Integrated Analysis Identifies Molecular Signatures and Specific Prognostic Factors for Different Gastric Cancer Subtypes

BACKGROUND: Gastric cancer (GC) is the fifth leading cause of cancer-related deaths worldwide. As an effective and easily performed method, microscopy-based Lauren classification has been widely accepted by gastrointestinal surgeons and pathologists for GC subtyping, but molecular characteristics of different Lauren subtypes were poorly revealed. METHODS: GSE62254 was used as a derivation cohort, and GSE15459 was used as a validation cohort. The difference between diffuse and intestinal GC on the gene expression level was measured. Gene ontology (GO) enrichment analysis was performed for both subgroups. Hierarchical clustering and heatmap exhibition were also performed. Kaplan-Meier plot and Cox proportional hazards model were used to evaluate survival grouped by the given genes or hierarchical clusters. RESULTS: A total of 4598 genes were found differentially expressed between diffuse and intestinal GC. Immunity- and cell adhesion–related GOs were enriched for diffuse GC, whereas DNA repair– and cell cycle–related GOs were enriched for intestinal GC. We proposed a 40-gene signature (χ² = 30.71, P < .001) that exhibits better discrimination for prognosis than Lauren classification (χ² = 12.11, P = .002). FRZB [RR (95% CI) = 1.824 (1.115-2.986), P = .017] and EFEMP1 [RR (95% CI) = 1.537 (0.969-2.437), P = .067] were identified as independent prognostic factors only in diffuse GC but not in intestinal GC patients. KRT23 [RR (95% CI) = 1.616 (0.938-2.785), P = .083] was identified as an independent prognostic factor only in intestinal GC patients but not in diffuse GC patients. Similar results were achieved in the validation cohort. CONCLUSION: We found that GCs with different Lauren classifications had different molecular characteristics and identified FRZB, EFEMP1, and KRT23 as subtype-specific prognostic factors for GC patients.     

A Long Noncoding RNA Signature That Predicts Pathological Complete Remission Rate Sensitively in Neoadjuvant Treatment of Breast Cancer

BACKGROUND: Mounting evidence suggests that long noncoding RNAs (lncRNAs) are closely related to pathological complete response (pCR) in neoadjuvant treatment of breast cancer. Here, we construct lncRNA associated models to predict pCR rate. METHODS: LncRNA expression profiles of breast cancer patients treated with neoadjuvant chemotherapy (NAC) were obtained from Gene Expression Omnibus by repurposing existing microarray data. The prediction model was firstly built by analyzing the correlation between pCR and lncRNA expression in the discovery dataset GSE 25066 (n = 488). Another three independent datasets, GSE20194 (n = 278), GSE20271 (n = 178), and GSE22093 (n = 97), were integrated as the validation cohort to assess the prediction efficiency. RESULTS: A novel lncRNA signature (LRS) consisting of 36 lncRNAs was identified. Based on this LRS, patients with NAC treatment were divided into two groups: LRS-high group and LRS-low group, with positive correlation of pCR rate in the discovery dataset. In the validation cohort, univariate and multivariate analyses both demonstrated that high LRS was associated with higher pCR rate. Subgroup analysis confirmed that this model performed well in luminal B [odds ratio (OR) = 5.4; 95% confidence interval (CI) = 2.7-10.8; P = 1.47e-06], HER2-enriched (OR = 2.5; 95% CI = 1.1-5.7; P = .029), and basal-like (OR = 5.5; 95% CI = 2.3-16.2; P = 5.32e-04) subtypes. Compared with other preexisting prediction models, LRS demonstrated better performance with higher area under the curve. Functional annotation analysis suggested that lncRNAs in this signature were mainly involved in cancer proliferation process. CONCLUSION: Our findings indicated that our lncRNA signature was sensitive to predict pCR rate in the neoadjuvant treatment of breast cancer, which deserves further evaluation.     

