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Introduction/BackgroundEpithelial ovarian cancer (EOC), notably high-grade serous EOC (HGS-EOC), is a prevalent and lethal cancer in women. Despite the efficacy of initial treatment involving primary surgical cytoreduction and platinum-based chemotherapy, high relapse rates contribute to poor outcomes. This study leverages single-cell RNA-Seq data to delve into gene expression, immune signatures, and pathways, providing insights into the tumor microenvironment (TME) and immune profile of HGS-EOC.MethodologyThe single-cell RNA-Seq patient cohort comprises 35 samples from 15 patients, collected pre and post neoadjuvant chemotherapy (NACT) at specific sites: the primary site (ovary or nearby tissues), omentum (the most invaded membrane), and peritoneum (the second most invaded). The procedure involves dissociating fresh samples, conducting flow cytometry analysis with a panel of antibodies, and employing Illumina Next-Seq 2000 for single-cell RNA sequencing, carried out by co-investigators at Humanitas Clinical Institute, MilanResultsPreliminary results from analyzing a complete patient, encompassing a primary sample pre-NACT and three metastatic sites post-NACT, indicate a higher prevalence of the stromal component in metastatic samples compared to the primary site. Dimensionality reduction techniques and the ESTIMATE package are utilized to assess TME composition, deriving tumor, immune, and stromal scores from gene expression profiles.ConclusionThe findings underscore the pivotal role of the TME, particularly the stromal component, in tumor progression. While these initial results highlight distinctions in cell composition between primary and metastatic sites, further analyses with additional samples are imperative for a comprehensive understanding of cell behavior throughout disease progression.DisclosuresNoneAbstract 483 Figure 1

This study provides a comprehensive overview of the role of immunotherapy in the treatment of mismatch repair-deficient (MMRd) endometrial carcinomas. Immunotherapy has emerged as a transformative approach in the treatment of MMRd due to the high mutation rate and subsequent PD-1/PD-L1 overexpression seen in these tumors. This review analyzes the current landscape of existing randomized clinical trials, highlighting the efficacy of immune checkpoint inhibitors (ICIs) like pembrolizumab, avelumab, and dostarlimab. Additionally, the focus extends to the potential of combined therapeutic strategies, such as the integration of ICIs with targeted agents, while also exploring the application of immunotherapy in non-traditional settings beyond advanced or recurrent disease. This includes emerging roles in the adjuvant and neoadjuvant contexts to prevent recurrence and target early-stage disease. These findings underscore the importance of tailoring treatments based on the molecular characteristics of each tumor and paving the way for future advancements in the field of gynecologic oncology. Despite promising results, this article acknowledges the necessity of further research to refine patient selection criteria and explore combination strategies that can overcome resistance mechanisms.

The sustainable production of energy without environmental footprints is a challenge of paramount importance to satisfy the ever-increasing global demand and to promote economic and social growth through a greener perspective. Such awareness has significantly stimulated worldwide efforts aimed at exploring various energy paths and sources, in compliance with the ever more stringent environmental regulations. Research advancements in these fields are directly dependent on the design, fabrication, and implementation of tailored multi-materials for efficient energy production and harvesting and storage devices. Herein, we aim at providing a survey on the ongoing research activities related to various aspects of functional materials for energy production, conversion, and storage. In particular, we present the opportunities and the main open challenges related to multifunctional materials spanning from carbon-based nanostructures for chemical energy conversion, ferroelectric ceramics for energy harvesting, and phase change materials for thermal energy storage to metallic materials for hydrogen technologies, heat exchangers for wind energy, and amphiphobic coatings for the protection of solar panels. The relevance of designing tailored materials for power generation is also presented. Finally, the importance of applying life cycle assessment to materials is emphasized through the case study of AlTiN thin films.

