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Background: Whether poor oral health is associated with dementia risk remains unclear. Objective: We conducted a cohort study of 14,439 participants who were followed up for up to 40 years in Uppsala County, central Sweden, aiming to explore the association between poor oral health, namely the number of tooth loss, dental plaque status, and oral mucosal lesions, and the risk of dementia. Methods: We used Cox proportional hazards regression model to derive cause-specific hazard ratios (HR) and corresponding 95% confidence intervals (CI), while adjusting for baseline potential confounders as well as a time-varying covariate, Charlson’s Comorbidity Index score. Results: Dementia risk was substantially higher among those with a higher number of tooth loss; compared to the group with tooth loss 0-10, the HRs were 1.21 (95% CI: 1.02, 1.42), 1.17 (95% CI: 0.97, 1.40), and 1.30 (95% CI: 1.09, 1.54) respectively for groups with increasing number of tooth loss. There was some evidence of dose-risk association in this study, with a HR of 1.10 (1.04, 1.18) comparing adjacent groups (ptrend = 0.001). In a stratified analysis by attained age, tooth loss was more pronouncedly associated with the risk of dementia onset before age 80 (those with 21-32 versus 0-10 lost teeth, HR = 1.82, (95% CI: 1.32, 2.51); HR = 1.22 (95% CI: 1.10, 1.35) comparing adjacent groups, ptrend

To minimize the environmental burdens and to promote natural resource conservation and sustainability, a composite additive (CA) is proposed using paper and wood industry waste, i.e., lignosulphonate (LS) and lime (LM) as a replacement for conventional stabilizers. However, the implication of this proposed stabilizer for real construction scenarios requires a multi-objective optimization for a thorough guideline for practitioners. In this regard, the response surface methodology is used for the mix design optimization of the proposed CA for various construction scenarios (i.e., buildings, roadways, and slopes). An extensive testing program is designed and conducted to obtain different geotechnical parameters related to the mechanical, volumetric change, and hydraulic behavior of the soil with special attention to the stabilization mechanism. The interplay between variables (LS and LM) and responses is examined using the effective 3D surface diagrams, and mathematical models are derived for which the difference between R

Background: Bilirubin may prevent lipid peroxidation and have important antiatherosclerotic effects. We determined associations of serum bilirubin and lipid with peripheral atherosclerosis. Methods: We included 4290 participants (35% men; median age, 60 years) from the southeast China who underwent B-mode ultrasound examination. Increased intima-media thickness or a focal structure encroaching into the arterial lumen by at least 0.5 mm or >50% of the surrounding intima-media thickness value was regarded as having atherosclerosis. Fasting serum bilirubin and lipid levels were measured. Cholesterol/(HDL [high-density lipoprotein] cholesterol+bilirubin), and LDL (low-density lipoprotein cholesterol)/(HDL+bilirubin) ratios were calculated. Unconditional and multinomial logistic regression models were used to examine associations of bilirubin or lipid with prevalence of peripheral atherosclerosis. Mediation analyses were performed to assess the effect of bilirubin on atherosclerosis risk mediated via lipid. Results: Compared with participants with the lowest levels of bilirubin, those with the highest tertile were less likely to have carotid or femoral atherosclerosis (odds ratios were 0.55–0.74). The highest levels of bilirubin significantly reduced the odds of concurrent carotid and femoral atherosclerosis by 35% to 45%. Participants with the highest levels of cholesterol, LDL, cholesterol/(HDL+bilirubin), and LDL/(HDL+bilirubin) ratios had 2.8- to 3.7-fold increased odds of concurrent carotid and femoral atherosclerosis. LDL accounted for 25.65% of the total bilirubin-atherosclerosis association. LDL and cholesterol mediated the associations between direct bilirubin and atherosclerosis (proportion: 20.40%, 9.67%, respectively). Conclusions: Increased serum bilirubin levels are inversely associated with the prevalence of carotid or femoral atherosclerosis. LDL and cholesterol may mediate these associations.

