Carboplatin/taxane-induced gastrointestinal toxicity: a pharmacogenomics study on the SCOTROC1 trial

Carboplatin/taxane combination is first-line therapy for ovarian cancer. However, patients can encounter treatment delays, impaired quality of life, even death because of chemotherapy-induced gastrointestinal (GI) toxicity. A candidate gene study was conducted to assess potential association of genetic variants with GI toxicity in 808 patients who received carboplatin/taxane in the Scottish Randomized Trial in Ovarian Cancer 1 (SCOTROC1). Patients were randomized into discovery and validation cohorts consisting of 404 patients each. Clinical covariates and genetic variants associated with grade III/IV GI toxicity in discovery cohort were evaluated in replication cohort. Chemotherapy-induced GI toxicity was significantly associated with seven single-nucleotide polymorphisms in the ATP7B, GSR, VEGFA and SCN10A genes. Patients with risk genotypes were at 1.53 to 18.01 higher odds to develop carboplatin/taxane-induced GI toxicity (P<0.01). Variants in the VEGF gene were marginally associated with survival time. Our data provide potential targets for modulation/inhibition of GI toxicity in ovarian cancer patients

Fracture Characteristics of B1500HS Steel Hot Blank Parts

Warm and hot blanking processes were developed for solving problems in piercing and trimming of press-hardened parts, some fine blank parts with comprehensive mechanical properties could be produced by hot blanking. To establish the optimum blanking processes and evaluate the effect of blanking temperature on the sheared section surface and fracture direction. Along with the fracture mechanism and microstructure of the parts, a series of hot blanking experiments for B1500HS steels were carried out at different blanking temperatures (450–800°C) and an 8% die clearance. The experimental results show that with the blanking temperature, the smooth (burnish) zone width increases, and the fracture direction becomes nearly normal. The sheared section surface of the parts mainly demonstrates ductile fracture mainly, accompanied by local brittle fracture over the blanking temperature range of 450–600°C. A ductile fracture region contains a great amount of fine equiaxed dimples over the blanking temperature range of 650–800°C, their microstructure is of complete martensite.Разработаны процессы холодной и горячей вырубки, позволяющие решить проблемы пробивки и обрезки заготовок, полученных упрочнением под давлением. Показано, что горячая вырубка позволяет получать небольшие заготовки с полным набором механических свойств для определения оптимальных режимов вырубки и оценки влияния температуры на поверхность площадки сдвига и направление разрушения. Изучены механизм разрушения и микроструктура заготовок, выполнена серия экспериментов по горячей вырубке для стали B1500HS при различных температурах (450-800°С) и 8% отношении зазора в штампе. Экспериментально доказано, что с ростом температуры вырубки увеличивается ширина гладкой зоны, а направление разрушения становится близким к вертикальному. Поверхность площадки сдвига характеризуется вязким разрушением, сопровождающимся локальным хрупким разрушением в диапазоне температур 450-600°С. Область вязкого разрушения содержит большое количество мелких равноосных лунок в диапазоне температур 650-800°С, их микроструктура полностью состоит из мартенсита

Blood biomarkers for new-onset hypertension in midlife women:a nested case-control study

