Grade Components Research Articles

Influence of key histological characteristics on 18F-fluorodeoxyglucose /18F-choline positron emission tomography positivity in hepatocellular carcinoma: A machine learning study.

To determine the characteristics influence of key histological on 18F-fluorodeoxyglucose (18F-FDG) and 18F-choline positron emission tomography (PET) positivity in hepatocellular carcinoma (HCC). The 18F-FDG/18F-choline PET imaging findings of 103 histologically proven HCCs (from 62 patients, of which 47 underwent hepatectomy and 15 received liver transplantation) were retrospectively examined to assess the following key histological parameters: Grade, capsule, microvascular invasion (mVI), macrovascular invasion (MVI), and necrosis. Using a ratio of 70/30 for training and testing sets, respectively, a penalized classification model (Elastic Net) was trained using 100 repeated cross-validation procedures (10-fold cross-validation for hyperparameter optimization). The contribution of each histological parameter to the PET positivity was determined using the Shapley Additive Explanations method. Receiver operating characteristic curves with and without dimensionality reduction were finally estimated and compared. Among the five key histological characteristics of HCC (Grade, capsule, mVI, MVI, and necrosis), mVI and tumor Grade (I-III) showed the highest relevance and robustness in explaining HCC uptake of 18F-FDG and 18F-choline. MVI and necrosis status both showed high instability in outcome predictions. Tumor capsule had a minimal influence on the model predictions. On retaining only mVI and Grades I-III for the final analysis, the area under the receiver operating characteristic (ROC) curve values were maintained (0.68 vs. 0.63, 0.65 vs. 0.64, and 0.65 vs. 0.64 for 18F-FDG, 18F-choline, and their combination, respectively). 18F-FDG/18F-choline PET positivity appears driven by both the Grade and mVI components in HCC. Consideration of the tumor microenvironment will likely be necessary to improve our understanding of multitracer PET positivity.

Root closure of ideals

We introduce two closure operations on ideals in commutative rings related to the ring operation of root closure. One closure is the result of iterating a root-like operation on ideals infinitely many times, and the other closure arises as a graded component of the root closure of the Rees algebra applied to an ideal. We study the properties of these closures and prove they are distinct operations.

Multicomponent hyperspectral grade evaluation of ilmenite using spectral-spatial joint features.

Obtaining a comprehensive understanding of ore grade information is of significant importance for evaluating the value of ore. However, the real-time detection of multicomponent grade needs more effective online methods. This study proposes a novel approach utilizing hyperspectral imaging (HSI) to evaluate the grade information of nine major ilmenite components by integrating spectral and spatial data. Four multivariate input-output models were developed to mitigate variable interference to predict each component's grade. The results demonstrated that the backpropagation neural network (BPNN) model built from iPLS-VCPA-IRIV feature selection spectral data worked best (RP2 = 0.9935, RMSEP = 0.1364, RPD = 12.8986, and RPIQ = 21.4871, with a computational time of approximately 0.8 s). Furthermore, applying the best optimal combination algorithm for multicomponent grade inversion yielded highly accurate results, in which 97% of the component inversion residuals were less than 1. This investigation affirms that HSI enables rapid and accurate prediction and inversion of the multicomponent grade of ilmenite, thereby presenting a promising alternative to online analysis in the mineral field.

Interobserver reproducibility of RENAL nephrometry score in comparison to simplified PADUA Renal nephrometry score

