Nuclear Grade Research Articles

Can Gender-Specific Renal and Visceral Fat Be Evaluated by CT Predict Fuhrman Nuclear Classification of Clear Cell Renal Cell Carcinoma?

Evidence of the association between obesity and renal cell carcinoma progression is contradictory. The effects of renal cell carcinoma on fat distribution are still unknown. The goal of this study was to determine the ability of various forms of fat deposition to predict the Fuhrman nuclear grade of clear cell renal cell carcinoma [ccRCC]. This retrospective study included 320 patients with pathologically proven ccRCC [215 men and 105 women; 263 low-grade ccRCC and 57 highgrade ccRCC]. Based on computed tomography scans, adipose tissue in various body regions was classified into the perirenal fat area [PFA], visceral fat area [VFA], total fat area [TFA], subcutaneous fat area [SFA], and hepatic steatosis [HS]. Subsequently, the relative VFA [rVFA] was computed. Age, sex, body mass index, and maximal tumor diameter were also regarded as clinical factors. Univariate and multivariate logistic regression studies were conducted to evaluate whether there was an association between body fat composition and the Fuhrman classification and whether it was related to gender. After correcting for age, males with low-grade ccRCC exhibited higher TFA [257.6 vs. 203.0, p = 0.002], VFA [151.6 vs.115.5, p = 0.007], SFA [106.0 vs. 87.5, p = 0.015], PFA [55.1 vs. 30.4, p < 0.001], and HS [18% vs. 0%, p = 0.031] than those with high-grade ccRCC. There was no significant difference among rVFA in males. In females, there was no significant difference in any of the parameters. VFA and PFA remained independent predictors for high-grade ccRCC in males in both the monovariate [VFA: odds ratio [OR] 0.992, 95% confidence interval [CI] 0.987-0.997, p = 0.004; PFA: OR 0.949, 95% CI 0.930-0.970, p < 0.001] and multivariate [VFA: OR 1.028, 95% CI 1.001-1.074, p < 0.001; PFA: OR 0.878, 95% CI 0.833-0.926, p < 0.001] models. Gender-specific adipose tissue in different locations demonstrated varied values for predicting high-grade ccRCC and may be utilized as an independent predictor of high-grade ccRCC in male patients.

Expression of PD-L1 in breast invasive lobular carcinoma.

The purpose of this study was to investigate the expression of PD-L1 in invasive lobular carcinoma (ILC) and to determine its implications. Tissue microarrays were constructed for 101 cases of ILC, and immunohistochemical staining for PD-L1 (using 22C3, SP142, and SP263 antibodies) was performed to examine the correlation between staining results and clinicopathologic parameters. The positive cut-off values were defined as tumor cell (TC)≥1%, immune cell (IC)>0%, and IC≥1%. The range of PD-L1 TC positivity was 0.0-2.0%, with PD-L1 SP263 TC showing the highest positivity of 2.0%. The range of PD-L1 IC positivity was 0-21.8% for IC ≥ 1%, with PD-L1 22C3 IC showing the highest positivity. When PD-L1 IC was positive (IC≥1%), the highest antibody agreement was observed between SP263 and SP142 (OA = 93.1%), while the lowest agreement was observed between 22C3 and SP263 (OA = 73.3%, κ = 0.040). PD-L1 22C3 IC positivity (≥1%) was associated with high nuclear grade (p = 0.002), HER-2 positivity (p = 0.019), and pleomorphic type (p = 0.002). PD-L1 expression in ILC shows a low TC positivity rate (0-2%) with various antibody clones and a variable IC positivity rate (0-21.8%). Pleomorphic type ILC exhibits higher PD-L1 IC positivity.

Incidence and Pattern of Recurrence after Surgical Resection in Organ-Confined Renal Cell Carcinoma.

