Effects of Expert-Determined Reference Standards in Evaluating the Diagnostic Performance of a Deep Learning Model: A Malignant Lung Nodule Detection Task on Chest Radiographs.

OBJECTIVE: Little is known about the effects of using different expert-determined reference standards when evaluating the performance of deep learning-based automatic detection (DLAD) models and their added value to radiologists. We assessed the concordance of expert-determined standards with a clinical gold standard (herein, pathological confirmation) and the effects of different expert-determined reference standards on the estimates of radiologists' diagnostic performance to detect malignant pulmonary nodules on chest radiographs with and without the assistance of a DLAD model. MATERIALS AND METHODS: This study included chest radiographs from 50 patients with pathologically proven lung cancer and 50 controls. Five expert-determined standards were constructed using the interpretations of 10 experts: individual judgment by the most experienced expert, majority vote, consensus judgments of two and three experts, and a latent class analysis (LCA) model. In separate reader tests, additional 10 radiologists independently interpreted the radiographs and then assisted with the DLAD model. Their diagnostic performance was estimated using the clinical gold standard and various expert-determined standards as the reference standard, and the results were compared using the t test with Bonferroni correction. RESULTS: The LCA model (sensitivity, 72.6%; specificity, 100%) was most similar to the clinical gold standard. When expert-determined standards were used, the sensitivities of radiologists and DLAD model alone were overestimated, and their specificities were underestimated (all p-values < 0.05). DLAD assistance diminished the overestimation of sensitivity but exaggerated the underestimation of specificity (all p-values < 0.001). The DLAD model improved sensitivity and specificity to a greater extent when using the clinical gold standard than when using the expert-determined standards (all p-values < 0.001), except for sensitivity with the LCA model (p = 0.094). CONCLUSION: The LCA model was most similar to the clinical gold standard for malignant pulmonary nodule detection on chest radiographs. Expert-determined standards caused bias in measuring the diagnostic performance of the artificial intelligence model.

Data mining of coronavirus: SARS-CoV-2, SARS-CoV and MERS-CoV.

OBJECTIVE: In this study we compare the amino acid and codon sequence of SARS-CoV-2, SARS-CoV and MERS-CoV using different statistics programs to understand their characteristics. Specifically, we are interested in how differences in the amino acid and codon sequence can lead to different incubation periods and outbreak periods. Our initial question was to compare SARS-CoV-2 to different viruses in the coronavirus family using BLAST program of NCBI and machine learning algorithms. RESULTS: The result of experiments using BLAST, Apriori and Decision Tree has shown that SARS-CoV-2 had high similarity with SARS-CoV while having comparably low similarity with MERS-CoV. We decided to compare the codons of SARS-CoV-2 and MERS-CoV to see the difference. Though the viruses are very alike according to BLAST and Apriori experiments, SVM proved that they can be effectively classified using non-linear kernels. Decision Tree experiment proved several remarkable properties of SARS-CoV-2 amino acid sequence that cannot be found in MERS-CoV amino acid sequence. The consequential purpose of this paper is to minimize the damage on humanity from SARS-CoV-2. Hence, further studies can be focused on the comparison of SARS-CoV-2 virus with other viruses that also can be transmitted during latent periods.

Selective one-pot syntheses of Pt(II)-Cu(I) heterobimetallic complexes of 4,5-diazafluorenide derivatives.

We report both the stepwise and one-pot syntheses of Pt(II)-Cu(I) hetero-dinuclear complexes using 4,5-diazafluorenide (L(-)) and 9-(2-(diphenylphosphino)ethyl)-4,5-diazafluorenide (L(p)(-)) as binucleating ligands. In the case of L(p)(-), the tethered phosphine arm helps anchor the Pt(II) centre onto the carbon site of the diazafluorenide and the Cu(I) centre is bound to the N,N-chelate site. In the case of L(-), the Cu(I) centre is bound to the carbon site of diazafluorenide and the Pt(II) centre is coordinated to the N,N-chelate site.

Neck circumference correlates with tumor size and lateral lymph node metastasis in men with small papillary thyroid carcinoma.