Abstract Introduction: Nephron-sparing surgery (NSS) is the standard of care for renal tumors, especially in the early stages. RENAL Nephrometry scores provide a comprehensive presurgical predictive module for the choice of NSS or Radical Nephrectomy. The validity and reliability of Nephrometry scores is being tested continuously with advancement in the surgical techniques. The Simplified PADUA Nephrometry score (SPARE NS) is a newer proposed score which aims to better the reproducibility of the previously established nephrometry scores. Materials and Methods: The retrospective observational study studied the comparative inter-observer reliability of RENAL (RENAL NS) and SPARE nephrometry scoring systems amongst two radiologists while assessing solid renal tumors in contrast-enhanced computed tomography scans of 42 patients. Interobserver reliability for all components of both scores, final scores and risk grading was done by Kendall’s Concordance Coefficient (Tau). Results: Both RENAL NS and SPARE NS showed strong to excellent agreement (RENAL NS = 78.57% and SPARE NS = 88.09%) among observers with comparable correlation co-efficient (RENAL NS = 0.944 and SPARE NS = 0.935). Lesion radius and exophytic/endophytic properties were the most reproducible components of RENAL NS with 97.61% and 92.85% agreement, respectively. Location across polar lines was the least reproducible component with 85.71% agreement among observers. Exophytic rate (97.61%) and Rim location were the most reproducible components of SPARE NS. The final lesion risk stratification by both observers for both was concordant in 92.85% of cases. Conclusion: The SPARE system of scoring matches up to the RENAL NS in total score and risk stratification reproducibility. However, the individual components of the SPARE score are more reproducible than those of RENAL NS, bringing about better compliance among radiology consultants. Comparable reproducibility with the RENAL NS, lesser number of variables, and ease of doing make SPARE NS a plausible option for the customary preoperative assessment of renal tumors.

Deep learning supported mitoses counting on whole slide images: A pilot study for validating breast cancer grading in the clinical workflow

IntroductionBreast cancer (BC) prognosis is largely influenced by histopathological grade, assessed according to the Nottingham modification of Bloom-Richardson (BR). Mitotic count (MC) is a component of histopathological grading but is prone to subjectivity. This study investigated whether mitoses counting in BC using digital whole slide images (WSI) compares better to light microscopy (LM) when assisted by artificial intelligence (AI), and to which extent differences in digital MC (AI assisted or not) result in BR grade variations. MethodsFifty BC patients with paired core biopsies and resections were randomly selected. Component scores for BR grade were extracted from pathology reports. MC was assessed using LM, WSI, and AI. Different modalities (LM-MC, WSI-MC, and AI-MC) were analyzed for correlation with scatterplots and linear regression, and for agreement in final BR with Cohen’s κ. ResultsMC modalities strongly correlated in both biopsies and resections: LM-MC and WSI-MC (R2 0.85 and 0.83, respectively), LM-MC and AI-MC (R2 0.85 and 0.95), and WSI-MC and AI-MC (R2 0.77 and 0.83). Agreement in BR between modalities was high in both biopsies and resections: LM-MC and WSI-MC (κ 0.93 and 0.83, respectively), LM-MC and AI-MC (κ 0.89 and 0.83), and WSI-MC and AI-MC (κ 0.96 and 0.73). ConclusionThis first validation study shows that WSI-MC may compare better to LM-MC when using AI. Agreement between BR grade based on the different mitoses counting modalities was high. These results suggest that mitoses counting on WSI can well be done, and validate the presented AI algorithm for pathologist supervised use in daily practice. Further research is required to advance our knowledge of AI-MC, but it appears at least non-inferior to LM-MC.

Prognostic significance of minor high grade component in non-invasive papillary urothelial carcinoma of urinary bladder: (A study of 273 consecutive cases over a period of 3 years)

PurposeOur study aimed to determine the prognostic significance of minor high-grade components (HGC) in non-invasive papillary urothelial carcinomas compared with pure low-grade and high-grade tumors. Material and methodsWe retrospectively retrieved 273 in-house cases of non-invasive papillary urothelial carcinomas (pTa) from 2016 to 2018 for which follow up data was available in hospital archives. We stratified our data into four main groups (G). G1, pure low-grade (n = 164); G2, HGC ≤5 % (n = 17); G3, HGC >5 % to ≤25 % (n = 14); and G4, pure high-grade (n = 78). Prognosis was assessed in terms of recurrence, grade and stage of progression, metastasis, and death. The mean follow up duration was 34.72 ± 20 months (range 20–60 months). ResultsAll four groups showed no difference in tumor recurrence (G1 81.7 %, G2 88.2 %, G3 92.9 %, G4 92.3 % p-value 0.183). In terms of grade progression, there was no significant difference in G2 35.3 % and G3 35.7 % and both groups showed worst prognosis compared to G1 16.5 % p-value 0.04. Regarding stage progression (G1 6.7 %, G2 23.5 %, G3 28.6 %, G4 41% p-value 0.001), metastasis (G1 5.5 %, G2 5.9 %, G3 7.1 %, G4 17.9 % p-value 0.01) and death (G1 4.3 %, G2 5.9 %, G3 7.1 %, G4 15.4 % p-value 0.02) there was no significant difference in G2 and G3 and both groups showed worst prognosis than G1 and better than G4. ConclusionUrothelial carcinomas with minor high-grade component ≤25 % behaved worst than pure low grade and better than pure high grade and should be treated as distinct grade entity.