To evaluate the incidence and pattern of recurrence after surgery in patients with organ-confined renal cell carcinoma (RCC) to establish an appropriate follow-up plan. In this retrospective study, we evaluated data from 2960 patients who underwent radical or partial nephrectomy for stage 1 or 2 RCC. We investigated the location of first recurrence and recurrence-free survival (RFS) by plotting Kaplan-Meier curves and analyzed the associated variables using Cox regression analysis. During a median follow-up of 59 months, the 10-year RFS rates were 94.5%, 75.0%, and 57.9%, for T1a, T1b, and T2 RCC, respectively. A total of 211 patients experienced recurrence: 67 after 5 years, and 14 after 10 years. The most common sites of the first recurrence were the lungs, bones, and contralateral kidneys. Male sex, older age, higher pathologic T stage, higher nuclear grade, clear-cell RCC, and presence of differentiation were associated with recurrence. Among patients followed up for more than 60 months, higher pathologic T stage and grade, as well as clear cell RCC were predictors of RFS. Late recurrence after surgery is common in patients with organ-confined RCC, with recurrence occurring even after 10 years. Consequently, long-term follow-up, of perhaps 10 years or more, including imaging studies of the abdomen, lungs, and bone, should be considered for the early detection of recurrence.

Uloga ekspresije humanog epididimisnog proteina 4 u odnosu na kliničko-patološke karakteristike tumora bubrega

Introduction: Widespread routine ultrasound diagnostics enables early detection of kidney tumors. However, due to nonspecific symptomatology and signs that usually appear as the disease progresses, there are still patients whose diagnosis is made only in advanced stages of the disease. Aim: Our aim was to investigate the correlation of human epididymis protein 4 (HE4) expression, including the intensity and localization of HE4 positivity, with the clinical and pathohistological characteristics of kidney tumors. Material and Methods: The study included 96 kidney tumors diagnosed between 2010 and 2013 at the Institute of Pathology in Belgrade. Anti-HE4 antibodies were used for immunohistochemical analysis. Demographic, clinical, and pathohistological characteristics were examined in relation to HE4 expression. Results: No correlation was observed between HE4 expression in kidney tumors and patients' gender and the nuclear grade of tumors. However, HE4 expression was significantly more frequent in larger tumors, specifically in T3 and T4 tumors, compared to T1 and T2 tumors (p=0.009; p=0.006, respectively). No correlation was observed between HE4 expression and the pathohistological type of kidney tumors, but it is important to emphasize that membrane expression of HE4, unlike most renal cell carcinomas, was not observed in oncocytomas. Conclusion: It's possible that HE4 plays a role in progression of kidney tumor growth. Membrane expression of HE4 could be used as a new parameter in differentiating renal cell carcinomas from oncocytomas.

A Nuclei-Focused Strategy for Automated Histopathology Grading of Renal Cell Carcinoma.

The rising incidence of kidney cancer underscores the need for precise and reproducible diagnostic methods. In particular, renal cell carcinoma (RCC), the most prevalent type of kidney cancer, requires accurate nuclear grading for better prognostic prediction. Recent advances in deep learning have facilitated end-to-end diagnostic methods using contextual features in histopathological images. However, most existing methods focus only on image-level features or lack an effective process for aggregating nuclei prediction results, limiting their diagnostic accuracy. In this paper, we introduce a novel framework, Nuclei feature Assisted Patch-level RCC grading (NuAP-RCC), that leverages nuclei-level features for enhanced patch-level RCC grading. Our approach employs a nuclei-level RCC grading network to extract grade-aware features, which serve as node features in a graph. These node features are aggregated using graph neural networks to capture the morphological characteristics and distributions of the nuclei. The aggregated features are then combined with global image-level features extracted by convolutional neural networks, resulting in a final feature for accurate RCC grading. In addition, we present a new dataset for patch-level RCC grading. Experimental results demonstrate the superior accuracy and generalizability of NuAP-RCC across datasets from different medical institutions, achieving a 6.15% improvement in accuracy over the second-best model on the USM-RCC dataset.

Inflammatory breast cancer: An overview about the histo-pathological aspect and diagnosis.

