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.

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.

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.

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.

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.

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.

Comparison of the Phytochemical Composition and Antibacterial Activities of the Various Extracts from Leaves and Twigs of Illicium verum.

Previous studies have revealed the numerous biological activities of the fruits of Illicium verum; however, the activities of its leaves and twigs have remained undiscovered. The study aimed to investigate the phytochemical components and antibacterial activity of the various extracts from the leaves and twigs of Illicium verum. The herbal extracts were prepared by supercritical CO2 extraction (SFE) and 95% ethanol extraction, followed by partition extraction based on solvent polarity. Analysis of antimicrobial activity was conducted through the usage of nine clinical antibiotic- resistant isolates, including Staphylococcus aureus, Pseudomonas aeruginosa and Acinetobacter baumannii. Among the tested samples, the SFE extracts exhibited broader and stronger antibacterial activities against the test strains, with a range of MIC between 0.1-4.0 mg/mL and MBC between 0.2-4.5 mg/mL. Observations made through scanning electron microscopy revealed potential mechanism of the antimicrobial activities involved disruption of membrane integrity of the test pathogens. Evaluation of the chemical composition by gas chromatography-mass spectrometry indicated the presence of anethole, anisyl aldehyde, anisyl acetone and anisyl alcohol within the SFE extracts, demonstrating significant correlations with the antibacterial activities observed. Therefore, the leaves and twigs of Illicium verum hold great potential in being developed as new natural antibacterial agents.

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.

Higher-order clinical risk factor interaction analysis for overall mortality in maintenance hemodialysis patients.

BACKGROUND AND AIMS: In Taiwan, approximately 90% of patients with end-stage renal disease receive maintenance hemodialysis. Although studies have reported the survival predictability of multiclinical factors, the higher-order interactions among these factors have rarely been discussed. Conventional statistical approaches such as regression analysis are inadequate for detecting higher-order interactions. Therefore, this study integrated receiver operating characteristic, logistic regression, and balancing functions for adjusting the ratio in risk classes and classification errors for imbalanced cases and controls using multifactor-dimensionality reduction (MDR-ER) analyses to examine the impact of interaction effects between multiclinical factors on overall mortality in patients on maintenance hemodialysis. METERIALS AND METHODS: In total, 781 patients who received outpatient hemodialysis dialysis three times per week before 1 January 2009 were included; their baseline clinical factor and mortality outcome data were retrospectively collected using an approved data protocol (201800595B0). RESULTS: Consistent with conventional statistical approaches, the higher-order interaction model could indicate the impact of potential risk combination unique to patients on maintenance hemodialysis on the survival outcome, as described previously. Moreover, the MDR-based higher-order interaction model facilitated higher-order interaction effect detection among multiclinical factors and could determine more detailed mortality risk characteristics combinations. CONCLUSION: Therefore, higher-order clinical risk interaction analysis is a reasonable strategy for detecting non-traditional risk factor interaction effects on survival outcome unique to patients on maintenance hemodialysis and thus clinically achieving whole-scale patient care.

Identification of High-Order Single-Nucleotide Polymorphism Barcodes in Breast Cancer Using a Hybrid Taguchi-Genetic Algorithm: Case-Control Study.

BACKGROUND: Breast cancer has a major disease burden in the female population, and it is a highly genome-associated human disease. However, in genetic studies of complex diseases, modern geneticists face challenges in detecting interactions among loci. OBJECTIVE: This study aimed to investigate whether variations of single-nucleotide polymorphisms (SNPs) are associated with histopathological tumor characteristics in breast cancer patients. METHODS: A hybrid Taguchi-genetic algorithm (HTGA) was proposed to identify the high-order SNP barcodes in a breast cancer case-control study. A Taguchi method was used to enhance a genetic algorithm (GA) for identifying high-order SNP barcodes. The Taguchi method was integrated into the GA after the crossover operations in order to optimize the generated offspring systematically for enhancing the GA search ability. RESULTS: The proposed HTGA effectively converged to a promising region within the problem space and provided excellent SNP barcode identification. Regression analysis was used to validate the association between breast cancer and the identified high-order SNP barcodes. The maximum OR was less than 1 (range 0.870-0.755) for two- to seven-order SNP barcodes. CONCLUSIONS: We systematically evaluated the interaction effects of 26 SNPs within growth factor-related genes for breast carcinogenesis pathways. The HTGA could successfully identify relevant high-order SNP barcodes by evaluating the differences between cases and controls. The validation results showed that the HTGA can provide better fitness values as compared with other methods for the identification of high-order SNP barcodes using breast cancer case-control data sets.