Reading Comprehension Component of Grades 7 and 8 English and Filipino Textbooks

This study aimed to analyze and evaluate the reading comprehension component in the selected Grades 7 and 8 English and Filipino textbooks used by the selected private schools in Cebu City. Content analysis and text analysis were used as research designs in evaluating the 21 textbooks used during the academic year 2012-2013 and academic year 2013-2014. Results in English textbooks revealed that among the competencies, strategies predominated among schema building, literary texts, and expository texts whereas in Grade 7 & 8 Filipino textbooks, schema building and strategies predominated. Grade 7 & Grade 8 English Textbooks used by USC South Campus and Sacred Heart of Jesus - Hijas de Jesus met the K to 12 Guidelines for reading comprehension set by the Department of Education. Moreover, Grade 7 & Grade 8 Filipino textbooks used by St. Theresa’s College only met the standards. Consequently, these textbooks are recommended to be used for Grade 7 and Grade 8 students in private schools.

Improving mitotic cell counting accuracy and efficiency using phosphohistone-H3 (PHH3) antibody counterstained with haematoxylin and eosin as part of breast cancer grading.

Mitotic count in breast cancer is an important prognostic marker. Unfortunately, substantial inter- and intraobserver variation exists when pathologists manually count mitotic figures. To alleviate this problem, we developed a new technique incorporating both haematoxylin and eosin (H&E) and phosphorylated histone H3 (PHH3), a marker highly specific to mitotic figures, and compared it to visual scoring of mitotic figures using H&E only. Two full-face sections from 97 cases were cut, one stained with H&E only, and the other was stained with PHH3 and counterstained with H&E (PHH3-H&E). Counting mitoses using PHH3-H&E was compared to traditional mitoses scoring using H&E in terms of reproducibility, scoring time, and the ability to detect mitosis hotspots. We assessed the agreement between manual and image analysis-assisted scoring of mitotic figures using H&E and PHH3-H&E-stained cells. The diagnostic performance of PHH3 in detecting mitotic figures in terms of sensitivity and specificity was measured. Finally, PHH3 replaced the mitosis score in a multivariate analysis to assess its significance. Pathologists detected significantly higher mitotic figures using the PHH3-H&E (median ± SD, 20 ± 33) compared with H&E alone (median ± SD, 16 ± 25), P < 0.001. The concordance between pathologists in identifying mitotic figures was highest when using the dual PHH3-H&E technique; in addition, it highlighted mitotic figures at low power, allowing better agreement on choosing the hotspot area (k=0.842) in comparison with standard H&E (k=0.625). A better agreement between image analysis-assisted software and the human eye was observed for PHH3-stained mitotic figures. When the mitosis score was replaced with PHH3 in a Cox regression model with other grade components, PHH3 was an independent predictor of survival (hazard ratio [HR] 5.66, 95% confidence interval[CI] 1.92-16.69; P=0.002), and even showed a more significant association with breast cancer-specific survival (BCSS) than mitosis (HR 3.63, 95% CI 1.49-8.86; P=0.005) and Ki67 (P=0.27). Using PHH3-H&E-stained slides can reliably be used in routine scoring of mitotic figures and integrating both techniques will compensate for each other's limitations and improve diagnostic accuracy, quality, and precision.

THE HEROES AND THEIR DIFFERENT VOICES IN THE DIALOGUE EDUCATIONAL READINGS ON THE TOPIC OF NATIVE AND FOREIGN IN XI GRADE

The curriculum in Bulgarian language and literature for XI grade component Literature (general education) is oriented to the thematic point of education. The section related to the universal theme of the relations between the native and the foreign offers different points of view through the works "The Iron Lantern", "Bai Ganyo" and "The Balkan Syndrome". Dialogic readings unlock intertextual connections with works from different fields of art.