Summary A new species of Xiphinema americanum group was recovered in the rhizosphere of holly (Ilex purpurea) imported from Japan. It is described and illustrated in the present study as X. purpureum n. sp. The new species is characterised by moderately long females 2267 (2115-2550) μm, round lip region slightly offset from the rest of the body, 103.5 (98.5-109.0) μm long odontostyle, genital branches without discernible endosymbiotic bacteria, vulva located at 54.1 (51.6-57.1)% of the body, tail 30 (24.3-33.4) μm long with a broadly rounded terminus, male absent and four juvenile developmental stages. The polytomous codes of the new species are as follows: A4/5, B2/3, C1/2, D2/3, E3, F1, G1, H2, I1/2/3. The new species was molecularly characterised using near full length 18S, ITS1, and 28S D2-D3 regions of rRNA, and mitochondrial cytochrome c oxidase subunit I gene sequences. The phylogenetic analyses placed X. purpureum n. sp. with X. americanum group species, particularly with X. brevicolle complex species. This is the third X. americanum group species described from Japan.

The soybean cyst nematode (SCN; Heterodera glycines Ichinohe 1952) is one of the most economically important pathogens of soybean. The species impacts soybean production worldwide and causes significant yield loss even in the absence of visible aboveground symptoms. This diagnostic guide describes the host range, signs, symptoms, and geographic distribution of SCN, and includes information regarding pathogen identification, storage, and pathogenicity tests for this nematode.

In the conventional method for the estimation of the hydraulic conductivity of unsaturated soil, only the capillary water is considered in the estimation. However, it is known that a water film can be formed around soil particles due to the adsorptive force. The water may migrate in the soil through the water film. As a result, both water flow in the capillary water and water film should be considered in the estimation. In this paper, a new equation was proposed for the estimation of the hydraulic conductivity of unsaturated soil by considering the film flow. The proposed method was verified with the experimental data from the literature. It is recommended that both capillary water flow and film flow should be considered in the estimation of the hydraulic conductivity of unsaturated soil.

The incidence of esophageal adenocarcinoma (EA) has drastically increased in the United States since 1970s for unclear reasons. We hypothesized that the widespread usage of antibiotics has increased the procarcinogenic potential of the orodigestive microbiota along the sequence of gastroesophageal reflux (GR), Barrett's esophagus (BE) and EA phenotypes. This case control study included normal controls (NC) and three disease phenotypes GR, BE and EA. Microbiota in the mouth, esophagus, and stomach, and rectum were analyzed using 16S rRNA gene sequencing. Overall, we discovered 44 significant pairwise differences in abundance of microbial taxa between the four phenotypes, with 12 differences in the mouth, 21 in the esophagus, two in the stomach, and nine in the rectum. Along the GR→BE→EA sequence, oral and esophageal microbiota were more diversified, the dominant genus Streptococcus was progressively depleted while six other genera Atopobium, Actinomyces, Veillonella, Ralstonia, Burkholderia and Lautropia progressively enriched. In NC, Streptococcus appeared to control populations of other genera in the foregut via numerous negative and positive connections, while in disease states, the rich network was markedly simplified. Inferred gene functional content showed a progressive enrichment through the stages of EA development in genes encoding antibiotic resistance, ligands of Toll-like and NOD-like receptors, nitrate-nitrite-nitric oxide pathway and acetaldehyde metabolism. The orodigestive microbiota is in a progressive dysbiotic state along the GR-BE-EA sequence. The increasing dysbiosis and antibiotic and procarcinogenic genes in the disease states warrants further study to define their roles in EA pathogenesis.

