Enhancing Vault Prediction and ICL Sizing Through Advanced Machine Learning Models.

PURPOSE: To use artificial intelligence (AI) technology to accurately predict vault and Implantable Collamer Lens (ICL) size. METHODS: The methodology focused on enhancing predictive capabilities through the fusion of machine-learning algorithms. Specifically, AdaBoost, Random Forest, Decision Tree, Support Vector Regression, LightGBM, and XGBoost were integrated into a majority-vote model. The performance of each model was evaluated using appropriate metrics such as accuracy, precision, F1-score, and area under the curve (AUC). RESULTS: The majority-vote model exhibited the highest performance among the classification models, with an accuracy of 81.9% area under the curve (AUC) of 0.807. Notably, LightGBM (accuracy = 0.788, AUC = 0.803) and XGBoost (ACC = 0.790, AUC = 0.801) demonstrated competitive results. For the ICL size prediction, the Random Forest model achieved an impressive accuracy of 85.3% (AUC = 0.973), whereas XG-Boost (accuracy = 0.834, AUC = 0.961) and LightGBM (accuracy = 0.816, AUC = 0.961) maintained their compatibility. CONCLUSIONS: This study highlights the potential of diverse machine learning algorithms to enhance postoperative vault and ICL size prediction, ultimately contributing to the safety of ICL implantation procedures. Furthermore, the introduction of the novel majority-vote model demonstrates its capability to combine the advantages of multiple models, yielding superior accuracy. Importantly, this study will empower ophthalmologists to use a precise tool for vault prediction, facilitating informed ICL size selection in clinical practice. [J Refract Surg. 2024;40(3):e126-e132.].

Gold Nanoparticles Enhancing Generation of ROS for Cs-137 Radiotherapy.

Radiotherapy is an important modality for the treatment of cancer, e.g., X-ray, Cs-137 γ-ray (peak energy: 662 keV). An important therapy pathway of radiation is to generate the double strand breaks of DNA to prohibit the proliferation of cancer cells. In addition, the excessive amount of reactive oxygen species (ROS) is induced to damage the organelles, which can cause cellular apoptosis or necrosis. Gold nanoparticles (GNPs) have been proven potential as a radiosensitizer due to the high biocompatibility, the low cytotoxicity and the high-Z property (Z = 79) of gold. The latter property may allow GNPs to induce more secondary electrons for generating ROS in cells as irradiated by high-energy photons. In this paper, the radiobiological effects on A431 cells with uptake of 55-nm GNPs were studied to investigate the GNPs-enhanced production of ROS on these cells as irradiated by Cs-137 γ-ray. The fluorescence-labeling image of laser scanning confocal microscopy (LSCM) shows the excessive expression of ROS in these GNPs-uptake cells after irradiation. And then, the follow-up disruption of cytoskeletons and dysfunction of mitochondria caused by the induced ROS are observed. From the curves of cell survival fraction versus the radiation dose, the radiosensitization enhancement factor of GNPs is 1.29 at a survival fraction of 30%. This demonstrates that the tumoricidal efficacy of Cs-137 radiation can be significantly raised by GNPs. Because of facilitating the production of excessive ROS to damage tumor cells, GNPs are proven to be a prospective radiosensitizer for radiotherapy, particularly for the treatment of certain radioresistant tumor cells. Through this pathway, the tumoricidal efficacy of radiotherapy can be raised.

Critical role of synovial tissue-resident macrophage niche in joint homeostasis and suppression of chronic inflammation.

Little is known about the mechanisms regulating the transition of circulating monocytes into pro- or anti-inflammatory macrophages in chronic inflammation. Here, we took advantage of our novel mouse model of rheumatoid arthritis, in which Flip is deleted under the control of a CD11c promoter (HUPO mice). During synovial tissue homeostasis, both monocyte-derived F4/80int and self-renewing F4/80hi tissue-resident, macrophage populations were identified. However, in HUPO mice, decreased synovial tissue-resident macrophages preceded chronic arthritis, opened a niche permitting the influx of activated monocytes, with impaired ability to differentiate into F4/80hi tissue-resident macrophages. In contrast, Flip-replete monocytes entered the vacated niche and differentiated into tissue-resident macrophages, which suppressed arthritis. Genes important in macrophage tissue residency were reduced in HUPO F4/80hi macrophages and in leukocyte-rich rheumatoid arthritis synovial tissue monocytes. Our observations demonstrate that the macrophage tissue-resident niche is necessary for suppression of chronic inflammation and may contribute to the pathogenesis of rheumatoid arthritis.

