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Introduction/BackgroundEndometrial cancer (EC) is mostly diagnosed at an early stage with a favorable overall survival. 5-year survival decreases from 95% for localized disease to less than 20% for metastatic disease. Survival is related to known prognostic factors. Nevertheless, they are not sufficient to predict either outcome or recurrence rate/site: to decipher the underlying aberrant biomolecular pathways seems to be promising, although it is not yet applicable in a clinical setting. In that purpose, to investigate EC recurrence patterns according to ESMO-ESGO-ESTRO risk classes, could be beneficial for an early recurrences detection and treatment with a survival rate improvement.Methodology758 women diagnosed with EC, and a 5-years follow-up, were enrolled: they were divided into the ESMO-ESGO-ESTRO risk classes (low LR, intermediate IR, intermediate-high I-HR, and high risk HR) and surgically treated as recommended, followed by adjuvant therapy, when appropriated.ResultsRecurrences were detected in 19,5%. Higher recurrence rate (RR) was significantly detected (p<0,001) in the HR group (40,3%) compared to LR (9,6%), IR (16,7%) and I-HR (17,1%). Recurrences were detected more frequently at distant sites (64%) compared to pelvic (25,3%) and lymph nodes (10,7%) recurrences (p<0,0001): this trend was evident in all risk classes except for the LR group, where no differences were detected between local and distant recurrences. 5-year distant-free (LR 99%, IR 94%, I-HR 86%, HR 88%) and local-free survivals (LR 99%, IR 100%, I-HR 98%, HR 95%) significantly differ between groups (p<0,0001 and p=0,003, respectively), even when we stratified according to adjuvant therapy (AT) approach. AT did not modify RRs in all risk classes, except for LR group (p=0,01) (85,71% of recurrences occur if no AT was administered).ConclusionThese results strengthen the need to identify biological factors to stratify patients at higher risk of relapse, independently or in addition to their risk class prognosis and current surgical and clinical managements.DisclosureNothing to disclose.

ObjectiveThe primary aim is to evaluate the surgical and oncological outcome of robotic radical hysterectomy (RRH) plus pelvic lymphadenectomy in locally advanced cervical cancer (LACC) after neoadjuvant chemotherapy (NACT). The secondary aim is to compare the surgical and oncological results of RRH after NACT with a historical cohort of patients undergoing laparoscopic radical hysterectomy or abdominal radical hysterectomy plus pelvic lymphadenectomy for LACC after NACT.MethodsWe enrolled a total of 41 patients in this study with LACC undergoing RRH, who achieved a clinical partial or complete response to NACT. The surgical and oncological outcomes of 2 historical groups were compared: the laparoscopic group (41 patients) with the laparotomic group (43 patients).ResultsThe median estimated blood loss, operative time, and length of hospital stay were statistically significant and in favor of the robotic group. No conversion to laparotomy in the robotic group was necessary. There were no significant differences between the 3-year overall survival and disease-free survival rates in the minimally invasive groups; nevertheless, the robotic group showed the same recurrence rate of laparoscopic in a short-interval follow-up.ConclusionsThe robotic approach could be considered a feasible and safe alternative to other surgical options. Multicenter randomized clinical trials with longer follow-ups are necessary to evaluate the overall oncologic outcomes of this procedure.

Patients with type 2 diabetes are at increased susceptibility to a prolonged QT interval. Furthermore, insulin secretagogues, drugs used to treat diabetes, may prolong QT interval and provoke arrhythmias. We evaluated whether secretagogues can affect QTc interval during cardiac stress test in 20 patients with type 2 diabetes treated with secretagogues. ECG stress test was performed in all patients. QTc interval was calculated both before cardiac stress test (BCST) and at acme of cardiac stress test (ACST). Diabetic patients treated with secretagogues showed longer QTc-ACST values than those treated with metformin only. QTc-ACST values resulted shorter than QTc-BCST values in control group. Diabetic patients treated with secretagogues showed QTc-ACST values significantly longer than QTc-BCST values. In our study, diabetic patients treated with secretagogues did not show the QTc physiologic decrease that is a protective against arrhythmias. These results suggest to evaluate, in these patients, QT length, even during routine cardiac stress test.

Track structures and resulting DNA damage in human cells have been simulated for hydrogen, helium, carbon, nitrogen, oxygen and neon ions with 0.25–256 MeV/u energy. The needed ion interaction cross sections have been scaled from those of hydrogen; Barkas scaling formula has been refined, extending its applicability down to about 10 keV/u, and validated against established stopping power data. Linear energy transfer (LET) has been scored from energy deposits in a cell nucleus; for very low-energy ions, it has been defined locally within thin slabs. The simulations show that protons and helium ions induce more DNA damage than heavier ions do at the same LET. With increasing LET, less DNA strand breaks are formed per unit dose, but due to their clustering the yields of double-strand breaks (DSB) increase, up to saturation around 300 keV/μm. Also individual DSB tend to cluster; DSB clusters peak around 500 keV/μm, while DSB multiplicities per cluster steadily increase with LET. Remarkably similar to patterns known from cell survival studies, LET-dependencies with pronounced maxima around 100–200 keV/μm occur on nanometre scale for sites that contain one or more DSB, and on micrometre scale for megabasepair-sized DNA fragments.