Background Eosinophilic gastrointestinal disorders (EGIDs) include inflammatory conditions with enteric infiltration of eosinophils and resulting symptoms. This study aims to examine a population-based sample of patients for prevalence, mortality, and cancer risk in EGIDs distal to the esophagus. Methods Nationwide, population-based cohort study. EGID was identified through relevant biopsy codes from Sweden’s all 28 pathology departments through the ESPRESSO cohort. Individuals with EGID were then matched to general population reference individuals with similar age and sex. Study participants were linked to Swedish healthcare registers. Through Cox regression, we calculated adjusted hazard ratios (aHRs) adjusting for sex, age, county, calendar period, and education. Results In total, 2429 patients (56% female) were found to have EGID distal to the esophagus, representing a prevalence of about 1/4800 in the Swedish population. Mean age was 44 years with 11% children at the time of diagnosis. Mortality was increased 17% in patients with EGIDs compared to reference individuals (aHR = 1.17; 95%CI = 1.04–1.33). Excess mortality was seen in gastric and small bowel eosinophilic disease, but not colonic disease (aHR = 1.81; 95%CI = 1.32–2.48, aHR = 1.50; 95%CI = 1.18–1.89, and aHR = 0.99; 95%CI = 0.85–1.16, respectively). Cause specific mortality was driven by cancer-related death (aHR = 1.33; 95%CI = 1.05–1.69). However, this study failed to show an increase in incident cancers (aHR = 1.14; 95%CI = 0.96–1.35). Comparison of EGID individuals with their siblings yielded similar aHRs. Conclusions This study found an increased risk of death in patients with EGIDs distal to the esophagus, with cancer death driving the increase. Proximal gut disease seems to confer the greatest risk. There was no increase in incident cancers.

Background Although primary health care (PHC) has been proven to be effective in preventing and treating chronic diseases, the visits rate of PHC institutions is still not ideal. Some patients initially express a willingness to visit PHC institutions but end up seeking health services at non-PHC institutions, and the reasons for this behavior remain unclear. Therefore, the objective of this study is to analyze the factors that contribute to behavioral deviations among chronic disease patients who originally intended to visit PHC institutions. Methods Data were collected from a cross-sectional survey among chronic disease patients with original intention to visit PHC institutions in Fuqing City, China. The analysis framework was guided by Andersen’s behavioral model. Logistic regression models were employed to analyze the factors affecting the behavioral deviations among chronic disease patients with a willingness to visit PHC institutions. Results A total of 1,048 individuals were finally included and about 40% of the participants with the original willingness to seek care from PHC institutions finally chose non-PHC institutions in their subsequent visits. The results of logistic regression analyses indicated that at the predisposition factor level, older participants (aOR60-69 = 0.602, P 70-75 = 0.475, P P P P P P Conclusions The deviations between the original willingness of PHC institution visits and subsequent behavior among chronic disease patients were associated with a number of predisposing, enabling, and need factors. Developing the health insurance system, strengthening the technical capacity of PHC institutions, and steadily developing a new concept of orderly healthcare-seeking behavior among chronic disease patients, will help promote their access to PHC institutions as well as improve the effectiveness of the tiered medical system for chronic disease care.

BackgroundFatty liver, obesity, and dyslipidemia are associated with prediabetes or diabetes risk, and hyperuricemia co-exists. The present study evaluated the role of multiple mediators, namely, fatty liver, body mass index (BMI), and dyslipidemia, in the association between hyperuricemia and diabetes status.MethodsBaseline data from the ongoing Fuqing cohort (5,336 participants) were analyzed to investigate the association of hyperuricemia with diabetes status using a multinomial logistic regression model. Furthermore, causal mediation analysis with the weighting-based approach was performed to estimate hyperuricemia’s total natural direct effect (tnde), total natural indirect effect (tnie), and total effect (te) on prediabetes and diabetes risk, mediating jointly via fatty liver, BMI, and dyslipidemia.ResultsIn multinomial analysis without considering mediators’ effects, hyperuricemia was associated with a higher risk of prediabetes only (odds ratio: 1.25; 95% CI: 1.09–1.43; p < 0.001). When fatty liver, BMI, and dyslipidemia were considered as multiple mediators in the association, hyperuricemia was linked to both prediabetes [tnde: 1.11, 95% CI: 1.04–1.11; tnie: 1.07, 95% CI: 1.05–1.09; and overall proportion mediated (pm): 42%, 95% CI: 27%–73%] and diabetes risk (tnde: 0.96, 95% CI: 0.82–1.14; tnie: 1.25, 95% CI: 1.18–1.33; and pm: 100%, 95% CI: 57%–361%). Hyperuricemia showed significant tnde, te, and tnie, mediated by fatty liver jointly with dyslipidemia (pm = 17%) or BMI (pm = 35%), on prediabetes risk.ConclusionHyperuricemia could increase prediabetes or diabetes risk, partially mediated by fatty liver, BMI, and dyslipidemia. Fatty liver is the crucial mediator in the association between hyperuricemia and prediabetes.

