Activated androgen receptor binds to androgen-responsive elements (AREs) in genome to regulate target gene transcription and, consequently, mediates physiological or tumorigenic processes of the ...prostate. Our aim was to determine whether genetic variants in AREs are associated with clinical outcomes after androgen-deprivation therapy (ADT) in prostate cancer patients.
We systematically investigated 55 common single-nucleotide polymorphisms (SNPs) in the genome-wide insilico-predicted AREs in a cohort of 601 men with advanced prostate cancer treated with ADT. The prognostic significance of these SNPs on disease progression, prostate cancer-specific mortality (PCSM) and all-cause mortality (ACM) after ADT was assessed by Kaplan–Meier analysis and Cox regression model.
In univariate analysis, two, five, and four SNPs were associated with disease progression, PCSM, and ACM, respectively. After adjusting for known prognostic factors, ARRDC3 rs2939244, FLT1 rs9508016, and SKAP1 rs6504145 remained as significant predictors for PCSM and FBXO32 rs7830622 and FLT1 rs9508016 remained as significant predictors for ACM in multivariate analysis. Moreover, strong combined genotype effects on PCSM and ACM were also observed (Ptrend < 0.001).
Our results suggest that SNPs in AREs influence prostate cancer survival and may further advance our understanding of the disease progression.
The results of recent research on the dynamic response, failure mechanism, and changes in the load-transfer paths of a half-scale three-story, three-bay, and three-span reinforced concrete frame ...subjected to a series of sudden column removals are presented. Three phases of testing were carried out, including the removal of a corner column and a column adjacent to the corner column along the short span direction, two middle exterior columns along the long span direction, and one interior column. The column removal was enabled by using a gas cannon. The dynamic response at critical locations after the imposed failure of the respective columns was observed. The removal of the corner column followed by the adjacent column resulted in only an essentially elastic response of the structure. The removal of an interior column resulted in only small deflections. The removal of the two first-story exterior columns resulted in significant vertical deflections of the middle exterior columns and significant yielding at adjacent beams that framed into the two middle exterior columns.
. Huang C‐N, Huang S‐P, Pao J‐B, Hour T‐C, Chang T‐Y, Lan Y‐H, Lu T‐L, Lee H‐Z, Juang S‐H, Wu P‐P, Huang C‐Y, Hsieh C‐J, Bao B‐Y (Kaohsiung Medical University Hospital, Kaohsiung; Kaohsiung Medical ...University, Kaohsiung; Taipei City Hospital, Taipei; Kaohsiung Medical University, Kaohsiung; China Medical University, Taichung; National Taiwan University Hospital; Oriental Institute of Technology; National Taiwan University, Taipei; China Medical University Hospital, Taichung, Taiwan). Genetic polymorphisms in oestrogen receptor‐binding sites affect clinical outcomes in patients with prostate cancer receiving androgen‐deprivation therapy. J Intern Med 2012; 271: 499–509.
Background. Accumulating evidence indicates that oestrogens have significant direct effects on normal prostate development and carcinogenesis. The majority of the biological activities of oestrogens are mediated through the oestrogen receptor (ER), which functions as a hormone‐inducible transcription factor to regulate target gene expression by binding to oestrogen response elements (EREs) in the regulatory regions of target genes. Sequence variants in EREs might affect the ER–ERE interaction and subsequent physiological activities. Therefore, we tested whether common single‐nucleotide polymorphisms (SNPs) inside EREs are related to the clinical outcomes of androgen‐deprivation therapy (ADT) in men with prostate cancer.
Methods. We systematically evaluated 49 ERE SNPs predicted using a genome‐wide database in a cohort of 601 men with advanced prostate cancer treated with ADT. The prognostic significance of these SNPs on disease progression, prostate cancer‐specific mortality (PCSM) and all‐cause mortality (ACM) after ADT was assessed using Kaplan–Meier analysis and a Cox regression model.