An improved fuzzy set-based multifactor dimensionality reduction for detecting epistasis.

OBJECTIVE: Epistasis identification is critical for determining susceptibility to human genetic diseases. The rapid development of technology has enabled scalability to make multifactor dimensionality reduction (MDR) measurements an effective calculation tool that achieves superior detection. However, the classification of high-risk (H) or low-risk (L) groups in multidrug resistance operations calls for extensive research. METHODS AND MATERIAL: In this study, an improved fuzzy sigmoid (FS) method using the membership degree in MDR (FSMDR) was proposed for solving the limitations of binary classification. The FS method combined with MDR measurements yielded an improved ability to distinguish similar frequencies of potential multifactor genotypes. RESULTS: We compared our results with other MDR-based methods and FSMDR achieved superior detection rates on simulated data sets. The results indicated that the fuzzy classifications can provide insight into the uncertainty of H/L classification in MDR operation. CONCLUSION: FSMDR successfully detected significant epistasis of coronary artery disease in the Wellcome Trust Case Control Consortium data set.

Class Balanced Multifactor Dimensionality Reduction to Detect Gene-Gene Interactions.

Detecting gene-gene interactions in single-nucleotide polymorphism data is vital for understanding disease susceptibility. However, existing approaches may be limited by the sample size in case-control studies. Herein, we propose a balance approach for the multifactor dimensionality reduction (BMDR) method to increase the accuracy of estimates of the prediction error rate in small samples. BMDR explicitly selects the best model by evaluating the average of prediction error rates over k-fold cross-validation without cross-validation consistency selection. In this study, we used several epistatic models with and without marginal effects under different parameter settings (heritability and minor allele frequencies) to evaluate the performance of existing approaches. Using simulated data sets, BMDR successfully detected gene-gene interactions, particularly for data sets with small sample sizes. A large data set was obtained from the Wellcome Trust Case Control Consortium, and results indicated that BMDR could effectively detect significant gene-gene interactions.

Effective hybrid approach for protein structure prediction in a two-dimensional Hydrophobic-Polar model.

Hydrophobic-polar (HP) models are widely used to predict protein folding and hydrophobic interactions. Numerous optimization algorithms have been proposed to predict protein folding using the two-dimensional (2D) HP model. However, to obtain an optimal protein structure from the 2D HP model remains challenging. In this study, an algorithm integrating particle swarm optimization (PSO) and Tabu search (TS), named PSO-TS, was proposed to predict protein structures based on the 2D HP model. TS can help PSO to avoid getting trapped in a local optima and thus to remove the limitation of PSO in predicting protein folding by the 2D HP model. In this study, a total of 28 protein sequences were used to evaluate the accuracy of PSO-TS in protein folding prediction. The proposed PSO-TS method was compared with 15 other approaches for predicting short and long protein sequences. Experimental results demonstrated that PSO-TS provides a highly accurate, reproducible, and stabile prediction ability for the protein folding by the 2D HP model.

Application of simulation-based CYP26 SNP-environment barcodes for evaluating the occurrence of oral malignant disorders by odds ratio-based binary particle swarm optimization: A case-control study in the Taiwanese population.