Transcriptional profiling of pediatric cholestatic livers identifies three distinct macrophage populations.

BACKGROUND & AIMS: Limited understanding of the role for specific macrophage subsets in the pathogenesis of cholestatic liver injury is a barrier to advancing medical therapy. Macrophages have previously been implicated in both the mal-adaptive and protective responses in obstructive cholestasis. Recently two macrophage subsets were identified in non-diseased human liver; however, no studies to date fully define the heterogeneous macrophage subsets during the pathogenesis of cholestasis. Here, we aim to further characterize the transcriptional profile of macrophages in pediatric cholestatic liver disease. METHODS: We isolated live hepatic immune cells from patients with biliary atresia (BA), Alagille syndrome (ALGS), and non-cholestatic pediatric liver by fluorescence activated cell sorting. Through single-cell RNA sequencing analysis and immunofluorescence, we characterized cholestatic macrophages. We next compared the transcriptional profile of pediatric cholestatic and non-cholestatic macrophage populations to previously published data on normal adult hepatic macrophages. RESULTS: We identified 3 distinct macrophage populations across cholestatic liver samples and annotated them as lipid-associated macrophages, monocyte-like macrophages, and adaptive macrophages based on their transcriptional profile. Immunofluorescence of liver tissue using markers for each subset confirmed their presence across BA (n = 6) and ALGS (n = 6) patients. Cholestatic macrophages demonstrated reduced expression of immune regulatory genes as compared to normal hepatic macrophages and were distinct from macrophage populations defined in either healthy adult or pediatric non-cholestatic liver. CONCLUSIONS: We are the first to perform single-cell RNA sequencing on human pediatric cholestatic liver and identified three macrophage subsets with distinct transcriptional signatures from healthy liver macrophages. Further analyses will identify similarities and differences in these macrophage sub-populations across etiologies of cholestatic liver disease. Taken together, these findings may allow for future development of targeted therapeutic strategies to reprogram macrophages to an immune regulatory phenotype and reduce cholestatic liver injury.

Simultaneous detection of multiple bacterial and viral aquatic pathogens using a fluorogenic loop-mediated isothermal amplification-based dual-sample microfluidic chip.

Rapid and user-friendly diagnostic tests are necessary for early diagnosis and immediate detection of diseases, particularly for on-site screening of pathogenic microorganisms in aquaculture. In this study, we developed a dual-sample microfluidic chip integrated with a real-time fluorogenic loop-mediated isothermal amplification assay (dual-sample on-chip LAMP) to simultaneously detect 10 pathogenic microorganisms, that is Aeromonas hydrophila, Edwardsiella tarda, Vibrio harveyi, V. alginolyticus, V. anguillarum, V. parahaemolyticus, V. vulnificus, infectious hypodermal and haematopoietic necrosis virus, infectious spleen and kidney necrosis virus, and white spot syndrome virus. This on-chip LAMP provided a nearly automated protocol that can analyse two samples simultaneously, and the tests achieved limits of detection (LOD) ranging from 100 to 10-1  pg/µl for genomic DNA of tested bacteria and 10-4 to 10-5  pg/µl for recombinant plasmid DNA of tested viruses, with run times averaging less than 30 min. The coefficient of variation for the time-to-positive value was less than 10%, reflecting a robust reproducibility. The clinical sensitivity and specificity were 93.52% and 85.53%, respectively, compared to conventional microbiological or clinical methods. The on-chip LAMP assay provides an effective dual-sample and multiple pathogen analysis, and thus would be applicable to on-site detection and routine monitoring of multiple pathogens in aquaculture.

miR-524-5p inhibits angiogenesis through targeting WNK1 in colon cancer cells.

