Forecasting the incidence frequencies of schizophrenia using deep learning.

Mental disorders are becoming increasingly prevalent worldwide, and accurate incidence forecasting is crucial for effective mental health strategies. This study developed a long short-term memory (LSTM)-based recurrent neural network model to predict schizophrenia in inpatients in Taiwan. Data was collected on individuals aged over 20 years and diagnosed with schizophrenia between 1998 and 2015 from the National Health Insurance Research Database (NHIRD). The study compared six models, including LSTM, exponential smoothing, autoregressive integrated moving average, particle swarm optimization (PSO), PSO-based support vector regression, and deep neural network models, in terms of their predictive performance. The results showed that the LSTM model had the best accuracy, with the lowest mean absolute percentage error (2.34), root mean square error (157.42), and mean average error (154,831.70). This finding highlights the reliability of the LSTM model for forecasting mental disorder incidence. The study's findings provide valuable insights that can help government administrators devise clinical strategies for schizophrenia, and policymakers can use these predictions to formulate healthcare education and financial planning initiatives, fostering support networks for patients, caregivers, and the public.

Use of machine learning algorithms to determine the relationship between air pollution and cognitive impairment in Taiwan.

Air pollution has become a major global threat to human health. Urbanization and industrialization over the past few decades have increased the air pollution. Plausible connections have been made between air pollutants and dementia. This study used machine learning algorithms (k-nearest neighbors, random forest, gradient-boosted decision trees, eXtreme gradient boosting, and CatBoost) to investigate the association between cognitive impairment and air pollution. Data from the Taiwan Biobank and 75 air-pollution-monitoring stations in Taiwan were analyzed to determine individual levels of exposure to air pollutants. The pollutants examined were particulate matter with a diameter of ≤ 2.5 µm (PM2.5), nitrogen dioxide, nitric oxide, carbon monoxide, and ozone. The results revealed that the most strongly correlated with cognitive impairment were ozone, PM2.5, and carbon monoxide levels with adjustment of educational level, age, and household income. The model based on these factors achieved accuracy as high as 0.97 for detecting cognitive impairment, indicating a positive association between air pollutions and cognitive impairment.

Mediation analysis for TNF-α as a mediator between multiple metal exposure and kidney function.

The association between metal mixtures and kidney function has been reported. However, reports on the mechanism of metal toxicity were limited. Oxidative stress was reported as a possible cause. This study aimed to determine the association between of kidney function and metals, such as arsenic (As), cadmium (Cd), cobalt (Co), copper (Cu), lead (Pb), selenium (Se), and zinc (Zn), and to explore the possible mediating role of tumor necrosis factor alpha (TNF-α) between metal toxicity and kidney function. In this study, we recruited 421 adults from a health examination. The concentration of blood metals was analyzed using inductively coupled plasma mass spectrometry. We used linear regression models to assess the association between metals and TNF-α. Then, mediation analysis was applied to investigate the relationship between metal exposure, TNF-α, and kidney function. In univariate linear regression, blood As, Cd, Co, Cu, Pb, and Zn levels significantly increased TNF-α and decreased kidney function. Higher blood As and Pb levels significantly increased TNF-α in multivariable linear regressions after adjusting for covariates. We found that blood levels of As (coefficients = -0.021, p = 0.011), Pb (coefficients = -0.060, p < 0.001), and Zn (coefficients = -0.230, p < 0.001) showed a significant negative association with eGFR in the multiple-metal model. Furthermore, mediation analysis showed that TNF-α mediated 41.7 %, 38.8 %, and 20.8 % of blood Cd, As and Pb, respectively. Among the essential elements, TNF-α mediated 24.5 %, 21.5 % and 19.9 % in the effects of blood Co, Cu, and Zn on kidney function, respectively. TNF-α, acting as a mediator, accounted for 20.1 % of the contribution between the WQS score of metal mixtures and the eGFR (p < 0.001). This study suggested that TNF-α may be a persuasive pathway mediating the association between metals and kidney function. Inflammation and kidney injury could be the underlying mechanisms of metal exposure. However, there is still a need to clarify the biochemical mechanism in follow-up studies.

