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Background: The prevalence of Helicobacter pylori–negative gastric cancer (HpNGC) can be as low as 1%, when infection is assessed using more sensitive tests or considering the presence of gastric atrophy. HpNGC may share a high-risk profile contributing to the occurrence of cancer in the absence of infection. We estimated the proportion of HpNGC, using different criteria to define infection status, and compared HpNGC and positive cases regarding gastric cancer risk factors. Methods: Cases from 12 studies from the Stomach cancer Pooling (StoP) Project providing data on H. pylori infection status determined by serologic test were included. HpNGC was reclassified as positive (eight studies) when cases presented CagA markers (four studies), gastric atrophy (six studies), or advanced stage at diagnosis (three studies), and were compared with positive cases. A two-stage approach (random-effects models) was used to pool study-specific prevalence and adjusted odds ratios (OR). Results: Among non-cardia cases, the pooled prevalence of HpNGC was 22.4% (n = 166/853) and decreased to 7.0% (n = 55) when considering CagA status; estimates for all criteria were 21.8% (n = 276/1,325) and 6.6% (n = 97), respectively. HpNGC had a family history of gastric cancer more often [OR = 2.18; 95% confidence interval (CI), 1.03–4.61] and were current smokers (OR = 2.16; 95% CI, 0.52–9.02). Conclusion: This study found a low prevalence of HpNGC, who are more likely to have a family history of gastric cancer in first-degree relatives. Impact: Our results support that H. pylori infection is present in most non-cardia gastric cancers, and suggest that HpNGC may have distinct patterns of exposure to other risk factors.

Head and neck squamous cell carcinoma (HNSCC) is a highly aggressive tumor with poor clinical outcomes due to recurrence, metastasis, and treatment resistance. Cancer stem cells (CSCs), a small population among tumor cells, are proposed to be responsible for tumor initiation, progression, metastasis, drug resistance, and recurrence. Here we show that high LSD1 expression was a predictor of poor prognosis for HNSCC patients. We found that high expression of LSD1 is essential for the maintenance of the CSC properties by regulating Bmi-1 expression. Moreover, tumor LSD1 ablation suppresses CSC-like characteristics in vitro and inhibits tumorigenicity in vivo in immune-deficient xenografts. However, this deletion induces the upregulation of PDL1 levels, which compromises antitumor immunity and reduces antitumor efficacy in an immune-competent mouse model. Functionally, the combination of LSD1 inhibitor and anti-PD-1 monoclonal antibody can overcome tumor immune evasion and greatly inhibit tumor growth, which was associated with reduced Ki-67 level and augmented CD8+ T cell infiltration in immunocompetent tumor-bearing mouse models. In summary, these findings provide a novel and promising combined strategy for the treatment of HNSCC using a combination of LSD1 inhibition and PD-1 blockade.

Over the past four decades, the Chinese government has conducted three surveys on the distribution of causes of death and built cancer registration. In order to shine a new light on better cancer prevention strategies in China, we evaluated the profile of cancer mortality over the forty years and analyzed the policies that have been implemented.We described spatial and temporal changes in both cancer mortality and the ranking of major cancer types in China based on the data collected from three national surveys during 1973-1975, 1990-1992, 2004-2005, and the latest cancer registration data published by National Central Cancer Registry of China. The mortality data were compared after conversion to age-standardized mortality rates based on the world standard population (Segi's population). The geographical distribution characteristics were explored by marking hot spots of different cancers on the map of China.From 1973 to 2016, China witnessed an evident decrease in mortality rate of stomach, esophageal, and cervical cancer, while a gradual increase was recorded in lung, colorectal, and female breast cancer. A slight decrease of mortality rate has been observed in liver cancer since 2004. Lung and liver cancer, however, have become the top two leading causes of cancer death for the last twenty years. From the three national surveys, similar profiles of leading causes of cancer death were observed among both urban and rural areas. Lower mortality rates from esophageal and stomach cancer, however, have been demonstrated in urban than in rural areas. Rural areas had similar mortality rates of the five leading causes of cancer death with the small urban areas in 1973-1975. Additionally, rural areas in 2016 also had approximate mortality rates of the five leading causes with urban areas in 2004-2005. Moreover, stomach, esophageal, and liver cancer showed specific geographical distributions. Although mortality rates have decreased at most of the hotspots of these cancers, they were still higher than the national average levels during the same time periods.Building up a strong primary public health system especially among rural areas may be one critical step to reduce cancer burden in China.

Background Dietary factors, such as consumption of preserved foods, fresh vegetables, and fruits, have been linked to the risk of nasopharyngeal carcinoma (NPC). However, little is known about associations between dietary patterns and the risk of NPC in NPC-endemic areas. Objectives We aimed to evaluate whether dietary patterns are associated with NPC risk. Methods We studied 2554 newly diagnosed NPC patients aged 20–74 y living in 3 endemic regions of southern China, and 2648 population-based controls frequency-matched to case patients by age, sex, and region, between 2010 and 2014. Dietary components were derived from food frequency data in adulthood and adolescence using principal component analysis. Four dietary components were identified and highly similar in adulthood and adolescence. We used multivariable unconditional logistic regression to calculate ORs with 95% CIs for the association between dietary patterns and NPC risk. Results Compared with the lowest quartile, individuals in the highest quartile of the “plant-based factor” in adulthood had a 52% (OR: 0.48; 95% CI: 0.38, 0.59) decreased risk of NPC, and those in the highest quartile of the “animal-based factor” had a >2-fold (OR: 2.26; 95% CI: 1.85, 2.77) increased risk, with a monotonic dose-response trend (P-trend