BACKGROUND/AIMS: Obesity is correlated with numerous diseases, including thyroid cancer, but the clinical significance of obesity with regard to the clinical characteristics of thyroid cancer remains unclear. Neck circumference is an index of upper-body adipose tissue distribution. METHODS: In total, 401 patients with papillary thyroid carcinoma (PTC) measuring ≤ 2 cm were included. Neck circumference was measured horizontally at the level just below the thyroid cartilage on preoperative neck computed tomographic images. RESULTS: Neck circumference correlated significantly with tumor size in men (p = 0.001) but not in women (p = 0.930). Body mass index (BMI) did not significantly correlate with tumor size in either sex. Neck circumference was significantly larger in men with lateral lymph node (LN) metastasis than in those without (p = 0.004). Neck circumference and BMI did not differ significantly in women according to other factors such as tumor size, multifocality, extrathyroid extension, and LN metastasis. Tumor size and the prevalence of lateral LN metastasis in men tended to increase in the middle/large neck circumference subgroup compared with those in the low neck circumference subgroup. Multivariate logistic regression analysis revealed that neck circumference (p = 0.009) was a predictor for the presence of lateral LN metastasis in men. BMI was not a predictive factor for lateral LN involvement in either sex. CONCLUSIONS: Neck circumference, an indicator of central or visceral obesity but not BMI, may be associated with some prognostic factors in men with small PTC.

Benign cystic nodules may have ultrasonographic features mimicking papillary thyroid carcinoma during interval changes.

It had been observed that some cystic nodules change morphologically with ultrasonographic (US) features suspicious for malignancy. The aim of this study was to evaluate the US characteristics of benign cystic nodules mimicking papillary thyroid carcinoma (PTC) during interval changes. Between January 2009 and October 2009, 26 patients with benign cystic nodules showing marked hypoechogenicity in US during the follow-up period were enrolled. During the same period, 38 patients with marked hypoechogenicity in US were enrolled for the PTC group. We evaluated the differences in US characteristics between the 2 groups. Nodule size, margin, echogenic dot and vascularity were not significantly different between the 2 groups. Nodule shape was significantly different between the 2 groups with a lower prevalence of taller than wide in the benign cystic group (11.5% vs. 39.5%, P=0.022). Other coexisting cystic nodules were more frequently observed in benign cystic group (48.3% vs. 5.3%, P=0.001). If echogenic dot was detected in benign cystic nodule, it was more than 1 mm in size without posterior acoustic shadowing unlike echogenic dots in the PTC group. In conclusion, some of the benign cystic nodules may have suspicious malignant features on US during interval changes. A careful assessment of US findings and a previous history may be of value in discriminating them from PTC.

Cystatin C as an early biomarker of nephropathy in patients with type 2 diabetes.

This study was done to evaluate clinical usefulness of cystatin C levels of serum and urine in predicting renal impairment in normoalbuminuric patients with type 2 diabetes and to evaluate the association between albuminuria and serum/urine cystatin C. Type 2 diabetic patients (n = 332) with normoalbuminuria (n = 210), microalbuminuria (n = 83) and macroalbuminuria (n = 42) were enrolled. Creatinine, urinary albumin levels, serum/urine cystatin C and estimated glomerular filtration rate (eGFR by MDRD [Modification of Diet in Renal Disease] and CKD-EPI [Chronic Kidney Disease Epidemiology Collaboration] equations) were determined. The cystatin C levels of serum and urine increased with increasing degree of albuminuria, reaching higher levels in macroalbuminuric patients (P < 0.001). In multiple regression analysis, serum cystatin C was affected by C-reactive protein (CRP), sex, albumin-creatinine ratio (ACR) and eGFR. Urine cystatin C was affected by triglyceride, age, eGFR and ACR. In multivariate logistic analysis, cystatin C levels of serum and urine were identified as independent factors associated with eGFR < 60 mL/min/1.73 m(2) estimated by MDRD equation in patients with normoalbuminuria. On the other hand, eGFR < 60 mL/min/1.73 m(2) estimated by CKD-EPI equation was independently associated with low level of high-density lipoprotein in normoalbuminuric patients. The cystatin C levels of serum and urine could be useful markers for renal dysfunction in type 2 diabetic patients with normoalbuminuria.

Prodigiosin isolated from Hahella chejuensis suppresses lipopolysaccharide-induced NO production by inhibiting p38 MAPK, JNK and NF-kappaB activation in murine peritoneal macrophages.