Prognostic Value of Molecular Breast Cancer Subtypes based on Her2, ESR1, PGR and Ki67 mRNA-Expression in Muscle Invasive Bladder Cancer

INTRODUCTION: Gene expression analyses have identified similarities between bladder and breast cancer, where clinical risk stratification is based on Her2, ESR1, PGR and Ki67 expression. The aim of the study was to assess the respective marker gene expression in patients treated with radical cystectomy for muscle-invasive bladder cancer (MIBC) and to evaluate the applicability of breast cancer subtypes for MIBC risk stratification. MATERIALS & METHODS: 102 patients treated with radical cystectomy for MIBC were assessed. Using routine FFPE tissue and an IVD validated kit, mRNA expression was measured by single step RT-qPCR. Partition test were employed to define cut-off values for high or low marker gene expression. Association of expression with outcome was assessed using Kaplan-Meier analysis and multivariate cox regression analysis. Finally, we performed validation of our results in the MD-Anderson cohort (n = 57). RESULTS: Cancer specific survival (CSS) was impaired in patients with high gene expression of Her2 (P = 0.0009) and ESR1 (P = 0.04). In the multivariate regression model Her2 expression remained significant for the prediction of CSS (HR = 2.11, CI 1.11-4.21, P = 0.024). Furthermore, molecular stratification by breast cancer subgroups was significant (P = 0.023) for CSS prediction. Especially the differentiation between Her2-positive and Luminal A (HR = 4.41, CI 1.53-18.71, P = 0.004) and Luminal B (HR = 1.96, CI 0.99-4.08, P = 0.053) respectively was an independent prognostic parameter for CSS. External validation resulted in comparable risk stratification with differences in fractional subgroups distribution. CONCLUSION: Gene expression of Her2, ESR1, PGR, Ki67 and corresponding breast cancer subtypes allow a risk-stratification in MIBC, whereby Her2 overexpressing tumors reveal a particularly poor prognosis.     

A Validated Prognostic Biomarker Score for Adult Patients with Nonmetastatic Soft Tissue Sarcomas of the Trunk and Extremities

BACKGROUND: The prognostic value of serum biomarkers in soft tissue sarcoma (STS) is limited, and its clinical applicability is compromised by a common inability to adjust for important confounders. The aim of this study was to determine the prognostic value of pretreatment biomarkers on disease-specific survival (DSS) adjusted for confounders. METHODS: The study included 818 patients with localized STS. Pretreatment levels of albumin, C-reactive protein, hemoglobin, neutrophils, and lymphocytes were tested individually and combined in prognostic scores: neutrophil/lymphocyte ratio (NLR), Glasgow Prognostic Score (GPS), and Aarhus Composite Biomarker Score (ACBS) which includes all five biomarkers. Patients were randomly split into a test cohort and a validation cohort. The prognostic value of biomarkers on DSS was estimated using crude and adjusted Cox proportional hazard models. The different biomarker scores were compared using Akaike's information criteria. RESULTS: In the test cohort of 403 patients, all biomarkers except lymphocyte count were significant prognostic factors for DSS also after adjusting for confounders. NLR, GPS, and ACBS were independently associated with decreased survival; however, ACBS was significantly superior to NLR (P = .02) and GPS (P = .002). These findings were validated in the randomly assigned validation cohort of 415 patients. In the pooled data of 818 patients, the ACBS performed better than GPS and NLR. ACBS 2 was independently associated with decreased DSS compared to ACBS 0, hazard ratio 2.3[95% confidence interval: 1.5-3.5], P < .001. CONCLUSION: Patients with abnormal values in more than one serum biomarkers had a significant additional risk of dying compared to patients with only one abnormal value. ACBS was validated as an independent prognostic factor that is superior to both NLR and GPS.     

The Pulmonary Fibrosis Associated MUC5B Promoter Polymorphism Is Prognostic of the Overall Survival in Patients with Non–Small Cell Lung Cancer (NSCLC) Receiving Definitive Radiotherapy