Objective:To determine if inflammation in proximity of the motor unit may contribute to neurodegeneration in amyotrophic lateral sclerosis (ALS). Methods: We identified all patients diagnosed in Sweden with concurrent ALS and multiple sclerosis (MS), myasthenia gravis (MG), inflammatory polyneuropathies (IP), or dermatopolymyositis (DMPM) during 1991-2014 according to the Swedish Patient Register (N = 263). We validated medical records for 92% of these patients (18 records were not retrieved and three did not contain enough information) and compared patients with a confirmed overlap (N = 28) with an independent sample of patients with solely ALS (N = 271). Results: Ninety-one patients were deemed as not having ALS (34.6%). Among the remaining 151 with validated ALS, 12 had also a confirmed MS diagnosis, nine a confirmed MG diagnosis, four a confirmed IP diagnosis, and three a confirmed DMPM diagnosis. Seventeen of the patients were women and 11 were men. Seventy-nine percent of the patients with a confirmed overlap had MS, MG, IP, or DMPM diagnosed prior to ALS. Compared to patients with only ALS, the concurrent patients were significantly older at symptoms onset, had higher prevalence of bulbar onset, but used Riluzole and noninvasive ventilation less frequently. Conclusions: We found that a high concurrence of ALS and MS/MG/IP/DMPM diagnoses is largely due to diagnostic uncertainty. A minority of patients had a true concurrence, where MS, MG, IP, and DMPM preceded the ALS diagnosis, which might be due to chance alone. Four patients were diagnosed with MG shortly after onset of ALS, suggesting that neurodegeneration might trigger autoimmunity.

The associations between several blood inflammatory indicators and risk of vascular plaques remain inconclusive. A total of 4596 native rural residents in Southeast China were enrolled from the Fuqing cohort study. Blood cell counts and their composite indexes including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and 2 novel indicators (systemic immune inflammation index (SII) and systemic immune inflammation response index (SIRI)) were considered as inflammatory indicators. Common carotid and femoral intima-media thickness (IMT) and plaques were assessed using B-mode ultrasound. Unconditional or multinomial logistic regression was used to evaluate potential associations. The prevalence of multiple femoral plaques (defined as IMT ≥1.5 mm) was significantly higher among participants with the highest tertile of total leukocyte count (odds ratio, 1.78), neutrophil count (1.88), monocyte count (2.51), platelet count (1.68), NLR (1.93), PLR (1.57), SII (2.10), and SIRI (2.94). Higher levels of neutrophil count, platelet count, NLR, and SII were also found to have significant linear dose-response relationships with the prevalence of stenosis, especially in femoral arteries. In conclusion, several blood inflammatory biomarkers may contribute to, or are associated with, the presence of IMT ≥1.5 mm or stenosis especially in femoral arteries.

According to the conceptual design of high-level radioactive waste (HLW) disposal repositories, the buffer barrier will be constructed by compacted bentonite blocks, which will inevitably produce technological gaps (voids) in the repository. During the consequent long-term operation of the repository, the technological gaps will be gradually filled up on hydration of the bentonite blocks with infiltration of underground water from the host rock. This hydration process will be accompanied by variations of the hydro-mechanical behavior of the buffer system. Therefore, it is necessary to study the changing process of the hydro-mechanical behavior of bentonite blocks with consideration of influences of the technological gaps. In the present work, a series of hydration tests were carried out on compacted GMZ bentonite specimens with initial annular gaps. During the hydration, variations of swelling pressure and hydraulic conductivity were measured. After each test, distributions of dry density and water content in the specimen were determined and the microstructure at different positions was investigated. Results show that, the swelling pressure of the specimen increased rapidly first and then decreased slightly during the hydration process, while the hydraulic conductivity kept decreasing with time. Moreover, closure of the technological gaps induced heterogeneity of the bentonite blocks, which was characterized by the decrease of dry density and the increase of water content with increasing distance to the center of the specimen. With the hydration time elapsed, the bentonite blocks could be divided into compression zone and swelling zone along the radius. In the compression zone, the dry density of the specimen gradually increased, with a decrease in the total pore void ratio and the macro-pores void ratio. In the swelling zone, the dry density decreased with an increase of the total pore void ratio and the undetectable pore void ratio.

ObjectiveTo estimate the risk of non-Hodgkin’s lymphoma (NHL) and Hodgkin’s lymphoma (HL) in patients with inflammatory bowel disease (IBD).DesignWe undertook a two-country population cohort study with all patients diagnosed with IBD in Norway and Sweden from 1987 and 1993 through 2015 and 2016, respectively, and analysed the risk of NHL and HL. In Sweden, we also analysed prescriptions of thiopurines and anti-tumour necrosis factor (TNF)-α therapy from 2005. We calculated standardised incidence ratios (SIRs) with 95% CIs using the general populations as reference.ResultsAmong 131 492 patients with IBD with a medium follow-up of 9.6 years, we identified 369 cases of NHL and 44 cases of HL. The SIR of NHL was 1.3 (95% CI 1.1 to 1.5) in ulcerative colitis and 1.4 (95% CI 1.2 to 1.7) in Crohn’s disease. We found no compelling heterogeneity in analyses stratified by patient characteristics. We found a similar pattern and magnitude of excess risks for HL. At 10 years, cumulative incidence was 0.26% (95% CI 0.23% to 0.30%) and 0.06% (95% CI 0.04% to 0.08%) for NHL and HL, respectively. Higher excess risks were found among patients with NHL with concomitant primary sclerosing cholangitis (SIR 3.4; 95% CI 2.1 to 5.2) and in those prescribed thiopurines alone (SIR 2.8; 95% CI 1.4 to 5.7) or with anti-TNF-α agents (SIR 5.7; 95% CI 2.7 to 11.9).ConclusionPatients with IBD have a statistically significant increased risk of malignant lymphomas compared with the general population, but the absolute risk remains low.

The bound state in the continuum (BIC) is a singular point of polarization in the momentum space of a periodic structure. It has been demonstrated that vortex beams can be generated by utilizing the polarization vortex around BIC based on the geometric phase in momentum space. In this letter, we propose a reflective photonic crystal (PhC) to generate a vortex beam and demonstrate the superimposition of topological charges in the momentum space between PhC and the vortex beams. In addition to BICs, we demonstrate that other singularities like degenerate points can also be used to generate vortex beams.