Effects of repeated weight changes on mortality are not well established. In this prospective cohort study, we followed 34,346 individuals from 1997 to 2018 for all-cause mortality, and 2016 for cause-specific mortality. At baseline, participants self-reported amount and frequency of prior weight loss. During 20.6 (median) years of follow-up, we identified 5627 deaths; 1783 due to cancer and 1596 due to cardiovascular disease (CVD). We used Cox Proportional Hazards models to estimate multivariable‐adjusted Hazard Ratios (HRs) and 95% confidence intervals (CI). Participants with a weight loss > 10 kg had higher rates of all-cause (HR 1.22; 95%CI 1.09–1.36) and CVD mortality (HR 1.27; 95%CI 1.01–1.59) compared to individuals with no weight loss. Men who had lost > 10 kg had higher all-cause (HR 1.55; 95%CI 1.31–1.84) and CVD mortality (HR 1.55; 95%CI 1.11–2.15) compared to men with no weight loss. Participants who had lost ≥ 5 kg three times or more prior to baseline had increased rates of all-cause (HR 1.16; 95%CI 1.03–1.30) and CVD mortality (HR 1.49; 95%CI 1.20–1.85) compared to participants with no weight loss. We found no association between weight loss and cancer mortality. We conclude that previous and repeated weight loss may increase all-cause and CVD mortality, especially in men.

Mucosal melanoma has characteristically distinct genetic features and typically poor prognosis. The lack of representative mucosal melanoma models, especially cell lines, has hindered translational research on this melanoma subtype. In this study, we aimed to establish and provide the biological properties, genomic features and the pharmacological profiles of a mucosal melanoma cell line that would contribute to the understanding and treatment optimization of molecularly-defined mucosal melanoma subtype.The sample was collected from a 67-year-old mucosal melanoma patient and processed into pieces for the establishment of cell line and patient-derived xenograft (PDX) model. The proliferation and tumorigenic property of cancer cells from different passages were evaluated, and whole-genome sequencing (WGS) was performed on the original tumor, PDX, established cell line, and the matched blood to confirm the establishment and define the genomic features of this cell line. AmpliconArchitect was conducted to depict the architecture of amplified regions detected by WGS. High-throughput drug screening (HTDS) assay including a total of 103 therapeutic agents was implemented on the established cell line, and selected candidate agents were validated in the corresponding PDX model.A mucosal melanoma cell line, MM9H-1, was established which exhibited robust proliferation and tumorigenicity after more than 100 serial passages. Genomic analysis of MM9H-1, corresponding PDX, and the original tumor showed genetic fidelity across genomes, and MM9H-1 was defined as a triple wild-type (TWT) melanoma subtype lacking well-characterized "driver mutations". Instead, the amplification of several oncogenes, telomerase reverse transcriptase (TERT), v-Raf murine sarcoma viral oncogene homolog B1 (BRAF), melanocyte Inducing transcription factor (MITF) and INO80 complex ATPase subunit (INO80), via large-scale genomic rearrangement potentially contributed to oncogenesis of MM9H-1. Moreover, HTDS identified proteasome inhibitors, especially bortezomib, as promising therapeutic candidates for MM9H-1, which was verified in the corresponding PDX model in vivo.We established and characterized a new mucosal melanoma cell line, MM9H-1, and defined this cell line as a TWT melanoma subtype lacking well-characterized "driver mutations". The MM9H-1 cell line could be adopted as a unique model for the preclinical investigation of mucosal melanoma.