BACKGROUND: MUC5B is glycoprotein secreted by bronchial glands. A promoter variant in MUC5B, rs35705950, was previously found to be strongly associated with the incidence of idiopathic pulmonary fibrosis (IPF) and also the overall survival (OS) of such patients. Patients with IPF and patients with radiation pneumonitis (RP) have the similar pathologic process and clinical symptoms. However, the role of rs35705950 in patients receiving thoracic radiotherapy remains unclear. PATIENTS AND METHODS: In total, 664 patients with NSCLC receiving definitive radiotherapy (total dose ≥60 Gy) were included in our study. RP was scored via the Common Terminology Criteria for Adverse Events v3.0. OS was the second end point. MUC5B rs35705950 was genotyped, and Kaplan-Meier and Cox regression analyses were used to evaluate associations between MUC5B rs35705950 and the risk of RP or OS. RESULTS: The median patient age was 66 years (range 35-88); most (488 [73.2%]) had stage III of the disease. Until the last follow-up, 250 patients developed grade ≥ 2 RP, 82 patients developed grade ≥ 3 RP, and 440 patients died. The median mean lung dose was 17.9 Gy (range 0.15-32.74). No statistically significant associations were observed between genotypes of MUC5B rs35705950 and the incidence of RP ≥ grade 2 either in univariate analysis (hazard ratio [HR] 1.009, 95% confidence interval [CI] 0.728-1.399, P = .958) or in multivariate analysis (HR 0.921, 95% CI 0.645-1.315, P = .65). Similar results were also observed for RP ≥ grade 3, while TT/GT genotypes in MUC5B were significantly associated with poor OS in both univariate analysis (HR 1.287, 95% CI 1.009-1.640, P = .042) and multivariate analysis (HR 1.561, 95% CI 1.193-2.042, P = .001). CONCLUSION: MUC5B promoter polymorphism could be prognostic of the OS among NSCLC patients receiving definitive radiotherapy, although no significant associations were found with the risk of RP.     

Systematic Analysis of the Expression of the Mitochondrial ATP Synthase (Complex V) Subunits in Clear Cell Renal Cell Carcinoma

Mitochondrial dysfunction is common in cancer and the mitochondrial electron transport chain is often affected in carcinogenesis. To date, little is known about the expression of the ATP synthase subunits in clear cell renal cell carcinoma (ccRCC). The NextBio database was used to determine an expression profile of the ATP synthase subunits based on published microarray studies. We observed down-regulation of 23 out of 29 subunits of the ATP synthase. Differential expression was validated exemplarily for 12 genes (ATP5A1, ATP5B, ATPAF1, ATP5C1, ATP5D, ATP5O, ATP5F1, ATP5G1, ATP5G2, ATP5G3, ATP5I, ATP5S; screening cohort ccRCC n = 18 and normal renal tissue n = 10) using real-time PCR. Additional eight genes (ATP5A1, ATP5B, ATPAF1, ATP5F1, ATP5G1, ATP5G2, ATP5G3, ATP5S) were internally validated within an enlarged cohort (ccRCC n = 74; normal renal tissue n = 36). Furthermore, down-regulation of ATP5A1, ATPAF1, ATP5G1/G2/G3 was confirmed on the protein level using Western Blot and immunohistochemistry. We observed that altered expression of ATPAF1 and ATP5G1/G2/G3 was correlated with overall survival in patients with ccRCC. In conclusion, down-regulation of many ATP Synthase subunits occurs in ccRCC and is the basis for the reduced activity of the mitochondrial electron chain. Alteration of the expression of ATP5A1, ATPAF1, and ATP5G1/G2/G3 is characteristic for ccRCC and may be prognostic for ccRCC patients' outcome.     

Positive Expression of Programmed Death Ligand 1 in Peritumoral Liver Tissue is Associated with Poor Survival after Curative Resection of Hepatocellular Carcinoma

BACKGROUND: Recurrence or metastasis of hepatocellular carcinoma (HCC) is mainly intrahepatic after curative resection, demonstrating that the peritumoral environment is important but often neglected. Programmed death ligand 1 (PD-L1) in intratumoral liver tissues is a poor prognosis factor whose impact is removed after curative resection. However, PD-L1 expression remains in the peritumoral liver tissues and its distribution and prognostic value are still not clear. METHODS: We assessed the expression of PD-L1 by immunohistochemistry in peritumoral liver tissues from 90 HCC patients who underwent curative hepatectomy. The results were validated in an independent cohort of additional 90 HCC patients. RESULTS: We found PD-L1 positive expression in 31.11% (28/90) of peritumoral tissues. Peritumoral PD-L1 expression was associated with a significantly worse overall survival (OS) (P = .000) and disease-free survival (DFS) (P = .001) compared to the negative expression group. Additionally, peritumoral PD-L1 positivity significantly correlated with vascular invasion and a lower albumin level (≤35 g/L). Univariate and multivariate Cox regression models both revealed peritumoral PD-L1 as an independent prognostic factor for OS (HR = 2.853, P = .002) and DFS (HR = 2.362, P = .003). The prognostic value of PD-L1 positivity was validated in the independent data set. CONCLUSIONS: Our data suggest PD-L1 expression in peritumoral hepatocytes is an independent prognostic factor for OS and DFS. This implies that future anti-cancer therapy should target not only residual tumor cells but also the “soil” for promoting tumor growth. Peritumoral PD-L1 could be a good target for adjuvant therapy after hepatectomy.     

