Although microscopic analysis of tissue slides has been the basis for disease diagnosis for decades, intra- and inter-observer variabilities remain issues to be resolved. The recent introduction of digital scanners has allowed for using deep learning in the analysis of tissue images because many whole slide images (WSIs) are accessible to researchers. In the present study, we investigated the possibility of a deep learning-based, fully automated, computer-aided diagnosis system with WSIs from a stomach adenocarcinoma dataset. Three different convolutional neural network architectures were tested to determine the better architecture for tissue classifier. Each network was trained to classify small tissue patches into normal or tumor. Based on the patch-level classification, tumor probability heatmaps can be overlaid on tissue images. We observed three different tissue patterns, including clear normal, clear tumor and ambiguous cases. We suggest that longer inspection time can be assigned to ambiguous cases compared to clear normal cases, increasing the accuracy and efficiency of histopathologic diagnosis by pre-evaluating the status of the WSIs. When the classifier was tested with completely different WSI dataset, the performance was not optimal because of the different tissue preparation quality. By including a small amount of data from the new dataset for training, the performance for the new dataset was much enhanced. These results indicated that WSI dataset should include tissues prepared from many different preparation conditions to construct a generalized tissue classifier. Thus, multi-national/multi-center dataset should be built for the application of deep learning in the real world medical practice.
Adenocarcinoma ; Classification ; Dataset ; Diagnosis ; Learning ; Observer Variation ; Stomach

OBJECTIVE: To investigate pathologic discrepancies between colposcopy-directed biopsy (CDB) of the cervix and loop electrosurgical excision procedure (LEEP) in women with cytologic high-grade squamous intraepithelial lesions (HSILs).METHODS: We retrospectively identified 297 patients who underwent both CDB and LEEP for HSILs in cervical cytology between 2015 and 2018, and compared their pathologic results. Considering the LEEP to be the gold standard, we evaluated the diagnostic performance of CDB for identifying cervical intraepithelial neoplasia (CIN) grades 2 and 3, adenocarcinoma in situ, and cancer (HSIL+). We also performed age subgroup analyses.RESULTS: Among the study population, 90.9% (270/297) had pathologic HSIL+ using the LEEP. The diagnostic performance of CDB for identifying HSIL+ was as follows: sensitivity, 87.8%; specificity, 59.3%; balanced accuracy, 73.6%; positive predictive value, 95.6%; and negative predictive value, 32.7%. Thirty-three false negative cases of CDB included CIN2,3 (n=29) and cervical cancer (n=4). The pathologic HSIL+ rate in patients with HSIL− by CDB was 67.3% (33/49). CDB exhibited a significant difference in the diagnosis of HSIL+ compared to LEEP in all patients (p<0.001). In age subgroup analyses, age groups <35 years and 35–50 years showed good agreement with the entire data set (p=0.496 and p=0.406, respectively), while age group ≥50 years did not (p=0.036).CONCLUSION: A significant pathologic discrepancy was observed between CDB and LEEP results in women with cytologic HSILs. The diagnostic inaccuracy of CDB increased in those ≥50 years of age.
Adenocarcinoma in Situ ; Biopsy ; Cervical Intraepithelial Neoplasia ; Cervix Uteri ; Colposcopy ; Conization ; Dataset ; Diagnosis ; Early Detection of Cancer ; Female ; Humans ; Papanicolaou Test ; Retrospective Studies ; Sensitivity and Specificity ; Squamous Intraepithelial Lesions of the Cervix ; Uterine Cervical Neoplasms

PURPOSE: We determined whether elevated serum alkaline phosphatase (ALP) was related to prevalence, location, type, length, and recurrence of pterygium in a population from the Republic of Korea.METHODS: A nationwide cross-sectional dataset, the Korean National Health and Nutrition Examination Survey (2008–2011), was used in this study. All participants were > 30 years of age and underwent the ALP test and ophthalmic evaluation (n = 22,359). One-way analysis of variance, the chi-square test, and Fisher's exact test were used to compare characteristics and outcomes among participants. Multivariable logistic regression was used to examine the possible associations between serum ALP levels and various types of pterygium. Data were adjusted for known risk factors for development of pterygium and ALP elevation (age, sex, residence, sunlight exposure, drinking, smoking, hypertension, diabetes, BMI, AST, ALT, vitamin D, and HDL).RESULTS: The overall prevalence of pterygium was 8.1%, and participants with pterygium had higher levels of serum ALP (p < 0.001). Participants with higher serum ALP had a significantly higher prevalence of all types of pterygium than those in the lower serum ALP quartiles. After adjusting for potential confounding factors, multivariate logistic regression analysis revealed that ALP was associated with the prevalence of pterygium (odds ratio [OR], 1.001; p = 0.038). Trend analysis between the OR and ALP quartiles revealed a linear trend in overall prevalence and in the intermediate type of pterygium. Subgroup analysis revealed a stronger correlation in participants > 50 years of age. One-way analysis of variance revealed an association between the size of pterygium and serum ALP quartile levels. Serum ALP was not associated with recurrence of pterygium.CONCLUSIONS: Increased serum ALP was associated with the prevalence and size of pterygium.
Alkaline Phosphatase ; Cross-Sectional Studies ; Dataset ; Drinking ; Hypertension ; Korea ; Logistic Models ; Nutrition Surveys ; Prevalence ; Pterygium ; Recurrence ; Republic of Korea ; Risk Factors ; Smoke ; Smoking ; Sunlight ; Vitamin D