Results. Based on multiple hypothesis testing, BNC2 rs16934641 was found to be associated with disease progression; in addition, TACC2 rs3763763 was associated with PCSM, and ALPK1 rs2051778 and TACC2 rs3763763 were associated with ACM. These SNPs remained significant in multivariate analyses that included known clinicopathological predictors. Moreover, a combined genotype effect on ACM was observed when ALPK1 rs2051778 and TACC2 rs3763763 were analysed in combination. Patients with a greater number of unfavourable genotypes had a shorter time to ACM during ADT (P for trend <0.001).
Conclusion. The incorporation of ERE SNPs into models with known predictors might improve outcome prediction in patients with prostate cancer receiving ADT.
AbstractIn this study, an experimental investigation of the thermal effect of welding on the mechanical behavior of thermomechanical control process (TMCP) high-strength steel (HSS) Q690CFD is ...carried out. Twenty-four specimens in four groups with different welding heat input, strength mismatch ratio of weld filler and base material, heat treatment condition preheating (PH) and postweld heat treatment (PWHT), as well as mechanical boundary condition during the welding process are designed and tested. The thermal history and cooling rate are monitored and analyzed. The welding residual stress near the weld toe and the microstructure of the heat-affected zone (HAZ), as well as Vickers hardness, are respectively examined with the ASTM hole-drilling method, metallurgical microscope observation, and Vickers hardness tests. The effect of heat input (q), mismatch ratio (r), heat treatment, and mechanical boundary conditions on welding residual stress, microstructure, and hardness of the HAZ is investigated. The effect of welding heat input on the tensile behavior of the TMCP HSS is studied. Results indict that different heat inputs could have varied cooling times and cooling rates and hence could produce different distributions of residual stress. When the same PH and PWHT is applied, the heat treatment could have better stress-relief effect for the specimens without mismatching. In addition, the width of the HAZ increases steadily with the increase in heat input. A good yield and ultimate strength prediction from hardness can be observed for base steel and welded connections.
To prospectively evaluate multiple b-value diffusion-weighted imaging (DWI) in differentiating malignant from benign breast lesions.
The study cohort included 103 patients who underwent 3 T magnetic ...resonance imaging (MRI). The conventional sequences included T1-weighted dynamic contrast-enhanced, T1-weighted and T2-weighted fat-suppressed sequences, single b-value (b=0, 1000 s/mm2) DWI, and multiple b-values (12 values, from 0 to 3,000 s/mm2) DWI. Pathological diagnosis of breast lesions was based on the latest World Health Organization (WHO) guide on the pathology and immunohistochemistry of the breast. SPSS Statistics V19.0 was used for the statistics analysis.
The following parameters were calculated: apparent diffusion coefficient (ADC), tissue diffusivity (D), perfusion fraction (f), pseudo-diffusion coefficient (D∗), distributed diffusion coefficient (DDC), and alpha (α) by the same radiologist twice (interval time of 3 months). There was good inter/intra-observer agreement for each of the parameters. The D, D∗, f, DDC, and α values were significantly different among malignant tumours, benign lesions, and normal breast tissue (p<0.05).
D, f, DDC, α, and ADC values have good sensitivity and specificity, respectively. In addition, the combined use of D and f or DDC and α has good diagnostic performance. Thus, the applications of the new multi-b DWI variables or combined variables are promising.
•Evaluating multiple b-value DWI in differentiating malignant from benign breast lesions.•Demonstrating a novel DWI method using multiple b-values in the evaluation of breast lesions.•The applications of the new multi-b DWI variables or combined variables are promising.
Breast cancer incidence rates are increasing among Asian women, likely due to the changes in risk factors caused by globalization. Trends in breast cancer rates among Chinese women may differ from ...other Asian regions due to the implementation of a nationwide family planning program and resulting changes in women's reproductive practices. Appraisal of cancer trends can direct cancer control and public health planning, but relevant studies in China are scarce due to a lack of long-term data. We sought to evaluate secular time trends in breast cancer incidence and mortality using 40 years of cancer registry data for women in urban Shanghai.