MRI Texture Analysis Reflects Histopathology Parameters in Thyroid Cancer – A First Preliminary Study

OBJECT: Thyroid cancer represents the most frequent malignancy of the endocrine system with an increasing incidence worldwide. Novel imaging techniques are able to further characterize tumors and even predict histopathology features. Texture analysis is an emergent imaging technique to extract extensive data from an radiology images. The present study was therefore conducted to identify possible associations between texture analysis and histopathology parameters in thyroid cancer. METHODS: The radiological database was retrospectively reviewed for thyroid carcinoma. Overall, 13 patients (3 females, 23.1%) with a mean age of 61.6 years were identified. The MaZda program was used for texture analysis. The T1-precontrast and T2-weighted images were analyzed and overall 279 texture feature for each sequence was investigated. For every patient cell count, Ki67-index and p53 count were investigated. RESULTS: Several significant correlations between texture features and histopathology were identified. Regarding T1-weighted images, S(0;1)Sum Averg correlated the most with cell count (r = 0.82). An inverse correlations with S(5;0)AngScMom, S(5;0)DifVarnc S(5;0), DiffEntrp and GrNonZeros (r = ?0.69, ?0.66, ?0.69 and ?0.63, respectively) was also identified. For T2-weighted images, Variance with r = 0.63 was the highest coefficient, WavEnLL_S3 correlated inversely with cell count (r = ?0.57). WavEnLL_S2 derived from T1-weighted images was the highest coefficient r = ?0.80, S(0;5)SumVarnc was positively with r = 0.74. Regarding T2-weighted images WavEnHL_s-1 was inverse correlated with Ki67 index (r = ?0.77). S(1;0)Correlat was with r = 0.75 the best correlation with Ki67 index. For T1-weighed images S(5;0)SumofSqs was the best with r = 0.65 with p53 count. For T2-weighted images S(1;?1)SumEntrp was the inverse correlation with r = ?0.72, whereas S(0;4)AngScMom correlated positively with r = 0.63. CONCLUSIONS: MRI texture analysis derived from conventional sequences reflects histopathology features in thyroid cancer. This technique might be a novel noninvasive modality to further characterize thyroid cancer in clinical oncology.     

Induction Chemotherapy Has No Prognostic Value in Patients with Locoregionally Advanced Nasopharyngeal Carcinoma and Chronic Hepatitis B Infection in the IMRT Era

BACKGROUND: The effectiveness of induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) over CCRT alone in patients with locoregionally advanced nasopharyngeal carcinoma (NPC) and chronic hepatitis B infection in the intensity-modulated radiotherapy (IMRT) era is unknown. PATIENTS AND METHODS: A total of 249 patients with stage T1-2 N2-3 or T3-4 N1-3 NPC and chronic hepatitis B infection treated with IMRT were retrospectively reviewed. Propensity score matching (PSM) was employed to balance covariates; 140 patients were propensity-matched (1:1 basis). Survival outcomes in the IC + CCRT and CCRT groups were compared using the Kaplan–Meier method, log-rank test and Cox proportional hazards model. RESULTS: No significant survival differences were observed between IC + CCRT and CCRT (5-year overall survival, 88.3% vs. 82.2%; P = .484; disease-free survival, 73.9% vs. 75.2%; P = .643; distant metastasis-free survival, 84.1% vs. 85.1%; P = .781; and locoregional failure-free survival, 87.9% vs. 85.1%; P = .834). After adjusting for known prognostic factors in multivariate analysis, IC was not an independent prognostic factor for any outcome (all P > .05); subgroup analysis based on T category (T1-2/T3-4), N category (N0-1/N2-3), and overall stage (III/IV) confirmed these results. The incidence of hepatic function damage in the IC + CCRT and CCRT groups was not significantly different. CONCLUSION: IC + CCRT leads to comparable survival outcomes and hepatic function damage compared to CCRT alone in patients with locoregionally advanced NPC with chronic hepatitis B infection in the IMRT era. Further investigations are warranted.     