There is increasing evidence that microRNA (miRNA) abnormity is involved in the occurrence and the development of various malignancies, including colon cancer. MiRNA-524-5p has been reported to possess anticancer activity in various tumors, which function is seldom investigated in colon cancer cells. The aim of this study was to explore the effect of the miRNA-524-5p/with-no-lysine kinase 1 (WNK1) system on angiogenesis in a colon cancer cell line (HT-29 and COLO205 cells) and further investigate the potential mechanisms. We found miRNA-524-5p expression was relatively high in COLO205 cells and relatively low in HT-29 cells. Elevating miRNA-524-5p expression inhibited proliferation, induced cycle arrest, diminished vascular endothelial growth factor production, and thereby suppressed angiogenesis in HT-29 cells. WNK1 silencing exerted the ability of antiangiogenesis in HT-29 cells. Besides, miRNA-524-5p deficiency-induced angiogenesis was impeded by WNK1 silence in COLO205 cells. In a murine tumor model, miRNA-524-5p agomir treatment significantly suppressed colon cancer tumorigenicity with the downregulation of WNK1 expression. In summary, our results indicated that miRNA-524-5p inhibited angiogenesis in colon cancer cells via targeting WNK1.NEW & NOTEWORTHY MiRNA-524-5p inhibited angiogenesis in colon cancer cells via targeting with-no-lysine kinase 1.

DNA methylation regulates the neonatal CD4+ T-cell response to pneumonia in mice.

Pediatric acute lung injury, usually because of pneumonia, has a mortality rate of more than 20% and an incidence that rivals that of all childhood cancers combined. CD4+ T-cells coordinate the immune response to pneumonia but fail to function robustly among the very young, who have poor outcomes from lung infection. We hypothesized that DNA methylation represses a mature CD4+ T-cell transcriptional program in neonates with pneumonia. Here, we found that neonatal mice (3-4 days old) aspirated with Escherichia coli bacteria had a higher mortality rate than juvenile mice (11-14 days old). Transcriptional profiling with an unsupervised RNA-Seq approach revealed that neonates displayed an attenuated lung CD4+ T-cell transcriptional response to pneumonia compared with juveniles. Unlike neonates, juveniles up-regulated a robust set of canonical T-cell immune response genes. DNA methylation profiling with modified reduced representation bisulfite sequencing revealed 44,119 differentially methylated CpGs, which preferentially clustered around transcriptional start sites and CpG islands. A methylation difference-filtering algorithm detected genes with a high likelihood of differential promoter methylation regulating their expression; these 731 loci encoded important immune response and tissue-protective T-cell pathway components. Disruption of DNA methylation with the hypomethylating agent decitabine induced plasticity in the lung CD4+ T-cell marker phenotype. Altogether, multidimensional profiling suggested that DNA methylation within the promoters of a core set of CD4+ T-cell pathway genes contributes to the hyporesponsive neonatal immune response to pneumonia. These findings also suggest that DNA methylation could serve as a mechanistic target for disease-modifying therapies in pediatric lung infection and injury.

Perineural invasion and expression of nerve growth factor can predict the progression and prognosis of oral tongue squamous cell carcinoma.

BACKGROUND: Perineural invasion (PNI) and nerve growth factor (NGF) expression are found to be significantly associated with the progression and/or prognosis of several human cancers. METHODS: Immunohistochemical staining for S-100 and NGF proteins was performed to assess the PNI and NGF expression level in 116 oral tongue squamous cell carcinoma (OTSCC) specimens, respectively. RESULTS: The PNI rate increased from 22% of the original pathological report, through 39% after reevaluation of hematoxylin and eosin-stained tissue sections, to 51% with the help of anti-S-100 immunostaining. The positive PNI was significantly associated with larger tumor size (P = 0.033), positive lymph node metastasis (P = 0.001), advanced clinical stage (P < 0.001), greater tumor thickness (P < 0.001), close or positive section margin (P = 0.013), and higher grade of cancer invasion front pattern (P < 0.001). Moreover, the high NGF expression level was significantly correlated with larger tumor size (P = 0.009), positive lymph node metastasis (P = 0.004), advanced clinical stage (P < 0.001), greater tumor thickness (P = 0.005), close or positive section margin (P = 0.030), and the positive PNI (P = 0.009). In addition, OTSCC patients with positive PNI or high NGF expression level had significantly worse overall survival than those with negative PNI or low NGF expression level, respectively. CONCLUSIONS: Anti-S-100 immunostaining is an effective technique to detect occult PNI. Both the positive PNI and NGF expression level are valuable biomarkers that can predict the progression of OTSCC and prognosis of OTSCC patients.

