Search

Encoded by the CDX2 homeobox gene, the CDX2 protein assumes the role of a pivotal transcription factor localized within the nucleus of intestinal epithelial cells, orchestrating the delicate equilibrium of intestinal physiology while intricately guiding the precise development and differentiation of epithelial tissue. Emerging research has unveiled that positive immunohistochemical expression of this protein shows that the CDX2 gene exerts a potent suppressive impact on tumor advancement in colorectal cancer, impeding the proliferation and distant dissemination of tumor cells, while the inhibition or suppression of CDX2 frequently correlates with aggressive behavior in colorectal cancer. In this study, we conducted an immunohistochemical assessment of CDX2 expression on a cohort of 43 intraoperatively obtained tumor specimens from patients diagnosed with colon cancer at Colțea Clinical Hospital in Bucharest, between April 2019 and December 2023. Additionally, we shed light on the morphological diversity within colon tumors, uncovering varying differentiation grades within the same tumor, reflecting the variations in CDX2 expression as well as the genetic complexity underlying these tumors. Based on the findings, we developed an innovative immunohistochemical scoring system that addresses the heterogeneous nature of colon tumors. Comprehensive statistical analysis of CDX2 immunohistochemical expression unveiled significant correlations with known histopathological parameters such as tumor differentiation grades (p-value = 0.011) and tumor budding score (p-value = 0.002), providing intriguing insights into the complex involvement of the CDX2 gene in orchestrating tumor progression through modulation of differentiation processes, and highlighting its role in metastatic predisposition. The compelling correlation identified between CDX2 expression and conventional histopathological parameters emphasizes the prognostic significance of the CDX2 biomarker in colon cancer. Moreover, our novel immunohistochemical scoring system reveals a distinct subset of colon tumors exhibiting reserved prognostic outcomes, distinguished by their “mosaic” CDX2 expression pattern.

The strain engineering effects induced by different means, e.g., the substrate lattice mismatch and/or chemical doping, on the functional properties of perovskite thin films have triggered interest in the use of these materials in different applications such as energy storage/generation or photonics. The effects of the film’s thickness and strain state of the structure for the lead-free perovskite ferrite-based materials (BiFeO3-BFO; Y-doped BiFeO3-BYFO; LaFeO3-LFO) on their functional properties are highlighted here. As was previously demonstrated, the dielectric properties of BFO epitaxial thin films are strongly affected by the film thickness and by the epitaxial strain induced by the lattice mismatch between substrate and film. Doping the BiFeO3 ferroelectric perovskite with rare-earth elements or inducing a high level of structural deformation into the crystalline structure of LaFeO3 thin films have allowed the tuning of functional properties of these materials, such as dielectric, optical or photocatalytic ones. These changes are presented in relation to the appearance of complex ensembles of nanoscale phase/nanodomains within the epitaxial films due to strain engineering. However, it is a challenge to maintain the same level of epitaxial strain present in ultrathin films (

The aim of the research paper is to project a framework of the newly introduced reporting tool SAF-T. Based on the guidelines launched by OECD, different countries implemented the model as indicated or a customized one. The key question is whether the new reporting will increase the state revenues, as there will be more transparency and more online data reported by the companies. Poland and Hungary provided good results in increasing their revenues after the implementation of the tool. In Romania, the implementation is still in the early stage, while a quantitative model for analysis, if the reporting increased the revenues, could be developed in the future, based on the revenue results.

Introduction. Several studies have shown that neuroendocrine cells (NECs) are increased in the colorectal mucosa of patients with ulcerative colitis (UC) compared to normal, mainly in the left colon. A threshold of 3.2 NECs/crypt has been proposed by some authors for defining NEC hyperplasia in these patients. However, correlations of NEC changes with clinical parameters have not been described. The objective of this study was to analyze NEC histological changes, described by several descriptors, in UC patients and identify relevant clinicopathological correlations. Material and methods. We analyzed colonic biopsies from 42 UC patients by highlighting the neuroendocrine cells with Chromogranin A immunohistochemical stain. Positive cells were detected and quantified by computerized image analysis, and their morphology and distribution were assessed. The data obtained were described as mean and maximum number of cells per crypt, and number of crypts showing linear hyperplasia. Results. Increased numbers of cryptic NECs were identified (mean 3.62/crypt). A rising trend was observed for Nancy grades 2 and 3 and a small decrease for grade 4 at the site of most severely active inflammation. However, linear hyperplasia negatively correlated with increase of Nancy and Geboes grades of histological inflammation (rho=-0.326, p=0.013; respectively rho=-0.368, p=0.005) and with age (rp=-0.328, p=0.039). The maximum counts per crypt correlated positively with corticosteroid treatment (rp=0,332, p=0.012). The mean count per crypt negatively correlated with disease duration ( rp=-0.388, p=0.013). Conclusion. NEC hyperplastic changes correlate with important clinical and histological parameters and could impact on the management of UC patients.