Inflammatory Breast Cancer (IBC) is a rare and aggressive form of locally advanced breast cancer, classified as stage T4d according to the tumor-node-metastasisstaging criteria. This subtype of breast cancer is known for its rapid progression and significantly lower survival rates compared to other forms of breast cancer. Despite its distinctive clinical features outlined by the World Health Organization, the histopathological characteristics of IBC remain not fully elucidated, presenting challenges in its diagnosis and treatment. Histologically, IBC tumors often exhibit a ductal phenotype, characterized by emboli composed of pleomorphic cells with a high nuclear grade. These emboli are predominantly found in the papillary and reticular dermis of the skin overlaying the breast, suggesting a primary involvement of the lymphatic vessels. The tumor microenvironmentin IBC is a complex network involving various cells such as macrophages, monocytes, and predominantly T CD8+lymphocytes, and elements including blood vessels and extracellular matrix molecules, which play a pivotal role in the aggressive nature of IBC. A significant aspect of IBC is the frequent loss of expression of hormone receptors like estrogen and progesterone receptors, a phenomenon that is still under active investigation. Moreover, the overexpression of ERBB2/HER2 and TP53 in IBC cases is a topic of ongoing debate, with studies indicating a higher prevalence in IBC compared to non-inflammatory breast cancer. This overview seeks to provide a comprehensive understanding of the histopathological features and diagnostic approaches to IBC, emphasizing the critical areas that require further research.

A ranking-based multi-scale feature calibration network for nuclear cataract grading in AS-OCT images

Anterior Segment Optical Coherence Tomography (AS-OCT) is an important imaging technique for the grading of nuclear cataract. However, due to the complex interdependencies among 6 clinically-defined levels of cataract severity, it presents significant challenges to classify neighboring severity levels accurately and expeditiously, whether by human experts or computer-aided approaches. Existing deep learning-based models usually obtain 3 grades of nuclear cataract severity only, and often struggle to capture vital information related to the progression of neighboring severity levels, leading to inaccuracies in grading. In this paper, we introduce a novel method called Ranking-MFCNet, which utilizes both a ranking-based framework and a Multi-scale Feature Calibration network (MFCNet). To bolster the model’s capability for discriminating between neighboring severities that are prone to confusion, we treat the multi-category severity classification as a collection of distinct binary classification patterns. This strategy facilitates a systematic implementation of fine-grained nuclear cataract severity grading on an individual basis. Within each binary classification pattern, we propose an external attention-augmented Multi-scale Feature Calibration (eaMFC) module, which effectively captures the multi-scale characteristics inherent to the lens nucleus. Additionally, eaMFC allows for the calibration of shared attributes extracted by the external attention layer, thereby enhancing the model’s proficiency in modeling the distinctive traits related to opacity and sclerosis of the lens nucleus. We trained and validated our model on a dataset that contains 1608 AS-OCT images, and the extensive experiments have verified the effectiveness and superiority of our method over state-of-the-art cataract grading methods.

Clear cell renal cell carcinoma with syncytial giant cells: Not that rare

Syncytial giant cells (SGCs) are neoplastic giant cells of epithelial origin. The nuclear morphology of SGCs is uniform and similar to those of adjacent mononuclear tumor cells. Clear cell renal cell carcinoma (ccRCC) with SGCs is a rare microscopic morphology. In this study, the clinical and pathological data of 16 ccRCC cases with SGCs were retrospectively reviewed. The incidence of SGCs in pathological stages pT3 and above (12.1%, 8/66) was significantly higher than that in pT1 and pT2 (2.6%, 8/306) (P = 0.002). The incidence of SGCs in the WHO/ISUP nuclear grade 3 or 4 ccRCC (12.4%, 14/113) was significantly higher than that in grade 1 or 2 (0.8%, 2/259) (P < 0.001). Two forms of SGCs were observed, some exhibited nuclear pyknosis and degeneration. Of the 16 cases, eight cases were accompanied by necrosis and seven cases had lymphovascular invasion. Both SGCs and mononuclear tumor cells were positive for ccRCC markers (PAX8, CAIX, CD10 and Vimentin). None of the SGC nuclei were positive for Ki-67. Follow-up information was available on 14 patients, with a median follow-up time of 27.5 months. Ten patients were alive without disease, three were alive with metastatic disease, and one patient died 10 months after surgery. These findings indicated that SGCs are not rare, especially in ccRCC with high nuclear grade and pathological stage, and often co-exist with other adverse prognostic features. SGCs may be senescent tumor cells, the presence of SGCs should not be considered as Fuhrman and WHO/ISUP nuclear grading 4.