Data on invasive breast cancer incidence and mortality were collected by the Shanghai Cancer Registry. Age-standardized rates (ASRs) for incidence and mortality were calculated using the Segi/Doll 1960 world standard population. Age, period, and birth cohort effects were evaluated using age–period–cohort (APC) Poisson regression models. Overall linear trends, interpreted as the estimated annual percentage change (EAPC), were derived from the net drift in age–drift models.
A total of 53 885 breast cancer cases and 17 235 breast cancer-specific deaths were documented among women in urban Shanghai between 1 January 1973 and 31 December 2012. Breast cancer incidence and mortality ASRs increased by 141.2% and 26.6%, respectively. Significant age, cohort, and period effects were identified in both incidence and mortality APC models; cohort effects were pronounced. Overall, a substantial increase in breast cancer incidence (EAPC = 2.96%/year) and a moderate increase in breast cancer mortality (EAPC = 0.87%/year) was observed. A notable downward trend in mortality was identified among younger women born after 1960.
Forty years of cancer registry data document a tremendous increase in incidence and a slight increase in mortality for breast cancer among women in Shanghai. Effective, appropriate, and affordable breast cancer prevention and control strategies are urgently needed in China.
Cable-suspended parallel robot (CPR), in which cables are utilized to replace links to manipulate objects, is developed from parallel and serial cable-driven robot. Compared with the parallel robot, ...this kind of robot has more advantages. The cooperative variation of lengths of six cables pulls the feed cabin to track radio source with six degrees of freedom (DOFs). Similar to a parallel robot, the cable-cabin mechanism for 500-m aperture spherical radio telescope (FAST) can be viewed as a CPR. According to its 5-m scaled model, based on the inverse kinematics analysis the inverse dynamic formulation of CPR with non-negligible cable mass is established using Lagrangian dynamic formulation. Then, considering random wind forces acted on the cabin are simulated based on the characters of the mechanism, a fuzzy plus proportional–integral control (FPPIC) method, which can enhance the control performance for steady-state errors, is utilized to control the wind-induced vibration of the trajectory tracking of the feed cabin. Finally, we provide the examples of simulation and experiment to justify the dynamic modeling for control and to test the proposed method.
Testosterone has been found to play important roles in men's sexual function. However, the effects of testosterone can be modulated by androgen receptor (AR) CAG repeat polymorphism. It could also ...contribute to the risk of erectile dysfunction (ED). The aim of this study is to evaluate the interaction of serum testosterone levels and AR CAG repeat polymorphism on the risk of ED in aging Taiwanese men. This cross‐sectional data of Taiwanese men older than 40 years were collected from a free health screening held between August 2010 and August 2011 in Kaohsiung city, Taiwan. All participants completed a health questionnaires included five‐item version of the International Index of Erectile Function (IIEF‐5) and the International Prostate Symptoms Score, received a detailed physical examination and provided 20 cm3 whole blood samples for biochemical and genetic evaluation. The IIEF‐5 was used to evaluate ED. Serum albumin, total testosterone (TT), and sex hormone‐binding globulin levels were measured. Free testosterone level was calculated. AR gene CAG repeat polymorphism was determined by direct sequencing. Finally, 478 men with the mean age of 55.7 ± 4.8 years were included. When TT levels were above 330 ng/dL, the effect of testosterone level on erectile function seemed to reach a plateau and a significantly negative correlation between AR CAG repeat length and the score of IIEF‐5 was found (r = −0.119, p = 0.034). After adjusting for other covariates, the longer AR CAG repeat length was still an independent risk factor for ED in subjects with TT above 330 ng/dL (p = 0.006), but not in TT of 330 ng/dL or below. In conclusion, both serum testosterone levels and AR CAG repeat polymorphism can influence erectile function concomitantly. In subjects with normal TT concentration, those with longer AR CAG repeat lengths have a higher risk of developing ED.