Physical frailty identification using machine learning to explore the 5-item FRAIL scale, Cardiovascular Health Study index, and Study of Osteoporotic Fractures index.

Background: Physical frailty is an important issue in aging societies. Three models of physical frailty assessment, the 5-Item fatigue, resistance, ambulation, illness and loss of weight (FRAIL); Cardiovascular Health Study (CHS); and Study of Osteoporotic Fractures (SOF) indices, have been regularly used in clinical and research studies. However, no previous studies have investigated the predictive ability of machine learning (ML) for physical frailty assessment. The aim was to use two ML algorithms, random forest (RF) and extreme gradient boosting (XGBoost), to predict these three physical frailty assessment models. Materials and methods: Questionnaires regarding demographic characteristics, lifestyle habits, living environment, and physical frailty assessment were answered by 445 participants aged 60 years and above. The RF and XGBoost algorithms were used to assess their scores for the three physical frailty indices. Furthermore, feature importance and Shapley additive explanations (SHAP) were used to determine the important physical frailty factors. Results: The XGBoost algorithm obtained higher accuracy for predicting the three physical frailty indices; the areas under the curve obtained by the XGBoost algorithm for the 5-Item FRAIL, CHS, and SOF indices were 0.84. 0.79, and 0.69, respectively. The feature importance and SHAP of the XGBoost algorithm revealed that systolic blood pressure, diastolic blood pressure, age, and body mass index play important roles in all three physical frailty models. Conclusion: The XGBoost algorithm has a more accurate predictive rate than RF across all three physical frailty assessments. Thus, ML can be a useful tool for the early detection of physical frailty.

An Information Fusion System-Driven Deep Neural Networks With Application to Cancer Mortality Risk Estimate.

Next-generation sequencing (NGS) genomic data offer valuable high-throughput genomic information for computational applications in medicine. Using genomic data to identify disease-associated genes to estimate cancer mortality risk remains challenging regarding to computational efficiency and risk integration. For determining mortality-related genes, we propose an information fusion system based on a fuzzy system to fuse the numerous deep-learning-based risk scores, consider the significance of features related to time-varying effects and risk stratifications, and interpret the directional relationship and interaction between outcome and predictors. Fuzzy rules were implemented to integrate the considerations mentioned above by merging all the risk score models to achieve advanced risk estimation. The genomic data of head and neck squamous cell carcinoma (HNSCC) were used to evaluate the performance of the proposed computational approach. The results indicated that the proposed computational approach exhibited optimal ability to identify mortality risk-related genes in HNSCC patients. The results also suggest that HNSCC mortality is associated with cancer inflammatory response, the interleukin-17A signaling pathway, stellate cell activation, and the extracellular-regulated protein kinase five signaling pathway, which might offer new therapeutic targets HNSCC through immunologic or antiangiogenic mechanisms. The proposed information fusion system can promote the determination of high-risk genes related to cancer mortality. This study contributes a valid cancer mortality risk estimate that can identify mortality-related genes.

Exploring the association of metal mixture in blood to the kidney function and tumor necrosis factor alpha using machine learning methods.

