Prediction of response to anti-HER2 therapy using a multigene assay.

HER2-positive breast cancer (BC), which constitutes 13-15% of cases, shows variable response to anti-HER2 therapies. HER2-positivity, defined as protein overexpression (immunohistochemistry (IHC) score 3+) or equivocal expression (IHC 2+) with evidence of HER2 gene amplification, determines the eligibility to anti-HER2 therapy. MammaTyper® assay (Cerca Biotech GmbH) is a RT-qPCR BC subtyping platform based on the mRNA expression of ERBB2, ESR1, PGR, and MKI67.

Deciphering the Role of ASPM in Breast Cancer: A Comprehensive Multicohort Study.

Background: Assembly factor for spindle microtubules (ASPM) has gained significant attention in cancer research due to its association with tumor growth and progression. Through the analysis of large-scale genomic datasets, ASPM has been identified as the top upregulated gene in breast cancer (BC), characterized by high proliferation. This multicohort study aimed to investigate the clinicopathological and prognostic significance of ASPM mRNA and protein expression in BC.

Deciphering the Clinical Behaviour of Invasive Lobular Carcinoma of the Breast Defines an Aggressive Subtype.

Background: Invasive lobular carcinoma (ILC), the most common special type of breast cancer (BC), has unique clinical behaviour and is different from invasive ductal carcinoma of no special type (IDC-NST). However, ILC further comprises a diverse group of tumours with distinct features. This study aims to examine the clinicopathological and prognostic features of different variants of ILC, with a particular focus on characterising aggressive subtypes.

Artificial Intelligence-Based Mitosis Scoring in Breast Cancer: Clinical Application.

In recent years, artificial intelligence (AI) has demonstrated exceptional performance in mitosis identification and quantification. However, the implementation of AI in clinical practice needs to be evaluated against the existing methods. This study is aimed at assessing the optimal method of using AI-based mitotic figure scoring in breast cancer (BC).

Novel 2 Gene Signatures Associated With Breast Cancer Proliferation: Insights From Predictive Differential Gene Expression Analysis.

The use of proliferation markers provides valuable information about the rate of tumor growth, which can guide treatment decisions. However, there is still a lack of consensus regarding the optimal molecular markers or tests to use in clinical practice. Integrating gene expression data with clinical and histopathologic parameters enhances our understanding of disease processes, facilitates the identification of precise prognostic predictors, and supports the development of effective therapeutic strategies.

Quantitative expression of oestrogen receptor in breast cancer: Clinical and molecular significance.

Background: Oestrogen receptor (ER) positive breast cancer (BC) patients are eligible for endocrine therapy (ET), regardless of ER immunohistochemical expression level. There is a wide spectrum of ER expression and the response to ET is not uniform. This study aimed to assess the clinical and molecular consequences of ER heterogeneity with respect to ET-response.

AI-enabled routine H&E image based prognostic marker for early-stage luminal breast cancer.

Breast cancer (BC) grade is a well-established subjective prognostic indicator of tumour aggressiveness. Tumour heterogeneity and subjective assessment result in high degree of variability among observers in BC grading. Here we propose an objective Haematoxylin & Eosin (H&E) image-based prognostic marker for early-stage luminal/Her2-negative BReAst CancEr that we term as the BRACE marker.

AI-based intra-tumor heterogeneity score of Ki67 expression as a prognostic marker for early-stage ER+/HER2- breast cancer.

Early-stage estrogen receptor positive and human epidermal growth factor receptor negative (ER+/HER2-) luminal breast cancer (BC) is quite heterogeneous and accounts for about 70% of all BCs. Ki67 is a proliferation marker that has a significant prognostic value in luminal BC despite the challenges in its assessment. There is increasing evidence that spatial colocalization, which measures the evenness of different types of cells, is clinically important in several types of cancer.

Evaluation of tumour infiltrating lymphocytes in luminal breast cancer using artificial intelligence.

Background: Tumour infiltrating lymphocytes (TILs) are a prognostic parameter in triple-negative and human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC). However, their role in luminal (oestrogen receptor positive and HER2 negative (ER + /HER2-)) BC remains unclear. In this study, we used artificial intelligence (AI) to assess the prognostic significance of TILs in a large well-characterised cohort of luminal BC.

Differential response of HER2-positive breast cancer to anti-HER2 therapy based on HER2 protein expression level.

Background: Increasing data indicate that HER2-positive (HER2 + ) breast cancer (BC) subtypes exhibit differential responses to targeted anti-HER2 therapy. This study aims to investigate these differences and the potential underlying molecular mechanisms.

Methods: A large cohort of BC patients (n = 7390) was utilised.

Concordance of HER2-low scoring in breast carcinoma among expert pathologists in the United Kingdom and the republic of Ireland -on behalf of the UK national coordinating committee for breast pathology.

Background: Recent clinical evidence showed that breast cancer with low HER2 expression levels responded to trastuzumab deruxtecan therapy. The HER2-low cancers comprise immunohistochemistry (IHC) score 1+ and 2+ ISH non-amplified tumours, currently classified as HER2 negative. Little data exists on the reproducibility of pathologists reporting of HER2-low cancer.

Deciphering the Morphology of Tumor-Stromal Features in Invasive Breast Cancer Using Artificial Intelligence.

Tumor-associated stroma in breast cancer (BC) is complex and exhibits a high degree of heterogeneity. To date, no standardized assessment method has been established. Artificial intelligence (AI) could provide an objective morphologic assessment of tumors and stroma, with the potential to identify new features not discernible by visual microscopy.