Increased expression of MCM5 is significantly associated with aggressive progression and poor prognosis of oral squamous cell carcinoma.

BACKGROUND: Overexpression of MCM5 protein has been found to be significantly associated with the progression and prognosis of several human cancers. METHODS: This study used immunohistochemistry to examine the expression of MCM5 protein in 97 specimens of oral squamous cell carcinomas (OSCC), 80 specimens of oral epithelial dysplasia (OED, including 31 mild, 29 moderate, and 20 severe OED samples), and 20 specimens of normal oral mucosa (NOM). RESULTS: We found that the mean nuclear MCM5 labeling indices (LIs) increased significantly from NOM (15 ± 6%), through mild (25 ± 10%), moderate (34 ± 9%), and severe OED (43 ± 12%), to OSCC samples (61 ± 16%, P < 0.001). A significant correlation was found between the higher mean nuclear MCM5 LI and OSCCs with site at the tongue (P = 0.046), larger tumor size (P = 0.032), positive lymph node metastasis (P = 0.003), more advanced clinical stage (P = 0.002), higher histological grade (P = 0.002), deeper invasion depth (P = 0.0001), and perineural invasion (P = 0.0047). Only nuclear MCM5 LI â‰§ 60% was identified as independent unfavorable prognostic factor by multivariate regression analyses (P = 0.049). The Kaplan-Meier curve showed that patients with OSCC with a nuclear MCM5 LI â‰§ 60% had a significantly poorer cumulative survival than those with a nuclear MCM5 LI < 60% (log-rank test, P = 0.0062). CONCLUSIONS: The increased expression of MCM5 protein begins at the oral pre-cancerous stage. The higher expression of MCM5 protein is significantly associated with the aggressive progression and poor prognosis of OSCC.

Impaired expression and function of breast cancer resistance protein (Bcrp) in brain cortex of streptozocin-induced diabetic rats.

The aim of this study was to investigate whether diabetes mellitus (DM) affected breast cancer resistance protein (Bcrp) function and expression in rat brain. 5-week and 8-week diabetic rats were induced by streptozocin (STZ). Bcrp expression and function in brain cortex were assessed by western blot and measuring the brain-to-plasma concentration ratios of two typical substrates prazosin and cimetidine, respectively. The diabetic rats were treated with three different agents insulin, aminoguanidine (AG) and metformin (MET). It was found that the brain-to-plasma ratios of prazosin and cimetidine in diabetic rats were significantly higher than those of control rats, which were dependent on duration of diabetes. Lower levels of Bcrp were found in brain cortex of diabetic rats, which were in parallel with increase of brain-to-plasma ratios. Insulin treatment may attenuate the impairment of Bcrp expression and function induced by diabetes. Aminoguanidine and metformin treatment did not prevent the impairment of Bcrp function and expression in brain cortex of diabetic rats. All results gave a conclusion that STZ-induced DM may induce the impairment of function and expression of Bcrp in brain cortex, and lower levels of insulin may mainly contribute to Bcrp dysfunction in brain.

[Significance of clue cells in the diagnosis of male urogenital infection].

OBJECTIVE: To explore the significance of clue cells in the diagnosis of male urogenital infection. METHODS: Urethra swabs or prostatic fluid of 264 male outpatients were collected and smeared directly on the slice to find clue cells under the ultramicroscopy. Meanwhile, the positive patients' spouses were detected for bacterial vaginosis (BV). RESULTS: The positive rates of the urethra swabs and the prostatic fluid were 5.1% (11/215 ) and 2.0% (1/49), respectively. Nine cases in 11 of the patients' spouses (81.8%) were diagnosed as BV. CONCLUSION: BV pathogen can attack and attach to the epithelia of male genitals to form clue cells. Clue cells positive, along with clinical symptoms, contribute to the diagnosis of male urogenital bacterial infection.