Evaluación cognitiva global en personas vascoparlantes con demencia en estadios avanzados. Validación al euskera de la escala Severe Mini Mental State Examination (SMMSE-eus)

Introduction

Adaptation and validation to the Basque language of tests to assess advanced cognitive impairment is a not covered need for Basque-speaking people. The present work shows the validation of the Basque version of the Severe Mini Mental State Examination (SMMSE).

Utility of Genomic Analysis in Differentiating Synchronous and Metachronous Lung Adenocarcinomas from Primary Adenocarcinomas with Intrapulmonary Metastasis

Distinguishing synchronous and metachronous primary lung adenocarcinomas from adenocarcinomas with intrapulmonary metastasis is essential for optimal patient management. In this study, multiple lung adenocarcinomas occurring in the same patient were evaluated using comprehensive histopathologic evaluation supplemented with molecular analysis. The cohort included 18 patients with a total of 52 lung adenocarcinomas. Eleven patients had a new diagnosis of multiple adenocarcinomas in the same lobe (n = 5) or different lobe (n = 6). Seven patients had a history of lung cancer and developed multiple new tumors. The final diagnosis was made in resection specimens (n = 49), fine needle aspiration (n = 2), and biopsy (n = 1). Adenocarcinomas were non‐mucinous, and histopathologic comparison of tumors was performed. All tumors save for one were subjected to ALK gene rearrangement testing and targeted Next Generation Sequencing (NGS). Using clinical, radiologic, and morphologic features, a confident conclusion favoring synchronous/metachronous or metastatic disease was made in 65% of patients. Cases that proved challenging included ones with more than three tumors showing overlapping growth patterns and lacking a predominant lepidic component. Genomic signatures unique to each tumor were helpful in determining the relationship of multiple carcinomas in 72% of patients. Collectively, morphologic and genomic data proved to be of greater value and achieved a conclusive diagnosis in 94% of patients. Assessment of the genomic profiles of multiple lung adenocarcinomas complements the histological findings, enabling a more comprehensive assessment of synchronous, metachronous, and metastatic lesions in most patients, thereby improving staging accuracy. Targeted NGS can identify genetic alterations with therapeutic implications.     

Preliminary SAR and biological evaluation of antitubercular triazolothiadiazine derivatives against drug-susceptible and drug-resistant Mtb strains

Following up the SAR study of triazolothiadiazoles for their antitubercular activities targeting Mt SD in our previous study, on the principle of scaffold hopping, the C3 and C6 positions of triazolothiadiazine were examined systematically to define a preliminary structure–activity relationship (SAR) with respect to biological activity. This study herein highlights the potential of two highly potent advanced leads 6c-3, 6g-3 and several other compounds with comparable potencies as promising new candidates for the treatment of TB (6c-3, MIC-H37Rv = 0.25 μg/mL; MIC-MDRTB = 2.0 μg/mL; MIC-RDRTB = 0.25 μg/mL; Mt SD-IC₅₀ = 86.39 μg/mL; and 6g-3, MIC-H37Rv = 1.0 μg/mL; MIC-MDRTB = 4.0 μg/mL; MIC-RDRTB = 2.0 μg/mL; Mt SD-IC₅₀ = 73.57 μg/mL). Compounds 6c-3 and 6g-3 possessed a para-nitro phenyl at the 6 position showed low Vero and HepG2 cells toxicity, turning out to be two excellent lead candidates for preclinical trials. In addition, in vitro Mt SD inhibitory assay indicates that Mt SD is at least one of the targets for their antitubercular activity. Thus, they may turn out to be promising multidrug-resistance-reversing agents.     