This research aimed to approach relationships between metal mixture in blood and kidney function, tumor necrosis factor alpha (TNF-α) by machine learning. Metals levels were measured by Inductively Couple Plasma Mass Spectrometry in blood from 421 participants. We applied K Nearest Neighbor (KNN), Naive Bayes classifier (NB), Support Vector Machines (SVM), random forest (RF), Gradient Boosting Decision Tree (GBDT), Categorical boosting (CatBoost), eXtreme Gradient Boosting (XGBoost), Whale Optimization-based XGBoost (WXGBoost) to identify the effect of plasma metals, TNF-α, and estimated glomerular filtration rate (eGFR by CKD-EPI equation). We conducted not only toxic metals, lead (Pb), arsenic (As), cadmium (Cd) but also included trace essential metals, selenium (Se), copper (Cu), zinc (Zn), cobalt (Co), to predict the interaction of TNF-α, TNF-α/white blood count, and eGFR. The high average TNF-α level group was observed among subjects with higher Pb, As, Cd, Cu, and Zn levels in blood. No associations were shown between the low and high TNF-α level group in blood Se and Co levels. Those with lower eGFR group had high Pb, As, Cd, Co, Cu, and Zn levels. The crucial predictor of TNF-α level in metals was blood Pb, and then Cd, As, Cu, Se, Zn and Co. The machine learning revealed that As was the major role among predictors of eGFR after feature selection. The levels of kidney function and TNF-α were modified by co-exposure metals. We were able to acquire highest accuracy of over 85% in the multi-metals exposure model. The higher Pb and Zn levels had strongest interaction with declined eGFR. In addition, As and Cd had synergistic with prediction model of TNF-α. We explored the potential of machine learning approaches for predicting health outcomes with multi-metal exposure. XGBoost model added SHAP could give an explicit explanation of individualized and precision risk prediction and insight of the interaction of key features in the multi-metal exposure.

Prevalence of Carbapenem Resistance Genes among Acinetobacter baumannii Isolated from a Teaching Hospital in Taiwan.

The problem of antibiotic-resistant strains has become a global public issue; antibiotic resistance not only limits the choice of treatments but also increases morbidity, mortality and treatment costs. The multi-drug resistant Acinetobacter baumannii is occurring simultaneously in hospitals and has become a major public health issue worldwide. Although many medical units have begun to control the use of antibiotics and paid attention to the issue of drug resistance, understanding the transmission pathways of clinical drug-resistant bacteria and drug-resistant mechanisms can be effective in real-time control and prevent the outbreak of antibiotic-resistant pathogens. In this study, a total of 154 isolates of Acinetobacter baumannii obtained from Chia-Yi Christian Hospital in Taiwan were collected for specific resistance genotyping analysis. Ten genes related to drug resistance, including blaOXA-51-like, blaOXA-23-like, blaOXA-58-like, blaOXA-24-like, blaOXA-143-like, tnpA, ISAba1, blaPER-1, blaNDM and blaADC, and the repetitive element (ERIC2) were selected for genotyping analysis. The results revealed that 135 A. baumannii isolates (87.6%) carried the blaOXA-51-like gene, 4.5% of the isolates harbored the blaOXA-23-like gene, and 3.2% of the isolates carried the blaOXA-58-like gene. However, neither the blaOXA-24-like nor blaOXA-143-like genes were detected in the isolates. Analysis of ESBL-producing strains revealed that blaNDM was not found in the test strains, but 38.3% of the test isolates carried blaPER-1. In addition, blaADC, tnpA and ISAba1genes were found in 64.9%, 74% and 93% of the isolates, respectively. Among the carbapenem-resistant strains of A. baumannii, 68% of the isolates presenting a higher antibiotic resistance carried both tnpA and ISAba1 genes. Analysis of the relationship between their phenotypes (antibiotic resistant and biofilm formation) and genotypes (antibiotic-resistant genes and biofilm-related genes) studied indicated that the bap, ompA, ISAba1and blaOXA-51 genes influenced biofilm formation and antibiotic resistance patterns based on the statistical results of a hierarchical clustering dendrogram. The analysis of the antibiotic-resistant mechanism provides valuable information for the screening, identification, diagnosis, treatment and control of clinical antibiotic-resistant pathogens, and is an important reference pointer to prevent strains from producing resistance.

Application of deep learning to predict the low serum albumin in new hemodialysis patients.