Does the VHL polymorphisms rs779805 and rs1642742 affect renal cell carcinoma susceptibility, prognosis and survival in Central European population?

Renal cell carcinoma (RCC) is a common malignant tumor of the urinary system. The von Hippel-Lindau (VHL) tumor suppressor gene play an essential role in the tumorigenic pathway of clear cell RCC (ccRCC). This study was aimed to clarify the influence of VHL polymorphisms on ccRCC susceptibility and survival in Central European population. We genotyped 2 single-nucleotide polymorphisms (SNPs) rs779805 and rs1642742 in VHL gene and assessed their associations with ccRCC risk, clinicopathologic parameters, and prognosis in 171 cases. The selected SNPs were genotyped by ROCHE LifeCycler 96 using tumor tissue-derived DNA. Both SNPs do not directly influence ccRCC susceptibility and overall survival. A significant associations were found between allele G and genotypes AG and GG of rs779805 in the VHL tumor suppressor gene and increased tumor size, as well as high nuclear grade. Furthermore, a statistically significant association was observed between rs1642742 of VHL gene and low pathological tumor stage and between rs779805 of VHL gene and high pathological tumor stage. Both investigated SNPs can be important prognostic indicators of RCC in the Central European population, because statistically significant associations were observed between evaluated VHL polymorphisms and the best known factors with proven prognostic significance in kidney cancer.

Preoperative Dynamic Contrast-Enhanced and Diffusion-Weighted Breast Magnetic Resonance Imaging Findings for Prediction of Lymphovascular Invasion of the Lesions in Node-Negative Invasive Breast Cancer.

Purpose: Our single-centre retrospective study aimed to investigate the relationship between preoperative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) findings and apparent diffusion coefficient (ADC) values and lymphovascular invasion (LVI) status of the lesions in patients with clinically-radiologically lymph node-negative invasive breast cancer. Methods: A total of 250 breast lesions diagnosed in preoperative magnetic resonance imaging were identified. All patients were divided into 2 subgroups: LVI-negative and LVI-positive according to the pathological findings of surgical specimens. The 2 groups' DCE-MRI findings, ADC values, and histopathological results of lesions were compared. Results: LVI was detected in 100 of 250 lesions. Younger age than 45 years and larger lesion size than 20 mm were found to be associated with the presence of LVI (P < .001). High histological and nuclear grade (P = .001), HER2-enriched molecular subtype (P = .001), and Ki-67 positivity (P = .016) were significantly associated with LVI. The LVI positivity rate was significantly higher in the lesions with medium-rapid initial phase kinetic curve and washout delayed phase kinetic curve (P = .001). The presence of LVI was significantly associated with the presence of peritumoural edema, sentinel lymph node metastasis, adjacent vessel sign, and increased whole breast vascularity (P < .001). When diffusion-weighted imaging findings were evaluated, it was determined that tumoural ADC values lower than 1068 × 10-6 mm2/second (P = .002) and peritumoural-tumoural ADC ratios higher than 1.5 (P = .001) statistically increased the probability of LVI. Conclusion: The patient's age, various histopathological and DCE-MRI findings, tumoural ADC value, and peritumoural-tumoural ADC ratio may be useful in the preoperative prediction of LVI status in breast cancer lesions.