Introduction. Histological healing has become a therapeutic goal in patients with ulcerative colitis. However, a consensus on its precise definition has not been reached yet. A large number of complex histological scoring systems for ulcerative colitis are available in literature making standardization a complicated issue. The objective of the study was to identify a histological scoring system that is adequate for routine practice and thus contributes to standardization of histological reporting of inflammation activity in ulcerative colitis. Materials and methods. We retrospectively reviewed and scored 64 H&E stained slides using Nancy index (NI), Geboes score (GS) and Robarts Histopathology Index (RHI). The level of inter-rater and intra-rater agreement, time needed for scoring per slide, and correlation between the histological scores and Mayo endoscopic score were further analysed statistically. Results. The inter-rater agreement was very good for NI (kappa=0.861) and GS (kappa=0.820), and moderate for RHI (kappa=0.592), p

Sentinel-2 satellites provide systematic global coverage of land surfaces, measuring physical properties within 13 spectral intervals at a temporal resolution of five days. Computer-based data analysis is highly required to extract similarity by processing and to assist human understanding and semantic annotation in support of mapping Earth's surface. This article proposes a data mining concept that uses advanced data visualization and explainable features to enhance relevant aspects in the Sentinel-2 data and enable semantic analysis. There is a two-stage process. At first, spectral, texture, and physical parameters related features are extracted from the data and included in a learning process that models the data content according to statistical similarities. In parallel, the second processing stage maximizes the data impact on the human visual system to help image understanding and interpretation. Target classes are subject to exploratory visual analysis, such that both visual and latent characteristics are revealed to the user. The concept is further implemented as Sentinel-2 dedicated data analysis (DAS-Tool) plugin for the Sentinel Application Platform and deployed as an open-source tool empowering the Earth observation community with fast and reliable results. Accommodating multiple solutions for each processing phase, the plugin enables flexibility in information extraction and knowledge discovery that will bring the best accuracy in mapping applications. For demonstration purposes, the authors focus on a detailed benchmark against reference data (ground truth) for the Southern region of Romania, then use the selected algorithms in a forest fires scenario analysis for the Sydney region in Australia. The processing involves full-size Sentinel-2 images.

This work is focused on the application of a laser-based technique, i.e., matrix-assisted pulsed laser evaporation (MAPLE) for the development of electrochemical sensors aimed at the detection of nitrites in water. Commercial carbon-based screen-printed electrodes were modified by MAPLE via the application of a newly developed composite coating with different concentrations of carbon nanotubes (CNTs), chitosan, and iron (II) phthalocyanine (C32H16FeN8). The performance of the newly fabricated composite coatings was evaluated both by investigating the morphology and surface chemistry of the coating, and by determining the electro-catalytic oxidation properties of nitrite with bare and modified commercial carbon-based screen-printed electrode. It was found that the combined effect of CNTs with chitosan and C32H16FeN8 significantly improves the electrochemical response towards the oxidation of nitrite. In addition, the MAPLE modified screen-printed electrodes have a limit of detection of 0.12 µM, which make them extremely useful for the detection of nitrite traces.

In this work, thin films of lamellar clays were deposited by laser techniques (matrix assisted pulsed laser evaporation (MAPLE) and pulsed laser deposition (PLD)). The focus of this paper is the optimization of deposition parameters for the production of highly oriented crystalline films. The films were characterized by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), and scanning electron microscopy (SEM). Contact angle measurements were employed to identify the wetting properties of the deposited thin films. Hydrophobic to superhydrophilic films can be prepared by using different deposition techniques and deposition parameters. MAPLE led to superhydrophilic films with contact angles in the range 4°–8°, depending on the microstructure and surface roughness at micro and nano scale. The 1064 nm PLD had a high deposition rate and produced a textured film while at λ = 193 nm an extremely thin and amorphous layer was depicted. Oriented kaolinite films were obtained by MAPLE even at 5 wt.% kaolinite in the target.