Aims We aimed to assess the association between gut bacterial biomarkers during early pregnancy and subsequent risk of gestational diabetes mellitus (GDM) in Chinese pregnant women. Methods Within the Tongji-Shuangliu Birth Cohort study, we conducted a nested case-control study among 201 incident GDM cases and 201 matched controls. Fecal samples were collected during early pregnancy (at 6-15 weeks), and GDM was diagnosed at 24 to 28 weeks of pregnancy. Community DNA isolated from fecal samples and V3-V4 region of 16S rRNA gene amplicon libraries were sequenced. Results In GDM cases versus controls, Rothia, Actinomyces, Bifidobacterium, Adlercreutzia, and Coriobacteriaceae and Lachnospiraceae spp. were significantly reduced, while Enterobacteriaceae, Ruminococcaceae spp., and Veillonellaceae were overrepresented. In addition, the abundance of Staphylococcus relative to Clostridium, Roseburia, and Coriobacteriaceae as reference microorganisms were positively correlated with fasting blood glucose, 1-hour and 2-hour postprandial glucose levels. Adding microbial taxa to the base GDM prediction model with conventional risk factors increased the C-statistic significantly (P < 0.001) from 0.69 to 0.75. Conclusions Gut microbiota during early pregnancy was associated with subsequent risk of GDM. Several beneficial and commensal gut microorganisms showed inverse relations with incident GDM, while opportunistic pathogenic members were related to higher risk of incident GDM and positively correlated with glucose levels on OGTT.

Background The potential role of occupational exposures in the development of nasopharyngeal carcinoma (NPC) remains unclear, particularly in high-incidence areas. Methods The authors conducted a population-based case-control study, consisting of 2514 incident NPC cases and 2586 randomly selected population controls, in southern China from 2010 to 2014. Occupational history and other covariates were self-reported using a questionnaire. Multivariate logistic regression was used to estimate odds ratios (ORs) with 95% confidence intervals (CIs) for the risk of NPC associated with occupational exposures. Restricted cubic splines were used to evaluate potentially nonlinear duration-response relations. Results Individuals who had exposure to occupational dusts (OR, 1.45; 95% CI, 1.26-1.68), chemical vapors (OR, 1.37; 95% CI, 1.17-1.61), exhausts/smokes (OR, 1.42; 95% CI, 1.25-1.60), or acids/alkalis (OR, 1.56; 95% CI, 1.30-1.89) in the workplace had an increased NPC risk compared with those who were unexposed. Risk estimates for all 4 categories of occupational exposures appeared to linearly increase with increasing duration. Within these categories, occupational exposure to 14 subtypes of agents conferred significantly higher risks of NPC, with ORs ranging from 1.30 to 2.29, including dust from metals, textiles, cement, or coal; vapor from formaldehyde, organic solvents, or dyes; exhaust or smoke from diesel, firewood, asphalt/tar, vehicles, or welding; and sulfuric acid, hydrochloric acid, nitric acid, and concentrated alkali/ammonia. Conclusions Occupational exposures to dusts, chemical vapors, exhausts/smokes, or acids/alkalis are associated with an excess risk of NPC. If the current results are causal, then the amelioration of workplace conditions might alleviate the burden of NPC in endemic areas. Lay summary The role of occupational exposures in the development of nasopharyngeal carcinoma (NPC) remains unclear, particularly in high-incidence areas. The authors conducted a population-based study with 2514 incident NPC cases and 2586 population controls in southern China and observed that occupational exposures were associated with an increased risk of NPC. Duration-response trends were observed with increasing duration of exposure. These findings provide new evidence supporting an etiologic role of occupational exposures for NPC in a high-incidence region.

Purpose: Esophageal cancer is the sixth leading cause of cancer-related death worldwide, and is associated with a poor prognosis. Stromal tumor infiltrating lymphocytes (sTIL) and certain single nucleotide polymorphisms (SNPs) have been found to be predictive of patient survival. In this study, we explored the association between SNPs and sTIL regarding the predictability of disease-free survival in patients with esophageal squamous cell carcinoma (ESCC). Materials and methods: We collected 969 pathologically confirmed ESCC patients from 2010 to 2013 and genotyped 101 SNPs from 59 genes. The number of sTIL for each patient was determined using an automatic algorithm. A Kruskal-Wallis test was used to determine the association between genotype and sTIL. The genotypes and clinical factors related to survival were analyzed using a Kaplan-Meier curve, Cox proportional hazards model, and log-rank test. Results: The median age of the patients was 67 (42-85 years), there was a median follow-up of 851.5 days and 586 patients died. The univariable analysis showed that 10 of the 101 SNPs were associated with sTIL. Six SNPs were also associated with disease-free survival. A multivariable analysis revealed that sTIL, rs1801131, rs25487, and rs8030672 were independent prognostic markers for ESCC patients. The model combining SNPs, clinical characteristics and sTIL outperformed the model with clinical characteristics alone for predicting outcomes in ESCC patients. Conclusion: We discovered 10 SNPs associated with sTIL in ESCC and we built a model of sTIL, SNPs and clinical characteristics with improved prediction of survival in ESCC patients.

Objective: To investigate the associations of seminal plasma selenium (Se) concentrations with semen quality and to explore the mediating role of sperm mitochondrial DNA copy number (mtDNAcn). Design: Cross-sectional study with repeated measurements. Setting: Hubei Province Human Sperm Bank of China. Population: A total of 1159 healthy men who repeatedly provided 5617 semen samples were included. Main Outcome Measures: Seminal plasma Se concentration and sperm mtDNAcn of healthy men screened as potential sperm donors were determined using inductively coupled plasma mass spectrometry (ICP-MS) and real-time fluorescent quantitative PCR (RT-qPCR), respectively. Methods: Linear mixed-effects models and mediation analyses were performed. Result(s): After adjusting for potential confounders, we observed positive associations of seminal plasma Se concentrations with sperm concentration and total count (both p-Values for trend < 0.001). Volunteers in the highest vs. lowest quartiles of seminal plasma Se concentrations had 70.1% (95% CI: 53.3%, 88.9%) and 59.1% (95% CI: 40.5%, 80.2%) higher sperm concentration and total count, respectively. We also found inverse associations between within-subject pooled seminal plasma Se concentrations and sperm mtDNAcn, and between sperm mtDNAcn and sperm concentration, total count, total motility, and progressive motility (all p-Values for trend < 0.05). Mediation analyses showed that sperm mtDNAcn mediated 19.7% (95% CI: 15.9%, 25.3%) and 23.1% (95% CI: 17.4%, 33.4%) of the associations between within-subject average seminal plasma Se concentrations and sperm concentration and total count, respectively. Conclusions: Seminal plasma Se concentrations were positively associated with sperm concentration and total count, which was partly mediated by sperm mtDNAcn.

