PLATO camera ghosts: simulations and measurements on the engineering model (EM)

The PLAnetary Transits and Oscillations of stars mission (PLATO) is the M3 mission in ESA’s Cosmic Vision 2015-2025 Programme, see Rauer et al. (2014).1 The PLATO mission aims at detecting and characterizing extrasolar planetary systems, including terrestrial exoplanets around bright solar-type stars up to the habitable zone. To be able to perform the required high precision photometric monitoring of the large target stars sample, PLATO is based on a multi-telescope configuration consisting of 26 Cameras, so as to provide simultaneously a large field of view and a large collecting aperture. The optical design is identical for all cameras and consists of a 6-lens dioptric design with a 120 mm entrance pupil and an effective field of view of more than 1000 square degrees. As for every optical system, especially dioptric ones, the presence of optical ghosts can dramatically affect the scientific observations. Thanks to the application of an excellent anti-reflection coating, PLATO’s cameras are by design very insensitive to ghosts. However, the residual faint back reflections focused on the detectors have to be simulated and considered during science operation (target selection) and in data correction algorithms. This article describes the different optical analyses performed to estimate the importance of ghosts in PLATO’s cameras, as well as the simulations performed to support the preparation of the test campaign on the first PLATO camera: the engineering model. Finally, the test execution, data analysis and results are presented and compared to the simulated data

Temporal bone carcinoma: Classical prognostic variables revisited and modern clinico-pathological evidence

AimPrognostic factors, rational management, and the ongoing investigations regarding temporal bone squamous cell carcinoma (TBSCC) have been critically reviewed.BackgroundTBSCC is an uncommon, aggressive malignancy. Although some progress has been made in treating this aggressive tumor, the prognosis in advanced cases remains poor.Materials and methodsA systematic search of the literature for articles published between 2009 and October 2014 was performed using the PubMed ([[ce:inter-ref id="intr0005" xlink:href="http://www.pubmed.gov/"]]http://www.pubmed.gov) electronic database.ResultsGiven the particular anatomical site of TBSCC, its prognosis is significantly influenced by any direct involvement of nearby structures. The extent of the primary tumor is generally considered one of the most important prognostic factors and it is frequently related to prognosis even more strongly than N stage. For TBSCC, biomarker investigations in surgical specimens are only just beginning to appear in the oncological literature.ConclusionGiven the particular features of TBSCC, the sub-specialty of otologic oncology seems to be emerging as a defined area of practice involving multidisciplinary team comprising oto-neurosurgeons, head and neck surgeons, plastic surgeons, oncologists, radiotherapists, dedicated radiologists, and pathologists

Artificial intelligence in head and neck cancer diagnosis

Introduction: Artificial intelligence (AI) is currently being used to augment histopathological diagnostics in pathology. This systematic review aims to evaluate the evolution of these AI-based diagnostic techniques for diagnosing head and neck neoplasms. Materials and methods: Articles regarding the use of AI for head and neck pathology published from 1982 until March 2022 were evaluated based on a search strategy determined by a multidisciplinary team of pathologists and otolaryngologists. Data from eligible articles were summarized according to author, year of publication, country, study population, tumor details, study results, and limitations. Results: Thirteen articles were included according to inclusion criteria. The selected studies were published between 2012 and March 1, 2022. Most of these studies concern the diagnosis of oral cancer; in particular, 6 are related to the oral cavity, 2 to the larynx, 1 to the salivary glands, and 4 to head and neck squamous cell carcinoma not otherwise specified (NOS). As for the type of diagnostics considered, 12 concerned histopathology and 1 cytology. Discussion: Starting from the pathological examination, artificial intelligence tools are an excellent solution for implementing diagnosis capability. Nevertheless, today the unavailability of large training datasets is a main issue that needs to be overcome to realize the true potential