Women’s health is important for society. Despite the known biological and sex-related factors influencing the risk of diseases among women, the network of the full spectrum of diseases in women is underexplored. This study aimed to systematically examine the women-specific temporal pattern (trajectory) of the disease network, including the role of baseline physical examination indexes, and blood and urine biomarkers. In the UK Biobank study, 502,650 participants entered the cohort from 2006 to 2010, and were followed up until 2019 to identify disease incidence via linkage to the patient registers. For those diseases with increased risk among women, conditional logistic regression models were used to estimate odds ratios (ORs), and the binomial test of direction was further used to build disease trajectories. Among 301 diseases, 82 diseases in women had ORs > 1.2 and p

As the ban on methyl bromide widens, the need for an effective phytosanitary fumigant alternative grows. Currently available alternatives, phosphine and sulfuryl fluoride, lack efficacy against the pinewood nematode. Ethanedinitrile is a highly efficacious fumigant with chemical properties similar to methyl bromide. Ethanedinitrile was tested against pinewood nematodes in a large-scale field setting with southern yellow pine wood chips at dose rates of 75 and 120 g/m3 for 24 hours. All treatments resulted in complete control of pinewood nematodes whereas a nontreated control confirmed the presence of live nematodes. These preliminary results confirm the efficacy of ethanedinitrile against pinewood nematodes in pine wood chips under field conditions.

Background: Previous research indicates that poor dental health increases risks for certain types of cancers, including esophageal cancer. This study aimed to investigate the association with esophageal cancer using Swedish Dental Health Register. Methods: This is a prospective cohort study. The exposures were dental diagnoses classified into healthy, caries, root canal infection, mild inflammation, and periodontitis, as well as number of remaining teeth, at baseline and during multiple visits. The outcome was the incidence of esophageal cancer, which was further divided into esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC). Cox proportional hazards models were used to estimate hazard ratios (HR) and its corresponding confidence intervals (CI). Results: A total of 5,042,303 individuals were included in the study and 1,259 EAC and 758 ESCC cases were identified. Root canal infection at baseline was associated with 41% higher risk for EAC (HR, 1.41; 95% CI, 1.10–1.82), whereas periodontitis at baseline was linked to 32% and 45% higher risks for respective histopathological subtypes (HR for EAC, 1.32; 95% CI, 1.13–1.53; HR for ESCC, 1.45; 95% CI, 1.20–1.75). Fewer remaining teeth at baseline also increased the risks for both histopathological types of esophageal cancer, with a dose–response effect (Ptrend < 0.01). Cox regression analyses with time-varying exposures corroborated the above-mentioned results. Conclusions: Impaired dental health before cancer diagnosis is associated with excess risks for both histopathological subtypes of esophageal cancer. Impact: Our study provided corroborating evidence for the association between poor oral health and esophageal cancer risk.

Background Following progressive aging of the population worldwide, the prevalence of Parkinson disease is expected to increase in the next decades. Primary prevention of the disease is hampered by limited knowledge of preventable causes. Recent evidence regarding diet and Parkinson disease is inconsistent and suggests that dietary habits such as fat intake may have a role in the etiology. Objective To investigate the association between intake of total and specific types of fat with the incidence of Parkinson disease. Methods Participants from the Swedish National March Cohort were prospectively followed-up from 1997 to 2016. Dietary intake was assessed at baseline using a validated food frequency questionnaire. Food items intake was used to estimate fat intake, i.e. the exposure variable, using the Swedish Food Composition Database. Total, saturated, monounsaturated and polyunsaturated fat intake were categorized into quartiles. Parkinson disease incidence was ascertained through linkages to Swedish population-based registers. Cox proportional hazards regression models were used to estimate hazard ratios (HR) with 95% confidence intervals (CI) of the association between fat intake from total or specific types of fats and the incidence of Parkinson disease. The lowest intake category was used as reference. Isocaloric substitution models were also fitted to investigate substitution effects by replacing energy from fat intake with other macronutrients or specific types of fat. Results 41,597 participants were followed up for an average of 17.6 years. Among them, 465 developed Parkinson disease. After adjusting for potential confounders, the highest quartile of saturated fat intake was associated with a 41% increased risk of Parkinson disease compared to the lowest quartile (HR Q4 vs. Q1: 1.41; 95% CI: 1.04–1.90; p for trend: 0.03). Total, monounsaturated or polyunsaturated fat intake were not significantly associated with Parkinson disease. The isocaloric substitution models did not show any effect. Conclusions We found that a higher consumption of large amounts of saturated fat might be associated with an increased risk of Parkinson disease. A diet low in saturated fat might be beneficial for disease prevention.