Interaction with angiotensin-converting enzyme-encoding gene in female infertility: Insertion and deletion polymorphism studies

Angiotensin-converting enzyme (ACE), a key enzyme in the renin– angiotensin–aldosterone system, converts angiotensin I to angiotensin II. Ethnic origin should be carefully considered in studies pertaining to ACE I/D genotype and disease etiology. This study was evaluated between the ACE gene I/D polymorphism and female infertility in the Saudi population. Out of a A total of 300 women who participated in this study genomic DNA samples from the 150 infertile and 150 fertile women’s were isolated who has participated in this study. Genomic DNA was isolated using an Invitrogen kit according to the manufacturer’s protocol, and D allele specific primers were used for amplification by polymerase chain reaction. Electrophoresis was carried out on a 2% agarose gel. The mean age and BMI of the cases and controls were similar (p > 0.05), and a significant association was noted between the family history and female infertility (p = 0.0001). The D allele (OR: 1.67 [95% CI: 1.18–2.35], p = 0.003), DD genotype (OR: 2.46 [95% CI: 1.20–5.02], p = 0.01) and dominant model (OR: 1.97 [95% CI: 1.00–3.88], p = 0.04) were significantly associated with female infertility or fertility. The results of this study show that the ACE polymorphism plays an important role in female infertility in the Saudi population.     

Discovery of (R)-5-(benzo[d][1,3]dioxol-5-yl)-7-((1-(vinylsulfonyl)pyrrolidin-2-yl)methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine (B6) as a potent Bmx inhibitor for the treatment of NSCLC

Described as a Btk inhibitor, ibrutinib also potently inhibits Bmx and EGFR, two good targets for lung cancer. Owing to its high CLogP (4.07) and low aqueous solubility (<0.01 mg/ml), resulting in unfavorable bioavailability, ibrutinib requires high dosages to achieve good clinical response in the treatment of non-small cell lung cancer (NSCLC). In our effort to improve the CLogP of ibrutinib by structural optimization led to the discovery of a potent anti-cancer agent B6, with beneficial physicochemical parameters (CLogP = 2.56, solubility in water ≈ 0.1 mg/ml) meeting the principles of oral drugs. B6 exhibited anti-proliferation activities against EGFR-expressing cells, especially the mutant ones, such as H1975 (L858R/T790M, IC₅₀ = 0.92 ± 0.19 μM) and HCC827 (Del119 IC₅₀ = 0.014 ± 0.01 μM). Moreover, B6 significantly slowed down H1975 tumor growth with anti-tumor rate of 73.9% (p < 0.01). Enzyme potencies assay demonstrated B6 moderately selectively inhibited Bmx (IC₅₀ = 35.7 ± 0.1 nM) over other kinases. So, as a potent Bmx inhibitor, B6 has the potential to be an efficacious treatment for NSCLC with acquired drug resistance.     

NFATc1 Expression as a Prognosticator in Urothelial Carcinoma of the Upper Urinary Tract

We recently found that NFATc1, a member of the NFAT family and a key regulator of the immune response, could induce bladder carcinogenesis and cancer progression. In this study, we immunohistochemically stained for NFATc1 in upper urinary tract urothelial carcinoma (UUTUC) specimens and paired nonneoplastic urothelial tissues. NFATc1 was positive in 51 [52%; 40 (40%) weak (1+), 9 (9%) moderate (2+), and 2 (2%) strong (3+)] of 99 UUTUCs, which was significantly higher than in benign urothelium [30 (36%) of 83; 28 (34%) weak and 2 (2%) moderate] (0 vs 1+/2+/3+, P = .038; 0/1+ vs 2+/3+, P = .023). There were no significant associations between NFATc1 expression pattern and tumor grade or pT stage. However, the positive rates of NFATc1 expression tended to be higher in renal pelvic tumors (60%) than in ureteral tumors (42%; P = .080) as well as in pN+ tumors (75%) than in pN0 tumors (49%; P = .089). Kaplan-Meier and log-rank tests revealed that moderate (2+) to strong (3+) NFATc1 expression correlated with lower progression-free survival (P = .032) and cancer-specific survival (P = .005) rates in the 99 cases. Patients with high (2+/3+) NFATc1 muscle-invasive tumor (n = 9) also had a significantly higher risk of cancer-specific mortality (P = .021) compared to those with low (0/1+) NFATc1 muscle-invasive tumor (n = 53). Thus, compared with nonneoplastic urothelium, a significant increase in the expression of NFATc1 in UUTUC was seen, implying the involvement of NFATc1 signals in the development of UUTUC. The current results further suggest that NFATc1 overexpression serves as a predictor of poor prognosis in patients with UUTUC.     

