A Reappraisal of Lymphadenectomy in Common Gynecological Cancers

Objectives: Lymph node dissection (LND) in gynecological malignancies has always been a cornerstone in the diagnosis of metastasis, it is also considered an important prognostic factor, and a reliable guide to management strategies. However, its incidence of complications, namely lymphedema, vascular injuries and other lesions, has led to a reconsideration of its efficacy and a comparison of the role of systematic vs. sentinel lymph node (SLN) dissection. Mechanism: Review of the literature using keywords such as “lymph nodes”, “sentinel lymph nodes”, “morbidity and mortality”, “gynecological cancers”, “endometrial cancer”, “ovarian cancer”, and “cervical cancer”. Findings in Brief: In the case of endometrial cancer, several studies have investigated the efficacy of SLN compared with systematic LND. Most of the results demonstrated the efficacy of SLN dissection in endometrial cancer, with the added benefit of lower morbidity. In patients with ovarian cancer, the mainstay of treatment is debulking with optimal cytoreductive surgery. Recent studies have compared systematic lymphadenectomy to non-lymphadenectomy, with an additional advantage in the cases of lymphadenectomy. However, since its publication, the lymphadenectomy in ovarian cancers (LIONS) trial, has revolutionized the standard of care for patients with advanced ovarian cancer and has called into question the increased morbidity and mortality in systematic lymphadenectomy. In cervical cancers, lymph node status is considered to be the most important prognostic factor. In this case, limiting lymphadenectomy to the borders of the inferior mesenteric artery seems promising, and studies are currently being carried out to investigate the feasibility of SLN dissection instead of systematic lymph node dissection. Conclusions: SLN dissection is associated with lower morbidity and mortality, and has been shown to be superior to systematic lymphadenectomy in several studies. However, more research and specific guidelines are needed to better select either one or the other method in the management of gynecological cancers. Copyright: © 2023 The Author(s)

End-User Development for eXtended Reality using a multimodal Intelligent Conversational Agent

In the past years, both the research community and commercial products have proposed various solutions aiming to support end-user developers (EUDevs), namely users without extensive programming skills, to build and customize XR experiences. However, current tools may not fully eliminate the potential for user errors or misunderstandings. In this paper, we present EUD4XR, a methodology consisting of an intelligent conversational agent to provide contextual help, to EUDevs, during the authoring process. The key characteristics of this agent are its multimodality, comprehending the user’s voice, gaze, and pointing, combined with the environment status. Moreover, the agent could also demonstrate concepts, suggest components, and help explain errors further to reduce misunderstandings for end-user developers of VR/XR

Genetic characterization and implications for conservation of the last autochthonous Mouflon population in Europe

Population genetic studies provide accurate information on population structure, connectivity, and hybridization. These are key elements to identify units for conservation and define wildlife management strategies aimed to maintain and restore biodiversity. The Mediterranean island of Sardinia hosts one of the last autochthonous mouflon populations, descending from the wild Neolithic ancestor. The first mouflon arrived in Sardinia ~ 7000 years ago and thrived across the island until the twentieth century, when anthropogenic factors led to population fragmentation. We analysed the three main allopatric Sardinian mouflon sub-populations, namely: the native sub-populations of Montes Forest and Mount Tonneri, and the reintroduced sub-population of Mount Lerno. We investigated the spatial genetic structure of the Sardinian mouflon based on the parallel analysis of 14 highly polymorphic microsatellite loci and mitochondrial D-loop sequences. The Montes Forest sub-population was found to harbour the ancestral haplotype in the phylogeny of European mouflon. We detected high levels of relatedness in all the sub-populations and a mitochondrial signature of hybridization between the Mount Lerno sub-population and domestic sheep. Our findings provide useful insights to protect such an invaluable genetic heritage from the risk of genetic depletion by promoting controlled inter-population exchange and drawing informed repopulation plans sourcing from genetically pure mouflon stocks

Examples of multi-sensor determination of eruptive source parameters of explosive events at mount etna

International audienceMulti-sensor strategies are key to the real-time determination of eruptive source parameters (ESPs) of explosive eruptions necessary to forecast accurately both tephra dispersal and deposition. To explore the capacity of these strategies in various eruptive conditions, we analyze data acquiredby two Doppler radars, ground- and satellite-based infrared sensors, one infrasound array, visible video-monitoring cameras as well as data from tephra-fallout deposits associated with a weak and a strong paroxysmal event at Mount Etna (Italy). We find that the different sensors provide complementary observations that should be critically analyzed and combined to provide comprehensive estimates of ESPs. First, all measurements of plume height agree during the strong paroxysmal activity considered, whereas some discrepancies are found for the weak paroxysm due to rapid plume and cloud dilution. Second, the event duration, key to convert the total erupted mass (TEM) in the mass eruption rate (MER) and vice versa, varies depending on the sensor used, providing information on different phases of the paroxysm (i.e., unsteady lava fountaining, lava fountain-fed tephra plume, waning phase associated with plume and cloud expansion in the atmosphere). As a result, TEM and MER derived from different sensors also correspond to the different phases of the paroxysms. Finally, satellite retrievals for grain-size can be combined with radar data to provide a first approximation of total grain-size distribution (TGSD) in near real-time. Such a TGSD shows a promising agreement with the TGSD derived from the combination of satellite data and whole deposit grain-size distribution (WDGSD)

