Multiscale deep learning framework captures systemic immune features in lymph nodes predictive of triple negative breast cancer outcome in large-scale studies.

The suggestion that the systemic immune response in lymph nodes (LNs) conveys prognostic value for triple-negative breast cancer (TNBC) patients has not previously been investigated in large cohorts. We used a deep learning (DL) framework to quantify morphological features in haematoxylin and eosin-stained LNs on digitised whole slide images. From 345 breast cancer patients, 5,228 axillary LNs, cancer-free and involved, were assessed. Generalisable multiscale DL frameworks were developed to capture and quantify germinal centres (GCs) and sinuses. Cox regression proportional hazard models tested the association between smuLymphNet-captured GC and sinus quantifications and distant metastasis-free survival (DMFS). smuLymphNet achieved a Dice coefficient of 0.86 and 0.74 for capturing GCs and sinuses, respectively, and was comparable to an interpathologist Dice coefficient of 0.66 (GC) and 0.60 (sinus). smuLymphNet-captured sinuses were increased in LNs harbouring GCs (p < 0.001). smuLymphNet-captured GCs retained clinical relevance in LN-positive TNBC patients whose cancer-free LNs had on average ≥2 GCs, had longer DMFS (hazard ratio [HR] = 0.28, p = 0.02) and extended GCs' prognostic value to LN-negative TNBC patients (HR = 0.14, p = 0.002). Enlarged smuLymphNet-captured sinuses in involved LNs were associated with superior DMFS in LN-positive TNBC patients in a cohort from Guy's Hospital (multivariate HR = 0.39, p = 0.039) and with distant recurrence-free survival in 95 LN-positive TNBC patients of the Dutch-N4plus trial (HR = 0.44, p = 0.024). Heuristic scoring of subcapsular sinuses in LNs of LN-positive Tianjin TNBC patients (n = 85) cross-validated the association of enlarged sinuses with shorter DMFS (involved LNs: HR = 0.33, p = 0.029 and cancer-free LNs: HR = 0.21 p = 0.01). Morphological LN features reflective of cancer-associated responses are robustly quantifiable by smuLymphNet. Our findings further strengthen the value of assessment of LN properties beyond the detection of metastatic deposits for prognostication of TNBC patients. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Dopant-driven recombination delay and ROS enhancement in nanoporous Cd1-xCuxS heterogeneous photocatalyst for the degradation of DR-23 dye under visible light irradiation.

Developing an efficient heterogeneous photocatalyst for environmental remediation and treatment strategies using visible light harvesting processes is promising but challenging. Herein, Cd1-xCuxS materials have been synthesized and characterized by precise analytical tools. Cd1-xCuxS materials exhibited excellent photocatalytic activity for direct Red 23 (DR-23) dye degradation in visible light irradiation. The operational parameters, like dopant concentration, photocatalyst dose, pH, and initial concentration of dye were investigated during the process. The photocatalytic degradation process follows pseudo-first-order kinetics. As compared to other tested materials, 5% Cu doped CdS material revealed superior photocatalytic performance for the degradation of DR-23 (k = 13.96 × 10-3 min-1). Transient absorption spectroscopy, EIS, PL, and transient photocurrent indicated that adding copper to the CdS matrix improved the separation of photo-generated charge carriers by lowering the recombination rate. Spin-trapping experiments recognized the photodegradation primarily based on secondary redox products, i.e., hydroxyl and superoxide radicals. According to by Mott-Schottky curves, photocatalytic mechanism and photo-generated charge carrier density were elucidated regarding dopant-induced valence and conduction bands shifting. Thermodynamic probability of radical formation in line with the altered redox potentials by Cu doping has been discussed in the mechanism. The identification of intermediates by mass spectrometry study also showed a plausible breakdown mechanism for DR-23. Moreover, samples treated with nanophotocatalyst displayed excellent results when tested for water quality metrics such as DO, TDS, BOD, and COD. Developed nanophotocatalyst shows high recyclability with superior heterogeneous nature. 5% Cu-doped CdS also exhibit strong photocatalytic activity for the degradation of colourless pollutant bisphenol A (BPA) under visible light (k = 8.45 × 10-3 min-1). The results of this study offer exciting opportunities to alter semiconductors' electronic band structures for visible-light-induced photocatalytic activity for wastewater treatment.