Le garanzie fondamentali dell\u2019immigrato in Europa

Il volume contiene una riflessione collettiva sulle garanzie fondamentali dell\u2019immigrato in Europa. Esso fornisce agli operatori, agli studiosi e a quanti intendono approfondire il tema dell\u2019immigrazione un\u2019analisi del processo di progressivo arricchimento del sistema di protezione dei diritti fondamentali dei migranti, determinato dalle sentenze della Corte di giustizia dell\u2019Unione europea e dal dialogo che tale organo giurisdizionale ha intrattenuto con la Corte EDU. L\u2019opera mira anzitutto a far emergere il processo di elevazione delle garanzie avvenuto in favore delle diverse categorie di migranti a seguito dell\u2019intervento della Corte di giustizia. In alcuni casi, l\u2019accrescimento delle garanzie in questione \ue8 avvenuto sulla scia di importanti pronunce della Corte EDU, che hanno trainato la Corte di giustizia verso il superamento o il ridimensionamento di criteri stabiliti nel diritto derivato. La giurisprudenza relativa al regolamento Dublino rappresenta un chiaro esempio di questa dinamica. Il volume si propone pertanto anche di chiarire se il dialogo tra le due Corti europee in questo settore lascia presagire uno \u201cscavalcamento\u201d della Corte di giustizia da parte della Corte EDU nella tutela dei diritti fondamentali dei migranti oppure se tale dialogo avverr\ue0 \u2013 in linea con quanto accaduto pi\uf9 di frequente \u2013 secondo una dinamica di \u201creciproca contaminazione\u201d, nel rispetto delle peculiarit\ue0 dei rispettivi sistemi. Per meglio raggiungere gli obiettivi proposti i contributi che compongono il volume sono stati suddivisi in tre parti. Dopo talune indispensabili valutazioni di carattere generale sull\u2019evoluzione della politica comune dell\u2019immigrazione, il libro esamina, nell\u2019ordine, le garanzie di tipo sostanziale in favore dei migranti, la tutela degli status e delle relazioni familiari degli stranieri e, ancora, le garanzie procedurali e processuali offerte ai cittadini di Paesi terzi, a seconda della condizione (di soggiorno regolare, irregolare o di protezione internazionale) in cui essi si trovano. Vengono infine tratte le debite conclusioni

Role of Immune Microenvironment in Pancreatic Ductal Adenocarcinoma: Could It Be Considered a Predictor of Prognosis?

Background: Pancreatic ductal adenocarcinoma (PDAC) is characterized by a highly immunosuppressive tumor microenvironment (TME). The aim of this study is to determine the potential significant TME immune markers of long-term survival. Methods: We retrospectively included patients with a diagnosis of resectable PDAC having undergone upfront surgery. Immunohistochemical (IHC) staining using tissue microarray for PD-L1, CD3, CD4, CD8, FOXP3, CD20, iNOS and CD163 was performed in order to characterize the TME. The primary endpoint was long-term survival, defined as the Overall Survival > 24 months from surgery. Results: A total of 38 consecutive patients were included, and 14 (36%) of them were long-term survivors. Long-term survivors showed a higher density of CD8+ lymphocytes intra- and peri-acinar (p = 0.08), and a higher CD8/FOXP3 intra- and peri-tumoral ratio (p = 0.05). A low density of intra- and peri-tumoral FOXP3 infiltration is a good predictor of long-term survival (p = 0.04). A significant association of the low density of intra- and peri-tumoral tumor-associated macrophages (TAMs) iNOS+ with long-term survival was detected (p = 0.04). Conclusions: Despite the retrospective nature and small sample size, our study showed that the high infiltration of CD8+ lymphocytes and low infiltration of FOXP3+ and TAMs iNOS+ are predictors of good prognosis. A preoperative assessment of these potential immune markers could be useful and determinant in the staging process and in PDAC management

TSC loss is a clonal event in eosinophilic solid and cystic renal cell carcinoma: a multiregional tumor sampling study

Eosinophilic, solid and cystic (ESC) renal cell carcinoma (RCC) is characterized by a solid and cystic architecture with cells showing abundant eosinophilic cytoplasm with hobnail arrangement and a cytokeratin 7-negative/cytokeratin 20-positive immunophenotype. Recent studies have suggested that bi-allelic events affecting TSC genes might play an important role for such tumors. However, only indirect evidence of the clonal origin of TSC mutation has been gathered so far. Therefore, in this paper we aimed to perform multi-regional tumor sampling molecular analysis in four ESC RCC cases that had been completely embedded, three sporadic and one occurring in a patient with tuberous sclerosis complex (TSC). Histologically, the 4 cases showed cystic and solid architecture and cells with abundant eosinophilic cytoplasm with cytoplasmic stippling and round to oval nuclei. Immunohistochemistry showed at least focal expression of cytokeratin 20 in all tissue samples and negative cytokeratin 7, as well as diffuse positivity for S100A1 and at least focal expression of cathepsin K in three out of four cases. The sporadic cases showed the same somatic TSC1 mutations in all tissue samples analyzed, while the TSC-associated case showed the same TSC1 alteration in both normal tissue and all tumor samples analyzed, proving the germline nature of the alteration. In conclusion, our data demonstrate that clonal TSC loss is a key event in ESC RCC and support considering ESC RCC as an entity given its distinct morphologic, immunophenotypical and molecular characteristics