BACKGROUND: Serum albumin level is a crucial nutritional indicator for patients on dialysis. Approximately one-third of patients on hemodialysis (HD) have protein malnutrition. Therefore, the serum albumin level of patients on HD is strongly correlated with mortality. METHODS: In study, the data sets were obtained from the longitudinal electronic health records of the largest HD center in Taiwan from July 2011 to December 2015, included 1,567 new patients on HD who met the inclusion criteria. Multivariate logistic regression was performed to evaluate the association of clinical factors with low serum albumin, and the grasshopper optimization algorithm (GOA) was used for feature selection. The quantile g-computation method was used to calculate the weight ratio of each factor. Machine learning and deep learning (DL) methods were used to predict the low serum albumin. The area under the curve (AUC) and accuracy were calculated to determine the model performance. RESULTS: Age, gender, hypertension, hemoglobin, iron, ferritin, sodium, potassium, calcium, creatinine, alkaline phosphatase, and triglyceride levels were significantly associated with low serum albumin. The AUC and accuracy of the GOA quantile g-computation weight model combined with the Bi-LSTM method were 98% and 95%, respectively. CONCLUSION: The GOA method was able to rapidly identify the optimal combination of factors associated with serum albumin in patients on HD, and the quantile g-computation with DL methods could determine the most effective GOA quantile g-computation weight prediction model. The serum albumin status of patients on HD can be predicted by the proposed model and accordingly provide patients with better a prognostic care and treatment.

Overall mortality risk analysis for rectal cancer using deep learning-based fuzzy systems.

Colorectal cancer is a leading cause of cancer mortality worldwide, with an increasing incidence rate in developing countries. Integration of genetic information with cancer therapy guidance has shown promise in cancer treatment, indicating its potential as an essential tool in translation oncology. However, the high-throughput analysis and variability of genomic data poses a major challenge to conventional analytic approaches. In this study, we propose an advanced analytic approach, named "Fuzzy-based RNNCoxPH," incorporated fuzzy logic, recurrent neural networks (RNNs), and Cox proportional hazards regression (CoxPH) for detecting missense variants associated with high-risk of all-cause mortality in rectum adenocarcinoma. The test data set was downloaded from "Rectum adenocarcinoma, TCGA-READ" the Genomic Data Commons (GDC) portal. In this study, four model-based risk score models were derived using RNN, CoxPH, RNNCoxPHAddition, and RNNCoxPHMultiplication. The RNNCoxPHAddition and RNNCoxPHMultiplication models were obtained as the sum and product of the RNN risk degree matrix and the CoxPH risk degree matrix, respectively. Moreover, the fuzzy logic system was used to calculate the survival risk values of missense variants and classified their membership grade to improve the identification of high-risk gene variation locations associated with cancer mortality. The four models were integrated to develop an advanced risk estimation model. There were 20 028 variants associated with survival status, amongst 17 638 variants were associated with survival and 2390 variants associated with mortality. The proposed Fuzzy-based RNNCoxPH model obtained a balanced accuracy of 93.7%, which was significantly higher than that of the other four test methods. In particular, the CoxPH model is commonly used in medical researches and the XGBoost model is famous for its high accuracy in machine learning. The results suggest that the Fuzzy-based RNNCoxPH model exhibits a higher efficacy in identifying and classifying the missense variants related to mortality risk in rectum adenocarcinoma.

Dimensionality reduction approach for many-objective epistasis analysis.

