Polymorphisms of XRCC4 are involved in reduced colorectal cancer risk in Chinese schizophrenia patients

<p>Abstract</p> <p>Background</p> <p>Genetic factors related to the regulation of apoptosis in schizophrenia patients may be involved in a reduced vulnerability to cancer. XRCC4 is one of the potential candidate genes associated with schizophrenia which might induce colorectal cancer resistance.</p> <p>Methods</p> <p>To examine the genetic association between colorectal cancer and schizophrenia, we analyzed five SNPs (rs6452526, rs2662238, rs963248, rs35268, rs2386275) covering ~205.7 kb in the region of XRCC4.</p> <p>Results</p> <p>We observed that two of the five genetic polymorphisms showed statistically significant differences between 312 colorectal cancer subjects without schizophrenia and 270 schizophrenia subjects (rs6452536, p = 0.004, OR 0.61, 95% CI 0.44-0.86; rs35268, p = 0.028, OR 1.54, 95% CI 1.05-2.26). Moreover, the haplotype which combined all five markers was the most significant, giving a global <it>p </it>= 0.0005.</p> <p>Conclusions</p> <p>Our data firstly indicate that XRCC4 may be a potential protective gene towards schizophrenia, conferring reduced susceptibility to colorectal cancer in the Han Chinese population.</p

Genomic Analyses Reveal Mutational Signatures and Frequently Altered Genes in Esophageal Squamous Cell Carcinoma

Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers worldwide and the fourth most lethal cancer in China. However, although genomic studies have identified some mutations associated with ESCC, we know little of the mutational processes responsible. To identify genome-wide mutational signatures, we performed either whole-genome sequencing (WGS) or whole-exome sequencing (WES) on 104 ESCC individuals and combined our data with those of 88 previously reported samples. An APOBEC-mediated mutational signature in 47% of 192 tumors suggests that APOBEC-catalyzed deamination provides a source of DNA damage in ESCC. Moreover, PIK3CA hotspot mutations (c.1624G>A [p.Glu542Lys] and c.1633G>A [p.Glu545Lys]) were enriched in APOBEC-signature tumors, and no smoking-associated signature was observed in ESCC. In the samples analyzed by WGS, we identified focal (<100 kb) amplifications of CBX4 and CBX8. In our combined cohort, we identified frequent inactivating mutations in AJUBA, ZNF750, and PTCH1 and the chromatin-remodeling genes CREBBP and BAP1, in addition to known mutations. Functional analyses suggest roles for several genes (CBX4, CBX8, AJUBA, and ZNF750) in ESCC. Notably, high activity of hedgehog signaling and the PI3K pathway in approximately 60% of 104 ESCC tumors indicates that therapies targeting these pathways might be particularly promising strategies for ESCC. Collectively, our data provide comprehensive insights into the mutational signatures of ESCC and identify markers for early diagnosis and potential therapeutic targets

Use of computational fluid dynamics to estimate hemodynamic effects of respiration on hypoplastic left heart syndrome surgery : total cavopulmonary connection treatments

Total cavopulmonary connection (TCPC), a typical kind of Fontan procedure, is commonly used in the treatment of a functional single ventricle. The palliative cardiothoracic procedure is performed by connecting the superior vena cava and the inferior vena cava to the pulmonary arteries. Due to the difficulty of direct study in vivo, in this paper, computational fluid dynamics (CFD) was introduced to estimate the outcomes of patient-specific TCPC configuration. We mainly focused on the influence of blood pulsation and respiration. Fast Fourier transforms method was employed to separate the measured flow conditions into the rate of breath and heart beat. Blood flow performance around the TCPC connection was investigated by analyzing the results of time-varying energy losses, blood flow distribution rate, local pressure, and wall shear stress distributions. It was found that the value of energy loss including the influence of respiration was 1.5 times higher than the value of energy loss disregarding respiratory influences. The results indicated that the hemodynamic outcomes of TCPC treatment are obviously influenced by respiration. The influence of respiration plays an important role in estimating the results of TCPC treatment and thus should be included as one of the important conditions of computational haemodynamic analysis.12 page(s

Using of porous portion to simulate pulmonary resistance in the computational fluid dynamic models of Fontan connection