High-Throughput Microscopy Analysis of Mitochondrial Membrane Potential in 2D and 3D Models

Recent proteomic, metabolomic, and transcriptomic studies have highlighted a connection between changes in mitochondria physiology and cellular pathophysiological mechanisms. Secondary assays to assess the function of these organelles appear fundamental to validate these -omics findings. Although mitochondrial membrane potential is widely recognized as an indicator of mitochondrial activity, high-content imaging-based approaches coupled to multiparametric to measure it have not been established yet. In this paper, we describe a methodology for the unbiased high-throughput quantification of mitochondrial membrane potential in vitro, which is suitable for 2D to 3D models. We successfully used our method to analyze mitochondrial membrane potential in monolayers of human fibroblasts, neural stem cells, spheroids, and isolated muscle fibers. Moreover, by combining automated image analysis and machine learning, we were able to discriminate melanoma cells from macrophages in co-culture and to analyze the subpopulations separately. Our data demonstrated that our method is a widely applicable strategy for large-scale profiling of mitochondrial activity

Molecular profiling of appendiceal serrated lesions, polyps and mucinous neoplasms: a single-centre experience

PURPOSE: Non-neuroendocrine neoplasms of the appendix are a phenotypically heterogeneous group of lesions; a comprehensive molecular characterization of these tumors is still lacking.METHODS: A total of 52 samples taken from 49 patients was evaluated: 18 sessile serrated lesions (SSL; 3 with dysplasia), 2 high-grade tubular adenomas, 1 tubulo-villous adenoma,1 hyperplastic polyp, 18 low-grade appendiceal mucinous neoplasms (LAMN), 3 high-grade appendiceal mucinous neoplasms (HAMN) and 9 mucinous adenocarcinomas. Hotspot mutational profiling of the RNF43, SMAD4, KRAS, NRAS, BRAF and PIK3CA genes was performed. Expression of p53, MLH1, PMS2, MSH2, and MSH6 was evaluated by immunohistochemistry.RESULTS: KRAS was the most frequently mutated gene (53.9% of cases), followed by RNF43 (15.4%), and BRAF (13.5%). In particular: KRAS was mutated in 44.4% of adenocarcinomas, 66.7% of HAMNs, 61.1% of LAMNs, 53.3% of SSL without dysplasia and in 66.7% of SSL with dysplasia; RNF43 was mutated in 33.3% of adenocarcinomas, 66.7% of HAMNs, 11.1% of LAMNs and in 6.7% of SSL without dysplasia; BRAF was mutated in 11.1% of adenocarcinomas, 26.7% of SSL without dysplasia and in 5.6% of LAMNs. Only a case of high-grade tubular adenoma showed mismatch repair deficiency, while immunohistochemical expression of p53 was altered in 21.1% of cases.CONCLUSIONS: The histological phenotypic similarities between appendicular mucinous lesions and serrated colon lesions do not reflect a similar genetic landscape. Mismatch repair deficiency is a rare event during appendiceal mucinous carcinogenesis

Assessment of HER2 Protein Overexpression and Gene Amplification in Renal Collecting Duct Carcinoma: Therapeutic Implication

Collecting duct carcinoma (CDC) is rare and aggressive histology of kidney cancers. Although different therapeutic approaches have been tested, the 2-year survival remains very poor. Since CDC exhibits overlapping features with urothelial carcinoma, the analysis of shared molecular alterations could provide new insights into the understanding of this rare disease and also therapeutic options. We collected 26 CDC cases, and we assessed HER2 protein expression by immunohistochemistry (IHC) and gene amplification by fluorescence in-situ hybridization (FISH) according to 2018 ASCO/CAP HER2-testing recommendations. Six out of twenty-six (23%) tumors showed HER2 positive staining. In particular, 3+ score was present in 2/6 cases (33%), 2+ in 3/6 cases (50%) and 1+ in 1/6 cases (17%). The 6 HER2+ tumors were also analyzed by FISH to assess gene copy number. One out of six CDC with IHC 3+ was also HER2 amplified, showing an average HER2 copy number ≥4.0 (10.85) and a HER2/CEP17 ratio ≥ (5.63), while the 5/6 cases were HER2 negative. Based on the 2018 ASCO/CAP guidelines overall, 2/26 CDC cases (8%) were HER2+. The present study provides evidence for testing, in future studies, HER2 to assess its clinical value as a novel target for the treatment of this highly malignant cancer