Biopsy ; Classification ; Dataset ; Sensitivity and Specificity ; Thyroid Gland ; Thyroid Neoplasms ; Thyroid Nodule ; Ultrasonography

dataset of 883 CT scans from 467 subjects. Axial CT images obtained at the inferior endplate level of the 3rd lumbar vertebra were used for the analysis. Manually drawn segmentation maps of the skeletal muscle, visceral fat, and subcutaneous fat were created to serve as ground truth data. The performance of the fully convolutional network-based segmentation system was evaluated using the Dice similarity coefficient and cross-sectional area error, for both a separate internal validation dataset (426 CT scans from 308 subjects) and an external validation dataset (171 CT scans from 171 subjects from two outside hospitals).RESULTS: The mean Dice similarity coefficients for muscle, subcutaneous fat, and visceral fat were high for both the internal (0.96, 0.97, and 0.97, respectively) and external (0.97, 0.97, and 0.97, respectively) validation datasets, while the mean cross-sectional area errors for muscle, subcutaneous fat, and visceral fat were low for both internal (2.1%, 3.8%, and 1.8%, respectively) and external (2.7%, 4.6%, and 2.3%, respectively) validation datasets.CONCLUSION: The fully convolutional network-based segmentation system exhibited high performance and accuracy in the automatic segmentation of abdominal muscle and fat on CT images.]]>
Abdominal Muscles ; Adipose Tissue ; Artificial Intelligence ; Dataset ; Intra-Abdominal Fat ; Learning ; Muscle, Skeletal ; Muscles ; Sarcopenia ; Spine ; Subcutaneous Fat ; Tomography, X-Ray Computed

dataset from patient-derived xenograft model for TKI-treated ccRCC (GSE76068) was retrieved. Commonly altered pathways between the datasets were investigated by Ingenuity Pathway Analysis using commonly regulated differently expressed genes (DEGs). The significance of candidate DEG on intrinsic TKI resistance was assessed through immunohistochemistry in a separate cohort of 101 TKI-treated ccRCC cases.RESULTS: TNFRSF1A gene expression and tumor necrosis factor (TNF)-α pathway were upregulated in ccRCCs with acquired TKI resistance in both microarray datasets. Also, high expression (> 10% of labeled tumor cells) of TNF receptor 1 (TNFR1), the protein product of TNFRSF1A gene, was correlated with sarcomatoid dedifferentiation and was an independent predictive factor of clinically unfavorable response and shorter survivals in separated TKI-treated ccRCC cohort.CONCLUSION: TNF-α signaling may play a role in TKI resistance, and TNFR1 expression may serve as a predictive biomarker for clinically unfavorable TKI responses in ccRCC.]]>
Biomarkers ; Carcinoma, Renal Cell ; Cohort Studies ; Dataset ; Drug Resistance ; Gene Expression ; Gene Expression Profiling ; Heterografts ; Humans ; Immunohistochemistry ; Protein-Tyrosine Kinases ; Receptors, Tumor Necrosis Factor ; Receptors, Tumor Necrosis Factor, Type I ; Tumor Necrosis Factor-alpha

OBJECTIVE: To develop a scoring system stratifying the malignancy risk of mammographic microcalcifications using the 5th edition of the Breast Imaging Reporting and Data System (BI-RADS).MATERIALS AND METHODS: One hundred ninety-four lesions with microcalcifications for which surgical excision was performed were independently reviewed by two radiologists according to the 5th edition of BI-RADS. Each category's positive predictive value (PPV) was calculated and a scoring system was developed using multivariate logistic regression. The scores for benign and malignant lesions or BI-RADS categories were compared using an independent t test or by ANOVA. The area under the receiver operating characteristic curve (AUROC) was assessed to determine the discriminatory ability of the scoring system. Our scoring system was validated using an external dataset.RESULTS: After excision, 69 lesions were malignant (36%). The PPV of BI-RADS descriptors and categories for calcification showed significant differences. Using the developed scoring system, mean scores for benign and malignant lesions or BI-RADS categories were significantly different (p < 0.001). The AUROC of our scoring system was 0.874 (95% confidence interval, 0.840–0.909) and the PPV of each BI-RADS category determined by the scoring system was as follows: category 3 (0%), 4A (6.8%), 4B (19.0%), 4C (68.2%), and 5 (100%). The validation set showed an AUROC of 0.905 and PPVs of 0%, 8.3%, 11.9%, 68.3%, and 94.7% for categories 3, 4A, 4B, 4C, and 5, respectively.CONCLUSION: A scoring system based on BI-RADS morphology and distribution descriptors could be used to stratify the malignancy risk of mammographic microcalcifications.
Breast Neoplasms ; Breast ; Dataset ; Information Systems ; Logistic Models ; Mammography ; ROC Curve ; Subject Headings