X-ray grating interferometry design for the 4D GRAPH-X system

The 4D GRAPH-X (Dynamic GRAting-based PHase contrast x-ray imaging) project aims at developing a prototype of an x-ray grating-based phase-contrast imaging scanner in a laboratory setting, which is based on the Moire single-shot acquisition method in order to be optimized for analysing moving objects (in the specific case, a dynamic thorax phantom), that could evolve into a suitable tool for biomedical applications although it can be extended to other application fields. When designing an x-ray Talbot-Lau interferometer, high visibility and sensitivity are two important figures of merit, strictly related to the performance of the system in obtaining high quality phase contrast and dark-field images. Wave field simulations are performed to optimize the setup specifications and construct a high-resolution and high-sensitivity imaging system. In this work, the design of a dynamic imaging setup using a conventional milli-focus x-ray source is presented. Optimization by wave front simulations leads to a symmetric configuration with 5.25 mu m pitch at third Talbot order and 45 keV design energy. The simulated visibility is about 22%. Results from GATE based Monte Carlo simulations show a 19% transmission percentage of the incoming beam into the detector after passing through all the gratings and the sample. Such results are promising in view of building a system optimized for dynamic imaging

Novel copper complexes with glyoximes, amines, schiff bases, semi-and thiosemicarbazones ; synthesis and physico-chemical analysis

In our research project new copper(II) complexes were synthesized with -dioximes, amines, Schiff bases, semi- and thiosemicarbazones such as [Cu(DioxH)2L2], (DioxH2: methyl-butylglyoxime, ethyl-butyl-glyoxime, methyl-phenyl-glyoxime; L: diphenyl-amine, 2-methylimidazole, dibutyl-amine, 2-amino-4-methylpyridine, imidazole, 1-aminonaphthaline), [Cu(octan-2-one)2AL2], (A: hydrazine, phenylhydrazine, o-phenylene-diamine; L: 3-amino1H-1,2,4-triazole, 2-aminopyrimidine, 2-methylimidazole), [Cu(ketone-SC)2], [Cu(ketoneTSC)2], (ketone: propiophenone, butyrophenone; SC: semicarbazone; TSC: thiosemicarbazone), by the reaction of copper(II)-acetate in suitable solvent. After a short bibliographical survey, involving the classification and evolution of copper complexes with possible applications, we analyzed their physicochemical properties using FTIR, Raman, ESR, UV-VIS, powder X-ray diffraction (XRD), mass spectrometry, thermal analysis (TG, DTG, DTA) and SEM. The importance of this class of compounds lies in biochemistry as some of them are antibacterial agents and potential anti-tumour drugs

IDH2 inhibition enhances proteasome inhibitor responsiveness in hematological malignancies

Proteasome inhibitors (PIs) are extensively used for the therapy of multiple myeloma (MM) and mantle-cell lymphoma (MCL). However, patients continuously relapse or are intrinsically resistant to this class of drugs. Here, to identify targets that synergize with PIs, we carried out a functional screening in MM cell lines using a short hairpin RNA library against cancer driver genes. Isocitrate dehydrogenase 2 (IDH2) was identified as a top candidate, showing a synthetic lethal activity with the PI carfilzomib (CFZ). Combinations of FDA approved PIs with a pharmacological IDH2 inhibitor (AGI-6780) triggered synergistic cytotoxicity in MM, MCL, and Burkitt's lymphoma (BL) cell lines. CFZ/AGI-6780 treatment increased death of primary CD138+ cells from MM patients and exhibited a favorable cytotoxicity profile towards peripheral blood mononuclear cells and bone marrow-derived stromal cells. Mechanistically, CFZ/AGI-6780 combination significantly decreased tricarboxylic acid (TCA) cycle activity and ATP levels, as a consequence of enhanced IDH2 enzymatic inhibition. Specifically, CFZ treatment reduced the expression of nicotinamide phosphoribosyltransferase (NAMPT), thus limiting IDH2 activation through the NAD+-dependent deacetylase SIRT3. Consistently, combination of CFZ with either NAMPT or SIRT3 inhibitors impaired IDH2 activity and increased MM cell death. Finally, inducible IDH2 knockdown enhanced the therapeutic efficacy of CFZ in a subcutaneous xenograft model of MM, resulting in inhibition of tumor progression and extended survival. Taken together, these findings indicate that NAMPT/SIRT3/IDH2 pathway inhibition enhances the therapeutic efficacy of PIs, thus providing compelling evidence for treatments with lower and less toxic doses and broadening the application of PIs to other malignancies

Influence of Temperature and Humidity on Bakelite Resistivity

Presentation made at RPC99 and submitted to Elsevier PreprintThe use of phenolic or melaminic bakelite as RPC electrodes is widespread. The electrode resistivity is an important parameter for the RPC performance. As recent studies have pointed out, the bakelite resistivity changes with temperature and is influenced by humidity. In order to gain a quantitative understanding on the influence of temperature and humidity on RPC electrodes, we assembled an apparatus to measure resistivity in well-controlled conditions. A detailed description of the experimental set-up as well as the first resistivity measurements for various laminates in different environmental conditions are presented