Cell phone use and radio-frequency electromagnetic radiation (RF-EMF) are rapidly increasing and may be associated with lower semen quality, yet results from epidemiological studies are inconclusive. Information on electronic devices use was collected through standard questionnaires from 1454 men aged 22-45 years old. Semen volume, sperm concentration, total sperm count, total motility, progressive motility, and normal morphology in repeated specimens were determined by trained clinical technicians. Percent changes [95% confidence intervals (CIs)] were estimated as (10

A cancer diagnosis is part of a complex stochastic process, which involves patient's characteristics, diagnosing methods, an initial assessment of cancer progression, treatments and a certain outcome of interest. To evaluate the performance of diagnoses, one needs not only a consistent estimation of the causal effect under a specified regime of diagnoses and treatments but also reliable confidence interval, P-value and hypothesis testing of the causal effect. In this article, we identify causal effects under various regimes of diagnoses and treatments by the point effects of diagnoses and treatments and thus are able to estimate and test these causal effects by estimating and testing point effects in the familiar framework of single-point causal inference. Specifically, using data from a Swedish prognosis study of stomach cancer, we estimate and test the causal effects on cancer survival under various regimes of diagnosing and treating hospitals including the optimal regime. We also estimate and test the modification of the causal effect by age. With its simple setting, one can readily extend the example to a large variety of settings in the area of cancer diagnosis: different personal characteristics such as family history, different diagnosing procedures such as multistage screening, and different cancer outcomes such as cancer progression.

Background Accumulating evidence suggests a survival benefit after curative oesophageal cancer surgery in women compared with men. The aim of this study was to explore sex disparities in survival after surgery with curative intent in patients with oesophageal cancer. Methods This was a population-based cohort study, including all patients with oesophageal or gastric cancer who underwent surgery with a curative intent between 2006 and 2017 in Sweden. Female versus male mortality rate ratio (MRR) and excess mortality rate ratio (EMRR) were used as measures of survival. Two different parametric models were designed to account for potential confounders. Patients with gastric cancer were used as a comparison group as no differences in survival between sexes were expected among these patients. Results A total of 1301 patients underwent resection for oesophageal adenocarcinoma and 305 patients for oesophageal squamous cell carcinoma. Women had a lower EMRR (0.76, 95 per cent c.i. 0.58 to 1.01, P = 0.056; 0.52, 95 per cent c.i. 0.32 to 0.84, P = 0.007 respectively) in both histological subtypes. The effect was more profound in early clinical stages, in patients receiving neoadjuvant treatment, and without postoperative complications. No sex-related difference was observed in survival of patients with gastric cancer. Conclusions Women undergoing resection for oesophageal carcinoma have better survival compared with men.

Background Previous studies have reported inconsistent results regarding the association between poor dental health and pancreatic cancer risk. This study aimed to assess this association using a well-functioning nationwide dental health registry in Sweden. Methods Information of exposures (dental caries, root canal infection, mild inflammation, and periodontitis; the number of teeth) was ascertained from the Swedish Dental Health Register, and occurrence of pancreatic cancer was identified from both cancer and cause of death registries. Hazard ratios (HRs) were estimated using Cox models. Results During a median of 7.2 years of follow-up, 10,081 pancreatic cancers were identified among 5,889,441 individuals. Compared with the healthy status, a higher risk of pancreatic cancer was observed in individuals with root canal infection, mild inflammation, and periodontitis in the P for trend Conclusions Our results confirmed the association between poor dental health and pancreatic cancer risk, which warrants further studies on underlying mechanisms.

Background: The potential effect of alcohol or tea intake on the risk of nasopharyngeal carcinoma (NPC) remains controversial. Methods: In a population-based case–control study in southern China, we assessed alcohol or tea intake from 2,441 histopathologically confirmed NPC cases and 2,546 controls. We calculated mean daily ethanol (g/day) and tea intake (mL/day). Fully adjusted ORs with 95% confidence intervals (CI) were estimated using logistic regression; potential dose–response trends were evaluated using restricted cubic spline analysis. Results: Compared with nondrinkers, no significantly increased NPC risk in men was observed among current alcohol drinkers overall (OR, 1.08; 95% CI, 0.93–1.25), nor among current heavy drinkers (OR for ≥90 g/day ethanol vs. none, 1.32; 95% CI, 0.95–1.84) or former alcohol drinkers. Current tea drinking was associated with a decreased NPC risk (OR, 0.73; 95% CI, 0.64–0.84). Compared with never drinkers, those with the low first three quintiles of mean daily current intake of tea were at significantly lower NPC risk (OR, 0.53, 0.68, and 0.65, respectively), but not significant for the next two quintiles. Current daily tea intake had a significant nonlinear dose–response relation with NPC risk. Conclusions: Our study suggests no significant association between alcohol and NPC risk. Tea drinking may moderately reduce NPC risk, but the lack of a monotonic dose–response association complicates causal inference. Impact: Tea drinking might be a healthy habit for preventing NPC. More studies on biological mechanisms that may link tea with NPC risk are needed.

Root-knot nematodes (Meloidogyne spp.) are one of the most economically important plant parasites in the world, and significantly impacts soybean production in places where they are endemic. Several species of root-knot nematode are capable of causing significant damages to soybean and have broad host ranges that include common rotational crops and weeds. Symptoms of root-knot nematode infections may be confused with other diseases, nutritional disorders, or common root features associated with legumes. The purpose of this diagnostic guide is to provide information regarding identification, isolation, storage, and other relevant aspects of this pathosystem.