Differential effects of milk proteins on amino acid digestibility, post-prandial nitrogen utilization and intestinal peptide profiles in rats.

Objective: The aim of this study was to analyze the protein digestibility and postprandial metabolism in rats of milk protein matrices obtained by different industrial processes.

Material And Methods: The study was conducted on Wistar rats that consumed a meal containing different N-labeled milk proteins. Four milk matrices were tested: native micellar caseins (C1), caseins low in calcium (C2 low Ca), a matrix containing a ratio 63:37 of caseins and whey proteins (CW2) and whey proteins alone (W).

The role of the A monovalent cation in the AVF perovskite series. A quantum mechanical investigation.

The relative stability of various phases of five AVF compounds (A = Li, Na, K, Rb and Cs) is investigated starting from the cubic (C) 3̄ (221) prototype structure, with five atoms (one formula unit) in the primitive cell. To the authors' knowledge, only three of these compounds have been investigated experimentally (Na, K and Rb), and they are reported as being cubic. The picture emerging from the present simulation is quite different: CsVF and RbVF are dynamically stable in the cubic structure, KVF is tetragonal, with space group (SG) 4/ (no.

Combined proliferation and apoptosis index provides better risk stratification in breast cancer.

Aims: Breast cancer (BC) risk stratification is critical for predicting behaviour and guiding management decision-making. Despite the well-established prognostic value of cellular proliferation in BC, the interplay between proliferation and apoptosis remains to be defined. In this study, we hypothesised that the combined proliferation and apoptosis indices can provide a more accurate in-vivo growth rate measure and a precise prognostic predictor.

Mid-regional Proadrenomedullin Biomarker Predicts Coronavirus Disease 2019 Clinical Outcomes: A US-Based Cohort Study.

Background: Mid-regional proadrenomedullin (MR-proADM) is a biomarker released following endothelial damage. Studies have shown a correlation in predicting coronavirus disease 2019 (COVID-19) outcomes with MR-proADM levels. Our study aimed to investigate baseline MR-proADM as a predictor of a wider range of clinical outcomes of varying severity in patients admitted with COVID-19, and to compare to other biomarkers.

Refining the definition of HER2-low class in invasive breast cancer.

Background: Emerging evidence indicates that breast cancer (BC) patients whose tumours express HER2 protein without HER2 gene amplification (HER2-low), can benefit from antibody-drug conjugates (ADC). However, the current definition of HER2-low BC remains incomplete with low rates of concordance. This study aims to refine HER2-low definition with emphasis on distinguishing HER2 score 0 from score 1+ to identify patients who are eligible for ADC.

Extra-pulmonary applications of procalcitonin: .

Introduction: Procalcitonin (PCT) is a biomarker with established performance in the differentiation between bacterial and viral infections, predominantly in pulmonary infections, as well as the diagnosis and prognosis of bacterial sepsis. However, the role of PCT in extra-pulmonary infections is not well described.

Areas Covered: We reviewed the role of PCT in commonly experienced extra-pulmonary infections including meningitis, diabetic foot infection, prosthetic joint infection, osteomyelitis, and skin and soft tissue infection.

Moderate adiposity levels counteract protein metabolism modifications associated with aging in rats.

Purpose: Physiological parameters such as adiposity and age are likely to influence protein digestion and utilization. The aim of this study was to evaluate the combined effects of age and adiposity on casein protein and amino acid true digestibility and its postprandial utilization in rats.

Methods: Four groups were included (n = 7/8): 2 months/normal adiposity, 2 months/high adiposity, 11 months/normal adiposity and 11 months/high adiposity.

Transfusable neutrophil progenitors as cellular therapy for the prevention of invasive fungal infections.

The use of mature neutrophil (granulocyte) transfusions for the treatment of neutropenic patients with invasive fungal infections (IFIs) has been the focus of multiple clinical trials. Despite these efforts, the transfusion of mature neutrophils has resulted in limited clinical benefit, likely owing to problems of insufficient numbers and the very short lifespan of these donor cells. In this report, we employed a system of conditionally immortalized murine neutrophil progenitors that are capable of continuous expansion, allowing for the generation of unlimited numbers of homogenous granulocyte-macrophage progenitors (GMPs).

TLR Signaling Rescues Fungicidal Activity in Syk-Deficient Neutrophils.

An impaired neutrophil response to pathogenic fungi puts patients at risk for fungal infections with a high risk of morbidity and mortality. Acquired neutrophil dysfunction in the setting of iatrogenic immune modulators can include the inhibition of critical kinases such as spleen tyrosine kinase (Syk). In this study, we used an established system of conditionally immortalized mouse neutrophil progenitors to investigate the ability to augment Syk-deficient neutrophil function against with TLR agonist signaling.

Baseline procalcitonin as a predictor of bacterial infection and clinical outcomes in COVID-19: A case-control study.

Purpose: Coronavirus disease-2019 (COVID-19) is associated with a wide spectrum of clinical symptoms including acute respiratory failure. Biomarkers that can predict outcomes in patients with COVID-19 can assist with patient management. The aim of this study is to evaluate whether procalcitonin (PCT) can predict clinical outcome and bacterial superinfection in patients infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2).

Potential quality pitfalls of digitalized whole slide image of breast pathology in routine practice.

Using digitalized whole slide images (WSI) in routine histopathology practice is a revolutionary technology. This study aims to assess the clinical impacts of WSI quality and representation of the corresponding glass slides. 40,160 breast WSIs were examined and compared with their corresponding glass slides.