Background: The primary endpoint was to analyze the preoperatory inflammatory markers and platelet indices in papillary thyroid cancer (PTC) patients compared with patients with benign thyroid pathology. The secondary endpoints were to analyze the relationship between these markers and the pathological features of PTC and to compare their pre- and postoperative levels in PTC patients. Methods: In this retrospective case-control study, we analyzed the files of 1183 patients submitted to thyroidectomy between January 2012 and December 2018. A total of 234 patients with PTC (mean age 51.54 ± 13.10 years, 84.6% females) were compared with an age-, gender- and BMI-matched control group of 108 patients with histologic benign thyroid disorders. Results: PTC patients had higher platelet count (PLT) (p = 0.011), plateletcrit (PCT) (p = 0.006), neutrophil (p = 0.022) and fibrinogen (p = 0.005) levels. Subgroup analysis showed that PTC females had higher PLT (p = 0.006), PCT (p < 0.001) and erythrocyte sedimentation rate (ESR) (p = 0.005), while males had higher neutrophil (p = 0.040) levels. Papillary thyroid cancer patients under 55 years had higher PLT (p < 0.001) and PCT (p = 0.010), while patients over 55 years had higher mean platelet volume (p = 0.032), neutrophil-to-lymphocyte ratio (p = 0.013), ESR (p = 0.005) and fibrinogen (p = 0.019) levels. Preoperative values for platelet indices and inflammatory markers were similar to the postoperative determinations in PTC patients. Fibrinogen (AUROC = 0.602, p = 0.02; cut-off = 327.5 mg/dL, Se = 53.8%, Sp = 62.9%) and PLT (AUROC = 0.584, p = 0.012; cut-off = 223.5 × 103/mm3, Se = 73.1%, Sp = 42.6%) were independent predictors of the presence of PTC. Conclusions: Our data show that fibrinogen and platelet count could be promising, inexpensive, independent predictors for the presence of PTC when compared with benign thyroid disorders.

Tuning the intrinsic structural and stoichiometric properties by different means is used for increasing the green energy production efficiency of complex oxide materials. Here, we report on the formation of self-assembled nanodomains and their effects on the photoelectrochemical (PEC) properties of LaFeO3 (LFO) epitaxial thin films as a function of layer’s thickness. The variation with the film’s thickness of the structural parameters such as in-plane and out-of-plane crystalline coherence length and the coexistence of different epitaxial orientation—SrTiO3// LFO, SrTiO3// LFO and [110] LFO//[10] STO, as well as the appearance of self-assembled nanodomains for film’s thicknesses higher than 14 nm, is presented. LFO thin films exhibit different epitaxial orientations depending on their thickness, and the appearance of self-assembled nanopyramids-like domains after a thickness threshold value has proven to have a detrimental effect on the PEC functional properties. Using Nb:SrTiO3 as conductive substrate and 0.5 M NaOH aqueous solution for PEC measurements, the dependence of the photocurrent density and the onset potential vs. RHE on the structural and stoichiometric features exhibited by the LFO photoelectrodes are unveiled by the X-ray diffraction, high-resolution transmission electron microscopy, ellipsometry, and Rutherford backscattering spectroscopy results. The potentiodynamic PEC analysis has revealed the highest photocurrent density Jphotocurrent values (up to 1.2 mA/cm2) with excellent stability over time, for the thinnest LFO/Nb:SrTiO3 sample, both cathodic and anodic behavior being noticed. Noticeably, the LFO thin film shows unbiased hydrogen evolution from water, as determined by gas chromatography in aqueous 0.5 M NaOH solution under constant illumination.

Due to its physical and chemical properties, the n-type tungsten oxide (WO3) semiconductor is a suitable photoanode for water decomposition reaction. The responses of the photoelectrochemical PEC water-splitting properties as an effect of structural and optical changes of WO3 thin films, as well as the nature of electrolyte solutions, were studied in this work. The WO3 thins films have been obtained by pulsed laser deposition (PLD) on silicon (Si(001)) covered with platinum substrates using three different laser wavelengths. As the XRD (X-ray diffraction) and XTEM (cross-section transmission electron microscopy) analysis shows, the formation of highly crystalline monocline WO3 phase is formed for the film deposited at 1064 nm wavelength and poor crystalline phases with a large ordering anisotropy, characteristic of 2D structures for the films deposited at 355 nm and 193 nm wavelengths, respectively. The photogenerated current densities Jph depend on the laser wavelength, in both alkaline and acidic electrolyte. The maximum values of the photocurrent density have been obtained for the sample prepared with laser emitting at 355 nm. This behavior can be correlated with the coherent crystallized atomic ordering that appear for long distances (10–15 nm) in the (001) plane of the monoclinic WO3 phase structure films obtained at 355 nm laser wavelength. All the samples show poor current density in dark conditions and they are very stable in both acidic and alkaline solutions. The highest photocurrent density value is obtained in acidic solution for the WO3 thin film prepared by 355 nm laser (29 mA/cm2 at 1.6 V vs. RHE (1.35 V vs. Ag/AgCl)).