Bound states in the continuum (BICs) have been widely observed in many symmetric geometries in the optical system during the last decade. Here, we consider a scenario in which the structure is designed asymmetrically with anisotropic birefringent material embedded in one-dimensional photonic crystals. This kind of new shape opens the possibility of obtaining symmetry-protected BICs (SP-BICs) and Friedrich–Wintgen BICs (FW-BICs) form in tunable anisotropy axis tilt. Interestingly, these BICs can be observed as high-Q resonances by variation of the system’s parameters, such as the incident angle, which means the structure without being injected at Brewster's angle can also achieve BICs. Our findings might achieve active regulation and are easy to manufacture.

Background The health consequences of the use of Swedish snus, including its relationship with mortality, have not been fully established. We investigated the relationship between snus use and all-cause and cause-specific mortality (death due to cardiovascular diseases, cancer diseases and all other reasons, respectively) in a nationwide collaborative pooling project. Methods We followed 169 103 never-smoking men from eight Swedish cohort studies, recruited in 1978–2010. Shared frailty models with random effects at the study level were used in order to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) of mortality associated with snus use. Results Exclusive current snus users had an increased risk of all-cause mortality (aHR 1.28, 95% CI 1.20–1.35), cardiovascular mortality (aHR 1.27, 95% CI 1.15–1.41) and other cause mortality (aHR 1.37, 95% CI 1.24–1.52) compared with never-users of tobacco. The risk of cancer mortality was also increased (aHR 1.12, 95% CI 1.00–1.26). These mortality risks increased with duration of snus use, but not with weekly amount. Conclusions Snus use among men is associated with increased all-cause mortality, cardiovascular mortality, with death from other causes and possibly with increased cancer mortality.

Summary Punctodera mulveyi n. sp. is described and illustrated from turf grass (Poa annua) in golf course greens with other fescues in Bandon, Coos County, Oregon, USA. Females and cysts are characterised by a saccate, globose to ovoid or pear-shaped body with a protruding neck. The cuticle has a lace-like pattern of ridges and heavy punctations on the subsurface. Cysts have distinctive vulval and anal circumfenestral patterns with heavy bullae scattered around the fenestral area, these being absent in young cysts. Second-stage juveniles (J2) vermiform, tapering to a long and cylindrical tail with a bluntly rounded to occasionally clavate tail terminus. Morphologically the new species resembles all known species of Punctodera using both light microscopy and scanning electron microscopy observations, but differs from the other species either by the J2 body and stylet length, shape of head, tail and tail terminus, female and male stylet or spicule length, and in having distinctive vulval and anal circumfenestral patterns in the cysts. Molecular analysis with sequence alignments and phylogenetic trees of ITS rDNA, nuclear heat shock protein 90 and mitochondrial COI sequences separated P. mulveyi n. sp. from P. matadorensis, P. punctata, P. stonei and P. chalcoensis, but 18S and 28S were relatively conserved with a few bp differences and there were insufficient Punctodera species sequences to give strong support to a new species designation. A morphologically most closely related species, P. stonei from Canada, further supported the status of P. mulveyi n. sp. An identification key to all five nominal species of Punctodera is given.

Summary Over a period of 15 years, Schistonchus was collected from sycones of Ficus subgenus Urostigma section Malvanthera in eastern Australia, and was found to occur widely. Here, Schistonchus macrophylla macrophylla is redescribed from F. macrophylla and F. superba, and a new subspecies, Schistonchus m. lightfooti subsp. n., from F. rubiginosa and F. superba. Schistonchus m. lightfooti subsp. n., is characterised by having a long post-vulval uterine sac (PUS) with thickened walls and a narrowly rounded or pointed distal tip, procorpus which is usually longer than the stylet length, pyriform metacorpus, trapezoid-shaped head capsule, papillae arranged as one large pair adcloacal, a large pair at mid-tail length, and a small pair near the tail tip, no caudal alae, and a spatulate tail tip in females; and was collected from Sydney in New South Wales (NSW) to southern Queensland. Schistonchus m. macrophylla is characterised by having a procorpus shorter than or equal to the stylet length, an ovoid metacorpus, rectangular-shaped head capsule, long PUS with thickened wall only at its distal tip, caudal alae, and papillae arranged as one pair precloacal, one small pair adcloacal, and a large pair at mid-tail length. It was collected in NSW.

Alkaline solutions have significant effects on the mineral composition and on the microstructure of bentonite; in relevant geoenvironmental engineering applications, therefore, the properties of bentonite buffer materials must be taken into consideration in the presence of alkaline solutions. The objective of the present study was to determine the effect of alkaline conditions on the swelling of bentonite mixed with sand. Bentonite-sand mixtures were soaked in a NaOH solution and allowed to react over prescribed periods of 6, 12, and 24 months. Swelling deformation tests were conducted on the alkali-treated bentonite-sand mixtures; the swelling of the mixtures decreased significantly with increased reaction time. The fractal ec-σ relationship (ec is void ratio of bentonite, σ is vertical stress) was employed to express the swelling characteristics of the alkali-treated mixtures, wherein the swelling coefficient decreased as the bentonite content was reduced. Dissolution traces over the clay surfaces degraded the microstructural phase, thereby slightly increasing the fractal dimension. At higher dosages of bentonite, the swelling of bentonite-sand mixtures always followed a similar ec-σ relationship as that found for bentonite alone. On the contrary, in the mixtures with a small bentonite content that surpassed the designated threshold pressure, the void ratio of clay in the mixtures deviated from the ec-σ curve due to the appearance of the sand skeleton. The bentonite content for a particular bentonite-sand mixture at which deviation from the ec-σ curve began was ~50%. This deviation was almost negligible at 50% initial bentonite content in the bentonite-sand mixtures; after treatment with NaOH solution, however, a pronounced deviation in the ec-σ curve was observed which was caused mainly by the decrease in the bentonite percentage. Finally, the vertical pressure threshold was also estimated using the ec-σ relation for bentonite-sand mixtures with small bentonite contents over a range of various alkaline solution reaction times.