The understanding of the impact of radiation quality in early and late responses of biological targets to ionizing radiation exposure necessarily grounds on the results of mechanistic studies starting from physical interactions. This is particularly true when, already at the physical stage, the radiation field is mixed, as it is the case for neutron exposure. Neutron Relative Biological Effectiveness (RBE) is energy dependent, maximal for energies ~1 MeV, varying significantly among different experiments. The aim of this work is to shed light on neutron biological effectiveness as a function of field characteristics, with a comprehensive modeling approach: this brings together transport calculations of neutrons through matter (with the code PHITS) and the predictive power of the biophysical track structure code PARTRAC in terms of DNA damage evaluation. Two different energy dependent neutron RBE models are proposed: the first is phenomenological and based only on the characterization of linear energy transfer on a microscopic scale; the second is purely ab-initio and based on the induction of complex DNA damage. Results for the two models are compared and found in good qualitative agreement with current standards for radiation protection factors, which are agreed upon on the basis of RBE data.

Guided by the early findings of social scientists, practitioners have long advocated for greater contact between groups to reduce prejudice and increase social cohesion. Recent work, however, suggests that intergroup contact can undermine support for social change towards greater equality, especially among disadvantaged group members. Using a large and heterogeneous dataset (12,997 individuals from 69 countries), we demonstrate that intergroup contact and support for social change towards greater equality are positively associated among members of advantaged groups (ethnic majorities and cis-heterosexuals) but negatively associated among disadvantaged groups (ethnic minorities and sexual and gender minorities). Specification-curve analysis revealed important variation in the size—and at times, direction—of correlations, depending on how contact and support for social change were measured. This allowed us to identify one type of support for change—willingness to work in solidarity— that is positively associated with intergroup contact among both advantaged and disadvantaged group members. Using data from 69 countries, Hässler et al. show that intergroup contact and support for social change towards greater equality are positively associated among members of advantaged groups, but negatively associated among disadvantaged groups.

Our understanding of radiation-induced cellular damage has greatly improved over the past few decades. Despite this progress, there are still many obstacles to fully understand how radiation interacts with biologically relevant cellular components, such as DNA, to cause observable end points such as cell killing. Damage in DNA is identified as a major route of cell killing. One hurdle when modeling biological effects is the difficulty in directly comparing results generated by members of different research groups. Multiple Monte Carlo codes have been developed to simulate damage induction at the DNA scale, while at the same time various groups have developed models that describe DNA repair processes with varying levels of detail. These repair models are intrinsically linked to the damage model employed in their development, making it difficult to disentangle systematic effects in either part of the modeling chain. These modeling chains typically consist of track-structure Monte Carlo simulations of the physical interactions creating direct damages to DNA, followed by simulations of the production and initial reactions of chemical species causing so-called “indirect” damages. After the induction of DNA damage, DNA repair models combine the simulated damage patterns with biological models to determine the biological consequences of the damage. To date, the effect of the environment, such as molecular oxygen (normoxic vs. hypoxic), has been poorly considered. We propose a new standard DNA damage (SDD) data format to unify the interface between the simulation of damage induction in DNA and the biological modeling of DNA repair processes, and introduce the effect of the environment (molecular oxygen or other compounds) as a flexible parameter. Such a standard greatly facilitates intermodel comparisons, providing an ideal environment to tease out model assumptions and identify persistent, underlying mechanisms. Through inter-model comparisons, this unified standard has the potential to greatly advance our understanding of the underlying mechanisms of radiation-induced DNA damage and the resulting observable biological effects when radiation parameters and/or environmental conditions change.

The current study investigates attitudes toward one form of sex for resources: the so-called sugar relationships, which often involve exchanges of resources for sex and/or companionship. The present study examined associations among attitudes toward sugar relationships and relevant variables (e.g., sex, sociosexuality, gender inequality, parasitic exposure) in 69,924 participants across 87 countries. Two self-report measures of Acceptance of Sugar Relationships (ASR) developed for younger companion providers (ASR-YWMS) and older resource providers (ASR-OMWS) were translated into 37 languages. We tested cross-sex and cross-linguistic construct equivalence, cross-cultural invariance in sex differences, and the importance of the hypothetical predictors of ASR. Both measures showed adequate psychometric properties in all languages (except the Persian version of ASR-YWMS). Results partially supported our hypotheses and were consistent with previous theoretical considerations and empirical evidence on human mating. For example, at the individual level, sociosexual orientation, traditional gender roles, and pathogen prevalence were significant predictors of both ASR-YWMS and ASR-OMWS. At the country level, gender inequality and parasite stress positively predicted the ASR-YWMS. However, being a woman negatively predicted the ASR-OMWS, but positively predicted the ASR-YWMS. At country-level, ingroup favoritism and parasite stress positively predicted the ASR-OMWS. Furthermore, significant cross-subregional differences were found in the openness to sugar relationships (both ASR-YWMS and ASR-OMWS scores) across subregions. Finally, significant differences were found between ASR-YWMS and ASR-OMWS when compared in each subregion. The ASR-YWMS was significantly higher than the ASR-OMWS in all subregions, except for Northern Africa and Western Asia.