Deep learning models for histologic grading of breast cancer and association with disease prognosis

Histologic grading of breast cancer involves review and scoring of three well-established morphologic features: mitotic count, nuclear pleomorphism, and tubule formation. Taken together, these features form the basis of the Nottingham Grading System which is used to inform breast cancer characterization and prognosis. In this study, we develop deep learning models to perform histologic scoring of all three components using digitized hematoxylin and eosin-stained slides containing invasive breast carcinoma. We first evaluate model performance using pathologist-based reference standards for each component. To complement this typical approach to evaluation, we further evaluate the deep learning models via prognostic analyses. The individual component models perform at or above published benchmarks for algorithm-based grading approaches, achieving high concordance rates with pathologist grading. Further, prognostic performance using deep learning-based grading is on par with that of pathologists performing review of matched slides. By providing scores for each component feature, the deep-learning based approach also provides the potential to identify the grading components contributing most to prognostic value. This may enable optimized prognostic models, opportunities to improve access to consistent grading, and approaches to better understand the links between histologic features and clinical outcomes in breast cancer.

Topological invariants of groups and Koszul modules

We provide a uniform vanishing result for the graded components of the finite length Koszul module associated to a subspace K⊆∧2V as well as a sharp upper bound for its Hilbert function. This purely algebraic statement has interesting applications to the study of a number of invariants associated to finitely generated groups, such as the Alexander invariants, the Chen ranks, and the degree of growth and virtual nilpotency class. For instance, we explicitly bound the aforementioned invariants in terms of the first Betti number for the maximal metabelian quotients of (1) the Torelli group associated to the moduli space of curves, (2) nilpotent fundamental groups of compact Kähler manifolds, and (3) the Torelli group of a free group.

Reduced arc schemes for Veronese embeddings and global Demazure modules

We consider arc spaces for the compositions of Plücker and Veronese embeddings of the flag varieties for simple Lie groups of types ADE. The arc spaces are not reduced and we consider the homogeneous coordinate rings of the corresponding reduced schemes. We show that each graded component of a homogeneous coordinate ring is a cocyclic module over the current algebra and is acted upon by the algebra of symmetric polynomials. We show that the action of the polynomial algebra is free and that the fiber at the special point of a graded component is isomorphic to an affine Demazure module whose level is the degree of the Veronese embedding. In type A1 (which corresponds to the Veronese curve), we give the precise list of generators of the reduced arc space. In general type, we introduce the notion of global higher level Demazure modules, which generalizes the standard notion of the global Weyl modules, and identify the graded components of the homogeneous coordinate rings with these modules.

An Experimental Analysis of Grinding Parameters and Conditions on Surface Roughness of Finished Product

Higher grade or smooth surface finish mechanical components and mating parts with close limits and tolerances is one of the most important requirement of modern manufacturing industry. Grinding is the most dominating process among various manufacturing finish processes over final products that require in-depth investigation on how material removal processes influence the surface roughness of the finished products. In this work, an experimental analysis was carried out to evaluate the influence of various machining parameters and conditions on surface roughness of the final substrates. The main objective of this experimental work is to study the comparison of the effects of tools and conditions which are abrasive nature between Mild Steel (MS) and EN24 steel surface by using Depth of Cut (DOC).

Concordance of core needle biopsy and post-operative histo-pathological grading in breast cancer patient

Objectives: This study aimed to evaluate the concordance of histological types, grade and components of grading, between CNB and open surgical specimens.&#x0D; Methods: In this study patients with paired CNB and open surgical biopsy diagnosed with invasive breast cancer are involved, from January 2012 to October 2015 were recreated. Revision of (579) patients were done, but only (116) patients were included in our study according to inclusion criteria, in the breast center department of Slemani Teaching Hospital in Slemani Governorate.&#x0D; Results: There were 116 patients with invasive breast cancer analyzed for concordance rate between CNB and open surgical specimen for tumor type, grade, tubule formation, nuclear pleomorphism, and mitotic count were 93.1%, 73.3%, 77.6%, 73.3%, 62.9% respectively, mitotic count was under estimated in CNB samples(kappa 0.4 P value 0.001).&#x0D; Conclusion: These results indicate that pre-operative CNB can reliably provide useful preoperative prognostic and predictive information in breast cancer patients which can play a major role in planning treatment strategies. Core needle biopsy has significant accuracy in determining invasive breast cancer and histological type and grading.