Prognostic significance of annexin A2 and tumor associated macrophages (TAMs) in metastatic renal cell carcinoma and their relation to Sunitinib resistance

ABSTRACT Sunitinib, an antiangiogenic tyrosine kinase inhibitor, is the main treatment for metastatic renal cell carcinoma (mRCC). Development of resistance is a major obstacle against therapy success. The aim of this study was to assess annexin A2 and CD163+ tumor associated macrophages (TAMs) immunohistochemical expression in 50 mRCC cases as regard to patients’ prognosis and Sunitinib response. Also, to assess the correlation between annexin A2 and TAMs expression. High annexin A2 expression and TAMs density were associated with serum calcium level (P = 0.024 and 0.037, respectively), larger tumor size (P < 0.001), high tumor grade (P = 0.014 and <0.001, respectively), and the presence of tumor necrosis (P < 0.001). High annexin A2 and TAMs expressions were related to shorter patients’ overall survival (P = 0.009 and 0.001, respectively) and progression-free survival (P = 0.003 and 0.001, respectively). Annexin A2 was correlated with TAMs density (r = 0.890). Annexin A2 and TAMs are associated with poor prognostic parameters in mRCC patients, including high nuclear grade, increased tumor size, and the presence of tumor necrosis, together with shorter patients’ survivals and poor response to Sunitinib. Annexin A2 expression is correlated with TAMs density suggesting immunomodulatory role of annexin A2.

Assessment of Ki-67 proliferation index in prognosis prediction in patients with nonmetastatic clear cell renal cell carcinoma and tumor thrombus

PurposeTo determine the optimal cut-off value of Ki-67 for predicting the survival of patients with clear cell renal cell carcinoma (ccRCC) and tumor thrombus and to explore the correlation between Ki-67 expression and pathological features. Patients and MethodsWe retrospectively analyzed Ki-67 immunohistochemical staining of ccRCC and tumor thrombus resected from February 2006 to February 2022. The survival rate was evaluated using the Kaplan-Meier method. The optimal cut-off value of the Ki-67 expression for predicting survival was determined by the minimum P-value method. Clinicopathological data were compared based on Ki-67 status (low versus high expression). Univariate and multivariate Cox regression analysis was used to explore independent predictors. ResultsA total of 202 patients (median age, 58 years [IQR, 52–65 years], 147 men) with ccRCC and tumor thrombus were included in the study. The optimal cut-off value of Ki-67 for predicting survival was 30%. 159 (78.7%) and 43 (21.3%) patients were included in the low-expression and high-expression groups. Patients with Ki-67 high expression had significantly worse recurrence-free survival (P < 0.001) and cancer-specific survival (P < 0.001). Ki-67 high expression was associated with adverse pathological features, including tumor necrosis, ISUP nuclear grade, sarcomatoid differentiation, perirenal fat invasion, renal pelvis invasion, and inferior vena cava wall invasion (all P < 0.050). Ki-67 expression ≥ 30% (P = 0.016), tumor side (P = 0.003), diabetes (P = 0.040), blood loss (P = 0.016), inferior vena cava wall invasion (P = 0.016), and sarcomatoid differentiation (P = 0.014) were independent predictors of cancer-specific survival. ConclusionThe optimal cut-off level of Ki-67 in predicting the prognosis of ccRCC and tumor thrombus was 30%. The high expression of Ki-67 was associated with the aggressive pathological phenotype and poor prognosis.