Prodigiosin was isolated from marine bacteria Hahella chejuensis which has been recently discovered from Marado, Cheju Island, Republic of Korea. Immunosuppressive properties have been reported for prodigiosin members such as undecylprodigiosin, metacycloprodigiosin, prodigiosin and its synthetic analogue PNU156804 (PNU). However, the effect of this agent on macrophage function has not been characterized in detail. In the present study, we examined the effects of prodigiosin on the production of inflammatory cytokines and nitric oxide (NO) in lipopolysaccharide (LPS)-activated murine macrophage. When thioglycollate-elicited macrophages pre-exposed to prodigiosin (1-100 ng/ml) were stimulated with LPS, pretreatment with prodigiosin resulted in the inhibition of NO production and inducible nitric oxide synthase (iNOS) protein and mRNA expression in a concentration-dependent manner. In contrast, the production of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1) and IL-6 was not altered. Inhibition of iNOS protein expression appears to be at the transcriptional level, since prodigiosin decreased LPS-induced NF-kappaB activity through preventing the degradation of IkBalpha, with significant inhibition achieved following pretreatment with prodigiosin. However, prodigiosin did not exert any effect on AP-1 activity. Prodigiosin blocked phosphorylation of p38 mitogen-activated protein kinase (MAPK) and c-Jun NH(2)-terminal kinase (JNK), but not that of extracellular signal-regulated kinase 1/2 (ERK 1/2). These results indicate that the inhibition of these signaling molecules expression was correlated with the reduced production of NO in macrophages. Taken together, the present data suggest that prodigiosin reduces NO production and iNOS expression by inhibiting LPS-triggered p38 MAPK and JNK phosphorylation and NF-kappaB activation, thereby implicating a mechanism by which prodigiosin may exert its immunosuppressive effects.

Effects of supplementation with higher levels of manganese and magnesium on immune function.

The magnesium (Mg) and manganese (Mn) were evaluated for its effectiveness as an immunomodulator in rats. The treatments were as follows: Group 1, AIN-93M diet (0.05% Mg, 0.001% Mn); Group 2, high-dose Mg (0.1% Mg, 0.001% Mn); and Group 3, high dose Mn (0.05% Mg, 0.01% Mn) (n-12/group). After 12 weeks of supplementation, rats were sacrificed to assess the effect on a range of innate responses (tumoricidal activity, oxidative burst and nitric oxide) and the mitogen-stimulated lymphoproliferative response. Immune function was significantly affected in both the high dose Mg and the Mn group. Lymphocyte proliferative responses and NK cell activity were measured in pooled spleen from each group. The mitogen response of lymphocytes to LPS in the spleen was significantly reduced in high dose Mg-treated groups, whereas the response to ConA was not affected in both high dose minerals-treated groups. The reactive oxygen species level of macrophages was decreased in both groups. These effects were more pronounced in high dose Mg-treated group. Nitric oxide production was also decreased in high dose minerals-treated group. In addition, tumoricidal activities of splenic NK cell and peritoneal macrophage in mineral exposed rats were significantly increased. Moreover, percent death of macrophage was reduced in two groups receiving high dose mineral supplements. Taken together, the present data suggest that high dose trace min erals exert a differential effect on the function of immune cells.

Low proliferation and high apoptosis of osteoblastic cells on hydrophobic surface are associated with defective Ras signaling.

The hydrophobic (HPB) nature of most polymeric biomaterials has been a major obstacle in using those materials in vivo due to low compatibility with cells. However, there is little knowledge of the molecular detail to explain how surface hydrophobicity affects cell responses. In this study, we compared the proliferation and apoptosis of human osteoblastic MG63 cells adhered to hydrophilic (HPL) and hydrophobic surfaces. On the hydrophobic surface, less formation of focal contacts and actin stress fibers, a delay in cell cycle progression, and an increase in apoptosis were observed. By using fibroblast growth factor 1 (FGF1) as a model growth factor, we also investigated intracellular signaling pathways on hydrophilic and hydrophobic surfaces. The activation of Ras, Akt, and ERK by FGF1 was impaired in MG63 cells on the hydrophobic surface. The overexpression of constitutively active form of Ras and Akt rescued those cells from apoptosis and recovered cell cycle progression. Furthermore, their overexpression also restored the actin cytoskeletal organization on the hydrophobic surface. Finally, the proliferative, antiapoptotic, and cytoskeletal effects of constitutively active Ras in MG63 cells on the hydrophobic surface were blocked by wortmannin and PD98059 that inhibit Akt and ERK activation, respectively. Therefore, our results suggest that the activation of Ras and its downstream molecules Akt and ERK to an appropriate level is one of crucial elements in the determination of osteoblast cell responses. The Ras pathway may represent a cell biological target that should be considered for successful surface modification of biomaterials to induce adequate cell responses in the bone tissue.