On analytic groupoid cardinality

Groupoids graded by the groupoid of bijections between finite sets admit generating functions which encode the groupoid cardinalities of their graded components. As suggested in the work of Baez and Dolan, we use analytic continuation of such generating functions to define a complex-valued cardinality for groupoids whose usual groupoid cardinality diverges. The complex nature of such a cardinality invariant is shown to reflect a recursion of structure which we refer to as ‘nested equivalence’.

Aligning multiple choice assessments with active learning instruction: More accurate and equitable ways to measure student learning

In response to geoscience education research and calls for the need to reform STEM teaching in higher education, many geoscience faculty are adopting research-based pedagogies to improve student learning in their courses. Our own effort to reform our introductory geology course included daily student-centered activities and other reforms we expected would result in improved student performance, but did not. This paper describes our evaluation of student performance on multiple choice questions (MCQs), which are the largest component of student grades in the course. Student scores were highest on MCQs that were aligned with the style in which students learned material and that required students to interact with the question (active questions) rather than just regurgitating information (passive questions). We also examined whether the style of MCQs impacted student scores equitably and found that the grades of all students would have improved if we had asked MCQs that were aligned and active, and the improvements were equitable, but final grades remain biased.

Graded Components of Local Cohomology Modules II

Let A be a commutative Noetherian ring containing a field of characteristic zero. Let R = A[X1,…,Xm] be a polynomial ring and Am(A) = A〈X1,…,Xm, ∂1,…,∂m〉 be the m th Weyl algebra over A, where ∂i = ∂/∂Xi. Consider standard gradings on R and Am(A) by setting $\deg z=0$ for all z ∈ A, $\deg X_{i}=1$ , and $\deg \partial _{i} =-1$ for i = 1,…,m. We present a few results about the behavior of the graded components of local cohomology modules ${H_{I}^{i}}(R)$ , where I is an arbitrary homogeneous ideal in R. We mostly restrict our attention to the vanishing, tameness, and rigidity properties. To obtain this, we use the theory of D-modules and show that generalized Eulerian Am(A)-modules exhibit these properties. As a corollary, we further get that components of graded local cohomology modules with respect to a pair of ideals display similar behavior.

Vehicle routing for milk collection with gradual blending: A case arising in Chile

We introduce and solve a new multi-commodity Vehicle Routing Problem, motivated by a case study of milk collection in Chile. Different grades of raw milk are collected from a number of farms scattered over a large area and transported to a single plant, allowing milk blending at the trucks. Previous works allow blending different grades of milk in the trucks, but the resulting blend is classified as its worst grade component, even if there was a single drop of it in the blend. The novelty of our work is the use of a less conservative gradual blending rule that associates milk grades to ranges of somatic cell count per milliliter, resulting in a more accurate classification of milk. The volume and somatic cell count per milliliter of the milk produced at each farm are known before the collection, and the farms are paid accordingly. The problem is to route a heterogeneous fleet of vehicles to maximize total profit at the plant, i.e., the revenue from milk minus route cost. All the milk is collected and gradual blending is applied. We propose a mixed integer linear programming formulation and solve the problem using a branch-and-cut method for small instances, and an Iterated Local Search metaheuristic for real-size instances. Both are applied to a large set of standard instances and a real case in Chile. Our results show an increase in profit over previous milk collection strategies, of 20% and 28% for test instances and up to 30% for a real instance.