In epistasis analysis, single-nucleotide polymorphism-single-nucleotide polymorphism interactions (SSIs) among genes may, alongside other environmental factors, influence the risk of multifactorial diseases. To identify SSI between cases and controls (i.e. binary traits), the score for model quality is affected by different objective functions (i.e. measurements) because of potential disease model preferences and disease complexities. Our previous study proposed a multiobjective approach-based multifactor dimensionality reduction (MOMDR), with the results indicating that two objective functions could enhance SSI identification with weak marginal effects. However, SSI identification using MOMDR remains a challenge because the optimal measure combination of objective functions has yet to be investigated. This study extended MOMDR to the many-objective version (i.e. many-objective MDR, MaODR) by integrating various disease probability measures based on a two-way contingency table to improve the identification of SSI between cases and controls. We introduced an objective function selection approach to determine the optimal measure combination in MaODR among 10 well-known measures. In total, 6 disease models with and 40 disease models without marginal effects were used to evaluate the general algorithms, namely those based on multifactor dimensionality reduction, MOMDR and MaODR. Our results revealed that the MaODR-based three objective function model, correct classification rate, likelihood ratio and normalized mutual information (MaODR-CLN) exhibited the higher 6.47% detection success rates (Accuracy) than MOMDR and higher 17.23% detection success rates than MDR through the application of an objective function selection approach. In a Wellcome Trust Case Control Consortium, MaODR-CLN successfully identified the significant SSIs (P < 0.001) associated with coronary artery disease. We performed a systematic analysis to identify the optimal measure combination in MaODR among 10 objective functions. Our combination detected SSIs-based binary traits with weak marginal effects and thus reduced spurious variables in the score model. MOAI is freely available at https://sites.google.com/view/maodr/home.

Fuzzy-Based Multiobjective Multifactor Dimensionality Reduction for Epistasis Analysis.

Epistasis detection is vital for understanding disease susceptibility in genetics. Multiobjective multifactor dimensionality reduction (MOMDR) was previously proposed to detect epistasis. MOMDR was performed using binary classification to distinguish the high-risk (H) and low-risk (L) groups to reduce multifactor dimensionality. However, the binary classification does not reflect the uncertainty of the H and L classification. In this study, we proposed an empirical fuzzy MOMDR (EFMOMDR) to address the limitations of binary classification using the degree of membership through an empirical fuzzy approach. The EFMOMDR can simultaneously consider two incorporated fuzzy-based measures, including correct classification rate and likelihood rate, and does not require parameter tuning. Simulation studies revealed that EFMOMDR has higher 7.14% detection success rates than MOMDR, indicating that the limitations of binary classification of MOMDR have been successfully improved by empirical fuzzy. Moreover, EFMOMDR was used to analyze coronary artery disease in the Wellcome Trust Case Control Consortium dataset.

Machine learning approaches for the mortality risk assessment of patients undergoing hemodialysis.

Introduction: Mortality is a major primary endpoint for long-term hemodialysis (HD) patients. The clinical status of HD patients generally relies on longitudinal clinical observations such as monthly laboratory examinations and physical examinations. Methods: A total of 829 HD patients who met the inclusion criteria were analyzed. All patients were tracked from January 2009 to December 2013. Taken together, this study performed full-adjusted-Cox proportional hazards (CoxPH), stepwise-CoxPH, random survival forest (RSF)-CoxPH, and whale optimization algorithm (WOA)-CoxPH model for the all-cause mortality risk assessment in HD patients. The model performance between proposed selections of CoxPH models were evaluated using concordance index. Results: The WOA-CoxPH model obtained the highest concordance index compared with RSF-CoxPH and typical selection CoxPH model. The eight significant parameters obtained from the WOA-CoxPH model, including age, diabetes mellitus (DM), hemoglobin (Hb), albumin, creatinine (Cr), potassium (K), Kt/V, and cardiothoracic ratio, have also showed significant survival difference between low- and high-risk characteristics in single-factor analysis. By integrating the risk characteristics of each single factor, patients who obtained seven or more risk characteristics of eight selected parameters were dichotomized as high-risk subgroup, and remaining is considered as low-risk subgroup. The integrated low- and high-risk subgroup showed greater discrepancy compared with each single risk factor selected by WOA-CoxPH model. Conclusion: The study findings revealed WOA-CoxPH model could provide better risk assessment performance compared with RSF-CoxPH and typical selection CoxPH model in the HD patients. In summary, patients who had seven or more risk characteristics of eight selected parameters were at potentially increased risk of all-cause mortality in HD population.