Prediction of static failure in metal inert gas welded nuclear grade pipe 347 SS: Experimentation and finite-element analysis approach

Defect repair, one of primary concerns in the maintenance system for pipelines and other high strength components, is crucial in improving the reliability and economic benefits. Even though modern industries use several welding techniques to join metals, metal inert gas (MIG) welding is frequently preferred to weld stainless steel components by producing strong joints at high speed. In this study, MIG welding was used to butt weld 347 SS pipes. Research related to material failure is critical to engineers in order to find suitable application. Tensile test provides the static behavior of material. Therefore, predicting the strength and failure of material helps in satisfying industrial needs. Finite-element analysis (FEA) is an efficient technique to predict physical phenomenon virtually, therefore reducing the need for real-time prototypes. Johnson-Cook (J-C) material failure model is utilized to define failure in FEA model. Error percentage obtained while comparing FEA and experimental results of weld metal is 1.03%. Presence of niobium carbide is evident through the line map of energy-dispersive X-ray spectroscopy spectrum which prevents knife line attack through retarding chromium carbide precipitation at high temperature cycles. Welded samples with tensile strength of 583 ± 3 MPa exhibit better mechanical strength than base metal with tensile strength of 575 ± 2.5 MPa. This change in mechanical properties is caused by microstructural variation led by occurrence of constitutional supercooling while melt-pool solidifies. Failure mechanism of ductile fracture is understood from fractography (Tensile sample). Hence, this study provides a complete knowledge on failure mechanism of MIG-welded nuclear grade steel pipe under static loading. The failure mechanisms are explained in terms of FEA (J-C model) and fractography.

Dislocation-density-related constitutive model and its applicability to cyclic deformation and damage behavior of 316LN SS at 823 K

In the present investigation, an in-depth understanding of the relationship between dislocation kinetics and cyclic plasticity, along with the description of yield asymmetry behavior during loading and unloading in nuclear grade 316LN austenitic stainless steel at 823 K, was examined by employing a constitutive framework using the evolution of physically-based internal-state variables. The formulation encompassed a set of first-order simultaneous differential equations that governed the evolution of dislocation density, mean free path of dislocations, and back stress. These variables were interdependent with the power law which described the kinetics of plastic strain rate. The evolution equations were numerically integrated, and the simulated data were fitted to the experimental data up to stabilized cycle at a temperature of 823 K and total strain amplitudes of ±0.004, ±0.006, ±0.008 and ± 0.010. The predicted cyclic stress response as a function of the cyclic number displayed the continuous cyclic hardening from the first cycle to the initiation of stabilized cycle. Further, good agreement between the predicted and experimental hysteresis loops was found at different cycle numbers. The predicted dislocation density and tensile peak values of back/effective stress increased with cyclic hardening and approached the value of saturation at the stabilized cycle. On the other hand, a rapid decrease in mean free path with cycle number was noticed. An increase in total strain amplitude resulted in a systematic increase in dislocation density, peak stress, back stress and effective stress. At the total strain amplitudes above ±0.006, the predicted higher rates of dislocation accumulation and annihilation, and the faster evolution rate of back stress towards saturation led to the development of stable dislocation substructure configurations with a clear distinction between dislocation high/low dense regions. Furthermore, the applicability of the model was extended by including an empirical relationship between the damage variable and cycle number within the power law, thereby enabling predictions of the cyclic stress-strain response beyond the stabilized cycle.

The success rate of small renal mass core needle biopsy and its impact on lowering benign resection rate

BackgroundSmall renal mass (SRM) biopsy remains under-utilized due to stigma. Meanwhile, the alarmingly high benign findings in resected kidney masses highlight the need for improved preoperative diagnosis and patient selection.MethodsThe purpose of this study is to review the success rate of SRM biopsy and to evaluate its impact on patient management. A total of 168 percutaneous image-guided core needle biopsies (CNBs) of SRMs were retrieved at a tertiary academic center between 2015 and 2019. Subsequent treatment choices, side effects and outcomes were retrospectively reviewed.ResultsThe diagnostic rate of CNB was 86.9%. Benign neoplasms accounted for a significant portion (14.3%) of SRM. Renal cell carcinomas (RCCs) were the most common diagnoses (69.6%) as expected. In biopsy-resection correlation, the positive predictive value of CNB was 100%. Tumor typing and subtyping by CNB were highly accurate, 100% and 98.3% respectively. Nuclear grading for clear cell RCC was accurate in 83.8% cases. The CNB results had significant impact on treatment. Most patients with RCCs underwent either resection (54.1%) or ablation (33.9%), in contrast to observation in benign neoplasms (90.5%). Most importantly, the benign resection rate (3.2%) in this series was much lower than the national average.ConclusionCNB provided accurate diagnoses for the majority of SRMs and revealed benign diagnoses in a subset of clinically suspicious lesions. Employment of CNB in suspicious SRM may help avoid overtreatment for benign lesions.