PURPOSE: We developed predictive models using different programming languages and different computing platforms for machine learning (ML) and deep learning (DL) that classify clinical diagnoses in patients with epiphora. We evaluated the diagnostic performance of these models.METHODS: Between January 2016 and September 2017, 250 patients with epiphora who underwent dacryocystography (DCG) and lacrimal scintigraphy (LS) were included in the study. We developed five different predictive models using ML tools, Python-based TensorFlow, R, and Microsoft Azure Machine Learning Studio (MAMLS). A total of 27 clinical characteristics and parameters including variables related to epiphora (VE) and variables related to dacryocystography (VDCG) were used as input data. Apart from this, we developed two predictive convolutional neural network (CNN) models for diagnosing LS images. We conducted this study using supervised learning.RESULTS: Among 500 eyes of 250 patients, 59 eyes had anatomical obstruction, 338 eyes had functional obstruction, and the remaining 103 eyes were normal. For the data set that excluded VE and VDCG, the test accuracies in Python-based TensorFlow, R, multiclass logistic regression in MAMLS, multiclass neural network in MAMLS, and nuclear medicine physician were 81.70%, 80.60%, 81.70%, 73.10%, and 80.60%, respectively. The test accuracies of CNN models in three-class classification diagnosis and binary classification diagnosis were 72.00% and 77.42%, respectively.CONCLUSIONS: ML-based predictive models using different programming languages and different computing platforms were useful for classifying clinical diagnoses in patients with epiphora and were similar to a clinician's diagnostic ability.
Classification ; Dataset ; Diagnosis ; Humans ; Lacrimal Apparatus Diseases ; Learning ; Logistic Models ; Machine Learning ; Nuclear Medicine ; Programming Languages ; Radionuclide Imaging

OBJECTIVES: To estimate the number and risk of imported infections resulting from people visiting Asian and Latin American countries.METHODS: The dataset of visitors to 5 Asian countries with dengue were analyzed for 2016 and 2017, and in the Philippines, Thailand and Vietnam, imported cases of zika virus infection were also reported. For zika virus, a single imported case was reported from Brazil in 2016, and 2 imported cases reported from the Maldives in 2017. To understand the transmissibility in 5 Southeast Asian countries, the estimate of the force of infection, i.e., the hazard of infection per year and the average duration of travel has been extracted. Outbound travel numbers were retrieved from the World Tourism Organization, including business travelers.RESULTS: The incidence of imported dengue in 2016 was estimated at 7.46, 15.00, 2.14, 4.73 and 2.40 per 100,000 travelers visiting Philippines, Indonesia, Thailand, Malaysia and Vietnam, respectively. Similarly, 2.55, 1.65, 1.53, 1.86 and 1.70 per 100,000 travelers in 2017, respectively. It was estimated that there were 60.1 infections (range: from 16.8 to 150.7 infections) with zika virus in Brazil, 2016, and 345.6 infections (range: from 85.4 to 425.5 infections) with zika virus in the Maldives, 2017.CONCLUSION: This study emphasizes that dengue and zika virus infections are mild in their nature, and a substantial number of infections may go undetected. An appropriate risk assessment of zika virus infection must use the estimated total size of infections.
Asia, Southeastern ; Asian Continental Ancestry Group ; Brazil ; Commerce ; Dataset ; Dengue ; Humans ; Incidence ; Indian Ocean Islands ; Indonesia ; Korea ; Latin America ; Malaysia ; Philippines ; Risk Assessment ; Thailand ; Vietnam ; Zika Virus ; Zika Virus Infection

Brain disorder recognition has becoming a promising area of study. In reality, some disorders share similar features and signs, making the task of diagnosis and treatment challenging. This paper presents a rigorous and robust computer aided diagnosis system for the detection of multiple brain abnormalities which can assist physicians in the diagnosis and treatment of brain diseases. In this system, we used energy of wavelet sub bands, textural features of gray level co-occurrence matrix and intensity feature of MR brain images. These features are ranked using Wilcoxon test. The composite features are classifi ed using back propagation neural network. Bayesian regulation is adopted to fi nd the optimal weights of neural network. The experimentation is carried out on datasets DS-90 and DS-310 of Harvard Medical School. To enhance the generalization capability of the network, fi vefold stratifi ed cross validation technique is used. The proposed system yields multi class disease classifi cation accuracy of 100% in diff erentiating 90 MR brain images into 18 classes and 97.81% in diff erentiating 310 MR brain images into 6 classes. The experimental results reveal that the composite features along with BPNN classifi er create a competent and reliable system for the identifi cation of multiple brain disorders which can be used in clinical applications. The Wilcoxon test outcome demonstrates that standard deviation feature along with energies of approximate and vertical sub bands of level 7 contribute the most in achieving enhanced multi class classifi cation performance results.
Brain Diseases ; Brain ; Dataset ; Diagnosis ; Generalization (Psychology) ; Magnetic Resonance Imaging ; Schools, Medical ; Weights and Measures