INTRODUCTION: Genetic polymorphisms and social factors (alcohol consumption, betel quid (BQ) usage, and cigarette consumption), both separately or jointly, play a crucial role in the occurrence of oral malignant disorders such as oral and pharyngeal cancers and oral potentially malignant disorders (OPMD). MATERIAL AND METHODS: Simultaneous analyses of multiple single nucleotide polymorphisms (SNPs) and environmental effects on oral malignant disorders are essential to examine, albeit challenging. Thus, we conducted a case-control study (N = 576) to analyze the risk of occurrence of oral malignant disorders by using binary particle swarm optimization (BPSO) with an odds ratio (OR)-based method. RESULTS: We demonstrated that a combination of SNPs (CYP26B1 rs887844 and CYP26C1 rs12256889) and socio-demographic factors (age, ethnicity, and BQ chewing), referred to as the combined effects of SNP-environment, correlated with maximal risk diversity of occurrence observed between the oral malignant disorder group and the control group. The risks were more prominent in the oral and pharyngeal cancers group (OR = 10.30; 95% confidence interval (CI) = 4.58-23.15) than in the OPMD group (OR = 5.42; 95% CI = 1.94-15.12). CONCLUSIONS: Simulation-based "SNP-environment barcodes" may be used to predict the risk of occurrence of oral malignant disorders. Applying simulation-based "SNP-environment barcodes" may provide insight into the importance of screening tests in preventing oral and pharyngeal cancers and OPMD.

Biofilm Formation in Acinetobacter Baumannii: Genotype-Phenotype Correlation.

Strains of Acinetobacter baumannii are commensal and opportunistic pathogens that have emerged as problematic hospital pathogens due to its biofilm formation ability and multiple antibiotic resistances. The biofilm-associated pathogens usually exhibit dramatically decreased susceptibility to antibiotics. This study was aimed to investigate the correlation of biofilm-forming ability, antibiotic resistance and biofilm-related genes of 154 A. baumannii isolates which were collected from a teaching hospital in Taiwan. Biofilm-forming ability of the isolates was evaluated by crystal violet staining and observed by scanning electron microscopy. Antibiotic susceptibility was determined by disc diffusion method and minimum inhibitory concentration; the biofilm-related genes were screened by polymerase chain reaction. Results showed that among the 154 tested isolates, 15.6% of the clinical isolates were weak biofilm producers, while 32.5% and 45.4% of them possessed moderate and strong biofilm formation ability, respectively. The experimental results revealed that the multiple drug resistant isolates usually provided a higher biofilm formation. The prevalence of biofilm related genes including bap, blaPER-1, csuE and ompA among the isolated strains was 79.2%, 38.3%, 91.6%, and 68.8%, respectively. The results indicated that the antibiotic resistance, the formation of biofilm and the related genes were significantly correlated. The results of this study can effectively help to understand the antibiotic resistant mechanism and provides the valuable information to the screening, identification, diagnosis, treatment and control of clinical antibiotic-resistant pathogens.

Relationship between Clinicopathologic Variables in Breast Cancer Overall Survival Using Biogeography-Based Optimization Algorithm.

Breast cancer is the most common cancer among women and is considered a major public health concern worldwide. Biogeography-based optimization (BBO) is a novel metaheuristic algorithm. This study analyzed the relationship between the clinicopathologic variables of breast cancer using Cox proportional hazard (PH) regression on the basis of the BBO algorithm. The dataset is prospectively maintained by the Division of Breast Surgery at Kaohsiung Medical University Hospital. A total of 1896 patients with breast cancer were included and tracked from 2005 to 2017. Fifteen general breast cancer clinicopathologic variables were collected. We used the BBO algorithm to select the clinicopathologic variables that could potentially contribute to predicting breast cancer prognosis. Subsequently, Cox PH regression analysis was used to demonstrate the association between overall survival and the selected clinicopathologic variables. C-statistics were used to test predictive accuracy and the concordance of various survival models. The BBO-selected clinicopathologic variables model obtained the highest C-statistic value (80%) for predicting the overall survival of patients with breast cancer. The selected clinicopathologic variables included tumor size (hazard ratio [HR] 2.372, p = 0.006), lymph node metastasis (HR 1.301, p = 0.038), lymphovascular invasion (HR 1.606, p = 0.096), perineural invasion (HR 1.546, p = 0.168), dermal invasion (HR 1.548, p = 0.028), total mastectomy (HR 1.633, p = 0.092), without hormone therapy (HR 2.178, p = 0.003), and without chemotherapy (HR 1.234, p = 0.491). This number was the minimum number of discriminators required for optimal discrimination in the breast cancer overall survival model with acceptable prediction ability. Therefore, on the basis of the clinicopathologic variables, the survival prediction model in this study could contribute to breast cancer follow-up and management.