Use of Generalized Weighted Quantile Sum Regressions of Tumor Necrosis Factor Alpha and Kidney Function to Explore Joint Effects of Multiple Metals in Blood.

Exposure to heavy metals could lead to adverse health effects by oxidative reactions or inflammation. Some essential elements are known as reactors of anti-inflammatory enzymes or coenzymes. The relationship between tumor necrosis factor alpha (TNF-α) and heavy metal exposures was reported. However, the interaction between toxic metals and essential elements in the inflammatory response remains unclear. This study aimed to explore the association between arsenic (As), cadmium (Cd), lead (Pb), cobalt (Co), copper (Cu), selenium (Se), and zinc (Zn) in blood and TNF-α as well as kidney function. We enrolled 421 workers and measured the levels of these seven metals/metalloids and TNF-α in blood; kidney function was calculated by CKD-EPI equation. We applied weighted quantile sum (WQS) regression and group WQS regression to assess the effects of metal/metalloid mixtures to TNF-α and kidney function. We also approached the relationship between metals/metalloids and TNF-α by generalized additive models (GAM). The relationship of the exposure−response curve between Pb level and TNF-α in serum was found significantly non-linear after adjusting covariates (p < 0.001). Within the multiple-metal model, Pb, As, and Zn were associated with increased TNF-α levels with effects dedicated to the mixture of 50%, 31%, and 15%, respectively. Grouped WQS revealed that the essential metal group showed a significantly negative association with TNF-α and kidney function. The toxic metal group found significantly positive associations with TNF-α, serum creatinine, and WBC but not for eGFR. These results suggested Pb, As, Zn, Se, and mixtures may act on TNF-α even through interactive mechanisms. Our findings offer insights into what primary components of metal mixtures affect inflammation and kidney function during co-exposure to metals; however, the mechanisms still need further research.

Multiobjective optimization-driven primer design mechanism: towards user-specified parameters of PCR primer.

Primers are critical for polymerase chain reaction (PCR) and influence PCR experimental outcomes. Designing numerous combinations of forward and reverse primers involves various primer constraints, posing a computational challenge. Most PCR primer design methods limit parameters because the available algorithms use general fitness functions. This study designed new fitness functions based on user-specified parameters and used the functions in a primer design approach based on the multiobjective particle swarm optimization (MOPSO) algorithm to address the challenge of primer design with user-specified parameters. Multicriteria evaluation was conducted simultaneously based on primer constraints. The fitness functions were evaluated using 7425 DNA sequences and compared with a predominant primer design approach based on optimization algorithms. Each DNA sequence was run 100 times to calculate the difference between the user-specified parameters and primer constraint values. The algorithms based on fitness functions with user-specified parameters outperformed the algorithms based on general fitness functions for 11 primer constraints. Moreover, MOPSO exhibited superior implementation in all experiments. Practical gel electrophoresis was conducted to verify the PCR experiments and established that MOPSO effectively designs primers based on user-specified parameters.

DeepBarcoding: Deep Learning for Species Classification Using DNA Barcoding.

DNA barcodes with short sequence fragments are used for species identification. Because of advances in sequencing technologies, DNA barcodes have gradually been emphasized. DNA sequences from different organisms are easily and rapidly acquired. Therefore, DNA sequence analysis tools play an increasingly crucial role in species identification. This study proposed deep barcoding, a deep learning framework for species classification by using DNA barcodes. Deep barcoding uses raw sequence data as the input to represent one-hot encoding as a one-dimensional image and uses a deep convolutional neural network with a fully connected deep neural network for sequence analysis. It can achieve an average accuracy of >90 percent for both simulation and real datasets. Although deep learning yields outstanding performance for species classification with DNA sequences, its application remains a challenge. The deep barcoding model can be a potential tool for species classification and can elucidate DNA barcode-based species identification.

Deep Hybrid Convolutional Neural Network for Segmentation of Melanoma Skin Lesion.