BackgroundPTEN loss is a putative driver in histotypes of ovarian cancer (high-grade serous (HGSOC), endometrioid (ENOC), clear cell (CCOC), mucinous (MOC), low-grade serous (LGSOC)). We aimed to characterise PTEN expression as a biomarker in epithelial ovarian cancer in a large population-based study.MethodsTumours from 5400 patients from a multicentre observational, prospective cohort study of the Ovarian Tumour Tissue Analysis Consortium were used to evaluate associations between immunohistochemical PTEN patterns and overall survival time, age, stage, grade, residual tumour, CD8+ tumour-infiltrating lymphocytes (TIL) counts, expression of oestrogen receptor (ER), progesterone receptor (PR) and androgen receptor (AR) by means of Cox proportional hazard models and generalised Cochran-Mantel-Haenszel tests.ResultsDownregulation of cytoplasmic PTEN expression was most frequent in ENOC (most frequently in younger patients; p value = 0.0001) and CCOC and was associated with longer overall survival in HGSOC (hazard ratio: 0.78, 95% CI: 0.65-0.94, p value = 0.022). PTEN expression was associated with ER, PR and AR expression (p values: 0.0008, 0.062 and 0.0002, respectively) in HGSOC and with lower CD8 counts in CCOC (p value

We aimed to validate the prognostic association of p16 expression in ovarian high-grade serous carcinomas (HGSC) and to explore it in other ovarian carcinoma histotypes. p16 protein expression was assessed by clinical-grade immunohistochemistry in 6525 ovarian carcinomas including 4334 HGSC using tissue microarrays from 24 studies participating in the Ovarian Tumor Tissue Analysis consortium. p16 expression patterns were interpreted as abnormal (either overexpression referred to as block expression or absence) or normal (heterogeneous). CDKN2A (which encodes p16) mRNA expression was also analyzed in a subset (n = 2280) mostly representing HGSC (n = 2010). Association of p16 expression with overall survival (OS) was determined within histotypes as was CDKN2A expression for HGSC only. p16 block expression was most frequent in HGSC (56%) but neither protein nor mRNA expression was associated with OS. However, relative to heterogeneous expression, block expression was associated with shorter OS in endometriosis-associated carcinomas, clear cell [hazard ratio (HR): 2.02, 95% confidence (CI) 1.47-2.77, p < 0.001] and endometrioid (HR: 1.88, 95% CI 1.30-2.75, p = 0.004), while absence was associated with shorter OS in low-grade serous carcinomas (HR: 2.95, 95% CI 1.61-5.38, p = 0.001). Absence was most frequent in mucinous carcinoma (50%), and was not associated with OS in this histotype. The prognostic value of p16 expression is histotype-specific and pattern dependent. We provide definitive evidence against an association of p16 expression with survival in ovarian HGSC as previously suggested. Block expression of p16 in clear cell and endometrioid carcinoma should be further validated as a prognostic marker, and absence in low-grade serous carcinoma justifies CDK4 inhibition.

BackgroundThe newly developed Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) has consistently been shown to be prognostically significant in endometrial carcinomas (EC). Recently, we and others have demonstrated L1 cell-adhesion molecule (L1CAM) to be a significant indicator of high-risk disease in EC. In the current study, it was our aim to determine the prognostic significance of aberrant L1CAM expression in ProMisE subgroups in a large, single centre, population-based EC cohort.MethodsProMisE (POLE; MMR-D; p53 wt/NSMP; p53 abn) classification results from a cohort of 452 EC were available for analysis. L1CAM expression was studied by immunohistochemistry on whole slides. Correlations between clinicopathological data and survival were calculated.ResultsExpression of L1CAM was most frequent in p53 abnormal tumours (80%). L1CAM status was predictive of worse outcome among tumours with no specific molecular profile (p53 wt/NSMP) (p

ObjectiveTo evaluate myeloid differentiation primary response gene 88 (MyD88) and Toll-like receptor 4 (TLR4) expression in relation to clinical features of epithelial ovarian cancer, histologic subtypes, and overall survival.Patients and methodsWe conducted centralized immunohistochemical staining, semi-quantitative scoring, and survival analysis in 5263 patients participating in the Ovarian Tumor Tissue Analysis consortium. Patients were diagnosed between January 1, 1978, and December 31, 2014, including 2865 high-grade serous ovarian carcinomas (HGSOCs), with more than 12,000 person-years of follow-up time. Tissue microarrays were stained for MyD88 and TLR4, and staining intensity was classified using a 2-tiered system for each marker (weak vs strong).ResultsExpression of MyD88 and TLR4 was similar in all histotypes except clear cell ovarian cancer, which showed reduced expression compared with other histotypes (P