The Impact of HER2-Low Expression on Oncologic Outcomes in Hormone Receptor-Positive Breast Cancer.

Breast cancer is a prevalent malignancy with increasing incidence, particularly in Asian countries. Classification based on estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status is pivotal in determining treatment. Recent advances have challenged the traditional dichotomy in HER2 classification, prompting investigation into the HER2-low subtype's characteristics and outcomes. This retrospective study analyzed 10,186 non-metastatic hormone receptor (HR)-positive, HER2-negative breast cancer cases treated from 2008 to 2020. Data encompassed clinical, pathological, and treatment information. Oncologic outcomes included disease-free survival (DFS), overall survival (OS), and breast cancer-specific survival (BCSS). In total, 56.5% were HER2-low cases. Differences in patient characteristics were noted, with more BRCA1/2 mutations and higher mastectomy rates in the HER2-low group (p = 0.002, p < 0.001, respectively). Fewer received adjuvant chemotherapy or radiation therapy, and fewer histologic and nuclear grade 1 tumors were identified (all p < 0.001). With a median follow-up of 64 months (range: 13-174), HER2-low cases exhibited better DFS, OS, and BCSS than HER2-0 cases (p = 0.012, p = 0.013, and p = 0.013, respectively). Notably, the prognosis differed between premenopausal and postmenopausal subgroups, with BCSS benefitting premenopausal patients (p = 0.047) and DFS and OS benefitting postmenopausal patients in the HER2-low group (p = 0.004, p = 0.009, respectively). Multivariate analysis confirmed HER2 status as an independent predictor of these outcomes (p = 0.010, p = 0.008, and p = 0.014, respectively). This extensive single-center study elucidates the favorable prognosis associated with HER2-low status in HR-positive breast cancer. However, this effect differs among premenopausal and postmenopausal patients, necessitating further research into the underlying tumor biology.

Determination of impurity distribution in IG-11/110 nuclear graphite using TOF-SIMS

Graphite serves as moderator and structural material in various type of graphite-based reactors. The presence of impurities within the graphite matrix can lead to adverse consequences, including diminished fuel efficiency, heightened radionuclide production, and catalytic oxidation. High-purity graphite materials also find essential applications in diverse industries, such as semiconductor manufacturing and chemical analysis. In this study, we conducted an investigation into IG-11 graphite, which has an ash content of 347 ppm, and its purified version, IG-110 nuclear grade graphite, which has an ash content of 12.7 ppm, to understand the purification mechanism of polycrystalline graphite. The analysis of Time-of-flight secondary ion mass spectrometry spectra revealed that metallic impurities in IG-11 were primarily segregated within graphite porosities or appeared as discrete point inclusions, rather than uniformly distributed throughout the graphite matrix. IG-110 demonstrated a significant reduction in impurities such as Na, K, Ca, and Al compared to IG-11, but Ti was still present within its porosity. Notably, impurities residing on the walls of these porosities can accelerate graphite oxidation. The establishment of the theory on impurity segregation in porosities help to develop innovative graphite purification techniques that produce graphite with even greater purity and stronger oxidation resistance.