Comprehensive analysis of GTP cyclohydrolase I activity in Mycobacterium tuberculosis H37 Rv via in silico studies.

GTP cyclohydrolase I enzyme (GTPCH-I) is a rate limiting enzyme in the biosynthesis pathway of tetrahydrobiopterin (BH4) and tetrahydrofolate (THF) compounds; latter being are an essential compounds involved in many biological functions. This enzyme has been evaluated structurally and functionally in many organisms to understand its putative role in cell processes, kinetics, regulations, drug targeting in infectious diseases, pain sensitivity in humans, and so on. In Mycobacterium tuberculosis (a human pathogen causing tuberculosis), this GTPCH-I activity has been predicted to be present in Rv3609c gene (folE) of H37 Rv strain, which till date has not been studied in detail. In order to understand in depth, the structure and function of folE protein in M. tuberculosis H37 Rv, in silico study was designed by using many different bioinformatics tools. Comparative and structural analysis predicts that Rv3609c gene is similar to folE protein ortholog of Listeria monocytogenes (cause food born disease), and uses zinc ion as a cofactor for its catalysis. Result shows that mutation of folE protein at 52th residue from tyrosine to glycine or variation in pH and temperature can lead to high destability in protein structure. Studies here have also predicted about the functional regions and interacting partners involved with folE protein. This study has provided clues to carry out experimentally the analysis of folE protein in mycobacteria and if found suitable will be used for drug targeting.

Analysis of predicted amino acid biosynthesis in Rv3344c in Mycobacterium tuberculosis H37 Rv using bioinformatics tools.

According to World Health Organization (WHO) report, Mycobacterium tuberculosis H37 Rv (M. tuberculosis) affects one-third population of the world. Emergence of effective treatment/research against this disease is need of the hour. Therefore, we present some important aspects of Rv3344c, which is a PE_PGRS protein. Evidence shows that PE_PGRS proteins show fibronectin binding activity. This protein has affinity for calcium and also shows motifs of GTP-binding protein. It also shows the presence of sites for ribose-5-phosphate binding and motifs of aspartate-beta-semialdehyde dehydrogenase, both of which are involved in amino acid biosynthesis. Thus, this protein might be targeted to block the amino acid biosynthesis in M. tuberculosis. This article takes into consideration some important aspects of Rv3344c protein as its function is still unknown. This study includes retrieval of protein sequence database, multiple sequence alignment, protein-protein interaction, epitope prediction, localization, function prediction, phosphorylation site prediction, model building and its validation, ligand-binding prediction along with mutational analysis. Hence, this study might be an important step in the development of new drugs and treatment of tuberculosis.

Histologic grading of salivary gland mucoepidermoid carcinoma: A comparison of four grading systems and correlation with survival.

BACKGROUND: Mucoepidermoid carcinoma (MEC) is the most common malignant lesion of salivary glands. A number of histologic grading systems are in use for MEC with variable agreement between them. METHODS: This study was aimed at comparison of four grading systems for MEC: two qualitative (modified Healy and MSKCC grading) and two quantitative (AFIP and Brandwein grading). A retrospective search for diagnosed cases of MEC over eight years yielded 11 cases with adequate clinical details and histologic slides available for review. All cases were reviewed and graded as per the four grading systems. An inter-system agreement was assessed, and Kaplan-Meier analysis was performed to correlate the grading with clinical outcomes. RESULTS: A general agreement between all four grading systems was seen in 72.7% of cases. Brandwein grading assigned the highest percentage of high grades (18.2%), whereas Memorial Sloan-Kettering Cancer Center (MSKCC) assigned the highest percentage of low-grade MEC (72.7%). The agreement between MSKCC and modified Healy was highest at 90% of cases. There was generally a poor agreement between MSKCC and Brandwein grading systems. The MSKCC grading system showed a significant correlation with disease-free survival in MEC patients. CONCLUSION: Hence, the MSKCC grading system might serve as a better histologic grading system with a predictive value for the biologic behavior of the tumor. Further larger studies are required to validate these findings and implement the uniform use of MSKCC grading for MEC of salivary glands.

Visible-light induced effective and sustainable remediation of nitro organics pollutants using Pd-doped ZnO nanocatalyst.