In this study, we performed computational fluid dynamic (CFD) simulations in a patient-specific three-dimensional extracardiac conduit Fontan connection. The pulmonary resistance was incorporated in the CFD model by connecting porous portions in the left and right pulmonary arteries. The pressure in the common atrium was set as boundary conditions at the outlets of the pulmonary arteries. The flow rate in the innominate veins and the inferior vena cava (IVC) was set as inflow boundary conditions. Furthermore, the inflow rate of IVC was increased to 2 and 3 times of that measured to perform another two simulations and the resistance provided by the porous portions was compared among these three conditions. We found out that the pulmonary resistance set as porous portion in the CFD models remains relatively steady despite the change of the inflow rate. We concluded that, in the CFD simulations for the Fontan connections, porous portion could be used to represent pulmonary resistance steadily. The pulmonary resistance and pressure in the common atrium could be acquired directly by clinical examination. The employment of porous portion together with pressure in the common atrium in the CFD model could facilitate and accurate the set of outlet boundary conditions especially for those actual pulmonary flow splits was unpredictable such as virtual operative designs related CFD simulations.4 page(s

A Two-Stage Path Planning Algorithm Based on Rapid-Exploring Random Tree for Ships Navigating in Multi-Obstacle Water Areas Considering COLREGs

A two-stage ship path planning method is proposed, based on the Rapid-exploring Random Tree (RRT) algorithm, which is composed of global path planning and local path planning, addressing the important problem of finding an economical and safe path from start to destination for ships under dynamic environment, especially in waters with multiple obstacles and multiple target ships. The global path planning takes into consideration the ship draft and Under Keel Clearance to find navigable water using RRT, and reduces the path length and waypoints based on elliptic sampling and smoothing. In the local path planning, a dynamic collision risk detection model is constructed by introducing the Quaternion Ship Domain under a dynamic environment, and the restrictions of ship manoeuvrability and COLREGs are also involved. The simulation results show that the proposed model can find a satisfactory path within a few iterations, and keep clear of both static obstacles and dynamic ships. The research can be used to make and verify planned ship routes before sailing and to guide officers to make decisions regarding collision avoidance

Path Planning for Ferry Crossing Inland Waterways Based on Deep Reinforcement Learning

Path planning is a key issue for safe navigation of inland ferries. With the development of ship intelligence, how to enhance the decision&ndash;support system of a ferry in a complex navigation environment is one of the key issues. The inland ferries need to cross the channel frequently and, thus, risky encounters with target ships in the waterway are more frequent, so they need an intelligent decision&ndash;support system that can deal with complex situations. In this study, a reinforced deep learning method is proposed for path planning of inland ferries during crossing of the waterways. In the study, the state space, action space and reward function of the Deep Q-network (DQN) model are designed and improved to establish an autonomous navigation method for ferries considering both economy and safety. The DQN model also takes into account the crossing behavior, navigation economy and safety. Finally, the model is applied to case studies to verify its effectiveness

Self-organizing cooperation model for ships navigating in restricted one-way waterway

An effective ship scheduling strategy is critical for the efficiency of waterway transportation, especially in restricted one-way waterways. By treating ship traffic as a distributed system, a novel Ship Self-Organizing Cooperation algorithm (SSOCA) is proposed to evaluate the effects of self-organizing cooperation between ships. An assumption is made that overtaking is not allowed under the given safety requirement. Observing that traffic efficiency is influenced by speed differences, two types of delay times, wait time and navigation time as increased by speed reductions, are applied to evaluate traffic efficiency. The mathematical model of delay time is inferred in different entry sequences subsequently. Taking advantage of the delay model, each ship makes a decision regarding its own sequence to find the local optimum iteratively. An Arena-based ship traffic model is constructed. The simulation results indicate that average delay time for ships is decreased in comparison with the First Come First Served (FCFS) model. That advantage exists for different combinations of traffic flow parameters. Moreover, a balance between efficiency and computation is also achieved by distributing the computational burden to each ship

Thorea baiyunensis sp. nov. (Thoreales, Rhodophyta) and T. okadae, a new record from China

The freshwater red algal order Thoreales has a triphasic life history, of which the “Chantransia” phase is a small filamentous sporophyte. The “Chantransia” stage is difficult to distinguish from species in the genus Audouinella by its morphological characteristics. In this study, five “Chantransia” isolates (GX41, GX81, GD224, GD225, GD228) were collected from Guangxi Zhuang Autonomous Region and Guangdong Province in China. Based on morphological data, all five isolates were similar to A. pygmaea, whereas sequence data from the large subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase (rbcL) gene and the 5’ region of the mitochondrial cytochrome oxidase I gene (COI-5P) determined that these specimens represented the “Chantransia” stage of two species in the genus Thorea rather than Audouinella. Phylogenetic analyses of the concatenated genes supported the proposal of a new species, T. baiyunensis, and a new geographic record of T. okadae, a species previously described only in Japan. Therefore, combined with previous records, four species of this genus are now recognized in China, including T. hispida, T. violacea, T. baiyunensis and T. okadae