The association between atrophic gastritis (AG) and symptomatic gastroesophageal reflux disease (GERD) needs to be better assessed.We aimed to study this association in a twin setting, controlling for genetic and familial factors, in addition to a range of known covariates.We performed a co-twin control study based on the Swedish Twin Registry, including confirmed monozygotic (MZ) and dizygotic (DZ) twins. AG was determined by the measurement of serum pepsinogen I (PGI) and pepsinogen II (PGII), with different cut-off values. GERD was defined using a structured questionnaire, by questions on symptoms of heartburn, acid regurgitation, pain behind the breastbone, and drug history. Patients were grouped into total GERD, less frequent (lt;1/week), and frequent GERD (≥1/week).A total of 12,533 twins were included in the study, among whom 37.7% showed less frequent GERD, and 18.7% had frequent GERD. There was an inverse association between AG and GERD, especially for frequent GERD. When PGIlt;30 was used as cut-off value for AG, the odds ratio (OR) and corresponding 95% confidence interval (CI) was 0.52 (0.44, 0.62). When PGIlt;70 and PGI/PGIIlt;3 was used as cut-off value for AG, the OR (95% CI) was 0.53 (0.46, 0.63). A risk reduction for GERD was also observed in AG patients when the analysis was restricted in MZ or DZ twins.In this co-twin control study from the Swedish Twin Register, AG is persistently associated with a reduced risk for GERD, after controlling for genetic and shared familial factors.

Background Epstein-Barr virus (EBV) reactivation from latent to lytic infection has been considered as a key step in nasopharyngeal carcinoma oncogenesis. However, epidemiological evidence regarding environmental risk factors for EBV reactivation on a population level remains largely lacking. Methods We enrolled 1916 randomly selected adults from the general population of Guangdong and Guangxi, China, from 2010 to 2014. Information on environmental factors was collected via a structured interview. Serum immunoglobulin A antibodies against EBV viral capsid antigen and nuclear antigen 1 were measured by enzyme-linked immunosorbent assay to evaluate EBV reactivation status. We used logistic regression to calculate odds ratios (ORs) with 95% confidence intervals (CIs) for the associations of EBV reactivation with various environmental factors. Results No associations were observed between EBV reactivation and extensive environmental factors, including alcohol or tea drinking, a history of chronic ear/nose/throat diseases, use of medications or herbs, consumption of salted fish or preserved foods, oral hygiene, sibship structure, and various residential and occupational exposures. Only cigarette smoking was associated with EBV reactivation (current smokers vs never smokers; OR = 1.37; 95% CI = 1.02–1.83), with positive exposure-response trends with increasing intensity, duration, and pack-years of smoking. Conclusions Consistent with previous studies, we found an association between cigarette smoking and EBV reactivation. Other examined exposures were not associated with EBV reactivation. These null results could suggest either more complex interactions between exposures and EBV reactivation or a predominant role of host and/or viral genetic variation.

BackgroundPeptic ulcer disease (PUD) and gastric cancer (GC) are more prevalent in individuals with low socioeconomic status (SES) and share several risk factors. The aim of this study was to investigate the mediating role of PUD in the association between established risk factors and GC.MethodsWe conducted a pooled analysis of 12 studies from the Stomach Cancer Pooling Project Consortium, including a total of 4877 GC cases and 11 808 controls. We explored the mediating role of PUD in the association between SES, tobacco smoking, heavy alcohol drinking and salt intake, and GC. Also, we assessed the ORs and 95% CIs of the risk factors and both PUD and GC.ResultsPUD mediated 36% of the smoking effect mainly among men. Other risk factors were only slightly mediated by PUD (SES, 5.3%; heavy alcohol drinking, 3.3%; and salt intake, 2.5%). No significant difference was found when excluding PUD diagnosed within 2 years from GC.ConclusionsOur study provides innovative information on the mechanism of stomach mucosal damage leading to PUD and GC, with respect to the effect of tobacco smoking in particular.

Summary A new nematode species was recovered from the syconia of Ficus semicordata from Xishuangbanna Tropical Botanical Garden, Yunnan Province, China. It is described herein as Martininema semicordatae n. sp. and is characterised by having the combined characters of a long post-vulval uterine sac, excretory pore located at nerve ring level, amoeboid sperm, three pairs of subventral papillae on the male tail, rounded male tail tip with mucron, absence of gubernaculum (= apophysis), and a recurved, rose-thorn-shaped spicule lacking a terminal cucullus. Martininema semicordatae n. sp. differs from other sequenced species by differences in the partial small subunit (SSU) rRNA gene and D2-D3 expansion segments of the large subunit (LSU) rRNA gene. Phylogenetic analysis with LSU D2-D3 expansion segment sequences suggested that M. semicordatae n. sp. is clustered in a highly supported monophyletic clade with M. guangzhouense, M. fistulosus and M. baculum, and shares a common ancestor with these three species.

Summary Ficophagus from collecting trips in eastern Australia, made over 15 years, are summarised and show that species of the genus occurred widely in sycones of Ficus, subgenus Urostigma, section Malvanthera. Two new species (based on morphological differences and molecular sequencing) are described: Ficophagus elizabethae sp. n. from Ficus macrophylla, F. rubiginosa and F. obliqua, and Ficophagus richardi sp. n. from Ficus obliqua; and a morphospecies, Ficophagus Morphospecies malandicus from Ficus obliqua. Ficophagus elizabethae sp. n. is characterised by having the excretory pore (EP) opening from the level of the junction of the conus and shaft of the stylet to that of the knobs, a relatively long procorpus (1.0-2.5 times length of stylet), female tail with an obliquely truncate tail with a hyaline area and a finely to broadly rounded tip which may be mucronate; post-vulval uterine sac (PUS) ca one vulval body diam. (VBD) in length; rose-thorn-shaped spicule with distinct rostrum and prominent condylus; and genital papillae arranged as largest pair adcloacal, second pair posterior to mid-tail length, and third small pair near tail tip; and was collected from Sydney in New South Wales, to Bundaberg in Queensland (QLD). Ficophagus richardi sp. n. is characterised by having the EP opening at the level of the junction of the stylet shaft and conus, a labial cap which is raised around the opening for the stylet; procorpus 0.8-1.7 times length of the stylet, PUS Ficophagus Morphospecies malandicus is characterised by having the EP opening anterior to the junction of the stylet conus and shaft, procorpus 0.9-2 times length of stylet, a short PUS usually Ficophagus nematodes from figs of the section Malvanthera in eastern Australia.

