plaque accumulation in the arteries. Ultrasound (US) imaging, both conventional (CUS) and intravascular (IVUS), is crucial for the non-invasive assessment of atherosclerotic plaques. Deep learning (DL) techniques have recently gained attention as tools to improve the accuracy and efficiency of image analysis in this domain. This paper reviews recent advancements in DL-based methods for the segmentation, classification, and quantification of atherosclerotic plaques in US imaging, focusing on their performance, clinical relevance, and translational challenges. Methods: A systematic literature search was conducted in the PubMed, Scopus, and Web of Science databases, following PRISMA guidelines. The review included peer-reviewed original articles published up to 31 January 2025 that applied DL models for plaque segmentation, characterization, and/or quantification in US images. Results: A total of 53 studies were included, with 72% focusing on carotid CUS and 28% on coronary IVUS. DL architectures, such as UNet and attention-based networks, were commonly used, achieving high segmentation accuracy with average Dice similarity coefficients of around 84%. Many models provided reliable quantitative outputs (such as total plaque area, plaque burden, and stenosis severity index) with correlation coefficients often exceeding R = 0.9 compared to manual annotations. Limitations included the scarcity of large, annotated, and publicly available datasets; the lack of external validation; and the limited availability of open-source code. Conclusions: DL-based approaches show considerable promise for advancing atherosclerotic plaque analysis in US imaging. To facilitate broader clinical adoption, future research should prioritize methodological standardization, external validation, data and code sharing, and integrating 3D US technologies.

This paper aims to investigate failures induced by vibrations on machines, focusing on agricultural ones. The research on literature has brought to light a considerable amount of data on the driven vehicles and not much on the operating machines, including the ones that we looked for. For this reason, it was decided to direct a survey with the people who work with agricultural machinery every day: operators, sub-contractors, and producers. They were asked about the most frequent breakage, particularly in relation to the rotary harrow, the topic of this work. The questionnaire results showed the types of failures the harrow is most vulnerable to, indicating the times of failure and reparation and the need to set up a potentially useful preventive maintenance supporting system on these machines. Part of the work was then focused on the proposition of a method to investigate bearing failures in the rotary harrow, considering that these have been analyzed in the technical literature and in the survey as the most at-risk components. The proposed method in this work serves as a beginning for the development of a future on board sent-shore-based maintenance system for continuous monitoring of the bearing.