Parotid gland tumors constitute a significant proportion of head and neck neoplasms, and accurate non-invasive differentiation is essential for appropriate clinical management. Recent advances in ultrasound techniques, including shear-wave elastography (SWE), have shown promising diagnostic potential.

To evaluate the diagnostic performance of long-to-short axis ratio (L/S) and shear-wave velocity (SWV) values obtained by virtual touch imaging quantification (VTIQ) in differentiating pleomorphic adenoma (PA), Warthin tumor (WT), and malignant tumors (MT) of the parotid gland.

This study included 66 parotid masses from 63 patients who underwent conventional ultrasound and SWE examinations. B-mode features, Doppler vascular patterns, L/S ratios, and SWV values were recorded and compared with histopathological findings. Receiver operating characteristic (ROC) analysis was performed to determine optimal cutoff values, sensitivity, and specificity.

The cutoff value for differentiating WT and PA was 1.57 for the L/S ratio (sensitivity: 83.33%, specificity: 88.46%, p < 0.001). For distinguishing MT from PA, the L/S cutoff was 1.68 (sensitivity: 50.00%, specificity: 96.15%, p < 0.001). The optimal SWV cutoff for WT and PA differentiation was 5.02 m/s (sensitivity: 91.67%, specificity: 73.08%, p < 0.001), while for MT and PA differentiation, it was 6.30 m/s (sensitivity: 84.62%, specificity: 62.50%, p < 0.001).

The combined use of L/S ratio and SWV values obtained by VTIQ provides a reliable and non-invasive diagnostic approach for differentiating parotid gland tumors and may help reduce unnecessary biopsies.

Primary hepatic neuroendocrine tumour (PHNET) is an exceptionally rare neoplasm, accounting for approximately 0.3% of all neuroendocrine tumours. It presents with non specific clinical and radiological features, making pre operative diagnosis difficult. Differentiation from other paediatric liver lesions, such as hepatoblastoma, haemangioma and hepatocellular carcinoma, is challenging. We report the rare case of PHNET in a 9 year old boy who presented with abdominal pain and vomiting. Routine laboratory investigations, including liver function tests and serum alpha fetoprotein levels, were within the normal limits. Radiological evaluation suggested a diagnosis of sclerosed hepatic haemangioma. Definitive diagnosis was established by histopathological examination and immunohistochemistry. Surgical resection was performed, which remains the mainstay of treatment. The post operative course was uneventful and regular follow up. This case highlights the diagnostic difficulty of PHNET and underscores the importance of histopathological evaluation for accurate diagnosis and appropriate management.

Breast cancer remains the most prevalent malignancy among women worldwide, contributing significantly to global cancer-related morbidity and mortality. It is responsible for nearly 15% of all female cancer fatalities. It has a higher prevalence in developed nations.

The present study aimed to assess the predictive utility of Atherogenic index of plasma (AIP) in carcinoma breast cases in correlation with oxidative stress, immuno-biomarkers and body mass index (BMI).

Prospective interventional study. The Prospective Interventional Study was conducted in the Department of Biochemistry, Jawaharlal Nehru Medical College and the Histopathology and Radiology division of the Department of Pathology, JNMC, in collaboration with the Department of Surgery, JNMC and Acharya Vinoba Bhave Rural Hospital, Wardha, for the duration of 3 years. Total 81 samples were recruited for the study. The patient's history was taken, and a proper medical examination was carried out. The SPSS program for Windows, version 26.0 (SPSS, Chicago, Illinois, USA), was employed to conduct the statistical analysis. Categorical variables were analysed using either the Chi-square test or Fisher's exact test, while continuous variables were compared using the unpaired t -testing method. P ≤0.05 was deemed to be statistically significant.

A significant positive correlations between AIP and various parameters, including BMI ( r = 0.591, P < 0.001), superoxide dismutase ( r = 0.407, P < 0.001), high-sensitivity C-reactive protein ( r = 0.507, P < 0.001), Interleukin-10 (IL-10) ( r = 0.706, P < 0.001) and IL-18 ( r = 0.652, P < 0.001). Furthermore, a strong positive correlation with lipid profile was observed.

AIP could serve as a useful surrogate marker to assess not only lipid imbalance but also broader systemic changes that accompany breast cancer.

Polycystic ovarian syndrome (PCOS) has bidirectional effects on the skeleton due to hormonal dysfunction and insulin resistance (IR).

We examined bone mineral density (BMD) and its relationship with IR using the homeostasis model of assessment (HOMA) in patients with PCOS and matched controls.

In this case-control observational study, we included 74 patients newly diagnosed with PCOS and a similar number of age-and weight-matched healthy women as controls. Haematological, biochemical and hormonal parameters were measured in a fasting blood sample during the follicular phase, and the BMD Z score was calculated using dual energy X-ray absorptiometry. The results were analysed using relevant statistical methods, and P < 0.05 was considered significant.

