Genome-wide association study of lung adenocarcinoma in East Asia and comparison with a European population.

Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European studies, four loci were identified at 2p11, 4q32, 16q23, and 18q12. At the same time, most of our findings in East Asian populations showed no evidence of association in European populations. In our studies drawn from East Asian populations, a polygenic risk score based on the 25 loci had a stronger association in never-smokers vs. individuals with a history of smoking (Pinteraction = 0.0058). These findings provide new insights into the etiology of lung adenocarcinoma in individuals from East Asian populations, which could be important in developing translational applications

Genome-wide association study of lung adenocarcinoma in East Asia and comparison with a European population

Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European studies, four loci were identified at 2p11, 4q32, 16q23, and 18q12. At the same time, most of our findings in East Asian populations showed no evidence of association in European populations. In our studies drawn from East Asian populations, a polygenic risk score based on the 25 loci had a stronger association in never-smokers vs. individuals with a history of smoking (P interaction  = 0.0058). These findings provide new insights into the etiology of lung adenocarcinoma in individuals from East Asian populations, which could be important in developing translational applications

Wetland Function for Mitigating Floods in a Downstream Level Controlled River

In this study, we present a case study to assess backwater effects induced by hydraulic structures and restored stream vegetation on wetland flood reduction (peak discharge attenuation and peak time delay). A coupled surface-groundwater model, HydroGeoSphere, is applied for the subwatershed including the Yahara River, Cherokee Marsh and downstream Lake Mendota, where the Tenney dam and the Highway 113 bridge constriction are located. The effects with and without hydraulic structures on hydrological connectivity and flood storage capacity are compared. Furthermore, we examine the potential benefit of flood reduction for a large scale stream vegetation restoration at the study site. Results show that hydraulic structures and restored stream vegetation induced backwater can increase hydrological connectivity between river and wetlands. The total flood storage capacity dramatically increases for the integrated backwater wetland system. Overall it is suggested that the backwater wetland provide an optimal flood reduction by keeping the hydraulic structures and restoring the stream vegetation

An Urban Water Pollution Model for Wuhu City

An in-depth study of the temporal and spatial distribution of pollution loads can assist in the development of water pollution remediation. The research scope of this paper was the highly developed Wuhu City located south of the Yangtze River. Chemical oxygen demand (COD), NH3-H, and total phosphorus (TP) were chosen as the pollutant research objects of this study. Then, by combining the natural and social conditions within the scope of the study, a balanced system of pollution load generation and migration was described. A pollution load model of Wuhu City based on Load Calculator, MIKE 11, and ArcGIS was established. The results indicate that, in terms of the time distribution, the changes in the influx of the different pollutants were consistent. In terms of the spatial distribution, the major contributions to the annual pollution load were domestic pollution, urban surface runoff pollution, and poultry breeding pollution. The major contributors to the annual pollution load into the river were domestic pollution, urban surface runoff pollution, and sewage plant tail water pollution. This analysis provides references for the comprehensive management of local water environments

Laboratory Studies of Internal Solitary Waves Propagating and Breaking over Submarine Canyons

This paper carried out laboratory experiments to study evolution of internal solitary waves (ISWs) over submarine canyons with a combination of PIV (particle image velocimetry) and PLIF (planar laser-induced fluorescence) techniques. Taking canyon angle θ and collapse height ∆H as variables, Froude number Fr, head position, energy loss, vorticity field and turbulence intensity when ISWs propagate to the canyon were analyzed. According to the Froude number Fr values, the study cases can be divided into three types: Fr > 1.7 means complete internal hydraulic jump (IHJ); 1 < Fr < 1.7 denotes wavy IHJ and Fr < 1 represents no IHJ. The greater canyon angle, collapse depth and amplitude of the incident wave more easily generate IHJs, which can lead to more energy loss, greater vorticity and turbulence intensity in the canyon area. Among all canyon cases, vorticity and turbulence intensity of the no IHJ case showing an obvious bimodal distribution are smaller than IHJ cases. For wavy IHJ, the energy dissipation is not obvious, and the average turbulent intensity performs a “sharp unimodal distribution”. Complete IHJ cases last for a long time and cause violent mixing, the average turbulent intensity is the largest and its distribution presents a “gentle single peak” pattern. For the 180° conditions (no canyon cases), less energy is delivered to the reflected wave and more energy is dissipated near the terrain, so the energy loss is the largest in comparison to other conditions. These findings will deepen our understanding of the evolution mechanisms of ISWs propagating over submarine canyons

A CT-based deep learning model: visceral pleural invasion and survival prediction in clinical stage IA lung adenocarcinoma

Summary: Pathologic visceral pleural invasion (VPI) in patients with early-stage lung cancer can result in the upstaging of T1 to T2, in addition to having implications for surgical resection and prognostic outcomes. This study was designed with the goal of establishing and validating a CT-based deep learning (DL) model capable of predicting VPI status and stratifying patients based on their prognostic outcomes. In total, 2077 patients from three centers with pathologically confirmed clinical stage IA lung adenocarcinoma were enrolled. DL signatures were extracted with a 3D residual neural network. DL model was able to effectively predict VPI status. VPI predicted by the DL models, as well as pathologic VPI, was associated with shorter disease-free survival. The established deep learning signature provides a tool capable of aiding the accurate prediction of VPI in patients with clinical stage IA lung adenocarcinoma, thus enabling prognostic stratification

Phase II study of Pseudomonas aeruginosa-Mannose-Sensitive hemagglutinin in combination with capecitabine for Her-2-negative metastatic breast cancer pretreated with anthracycline and taxane.

Metastatic breast cancer (MBC) remains an incurable disease despite major therapeutic advances. Pseudomonas aeruginosa-mannose-sensitive hemagglutinin (PA-MSHA) has been established to have anti-proliferative effects against breast cancer cells in preclinical experiments, and is indicated for treatment of cancer in China. We performed a phase II trial combining PA-MSHA with capecitabine in patients with heavily pretreated MBC.Eligibility criteria included human epidermal growth factor receptor 2-negative MBC, prior therapy with anthracyclines and taxanes, at least one prior chemotherapy regimen for metastatic disease or early relapse after a taxane plus anthracycline adjuvant regimen, and adequate organ function and performance status. PA-MSHA 1 mg was administered subcutaneously every other day and capecitabine 1000 mg/m2 orally twice a day for 2 weeks on, 1 week off. The primary end point was progression-free survival.A total of 97 patients were enrolled. Median progression-free survival (PFS) was 4.0 months [95 % confidence interval (CI) 3.0-4.9], which was not significantly different from that in historical controls. However, median PFS was significantly longer (8.2 months; 95 % CI 6.7-9.7) in 24 patients with moderate immune-related adverse events (irAEs) such as fever or skin induration at the injection site than in those with no or mild irAEs (3.1 months, 95 % CI 2.5-3.6; p = 0.003). Overall survival was also improved in these patients (25.4 vs. 16.4 months; p = 0.044). PA-MSHA has a good safety profile, with only 6 patients (6.2 %) discontinuing treatment. PA-MSHA did not increase capecitabine-related toxicities such as hand-foot syndrome, nausea, and vomiting.Adding PA-MSHA to capecitabine has a good safety profile in patients with heavily pre-treated MBC, although benefit from this regimen might occur only in patients with moderate PA-MSHA-related adverse events.ClinicalTrials.gov NCT01380808