Background and Objectives: Cervical cancer (CC) represents a significant health concern worldwide, particularly for younger women. Cold knife (CK) conization and carbon dioxide (CO2) laser conization are two techniques commonly used to remove pre-invasive lesions, offering a potential curative intent in cases of incidental diagnosis of CC. This study aimed to assess the clinical implications and pathological outcomes of CK vs. CO2 laser conization for pre-invasive lesions. Materials and Methods: We retrospectively analyzed women who underwent CO2 or CK conization for high-grade preinvasive lesions (CIN2/3, CIS and AIS) between 2010 and 2022. Patient demographics, surgical details and pathological outcomes were collected. Pregnancy outcomes, including composite adverse obstetric rates, and oncological follow-up data, were also obtained. Results: In all, 1270 women were included; of them, 1225 (96.5%) underwent CO2, and 45 (3.5%) underwent CK conization. Overall, the rate of positive endocervical or deep margins was lower with CO2 laser compared to CK (4.3% vs. 13.3%, p = 0.015). Incidental CC was diagnosed in 56 (4.4%) patients, with 35 (62.5%) squamous and 21 (46.6%) adenocarcinomas. In a multivariate regression model, the relative risk for positive endocervical or deep margins is significantly greater in cases of incidental diagnosis of CC (p < 0.01). In cases of incidental diagnosis of CC, we found that the probabilities of having either positive endocervical or deep margins after CO2 laser or CK conization are similar, with a higher risk in case of adenocarcinoma lesion. Among women with CC, 42 (75%) opted for radical treatment, while 14 (25%) underwent a follow-up. Only one woman (7.1%) in the follow-up group, who had undergone CK conization, experienced a composite adverse obstetric outcome. No recurrences were observed after a median follow-up of 53 months. Conclusions: CO2 laser conization achieved a lower positive margin rate overall. CK and CO2 conization appear to be equivalent oncological options for incidental CC.

Background: The approach to adenocarcinoma in situ (AIS) is challenged by diagnostic complexity, limited high-quality evidence, and heterogeneous guidance. Methods: We conducted a narrative comparative review of global guidelines/recommendations (2012–2025; search updated 1 October 2025), extracting data across 38 topics related to AIS management and classifying indications into five categories of coverage/consensus. Results: Twenty documents from national or supranational bodies were included. A cross-guideline consensus emerged on eight core items (colposcopy for any glandular cytologic abnormality; role of HPV test; mandatory histologic confirmation; excisional treatment for histologic AIS; re-excision when margins are involved; criteria and type of hysterectomy; and expert/centralized management). Operational variability emerged in the excisional technique, pathways for discordant results, management during pregnancy, and follow-up protocols. Divergent guidance was most evident for indications to endocervical sampling, criteria for conservative management, and the need for hysterectomy after completed childbearing. Limited-coverage consensus involved the technique of initial histologic sampling, endometrial assessment, and pathways for cytology subtypes. Several areas remained unaddressed. Conclusions: While the essential management of AIS is well defined, uncertainty increases when treatment must be personalized. A core outcome set and rigorous multicenter studies are needed to reduce heterogeneity and enable truly evidence-based personalization.

Malignant pleural mesothelioma (MPM) is an aggressive tumor with a poor prognosis. As the available therapeutic options show a lack of efficacy, novel therapeutic strategies are urgently needed. Given its T-cell infiltration, we hypothesized that MPM is a suitable target for therapeutic cancer vaccination. To date, research on mesothelioma has focused on the identification of molecular signatures to better classify and characterize the disease, and little is known about therapeutic targets that engage cytotoxic (CD8+) T cells. In this study we investigate the immunopeptidomic antigen-presented landscape of MPM in both murine (AB12 cell line) and human cell lines (H28, MSTO-211H, H2452, and JL1), as well as in patients’ primary tumors. Applying state-of-the-art immuno-affinity purification methodologies, we identify MHC I-restricted peptides presented on the surface of malignant cells. We characterize in vitro the immunogenicity profile of the eluted peptides using T cells from human healthy donors and cancer patients. Furthermore, we use the most promising peptides to formulate an oncolytic virus-based precision immunotherapy (PeptiCRAd) and test its efficacy in a mouse model of mesothelioma in female mice. Overall, we demonstrate that the use of immunopeptidomic analysis in combination with oncolytic immunotherapy represents a feasible and effective strategy to tackle untreatable tumors. Malignant pleural mesothelioma is an aggressive cancer with a poor prognosis and limited therapeutic options. Here the authors report the immunopeptidomic landscape of murine and human mesothelioma tumors and demonstrate the anti-tumor potential of oncolytic adenoviruses coated with so-defined tumor-specific peptides in a mouse model of mesothelioma.