•A series of parametric study was carried out to investigate effect of geometry and imperfections on column strength.•α and χ are positively correlated: χ increases at different rates as α ...increases.•χ decreases with the increase of β at very low rate and the effect of β on χ is not very obvious.•Residual stress does not always have negative effect on χ.
The paper describes a numerical study on columns fabricated from high strength steel (HSS) plates with nominal yield stress of 690 MPa. The study comprised 4 benchmark models validated by testing data and 144H-section parametric study models. The benchmark models were firstly created and validated against testing data for the accuracy. A full-scale parametric study was carried out to investigate effect of flange width/thickness ratio (α), web height/thickness ratio (β), geometrical imperfection (D) and residual stress (R) on overall buckling behaviour of the columns. The purpose of the study was to understand the relationship between section geometry, imperfections and column strength fabricated by welding from 690 MPa high strength steel plates. The H-section HSS columns were studied in this paper for the buckling behaviour along the minor axis in which direction those columns have smaller stiffnesses.
It is shown that all those factors can be classified into three groups according to their impact on column strength (expressed with strength reduction factor χ): favourable factor (α), adverse factor (β and D) and uncertain factor (R). α and χ are positively correlated: χ increases at different rates as α increases. It is an effective way to increase α to improve column strength when α is a small value. χ decreases with the increase of β at very low rate and the effect of β on χ is not very obvious. D could produce more pronounced deterioration effect on ultimate strength of columns with higher α. The effect of residual stress (R) on H-section column strength is related with α: for the columns with higher α value, higher residual stress could produce more serious strength reduction effect. Residual stress does not always have negative effect on χ. It could produce beneficial effect on the ultimate strength of high strength steel H-section columns as long as α is reasonably small.
The paper also shows a comparison of analysis results with existing standards including Eurocode 3 and GB50017-2017. For Eurocode 3, curve a0 can accurately predict χ with λ¯ when D = 0.03%. When D = 0.20%, curve b gives the best-fit prediction.
Predicting antidepressant treatment response has been a clinical challenge for major depressive disorder (MDD). The inflammation hypothesis of depression suggests that cytokines play a key role in ...the pathophysiology of MDD and alterations in peripheral cytokine levels are associated with antidepressant treatment outcome. Present meta-analysis aimed to examine the association between baseline peripheral cytokine levels and the response to antidepressant treatment and to evaluate whether changes of cytokine levels were associated with the response to antidepressant treatment in patients with MDD. Human-based studies published in any language in peer-reviewed journals were systematically searched from the PubMed, Embase and Web of Science databases, from inception up to October 2018. The search terms included cytokine, depressive disorder and antidepressant and their synonyms. Case-control or case-case studies reporting on levels of IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, CRP, TNF-α, IFN-γ, GM-CSF, MIP-1α, and Eotaxin-1 in patients with MDD based on validated depression scales both before and after antidepressant treatment were included. Of 7408 identified records, 44 studies met inclusion. Standardized mean differences in each cytokine were evaluated, and random-effects meta-analyses were performed. MDD patients who responded to antidepressant treatment had lower baseline IL-8 levels than the nonresponders (Hedge's g = -0.28; 95%CI, -0.43 to -0.13; P = 0.0003; FDR = 0.004). Antidepressant treatment significantly decreased levels of TNF-α (Hedge's g = 0.60; 95%CI, 0.26-0.94; P = 0.0006; FDR = 0.004) only in responders, and responders showed significantly more decreased TNF-α levels compared with nonresponders (P = 0.046). These findings suggested that alterations in peripheral cytokine levels were associated with antidepressant treatment outcomes in MDD. Further investigations are warranted to elucidate sources of heterogeneity and examine the potentiality of using inflammatory cytokines as novel predictive markers for the pharmacological treatment of MDD.
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