Melanoma is a type of skin cancer that often leads to poor prognostic responses and survival rates. Melanoma usually develops in the limbs, including in fingers, palms, and the margins of the nails. When melanoma is detected early, surgical treatment may achieve a higher cure rate. The early diagnosis of melanoma depends on the manual segmentation of suspected lesions. However, manual segmentation can lead to problems, including misclassification and low efficiency. Therefore, it is essential to devise a method for automatic image segmentation that overcomes the aforementioned issues. In this study, an improved algorithm is proposed, termed EfficientUNet++, which is developed from the U-Net model. In EfficientUNet++, the pretrained EfficientNet model is added to the UNet++ model to accelerate segmentation process, leading to more reliable and precise results in skin cancer image segmentation. Two skin lesion datasets were used to compare the performance of the proposed EfficientUNet++ algorithm with other common models. In the PH2 dataset, EfficientUNet++ achieved a better Dice coefficient (93% vs. 76%-91%), Intersection over Union (IoU, 96% vs. 74%-95%), and loss value (30% vs. 44%-32%) compared with other models. In the International Skin Imaging Collaboration dataset, EfficientUNet++ obtained a similar Dice coefficient (96% vs. 94%-96%) but a better IoU (94% vs. 89%-93%) and loss value (11% vs. 13%-11%) than other models. In conclusion, the EfficientUNet++ model efficiently detects skin lesions by improving composite coefficients and structurally expanding the size of the convolution network. Moreover, the use of residual units deepens the network to further improve performance.

Progression Risk Score Estimation Based on Immunostaining Data in Oral Cancer Using Unsupervised Hierarchical Clustering Analysis: A Retrospective Study in Taiwan.

This study aimed to investigate whether the progression risk score (PRS) developed from cytoplasmic immunohistochemistry (IHC) biomarkers is available and applicable for assessing risk and prognosis in oral cancer patients. Participants in this retrospective case-control study were diagnosed between 2012 and 2014 and subsequently underwent surgical intervention. The specimens from surgery were stained by IHC for 16 cytoplasmic target markers. We evaluated the results of IHC staining, clinical and pathological features, progression-free survival (PFS), and overall survival (OS) of 102 oral cancer patients using a novel estimation approach with unsupervised hierarchical clustering analysis. Patients were stratified into high-risk (52) and low-risk (50) groups, according to their PRS; a metric consisting of cytoplasmic PLK1, PhosphoMet, SGK2, and SHC1 expression. Moreover, PRS could be extended for use in the Cox proportional hazard regression model to estimate survival outcomes with associated clinical parameters. Our study findings revealed that the high-risk patients had a significantly increased risk in cancer progression compared with low-risk patients (hazard ratio (HR) = 2.20, 95% confidence interval (CI) = 1.10-2.42, p = 0.026). After considering the influences of demographics, risk behaviors, and tumor characteristics, risk estimation with PRS provided distinct PFS groups for patients with oral cancer (p = 0.017, p = 0.019, and p = 0.020). Our findings support that PRS could serve as an ideal biomarker for clinical use in risk stratification and progression assessment in oral cancer.

Application of the Interaction between Tissue Immunohistochemistry Staining and Clinicopathological Factors for Evaluating the Risk of Oral Cancer Progression by Hierarchical Clustering Analysis: A Case-Control Study in a Taiwanese Population.