Objective Midlife in women is associated with an increase in prevalence of hypertension. Little is known on the risk factors of new-onset hypertension among middle-aged women. Methods In this nested case-control study, 1,430 women aged 40 to 60 years with repeated physical examinations between 2009 and 2019 were recruited. Data included age, body mass index, blood pressure (BP), and a series of blood biomarkers. Participants with hypertension were divided into two case-control samples: 388 cases with episodic new-onset hypertension (ie, one normal BP at the first visit and one abnormal BP during follow-up) each with two age-matched controls (n = 776) and 151 cases with regular new-onset hypertension (ie, normal BP at the first two visits and abnormal BP at two or more follow-up visits) each with three age-matched controls (n = 453). Multivariable-adjusted logistic regression was used to analyze the data. Results Our data showed very consistent results for episodic and regular new-onset hypertension, respectively, and verified known associations (odds ratio [95% confidence interval], per SD increase) with obesity (body mass index, 1.72 [1.49-1.98] and 1.81 [1.45-2.26]), inflammation (white blood cell count, 1.39 [1.23-1.58] and 1.38 [1.13-1.69]), and metabolic dysregulation (triglycerides, 1.25 [1.09-1.44] and 1.31 [1.08-1.58]; glucose, 1.46 [1.23-1.73] and 1.27 [1.05-1.54]) but, more surprisingly, also revealed positive associations with red blood cell count (1.27 [1.11-1.44] and 1.38 [1.14-1.68]), hemoglobin (1.18 [1.03-1.35] and 1.31 [1.05-1.64]), and platelet count (1.39 [1.20-1.61] and 1.33 [1.09-1.63]). Conclusions In addition to obesity and metabolic dysregulation, increased hemoglobin and counts of platelets, and red and white blood cells are associated with hypertension in this period. Future study may verify whether these associations are causal in nature and whether these variables are useful in risk stratification.</p

Blood biomarkers for new-onset hypertension in midlife women:a nested case-control study

Objective Midlife in women is associated with an increase in prevalence of hypertension. Little is known on the risk factors of new-onset hypertension among middle-aged women. Methods In this nested case-control study, 1,430 women aged 40 to 60 years with repeated physical examinations between 2009 and 2019 were recruited. Data included age, body mass index, blood pressure (BP), and a series of blood biomarkers. Participants with hypertension were divided into two case-control samples: 388 cases with episodic new-onset hypertension (ie, one normal BP at the first visit and one abnormal BP during follow-up) each with two age-matched controls (n = 776) and 151 cases with regular new-onset hypertension (ie, normal BP at the first two visits and abnormal BP at two or more follow-up visits) each with three age-matched controls (n = 453). Multivariable-adjusted logistic regression was used to analyze the data. Results Our data showed very consistent results for episodic and regular new-onset hypertension, respectively, and verified known associations (odds ratio [95% confidence interval], per SD increase) with obesity (body mass index, 1.72 [1.49-1.98] and 1.81 [1.45-2.26]), inflammation (white blood cell count, 1.39 [1.23-1.58] and 1.38 [1.13-1.69]), and metabolic dysregulation (triglycerides, 1.25 [1.09-1.44] and 1.31 [1.08-1.58]; glucose, 1.46 [1.23-1.73] and 1.27 [1.05-1.54]) but, more surprisingly, also revealed positive associations with red blood cell count (1.27 [1.11-1.44] and 1.38 [1.14-1.68]), hemoglobin (1.18 [1.03-1.35] and 1.31 [1.05-1.64]), and platelet count (1.39 [1.20-1.61] and 1.33 [1.09-1.63]). Conclusions In addition to obesity and metabolic dysregulation, increased hemoglobin and counts of platelets, and red and white blood cells are associated with hypertension in this period. Future study may verify whether these associations are causal in nature and whether these variables are useful in risk stratification.</p

PSO-based Parameter Estimation of Nonlinear Kinetic Models for β-Mannanase Fermentation

Particle swarm optimization (PSO), as a novel evolutionary algorithm involved in social interaction for global space search, was firstly used in kinetic parameter estimation. Based on three developed nonlinear kinetic equations for bacterial cell growth, total sugar utilization and β-mannanase production by Bacillus licheniformis under the support of a batch fermentation process, various PSO algorithms as well as gene algorithms (GA) were developed to estimate kinetic parameters. The performance comparison among these algorithms indicates the improved PSO (Trelea 1) is most suitable for kinetic parameter estimation of β-mannanase fermentation. In order to find the physical-chemical-meanings of kinetic parameters from many optimized results, multiobjective optimization with a normalized weight method was adopted. The 9 desired parameters in equations were obtained by the Trelea 1 type PSO with two batches fermentation data, and the results predicted by the models were also in good agreement with the experimental observations