The study participants ( n = 148) had a mean age of 23.6 ± 3.7 years and a body mass index (BMI) of 25.2 ± 3.2 kg/m 2 . Among the PCOS patients, 25 (34%) had a normal BMI and 49 (66%) were obese. The BMD at the femoral neck ( P = 0.4313) and lumbar spine ( P = 0.1410) was comparable between the PCOS and control groups. Correlation analysis showed a positive correlation of BMD with testosterone and 17-hydroxy progesterone (17OHP) ( P < 0.001). None of the BMD parameters correlated with HOMA in either group.

BMD at the lumbar spine and femoral neck was similar between patients with PCOS and controls. Further studies with a larger sample size, longer follow-up periods and fracture data are needed to confirm our findings.

We show continuous tumor exposure results in a loss of chimeric antigen receptor (CAR) T cell (CART) endocytic activity due to downregulation of Rab5. Loss of endocytic activity exacerbates the effects of trogocytosis, the bidirectional transfer of tumor target antigens and CARs between malignant cells and CARTs, resulting in CART dysfunction and fratricide. Constitutive expression of Rab5 within the CARTs reduced fratricide by reducing the amount of trogocytosed antigens on the cell surface, while simultaneously enhancing CAR availability through dissociation of CAR from target, recycling unbound CAR back to the plasma membrane, and limiting CAR capture by tumor cells. Rab5-expressing CARTs exhibited superior antitumor activity in both BCMA-CARTs isolated from the bone marrow of treated patients and mesothelin-specific CARTs in a solid tumor model. These studies uncover an unexpected relationship between endocytosis and CART function and suggest that pairing Rab5 with CAR expression could improve the clinical efficacy of CART therapy.

Esophageal squamous cell carcinoma (ESCC) is characterized by intrinsic radioresistance, primarily mediated by hyperactivation of DNA damage response (DDR) pathways. This repair capacity significantly diminishes radiotherapy efficacy, contributing to poor patient outcomes. Targeting DNA-dependent protein kinase catalytic subunit (DNA-PKcs), a master regulator of non-homologous end joining (NHEJ), represents a promising strategy to overcome radioresistance. Immunohistochemistry (IHC) was performed on paired biopsy specimens from esophageal squamous cell carcinoma (ESCC) patients (n = 20) collected before neoadjuvant radiotherapy and after surgical resection. In vitro, ESCC cell lines (TE13 and Eca9706) were co-treated with DNA-dependent protein kinase catalytic subunit (DNA-PKcs) inhibitors (AZD7648 or NU7741) or PRKDC-targeting siRNA plus irradiation. Subsequent functional assays were conducted to assess cell viability, apoptosis, cell cycle distribution, and underlying molecular mechanisms. In vivo, the combined efficacy of AZD7648 and irradiation was evaluated in xenograft tumor models. Phosphorylated DNA-PKcs (Ser2056) in ESCC tissues was significantly elevated following irradiation. Inhibition of DNA-PKcs markedly enhanced radiosensitivity in both ESCC cell lines and xenograft models, correlating with prolonged G2/M arrest and increased apoptosis. Mechanistically, the combined therapy activated the ATM (Ser1981)-Chk2 (Thr68) axis and concurrently enhanced phosphorylation of Chk1 at Ser345, reinforcing G2/M arrest through Wee1 kinase-mediated inhibitory phosphorylation of CDC2 at Tyr15. Consequently, irreparable DNA double-strand breaks (DSBs) accumulated, triggering Caspase-3-dependent cleavage of PARP and execution of the intrinsic apoptosis pathway. Our study reveals a novel mechanism by which DNA-PKcs inhibition augments radiosensitivity in ESCC. Targeting DNA-PKcs could represent a promising strategy to improve the efficacy of radiotherapy in ESCC, offering a potential therapeutic approach to overcome radioresistance.

Determining microsatellite instability (MSI) status in colon cancer is crucial for selecting treatment strategies in advanced stages. Thus, accurately identifying MSI status before treatment is essential.

This study aims to evaluate the utility of nomogram model that integrates clinicopathological indicators and pre-treatment CT-based radiomics features for predicting DNA mismatch repair deficiency (dMMR) /microsatellite instability (MSI) status in colon cancer prior to treatment.

A total of 201 colon cancer patients who had undergone preoperative contrast-enhanced CT scans were categorized into the dMMR/MSI group or the proficient Mismatch Repair (pMMR)/Microsatellite Stable (MSS) group based on surgical pathology results. Multivariate logistic regression was applied to identify independent clinical predictors. The least absolute shrinkage and selection operator (LASSO) regression was applied for dimensionality reduction of radiomics features. Clinical, radiomics, and nomogram models were established through logistic regression analysis based on the risk clinicopathological predictors and radiomics features.