Genetic heterogeneity and therapeutic target detection through microdissection in solid-type adenoid cystic carcinoma

Solid-type adenoid cystic carcinomas (ACCs) are highly aggressive and heterogeneous tumours. Because of their rarity, therapeutic strategies guided by genetic profiles based on next generation sequencing (NGS) have not been published for these tumours. Forty-nine solid-type ACCs including 43 tumours with a predominantly solid pattern, and six tumours comprising a roughly equal mixture of cribriform/tubular and solid histological forms were included in our study. The solid components from the 49 solid ACCs were enriched for mutations of genes in the NOTCH pathway (NOTCH1 61%, SPEN 24%) and chromatin remodelling pathway and the absence of myoepithelial cell differentiation. Cases with NOTCH1 mutations exhibited strong NICD expression, which was associated with poor overall and distant metastasis free survival. BRCA2 mutation and BCOR/BCORL1 mutations were observed in 20% and 18.4% of solid ACCs, respectively. In six of the solid ACCs, intratumour heterogeneity was delineated between the cribriform/tubular and solid components. NOTCH1 and FGFR2 mutations as well as NOTCH2 amplification were restricted to the solid component, indicating clonal selection within the same tumour. In two recurrent/metastatic solid ACCs, the subclones evolved in progression for local relapse and distant metastasis, although they manifested close genomic resemblance to primary tumours. Guided by the genetic profiles, the preclinical efficiency of the gamma-secretase inhibitor BMS-906024 was evaluated in patient derived xenograft models (PDXs) with activating NOTCH1 mutations and demonstrated robust antitumour effects. Our report revealed intratumour heterogeneity among solid-types within an ACC as well as the inter-tumour evolution of dominant clones among two primary and recurrent/metastatic tumours. In contrast to cribriform/tubular ACCs, solid-type ACCs should be approached with a distinct therapeutic strategy, particularly targeting NOTCH1. Microdissecting the highest grade component guided by histology is a highly recommended tumour sampling strategy and facilitates the detection of key molecular targets.

The role of spatial transcriptomic profiling to determine androgen receptor signaling and immune infiltration in prostate cancer

272 Background: Prostate cancer (PCa) in the transition zone (TZ) accounts for approximately 30% of disease and tends to present with higher PSAs with a lower risk of seminal vesicle invasion, extra-capsular extension, and risk of biochemical recurrence compared with peripheral zone (PZ) tumors. The underlying biological mechanism for these differences is poorly understood. Here, we performed spatial transcriptomic profiling to elucidate the molecular differences between TZ and PZ PCa. Methods: We identified three patients who underwent radical prostatectomy for PCa (one each with PZ only, TZ only, and both PZ and TZ tumors) and used the NanoString’s Digital Spatial Profiling (DSP) platform to quantify whole transcriptomic gene expression data (17,128 genes) in multiple regions of interest (ROI) per patient (42 cancer and 8 normal samples). Four morphology markers to facilitate ROI selection in both cancer and normal areas (SYTO13 for nucleus, PanCK for epithelium, SMA for stroma and CD45 for immune cells) were selected. Raw counts for 17,128 genes were imported to R v.4.1.0 for downstream data analyses. Counts were Q3 normalized and scaled (Z-score) to enable plotting of all genes on the same axes. Differential gene expression analysis using a linear model fit by empirical Bayes moderation, gene set enrichment analysis (GSEA) by cancer hallmarks, XCell gene sets for pathway enrichment and immune cell deconvolution using CIBERSORT was performed. Results: There were grade group (GG) 4 (n=10) and 5 (n=10) tumors in PZ and GG 3 (n=10), 4 (n=11) and 5 (n=1) cancers in TZ regions. We observed distinct gene expression profiles between PZ (n = 20) and TZ (n=22) tumors. Interestingly, androgen receptor (AR) signaling was significantly higher in TZ PCa ROIs compared to PZ ROIs in both GSEA (false discovery rate &lt; 5%) and the androgen subcomponent of the genomic prostate score (p&lt;0.001), regardless of grade, epithelial, stromal or immune component of the region. To standardize the comparison, CIBERSORT’s absolute immune signature scores were only computed for GG4 tumors and found to be significantly higher in PZ GG4 tumors compared to TZ GG4 tumors. Notably, CD4+ memory T cells were significantly higher in PZ GG4 regions compared to TZ GG4 tumor regions (p&lt;0.05). Conclusions: Here, we demonstrate distinct gene expression profiles of PZ and TZ PCa. Specifically, we observed higher AR signaling in TZ cancers and higher levels of immune infiltration on PZ cancers. This is in concordance with prior knowledge that TZ tumors may be associated with higher serum PSA and PZ tumors may be associated with inflammation. Further studies are needed to discern the biological and clinical significance of the different molecular features of PZ and TZ PCa.