The aim of this single-center case-control study is to investigate the feasibility and accuracy of oral cancer protein risk stratification (OCPRS) to analyze the risk of cancer progression. All patients diagnosed with oral cancer in Taiwan, between 2012 and 2014, and who underwent surgical intervention were selected for the study. The tissue was further processed for immunohistochemistry (IHC) for 21 target proteins. Analyses were performed using the results of IHC staining, clinicopathological characteristics, and survival outcomes. Novel stratifications with a hierarchical clustering approach and combinations were applied using the Cox proportional hazard regression model. Of the 163 participants recruited, 102 patients were analyzed, and OCPRS successfully identified patients with different progression-free survival (PFS) profiles in high-risk (53 subjects) versus low-risk (49 subjects) groups (p = 0.012). OCPRS was composed of cytoplasmic PLK1, phosphoMet, and SGK2 IHC staining. After controlling for the influence of clinicopathological features, high-risk patients were 2.33 times more likely to experience cancer progression than low-risk patients (p = 0.020). In the multivariate model, patients with extranodal extension (HR = 2.66, p = 0.045) demonstrated a significantly increased risk for disease progression. Risk stratification with OCPRS provided distinct PFS groups for patients with oral cancer after surgical intervention. OCPRS appears suitable for routine clinical use for progression and prognosis estimation.

Associations between Circulating Markers of Cholesterol Homeostasis and Macrovascular Events among Patients Undergoing Hemodialysis.

Current strategies targeting serum cholesterol bring limited benefits to mortality and macrovascular events prevention among hemodialysis patients. Direct measurements and analysis on circulating markers of cholesterol homeostasis could be promising solutions to this bottleneck. We prospectively enrolled 90 maintenance hemodialysis patients and 9 healthy controls in 2019 for 1 year. We measured circulating desmosterol and lathosterol as markers for cholesterol synthesis and campesterol and sitosterol for cholesterol absorption. At baseline, hemodialysis patients showed higher levels of campesterol (p = 0.023) compared to healthy controls. During follow-up, we identified 14 (15.4%) patients who experienced macrovascular events. Comparisons of cholesterol homeostasis markers between cohorts with and without macrovascular events showed no significant differences in markers of cholesterol synthesis or absorption. Using logistic regression analysis, the odds ratio was not statistically significant for the prediction of macrovascular events after full-adjusting for age, sex, diabetes, serum albumin, cholesterol, and triglyceride. We concluded that hemodialysis patients demonstrated higher level of cholesterols absorption, indicated by circulating campesterol compared to healthy subjects. Markers for cholesterol homeostasis were not significantly associated with macrovascular events during a 1-year follow-up. Our results shed light on the novel therapeutic target of modulating cholesterol absorption in HD patients.

Identification of mortality-risk-related missense variant for renal clear cell carcinoma using deep learning.

INTRODUCTION: Kidney renal clear cell carcinoma (KIRCC) is a highly heterogeneous and lethal cancer that can arise in patients with renal disease. DeepSurv combines a deep feed-forward neural network with a Cox proportional hazards function and could provide optimized survival results compared with convenient survival analysis. METHODS: This study used an improved DeepSurv algorithm to identify the candidate genes to be targeted for treatment on the basis of the overall mortality status of KIRCC subjects. All the somatic mutation missense variants of KIRCC subjects were abstracted from TCGA-KIRC database. RESULTS: The improved DeepSurv model (95.1%) achieved greater balanced accuracy compared with the DeepSurv model (75%), and identified 610 high-risk variants associated with overall mortality. The results of gene differential expression analysis also indicated nine KIRCC mortality-risk-related pathways, namely the tRNA charging pathway, the D-myo-inositol-5-phosphate metabolism pathway, the DNA double-strand break repair by nonhomologous end-joining pathway, the superpathway of inositol phosphate compounds, the 3-phosphoinositide degradation pathway, the production of nitric oxide and reactive oxygen species in macrophages pathway, the synaptic long-term depression pathway, the sperm motility pathway, and the role of JAK2 in hormone-like cytokine signaling pathway. The biological findings in this study indicate the KIRCC mortality-risk-related pathways were more likely to be associated with cancer cell growth, cancer cell differentiation, and immune response inhibition. CONCLUSION: The results proved that the improved DeepSurv model effectively classified mortality-related high-risk variants and identified the candidate genes. In the context of KIRCC overall mortality, the proposed model effectively recognized mortality-related high-risk variants for KIRCC.