Multivariate logistic regression identified patient age, pericentric lymph node metastasis, and CA72-4 levels as significant (P < 0.05). Four radiomic features were selected to construct the radiomics model. In the training set, the AUC values for the clinical model, Rad score, and combined model were 0.86, 0.89, and 0.94, respectively, and in the validation set, 0.81, 0.89, and 0.91, respectively. The Delong test showed the nomogram model outperformed both the clinical model and Rad score (P < 0.05). The calibration curve confirmed good consistency between predicted and actual outcomes for dMMR/MSI colon cancer using the combined model.

The nomogram model, which combines clinicopathological features with pre-treatment CT-based radiomics features, demonstrates greater predictive accuracy for dMMR/MSI colon cancer than the standalone clinical and radiomics models.

Triple-negative breast cancer (TNBC) presents a poorer prognosis than other breast cancer subtypes, attributed to its aggressive nature and the lack of specific therapeutic interventions. TNBC has high recurrence rates and limited survival despite current therapies, emphasizing the critical need for improved treatment options. TNBC exhibits increased levels of LRP6 expression, which is linked to tumor-related features such as growth, metastasis, poor prognosis, resistance to chemotherapy, and invasion. Therefore, LRP6 offers a promising option for therapeutic intervention in breast cancer.

This research aims to use in silico and bioinformatics techniques to develop an mRNA vaccine that specifically targets the LRP6 antigen.

The final vaccine construct comprised 431 amino acids, with a molecular weight of 47.5 kDa, theoretical pI of 5.11, and an instability index of 38.3 indicating stability. Population coverage analysis showed broad global coverage of 99.04%. Molecular docking revealed strong binding affinities to immune receptors, including HLA-A0201 (-812.0), HLA-A0301 (-707.1), HLA-DRB1*0101 (-955.7), and TLR9 (-1339.5). Immune simulation predicted high titers of IgG1 antibodies, sustained memory B cell populations (> 200 by Day 365), elevated CD4+ T cells (> 3000), and robust IFN-γ responses. Codon optimization yielded a high CAI value of 0.94 and GC content of 58.37%, supporting efficient expression in human systems.

Collectively, these results suggest that the designed LRP6-targeted mRNA vaccine could induce durable humoral and cellular immunity against TNBC and warrants further experimental validation.

Accurate size estimation of large (≥ 20 mm) colorectal laterally spreading tumors (LSTs) is essential for procedural planning, risk stratification, and predicting technical difficulty. Yet, the reliability of visual LST size assessment among endoscopists has not been systematically evaluated.

46 LSTs were recorded during colonoscopy. Twenty-four international expert endoscopists independently reviewed de-identified videos and provided visual estimates for (1) maximal diameter, (2) oral-anal axis, (3) left-right axis, and (4) percentage of colonic circumference involved. Each lesion was assessed twice in randomized order. Fleiss's kappa, Krippendorff's alpha, and intraclass correlation coefficients (ICC) were used to evaluate inter- and intra-rater agreement.

A total of 1104 measurements were collected. Inter-endoscopist kappa agreement for maximal diameter was poor (κ = 0.16), with similarly poor agreement for the oral-anal (κ = 0.15) and left-right axes (κ = 0.14). The percentage of circumferential involvement demonstrated moderate reproducibility (ICC 0.74 and 0.70 across rounds). Subgroup analyses showed consistently poor agreement for larger lesions for diameter-based methods, whereas circumferential percentage estimation ranged from poor to good depending on LST size and morphology. Intra-endoscopist agreement for diameter- and axis-based approaches showed wide variability (κ range 0.01-0.67), while circumferential estimates achieved good to excellent agreement for most endoscopists.

Visual estimation of large colorectal LST size is highly variable among expert endoscopists. Maximal diameter and axial lengths demonstrate poor inter- and intra-observer reliability. Circumferential extent is the most reproducible descriptor and may be the preferred approach for reporting LST size in clinical practice and research.

Colorectal cancer is one of the most common types of cancer with hereditary background. Due to the progress in DNA sequencing techniques, the number of identified cancers predisposing gene mutations is rising constantly. For some morphologically defined cancer predispositions like serrated polyposis, however, a genetic background is rarely identified. Even if this would exclude a hereditary predisposition, the elevated cancer risk remains, emphasizing the importance of histopathologic diagnoses.Hereditary colorectal cancer can be categorized into polypous and non-polypous predispositions. While the former elevate cancer risk by increasing the number of cancer precursors, the latter elevate cancer risk by increasing the likelihood of malignant transformation. It is the pathologist's responsibility to use morphologic criteria in combination with clinical data in order to raise suspicion of hereditary tumorigenesis and recommend genetic counselling. This article summarizes the current state of knowledge on hereditary colorectal cancer.The new German S3 guideline for colorectal cancer demands testing of all newly diagnosed colorectal cancers for Lynch syndrome association. Owing to this change in the guideline, this article will focus on diagnostic challenges of the DNA mismatch repair function.