Background Salivary adenoid cystic carcinoma (SACC), a rare cancer arising in the salivary glands, is characterized by high rates of relapse and distant metastasis. Epidermal growth factor receptor (EGFR) has been implicated in SACC carcinogenesis. However, prospective trials of EGFR-targeting therapies in SACC are limited, and the optimum regimen is unclear. Methods The effects of erlotinib on cell proliferation, colony formation, ALDH enzymatic activity and tumorsphere formation were investigated in SACC cells. Expression of the cancer stem cell markers Bmi-1 and Oct4 was evaluated using Western blotting. Results We found that while it robustly inhibited cell growth, targeting EGFR with erlotinib enriched the ALDH+ cell population and elevated the clonogenicity of SACC cells, suggesting an increase in stem cell-like potential. In addition, we found that suppression of EGFR kinase activity with erlotinib led to the activation of Notch1 signaling, leading to an increase in stem cell-like properties. Moreover, the γ-secretase inhibitor GSI treatment eliminated the erlotinib-induced increase in stem cell-like properties by decreasing Notch activity. Conclusion Our results provide an explanation for the worsened survival observed in some studies of erlotinib therapy in SACC and provide potential therapeutic strategies by combined blockade of the EGFR and Notch1 pathways.

Background The vagus nerve provides essential parasympathetic innervation to the gastrointestinal system and is known to have anti-inflammatory properties. Aims To explore the relationship between vagotomy and the risk of inflammatory bowel disease (IBD) and its major categories: Crohn's disease (CD) and ulcerative colitis (UC). Methods A matched cohort comprising 15 637 patients undergoing vagotomy was identified through the Swedish Patient Register from 1964 to 2010. Each vagotomised patient was matched for birth year and gender with 40 nonvagotomised individuals on the date of vagotomy. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for IBD using flexible parametric models adjusted for matching variables, year of vagotomy, birth country, chronic obstructive pulmonary disease and comorbidity index. Results We observed 119 (0.8%) patients with vagotomy developed IBD compared to 3377 (0.5%) IBD cases in nonvagotomised individuals. The crude incidence of IBD (per 1000 person-years) was 0.38 for vagotomised patients and 0.25 for nonvagotomised individuals. We observed a time-dependent elevated risk of IBD associated with vagotomy, for instance, the HR (95% CI) was 1.80 (1.40-2.31) at year 5 and 1.49 (1.14-1.96) at year 10 post-vagotomy. The association appeared to be stronger for truncal than selective vagotomy and limited to CD (HR was 3.63 [1.94-6.80] for truncal and 2.06 [1.49-2.84] for selective vagotomy) but not UC (1.36 [0.71-2.62] for truncal and 1.25 [0.95-1.63] for selective vagotomy). Conclusions We found a positive association between vagotomy and later IBD, particularly for CD. The finding indirectly underlines the beneficial role of the vagal tone in IBD.

Background: Medications that are used for treatment of metabolic disorders have been suggested to be associated with the development of amyotrophic lateral sclerosis (ALS). Methods: To examine the associations of antidiabetics and statins with the subsequent risk of ALS we conducted a population-based nested case-control study of 2475 Swedish residents diagnosed with ALS during July 2006 to December 2013 and 12375 population controls (five for each ALS case). We extracted information on filled prescriptions of antidiabetics and statins for both cases and controls from the Swedish Prescribed Drug Register during the years before ALS diagnosis. Conditional logistic regression was used to calculate odds ratios (ORs) for the associations of these medications with ALS risk. Results: Patients with ALS were less likely to have been prescribed with antidiabetics compared with controls [OR, 0.76; 95% confidence intervals (CI), 0.65–0.90]. Conversely, statins were not associated with ALS risk overall (OR, 1.08; 95% CI, 0.98–1.19), although a positive association was noted among women (OR, 1.28; 95% CI, 1.10–1.48). The latter association was mostly explained by ALS cases being more likely to have a first prescription of statins during the year before diagnosis compared with controls (OR, 2.54; 95% CI, 1.84–3.49). Conclusions: The inverse association of antidiabetics with ALS is consistent with the previously reported inverse association between type 2 diabetes and ALS risk. The increase in prescription of statins during the year before ALS diagnosis deserves attention because it might reflect an acceleration of the course of ALS due to statin use.

Summary A new nematode species was recovered from the syconia of Ficus hirta var. roxburghii from Chaozhou, Guangdong, China. It is described herein as Ficophagus chaozhouensis n. sp. and is characterised by possessing the combined characters of a short post-uterine sac, excretory pore located near the head, amoeboid sperm, three pairs of subventral papillae on the male tail, rounded male tail tip with mucron (occasionally swollen), absence of gubernaculum (or apophysis), a blunt rosethorn-shaped spicule without a terminal cucullus, and a digitate rostrum with a broadly squared tip. Ficophagus chaozhouensis n. sp. was separated from other sequenced species by differences in the partial small subunit (SSU) rRNA gene and D2-D3 expansion segments of the large subunit (LSU) rRNA gene. Phylogenetic analysis with LSU D2-D3 expansion segment sequences suggested that F. chaozhouensis n. sp. is clustered in the same highly supported monophyletic clade with F. aculeata, F. maxima and F. yoponensis, and is sister to F. aculeata.

Gait disturbance is considered to be a significant clinical manifestation of cerebral small vessel disease (CSVD). We aimed to investigate the association between different imaging markers of CSVD or total CSVD burden and gait disturbance in a community-dwelling population. In the cross-sectional Taizhou Imaging Study (TIS), 314 participants free of neurological disorders underwent MRI scanning and gait assessment with quantitative wearable devices as well as clinical rating scales. In linear regression, after adjustment for demographics and vascular risks, total CSVD burden was associated with prolonged 3-m walking (β=0.118, P=0.035), shorter stride length (β=-0.106, P=0.042), and poorer Timed-Up-and-Go (TUG) performance (β=0.146, P=0.009). Lacunes were positively associated with 3-m walking (β=0.118, P=0.037) and duration of TUG test (β=0.112, P=0.047). White matter hyperintensities and cerebral microbleeds were associated with prolonged stride time (β=0.134, P=0.024) and increased stance phase time percentage (β=0.115, P=0.038), respectively. Logistic regression revealed that participants with high CSVD burden or more lacunes were more likely to have an impaired gait velocity and an impaired TUG test. These results suggest that total CSVD burden and CSVD imaging markers are associated with gait disturbance among community-dwelling elderly people. Different CSVD imaging markers may cause gait disturbance through different pathways.