Anthropometric dimensions provide reliable estimates of abdominal adiposity: A validation study

Abdominal fat accumulation is a major risk factor for cardiometabolic morbidity and mortality. The purpose of the study is to assess the possibility of developing accurate estimation equations based on body measurements to determine total abdominal (TFA), subcutaneous (SFA) and visceral fat area (VFA). Hungarian volunteers (n = 198) aged between 20 and 81 years were enrolled in the study, which was conducted between July and November 2014. All persons underwent anthropometric measurements and computer tomographic (CT) scanning. Sex-specific multiple linear regression analyses were conducted in a subgroup of 98 participants to generate estimation models, then Bland–Altman's analyses were applied in the cross-validation group to compare their predictive efficiency. The variables best predicting VFA were hip circumference, calf circumference and waist-to-hip ratio (WHR) for males (R² = 0.713; SEE = 5602.1 mm²) and sagittal abdominal diameter (SAD), WHR, thigh circumference and triceps skinfold for females (R² = 0.845; SEE = 3835.6 mm²). The SFA prediction equation included SAD, thigh circumference and abdominal skinfold for males (R² = 0.848; SEE = 4124.1 mm²), body mass index and thigh circumference for females (R² = 0.861; SEE = 5049.7 mm²). Prediction accuracy was the highest in the case of TFA: hip circumference and WHR for males (R² = 0.910; SEE = 5637.2 mm²), SAD, thigh circumference and abdominal skinfold for females (R² = 0.915; SEE = 6197.5 mm²) were used in the equations. The results suggested that deviations in the predictions were independent of the amount of adipose tissue. Estimation of abdominal fat depots based on anthropometric traits could provide a cheap, reliable method in epidemiologic research and public health screening to evaluate the risk of cardiometabolic events.     

Traveling behavior of a termite in tunnels with different curvatures and base surface roughness

This study focused on understanding the termite traveling behavior. Artificial tunnels with different curvatures and base surface roughness were constructed. Each tunnel was 50 mm in length, with widths of W (W = 2, 3, or 4 mm). The distance between the two ends of the tunnel was D (D = 20, 30, 40, or 50 mm). A higher value of D means a lower curvature. The roughness, R (R = 60, 120, 240 and ∞), was generated by uniformly sanding the substrate with a sanding machine. A higher R value means a finer base surface. The symbol ∞ represents a smooth surface. Time (τ) taken by a termite to pass through the tunnel was measured. τ was longer in tunnels with a smooth surface compared with the tunnels with a rough surface. When W = 2, there was no effect of the roughness on speed. This is because the narrow tunnel width diluted the effects of the smoothness of the surface. When W = 3, τ was statistically shorter for R = 240, than for R = 60 and 120. This suggests that an appropriate surface roughness could positively contribute to the traveling speed.     

Genetic Variations of GWAS-Identified Genes and Neuroblastoma Susceptibility: a Replication Study in Southern Chinese Children

Neuroblastoma is one of the most commonly diagnosed solid cancers for children, and genetic factors may play a critical role in neuroblastoma development. Previous genome-wide association studies (GWASs) have identified nine genes associated with neuroblastoma susceptibility in Caucasians. To determine whether genetic variations in these genes are also associated with neuroblastoma susceptibility in Southern Chinese children, we genotyped 25 polymorphisms within these genes by the TaqMan method in 256 cases and 531 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the strength of the associations. We performed a meta-analysis to further evaluate the associations. Furthermore, we calculated the area under the receiver-operating characteristic curves (AUC) to assess which gene/genes may better predict neuroblastoma risk. We confirmed that CASC15 rs6939340 A > G, rs4712653 T > C, rs9295536 C > A, LIN28B rs221634 A > T, and LMO1 rs110419 A > G were associated with significantly altered neuroblastoma susceptibility. We also confirmed that rs6939340 A > G (G versus A: OR = 1.30, 95% CI = 1.13-1.50) and rs110419 G > A (A versus G: OR = 1.37, 95% CI = 1.19-1.58) were associated with increased neuroblastoma risk for all subjects. We also found that the combination of polymorphisms in CASC15, LIN28B, and LMO1 may be used to predict neuroblastoma risk (AUC = 0.63, 95% CI = 0.59-0.67). Overall, we verified five GWAS-identified polymorphisms that were associated with neuroblastoma susceptibility alteration for Southern Chinese population; however, these results need further validation in studies with larger sample sizes.