Immunoexpression of HER2 pathway related markers in HER2 invasive breast carcinomas treated with trastuzumab

PurposeWe evaluated the immunoexpression of potential markers involved in the HER2 pathway in invasive breast carcinoma with HER2 amplification treated with trastuzumab. MethodsSamples of ninety patients diagnosed and treated at two public Brazilian hospitals with overexpressed invasive carcinoma between 2009 and 2018 were included. Several markers (Bcl-2, CDK4, cyclin D1, EGFR, IGF1, IGF-1R, MDM2, MUC4, p16, p21, p27, p53, PTEN, RA, TNFα, and VEGF) were immune analyzed in the tumor by immunohistochemistry and then correlated with clinicopathological variables. ResultsTumor sample expression results determined potential markers of good prognosis with statistically significant values: cyclin D1 with a nuclear grade, and recurrence; IGF-1 with tumor size, and death; p16 with a response after treatment; PTEN with a response after treatment, and death. Markers of poor prognosis: p53 with histological, and nuclear grade; IGF-1R with a compromised lymph node. The treatment resistance rate after trastuzumab was 40%; the overall survival was 4.13 years (95% CI 5.1–12.5) and the disease-free survival was 3.6 years (95% CI 5.1–13.1). ConclusionsThe tumor samples profile demonstrated that cyclin D1, IGF-1, p16, and PTEN presented the potential for a good prognosis and p53 and IGF-1R for worse.

Yolov5 AI Deep Learning model driven Nuclear Pleomorphism Grading on Breast Cancer Pathology WSI for Nottingham Cancer Grading

Breast cancer is the second largest cancer caused in the world due to the uncontrollable growth in breast cells. Nottingham Grading is the internationally acceptable system to grade breast cancer. Nuclear pleomorphism is one of the breast cancer biomarkers for computing Nottingham grading. Pathologists grade nuclear pleomorphism on breast cancer glass tissue slides using a conventional microscope which is time consuming and has considerable inter-observer variability between pathologists. The paper proposed an Artificial Intelligence (AI) deep learning model to grade grade1, grade2, grade3 nuclear pleomorphism on breast cancer whole slide images (WSI). The proposed Yolov5 model is trained and tested on 1,30,000 WSI tiles having around two lakh annotations. The accuracy of the model is mAP 0.89. The proposed model saves the time and reduces the workload of the pathologist and also helps them to produce accurate results.

Microstructure evolution and constitutive analysis of nuclear grade AISI-316H austenitic stainless steel during thermal deformation

Compression experiments were performed on AISI-316H austenitic stainless steel using Gleeble-3800 at temperatures ranging from 900 °C and 1200 °C and strain rates ranging from 0.01 and 10 s−1, up to the actual strain of 0.69. The tests aimed to examine the material’s microstructure evolution and flow stress behavior. Based on OM and EBSD studies, it was found that thermal deformation mostly induces discontinuous dynamic recrystallization (DDRX). The proportion of recrystallization nucleation increases steadily with increasing deformation temperature, while the impact of strain rate on recrystallization is complex. At the same deformation temperature, the recrystallization volume fraction initially declines and rises as the strain rate rises. In low strain rate regime, the longer (deformation) time available for grain boundary migration, the higher recrystallization volume fraction. In high strain rate regime, the higher stored energy (and thus the increased boundary velocity) raises the probability of nucleation events, stimulating twin formation. As a result, the twin promotes a dynamic recrystallization (DRX) process. An abundance of Σ3 twins was notably observed in uniformly refined recrystallized grains at a true strain of 0.69, at a temperature of 1200 °C, and a strain rate of 10 s−1. As a result, it was discovered that DRX occurs at higher strain rates and deformation temperatures. In addition, the flow stress curves were modified to account for adiabatic heating at strain rates exceeding 1 s−1. The findings demonstrated that adiabatic heating increased when strain level and strain rate increased and deformation temperature decreased. The strain compensation Arrhenius model is developed following the given stress–strain curve while considering strain. The model exhibits high accuracy, with a correlation value of 0.986. According to a kinetic study, the average activation energy for hot deformation of the tested steel was 444.994 kJ/mol. These findings provide fundamental insights into the microstructure control technology and the outstanding mechanical properties of the austenitic stainless steel AISI-316H.