This study reports on early Eurasian evidence of artificial cranial modification (ACM) in a Late Upper Palaeolithic (LUP) individual (AC12) from Arene Candide Cave, Italy (ca. 12,620–12,190 Cal BP). We used virtual anthropology and geometric morphometrics to compare AC12’s cranial morphology with LUP, Mesolithic, and Neolithic Italian specimens, pathologically modified individuals, and a global sample of ACM cases. Our analyses consistently demonstrate a strong affinity between AC12 and the ACM group, distinct from other comparative samples. Statistical analyses confirm AC12 as a clear outlier for non-ACM groups, with high probabilities of belonging to the ACM cluster. This discovery provides evidence suggesting an earlier origin of ACM on the continent, confirming that this globally distributed practice has Palaeolithic roots. Situated within a complex LUP funerary site, this finding illuminates the deep antiquity of culturally mediated body modification and its role in signifying ascribed identity within ancient hunter-gatherer societies.

Five patients with acute myelogenous leukemia received hematopoietic stem-cell transplants from a haploidentical donor. They also received T cells from the donor. All five patients had a relapse, and at the time of relapse, genomic HLA typing of leukemic blasts could not detect the recipient's HLA haplotype that differed from the donor's. The loss of the haplotype was due to uniparental disomy. In vitro, the donor's T cells reacted against leukemic blasts obtained at the time of diagnosis, not against blasts obtained at relapse. The results indicate the presence of a mutation that allowed the leukemic cells to escape the immunosurveillance of the donor's T cells. Five patients with acute myelogenous leukemia received hematopoietic stem-cell transplants from a haploidentical donor. They also received T cells from the donor. All five patients had a relapse, and at the time of relapse, genomic HLA typing of leukemic blasts could not detect the recipient's HLA haplotype that differed from the donor's. Transplantation of hematopoietic stem cells from a haploidentical family donor who shares only one HLA haplotype with the recipient is a potentially curative option for patients with high-risk hematologic cancers who lack an HLA-matched donor. 1 – 3 The major limitation of this strategy is the risk of severe graft-versus-host disease (GVHD), which can result from alloreactions mediated by donor T cells against the recipient's unshared HLA haplotype. Since the publication of studies on extensively T-cell–depleted grafts, 1 , 2 a variety of strategies have been developed to prevent or control GVHD after transfer of haploidentical T cells. 4 , 5 The feasibility and efficacy of . . .

Background Limited data exist regarding ventilation in patients with class III obesity [body mass index (BMI) > 40 kg/m 2 ] and acute respiratory distress syndrome (ARDS). The aim of the present study was to determine whether an individualized titration of mechanical ventilation according to cardiopulmonary physiology reduces the mortality in patients with class III obesity and ARDS. Methods In this retrospective study, we enrolled adults admitted to the ICU from 2012 to 2017 who had class III obesity and ARDS and received mechanical ventilation for > 48 h. Enrolled patients were divided in two cohorts: one cohort (2012–2014) had ventilator settings determined by the ARDSnet table for lower positive end-expiratory pressure/higher inspiratory fraction of oxygen ( standard protocol-based cohort ); the other cohort (2015–2017) had ventilator settings determined by an individualized protocol established by a lung rescue team ( lung rescue team cohort ). The lung rescue team used lung recruitment maneuvers, esophageal manometry, and hemodynamic monitoring. Results The standard protocol-based cohort included 70 patients (BMI = 49 ± 9 kg/m 2 ), and the lung rescue team cohort included 50 patients (BMI = 54 ± 13 kg/m 2 ). Patients in the standard protocol-based cohort compared to lung rescue team cohort had almost double the risk of dying at 28 days [31% versus 16%, P  = 0.012; hazard ratio (HR) 0.32; 95% confidence interval (CI95%) 0.13–0.78] and 3 months (41% versus 22%, P  = 0.006; HR 0.35; CI95% 0.16–0.74), and this effect persisted at 6 months and 1 year (incidence of death unchanged 41% versus 22%, P  = 0.006; HR 0.35; CI95% 0.16–0.74). Conclusion Individualized titration of mechanical ventilation by a lung rescue team was associated with decreased mortality compared to use of an ARDSnet table.