Nitroaromatic compounds represent a class of highly toxic pollutants discharged into aquatic environments by various industrial activities, posing significant threats to ecological integrity and human health due to their persistent and hazardous nature. In this study, Pd-doped ZnO nanoparticles were investigated as a potential solution for the degradation of nitro organics, offering heightened photocatalytic efficacy and prolonged stability. The synthesis of Pd-doped ZnO NPs was achieved via the hydrothermal method, with subsequent analysis through XRD spectra and XPS confirming successful Pd doping within the ZnO matrix. Characterization through FESEM and HRTEM unveiled the heterogeneous morphologies of both undoped and Pd-doped ZnO nanoparticles. Additionally, UV-vis and PL spectroscopy provided insights into the optical properties, chemical bonding, and defect structures of the synthesized Pd-doped ZnO NPs. Pd doping induces a redshift in ZnO's absorption spectra, reducing the bandgap from 3.12 to 2.94 eV as Pd concentration rises from 0 to 0.2 wt.%. The photocatalytic degradation, following pseudo-first-order kinetics, achieved 90% nitrobenzene abatement (200 µg/L, pH 7) under visible light within 320 min with a catalyst loading of 16 µg/mL. The photocatalytic efficacy of 0.08 wt% Pd-doped ZnO (k = 0.058 min⁻1) exhibited a 25-fold enhancement compared to bare ZnO (k = 3.1 × 10-4 min-1). Subsequent quenching and ESR experiments identified hydroxyl radicals (OH•) as the predominant active species in the degradation mechanism. Mass spectrometry analysis unveiled potential breakdown intermediates, illuminating a plausible degradation pathway. The investigated Pd-doped ZnO nanoparticles demonstrated reusability for up to five successive treatment cycles, offering a sustainable solution to nitro organics contamination challenges.

Molecular surface-dependent light harvesting and photo charge separation in plant-derived carbon quantum dots for visible-light-driven OH radical generation for remediation of aromatic hydrocarbon pollutants and real wastewater.

Despite the growing emphasis on eco-friendly nanomaterials as energy harvesters, scientists are actively searching for metal-free photocatalysts to be used in environmental remediation strategies. Developing renewable resource-based carbon quantum dots (CQDs) as the sole photocatalyst to harvest visible light for efficient pollutant degradation is crucial yet challenging, particularly for addressing the escalating issue of water deterioration. Moreover, the photocatalytic decomposition of H2O2 under visible light irradiation remains an arduous task. Based on this, we designed two types of CQDs, C-CQDs (carboxylic-rich) and A-CQDs (amine-rich) with distinct molecular surfaces. Owing to the higher amount of upward band bending induced by amine-rich molecular surface, A-CQDs efficiently harvest the visible light and prevent recombination kinetics resulting in prolonged lifetimes (25 ps), and augmented charge carrier density (35.7 × 1018) of photoexcited charge carriers. A-CQDs enabled rapid visible-light-driven photolysis of H2O2 (k = 0.058 min-1) and produced higher quantity of •OH radicals (0.158 µmol/sec) for the mineralization of petroleum waste, BETX (i.e. Benzene, Ethylbenzene, Toluene and Xylene) (k = 0.017-0.026 min-1) and real textile wastewater (k = 0.026 min-1). To assess comparative toxicities of both remediated and non-remediated real wastewater samples in a time and dose depended manner, Drosophila melanogaster was used as a model organism. The findings unequivocally demonstrate the potential of remediated wastewater for watering urban forestry.

Study of growth differentiation factor-15 in polytransfused children with ß-thalassemia.

Background: Ineffective erythropoiesis is a predominant feature in ß-thalassemia major (ß-TM), causing marked erythroid expansion leading to highly raised levels of growth differentiation factor-15 (GDF-15), which, in turn, suppresses hepcidin production in liver resulting in increased iron absorption from gut. We aim to study the serum GDF-15 in polytransfused ß-TM patients and its correlation with serum ferritin and serum hepcidin. Method: Thirty-nine polytransfused ß-TM children aged between 5 and 17 years and 33 age- and gender-matched healthy controls were enrolled in the study. Complete blood count, serum GDF-15, serum ferritin, and serum hepcidin were performed. Results: The mean serum GDF-15, serum hepcidin, and serum ferritin levels were 638.65 ± 306.96 pg/ml, 108.21 ± 191.30 ng/ml, and 2274.60 ± 1216.08 ng/ml, respectively, which were significantly higher than control group (P < 0.001, P = 0.003, P < 0.001, respectively). There was significant positive correlation of GDF-15 with blood transfusions (r = 0.415, P = 0.009), positive correlation with serum ferritin (r = 0.653, P = 0), and significant negative correlation with serum hepcidin (r = -0.508, P = 0.001). Conclusion: The findings of the present study suggest that GDF-15 is an important regulator of hepcidin in ß-TM patients. GDF-15 and serum hepcidin together can be used to monitor iron overload and its related complications in such patients.