ImportanceCytotoxic CD8+ tumor-infiltrating lymphocytes (TILs) participate in immune control of epithelial ovarian cancer; however, little is known about prognostic patterns of CD8+ TILs by histotype and in relation to other clinical factors.ObjectiveTo define the prognostic role of CD8+ TILs in epithelial ovarian cancer.Design, setting, and participantsThis was a multicenter observational, prospective survival cohort study of the Ovarian Tumor Tissue Analysis Consortium. More than 5500 patients, including 3196 with high-grade serous ovarian carcinomas (HGSOCs), were followed prospectively for over 24 650 person-years.ExposuresFollowing immunohistochemical analysis, CD8+ TILs were identified within the epithelial components of tumor islets. Patients were grouped based on the estimated number of CD8+ TILs per high-powered field: negative (none), low (1-2), moderate (3-19), and high (≥20). CD8+ TILs in a subset of patients were also assessed in a quantitative, uncategorized manner, and the functional form of associations with survival was assessed using penalized B-splines.Main outcomes and measuresOverall survival time.ResultsThe final sample included 5577 women; mean age at diagnosis was 58.4 years (median, 58.2 years). Among the 5 major invasive histotypes, HGSOCs showed the most infiltration. CD8+ TILs in HGSOCs were significantly associated with longer overall survival; median survival was 2.8 years for patients with no CD8+ TILs and 3.0 years, 3.8 years, and 5.1 years for patients with low, moderate, or high levels of CD8+ TILs, respectively (P value for trend = 4.2 × 10−16). A survival benefit was also observed among women with endometrioid and mucinous carcinomas, but not for those with the other histotypes. Among HGSOCs, CD8+ TILs were favorable regardless of extent of residual disease following cytoreduction, known standard treatment, and germline BRCA1 pathogenic mutation, but were not prognostic for BRCA2 mutation carriers. Evaluation of uncategorized CD8+ TIL counts showed a near-log-linear functional form.Conclusions and relevanceThis study demonstrates the histotype-specific nature of immune infiltration and provides definitive evidence for a dose-response relationship between CD8+ TILs and HGSOC survival. That the extent of infiltration is prognostic, not merely its presence or absence, suggests that understanding factors that drive infiltration will be the key to unraveling outcome heterogeneity in this cancer.

ImportanceCytotoxic CD8+ tumor-infiltrating lymphocytes (TILs) participate in immune control of epithelial ovarian cancer; however, little is known about prognostic patterns of CD8+ TILs by histotype and in relation to other clinical factors.ObjectiveTo define the prognostic role of CD8+ TILs in epithelial ovarian cancer.Design, setting, and participantsThis was a multicenter observational, prospective survival cohort study of the Ovarian Tumor Tissue Analysis Consortium. More than 5500 patients, including 3196 with high-grade serous ovarian carcinomas (HGSOCs), were followed prospectively for over 24 650 person-years.ExposuresFollowing immunohistochemical analysis, CD8+ TILs were identified within the epithelial components of tumor islets. Patients were grouped based on the estimated number of CD8+ TILs per high-powered field: negative (none), low (1-2), moderate (3-19), and high (≥20). CD8+ TILs in a subset of patients were also assessed in a quantitative, uncategorized manner, and the functional form of associations with survival was assessed using penalized B-splines.Main outcomes and measuresOverall survival time.ResultsThe final sample included 5577 women; mean age at diagnosis was 58.4 years (median, 58.2 years). Among the 5 major invasive histotypes, HGSOCs showed the most infiltration. CD8+ TILs in HGSOCs were significantly associated with longer overall survival; median survival was 2.8 years for patients with no CD8+ TILs and 3.0 years, 3.8 years, and 5.1 years for patients with low, moderate, or high levels of CD8+ TILs, respectively (P value for trend = 4.2 × 10−16). A survival benefit was also observed among women with endometrioid and mucinous carcinomas, but not for those with the other histotypes. Among HGSOCs, CD8+ TILs were favorable regardless of extent of residual disease following cytoreduction, known standard treatment, and germline BRCA1 pathogenic mutation, but were not prognostic for BRCA2 mutation carriers. Evaluation of uncategorized CD8+ TIL counts showed a near-log-linear functional form.Conclusions and relevanceThis study demonstrates the histotype-specific nature of immune infiltration and provides definitive evidence for a dose-response relationship between CD8+ TILs and HGSOC survival. That the extent of infiltration is prognostic, not merely its presence or absence, suggests that understanding factors that drive infiltration will be the key to unraveling outcome heterogeneity in this cancer.