Rural areas are the weakest place for epidemic prevention and control, yet few studies have specifically conducted surveys in rural areas. The purpose of this study is to assess rural residents' knowledge of the COVID-19 and its prevention in China.A cross-sectional survey study containing 1,426 samples was conducted in Fuqing, China to assess rural residents' knowledge of the COVID-19 and its prevention. Logistic regression was used to identify potential differences in participants' knowledge of COVID-19 and its prevention and control in different population subgroups.The mean and median of residents' knowledge of COVID-19 was 5.53 and 6 points, respectively. The mean and median of residents' knowledge related to self-protection against COVID-19 was 10.34 and 11 points, respectively. Older adults (AOROur study suggests that when facing a pandemic like COVID-19, the key is to inform the public to understand simple and effective self-protection measures. Therefore, we call on the governments to give priority to publicity and education on self-prevention measures for the targeted populations and regions. This is most evident among the vulnerable groups like those who were unmarried, elderly, and those with low education or low income. Similar suggestions may be of use in other countries as well.

The intraclass correlation coefficients (ICCs) for the pooled QC samples of HBsAg, anti-HBs, HBeAg, anti-HBe, anti-HBc, were execellent (>0.9). The coefficients of variation (CVs) for the pooled QC samples of HBsAg, anti-HBs, HBeAg, anti-HBe, anti-HBc were all less than 20%.

Supplementary Table 1. Missing rates for three risk factors by study site in BEAGESS Supplementary Table 2. Genome-wide significant single nucleotide polymorphisms (SNPs) selected for GxE analysis. Supplementary Table 3. Odds ratios (95% confidence intervals) for risk factors in the BEACON study according to the number of minor alleles (rs2687201 or rs10419226), using a combined BE/EA case group. Inverse probability weighting techniques were used to account for the missing risk factor data in the GXE interaction analysis. The weights were computed based on a logistic regression model fit to the indicator variable of the risk factor being observed, adjusting for case control status, region (Australia, Europe, North America), age, sex, SNP genotype, and four principal components. Supplementary Table 4. Odds ratios (95% confidence intervals) for risk factors in the BEACON study according to the number of minor alleles (rs2687201 or rs10419226), using a combined BE/EA case group. Supplementary Table 5. Thirteen imputed SNPs found to interact with GERD more significantly than rs2687201 in relation to risk of Barrett's esophagus (BE). Supplementary Table 6.1 Annotations for top SNPs identified in GxE analysis (ordered by interaction P value). Supplementary Table 6.2 Genotype-Tissue Expression (GTEx) eQTL analysis of top 14 SNPs identified.

Background: Rising incidence of oropharyngeal cancers in numerous countries since the 1970s has been attributed to increased oral human papillomavirus (HPV) exposure. However, the contribution of coincidental declines in the surgical removal of the tonsils (tonsillectomy) is unknown. We quantified the association of tonsillectomy with risk of tonsillar, other oropharyngeal, and other head and neck cancers and the contribution of declines in tonsillectomies to cancer incidence trends.Methods: We conducted a nation-wide cohort study in Sweden (1970–2009). Tonsillectomies (N = 225,718) were identified through national patient registers, which were linked with the cancer register. Cancer incidence in the tonsillectomy cohort was compared with Sweden's general population through standardized incidence ratios (SIR).Results: Tonsillectomies were associated with reduced risk of tonsil cancers [SIRs 1+ years post-tonsillectomy = 0.31; 95% confidence interval (CI), 0.08–0.79 and 5+ years post-tonsillectomy = 0.17; 95% CI, 0.02–0.62], but unrelated to other oropharyngeal or other head and neck cancers (SIRs 1+ years post-tonsillectomy = 1.61; 95% CI, 0.77–2.95 and 0.92; 95% CI, 0.64–1.27, respectively). The cumulative incidence of tonsillectomy declined significantly (40%–50%) during 1970–2009. However, tonsil cancer incidence significantly increased during 1970–2009 both without and with corrections for declines in tonsillectomies (relative risks per 5-year periods = 1.23, P < 0.001 and 1.20, P < 0.001, respectively).Conclusions: The reduced tonsil cancer risk with tonsillectomy reflects the removal of most of the relevant tissue. The absence of associations with other head and neck cancers indicates that tonsillectomy may not impact carcinogenesis at other sites.Impact: The significant increases in oropharyngeal cancer incidence since the 1970s in Sweden appear independent of declines in tonsillectomies, reinforcing increased oral HPV exposure as the likely cause. Cancer Epidemiol Biomarkers Prev; 25(6); 944–50. ©2016 AACR.