Surface functionalized silver-doped ZnO nanocatalyst: a sustainable cooperative catalytic, photocatalytic and antibacterial platform for waste treatment.

The different dyes used and discharged in industrial settings and microbial pathogenic issues have raised serious concerns about the content of bodies of water and the impact that dyes and microbes have on the environment and human health. Efficient treatment of contaminated water is thus a major challenge that is of great interest to researchers around the world. In the present work, we have fabricated functionalized silver-doped ZnO nanoparticles (Ag-doped ZnO NPs) via a hydrothermal method for wastewater treatment. X-ray photoelectron spectroscopy analysis confirmed the doping of Ag with ZnO NPs, and X-ray diffractometry analysis showed a decreasing trend in the crystallite size of the synthesized ZnO NPs with increased Ag concentration. Field emission scanning electron microscopy study of pure ZnO NPs and Ag-doped ZnO NPs revealed nanocrystal aggregates with mixed morphologies, such as hexagonal and rod-shaped structures. Distribution of Ag on the ZnO lattice is confirmed by high-resolution transmission electron microscopy analysis. ZnO NPs with 4 wt% Ag doping showed a maximum degradation of ∼95% in 1.5 h of malachite green dye (80 mg L-1) under visible light and ∼85% in 4 h under dark conditions. Up to five successive treatment cycles using the 4 wt% Ag-doped ZnO NP nanocatalyst confirmed its reusability, as it was still capable of degrading ∼86% and 82% of the dye under visible light and dark conditions, respectively. This limits the risk of nanotoxicity and aids the cost-effectiveness of the overall treatment process. The synthesized NPs showed antibacterial activity in a dose-dependent manner. The zone of inhibition of the Ag-doped ZnO NPs was higher than that of the pure ZnO NPs for all doping content. The studied Ag-doped ZnO NPs thus offer a significant eco-friendly route for the effective treatment of water contaminated with synthetic dyes and fecal bacterial load.

Expression of MUC1, MUC2 and MUC5AC in salivary gland mucoepidermoid carcinoma: A case series with diagnostic implications.

Context: Mucoepidermoid Carcinoma (MEC) accounts for 10-15% of all salivary gland neoplasms and its management is related to tumour grading. The expression of mucin in the tumour cells presumably affects and predicts tumour behaviour. Aims: To analyse the expression of MUC1 (membrane bound mucin), MUC2 and MUC5AC (secreted mucins) in mucoepidermoid carcinoma and correlate with tumour grade and patient outcome. Settings and Design: In this retrospective correlation study the expression of MUC1, MUC2 and MUC5AC were investigated using immunohistochemistry in confirmed cases of MEC. Methods and Material: The staining patterns of MUC1, MUC2 and MUC5AC were analysed in 10 confirmed cases from the year 2013 to 2020. Statistical Analysis Used: SPSS 23 was used for bivariate correlations. Results: All of the tumours expressed MUC1, showing strong membranous to focal cytoplasmic localization in all cells. The goblet cell component expressed a strong apical membranous pattern. MUC2 expression was moderate, showed cytoplasmic localisation in 40% of mucinous cells and was minimal in intermediate cells and epidermoid cells. MUC 5AC expression was strong apical membranous in goblet cells and mainly negative in intermediate cells and epidermoid cells. Conclusions: Although MUC1 is a reliable marker for all cell types of MEC but has no significant correlation with the tumour grade. MUC 2 has not been found to be a reliable diagnostic marker and has no significant correlation with the tumour grade. MUC 5AC has been found to have a significant expression in tumours with lymphoid infiltrate. There was no statistically significant correlation of MUC expression with the site, tumour grade and patient outcome.