Previous findings concerning gastric atrophy as a potential risk factor for esophageal squamous cell carcinoma (ESCC) have been inconsistent. We aimed to test whether gastric atrophy and, further, its interaction with poor oral health elevated the risk of ESCC in a high-risk region of China. Our population-based case-control study in Taixing, China (2010–2014), recruited cases from local hospitals and the local cancer registry. Controls were selected randomly from the local population registry. Ultimately, 1,210 cases and 1,978 controls answered questionnaires and provided blood samples for assay of pepsinogens. Unconditional logistic regression models were used to estimate odds ratios and 95% confidence intervals. Gastric atrophy (defined as a serum level of pepsinogen I of

Aims We aimed to examine the associations of four extracranial artery indicators with cerebral small vessel disease (CSVD) and its total burden. Methods A total of 904 individuals aged 55-65 years old were included from the Taizhou Imaging Study. CSVD markers, including lacunes (LAC), white matter hyperintensities (WMH), cerebral microbleeds (CMB), and perivascular spaces (PVS), were rated based on brain magnetic resonance imaging. We also measured extracranial artery indices, including the brachial-ankle pulse wave velocity (baPWV), the ankle-brachial index, the carotid intima-media thickness (IMT), and carotid plaque. Linear and binary logistic regressions were adopted to test the associations among these four artery indicators and each CSVD marker when appropriate. Additionally, ordinal and multinomial logistic regressions were performed to assess the relationships between artery indicators and total CSVD score (range from 0-4 points). Results A total of 443 (49.0%) participants were found to have at least one of the CSVD markers, including 172 (19.0%) with WMH, 184 (20.4%) with LAC, 147 (16.3%) with CMB, and 226 (25.0%) with PVS. Increased baPWV was significantly associated with each CSVD marker, increasing carotid IMT was associated with LAC and PVS, and the presence of carotid plaque was associated with WMH volume and PVS. Moreover, per SD increment of baPWV (odds ratio [OR]: 1.29, 95% confidence interval [CI]: 1.11-1.50) and the presence of carotid plaque (OR: 1.42, 95% CI: 1.05-1.92) were significantly associated with greater total CSVD scores. Conclusion Increased baPWV and the presence of carotid plaque appear to be associated with total CSVD burden in rural regions in China.

Rationale: The oncogenesis of head and neck squamous cell carcinoma (HNSCC) is believed to result from oncogene activation and tumor suppressor inactivation. Here, we identified a new oncogenic role for the EREG gene in HNSCC. Methods: The TCGA database and immunohistochemistry assay were used to analyze expression of EREG in HNSCC tissues. Immunoblotting was performed to identify the EGFR-mediated pathways altered by EREG. The role of EREG in oncogenesis was investigated in vivo and in vitro. Results: Upregulated EREG expression predicted a poor prognosis and triggered HNSCC oncogenic transformation by activating the epidermal growth factor receptor (EGFR) signaling pathway. We also demonstrated the direct association of EREG with EGFR and that this binding required EGFR domains I and III and the N57 residue of EREG. Moreover, EREG overexpression was shown to promote HNSCC oncogenesis by inducing C-Myc expression, and the pharmacological inhibition of C-Myc rescued EREG-promoted HNSCC oncogenesis. Unlike other EGFR ligands, EREG could mimic EGFR mutations by sustaining the activation of the EGFR-Erk pathway, and high EREG expression was positively associated with the response to treatment with the EGFR inhibitor erlotinib. Furthermore, knockdown of EREG decreased sensitivity to erlotinib treatment in vitro and in vivo. Conclusions: These results identify the EREG-EGFR-C-Myc pathway as a crucial axis that drives HNSCC oncogenesis and show that EREG expression could be a predictive functional marker of sensitivity to erlotinib therapy in HNSCC.

Background: To explore the relationship between family history of esophageal cancer, SNPs, and the risk of esophageal squamous cell carcinoma (ESCC), we performed a population-based case–control study and developed a genetic family history–related risk (GFR) score and non–family history-related risk (GnFR) score to quantify the cumulative number of risk genotypes carried by each individual. Methods: We used data of 700 patients with nonfamilial ESCC, 341 patients with familial ESCC, 1,445 controls without a family history of esophageal cancer, and 319 controls with a family history. We genotyped 87 genetic variants associated with the risk for ESCC, and constructed GFR and GnFR scores for cases and controls. Results: Our results show that ESCC risk increased with higher GFR score (Ptrend = 0.0096). Among the familial subgroup, we observed a nearly 7-fold [95% confidence interval (CI), 1.92–24.77] higher risk of ESCC in the highest GFR score group. The corresponding estimate was only 2-fold (95% CI, 1.41–3.93) higher risk of ESCC, in the stratum without a reported family history of esophageal cancer. Certain cell signaling pathways and immune-related pathways were enriched, specifically in familial ESCC. Results from a reconstructed cohort analysis demonstrated that cumulative risk to get esophageal cancer by age 75 years was 13.3%, 10.2%, 8.2%, and 5.1%, respectively, in four subgroups as defined by first-degree relatives of cases or controls with high or low genetic risk score. In particular, the cohort of relatives of ESCC cases with low genetic risk score exhibit a higher cumulative risk than the cohort of relatives of controls with high genetic risk score. It demonstrates that environmental factors play a major role in esophageal cancer. Conclusions: Further studies are warranted to dissect the mechanisms of shared environmental and genetic susceptibility affecting the risk of getting ESCC. Impact: Our study highlights that the need of preventive strategies to screen certain genetic polymorphisms, especially in individuals whose relatives had ESCC.