Background: Whether or not hepatitis B virus (HBV) infection plays a role in the development of nasopharyngeal carcinoma (NPC) is largely unknown. Our study aimed to assess the association between HBV infection and the risk of NPC in Southern China.Methods: We conducted a case–control study including 711 NPC cases and two groups of controls. The first control group consisted of 656 individuals with other benign tumors unrelated to HBV infection and the second group consisted of 680 healthy population controls. Multivariable ORs and corresponding 95% confidence intervals (CI) for NPC were estimated by logistic regression.Results: Patients with NPC had higher prevalence of antibodies against hepatitis B core antigen–positive [anti-HBc-(+); 47.26%] compared with either benign tumor controls (39.33%; P < 0.01) or healthy controls (41.18%; P = 0.04). In multivariable models adjusting for a set of risk factors for NPC, anti-HBc-(+) was significantly associated with a higher risk of NPC [adjusted OR (AOR), 1.40; 95% CI, 1.12–1.74 compared with the benign tumor controls and AOR, 1.48; 95% CI, 1.05–2.08 compared with the healthy controls]. The association was not modified by hepatitis B surface antigen (HBsAg) status. Finally, compared with the healthy controls, individuals with both anti-HBc-(+) and EBV antibodies had largely increased risk of NPC (AOR, 141.82; 95% CI, 68.73–292.62).Conclusion: Our study suggests that HBV infection is associated with NPC risk in Southern China.Impact: Prevention for HBV infection may play a role in the development of NPC. Cancer Epidemiol Biomarkers Prev; 24(11); 1766–73. ©2015 AACR.

Supplementary Figure 1 - non-linear relation with 4 knots restricted cubic spline between LTL and pancreatic cancer risk.

Association between 387 SNPs and risk of EA, BE, or EA/BE combined

Supplementary Tables 1-4. Supplementary Table 1. Odds ratios (ORs) and 95% confidence intervals (CIs) of nasopharyngeal carcinoma (NPC) associated with oral health among ever smokers in southern China (2010-2014). Supplementary Table 2. Stratified odds ratios (ORs) and 95% confidence intervals (CIs) of nasopharyngeal carcinoma (NPC) associated with number of teeth lost after age 20 years.* Supplementary Table 3. Stratified odds ratios (ORs) and 95% confidence intervals (CIs)of nasopharyngeal carcinoma (NPC) associated with frequency of tooth brushing.* Supplementary Table 4. Odds ratios (ORs) and 95% confidence intervals (CIs) of nasopharyngeal carcinoma (NPC) associated with oral health in southern China - restricted to cases interviewed within 30 days of diagnosis (2010-2014).

Supplemental Figure 1: Description of tonsillectomy cohort for the Swedish nation-wide study (1970-2009.)Supplemental Table 1: Clinical indications for tonsillectomy, stratified by calendar period and age at tonsillectomy. Supplemental Table 2: Clinical indications for tonsillectomies conducted as in-patient versus out-patient procedures (2006-2009.) Supplemental Table 3: Association of tonsillectomy with risk of head and neck cancers, stratified by age at tonsillectomy, gender, and calendar era of tonsillectomy.Supplemental Table 4: Sensitivity analyses of the association of tonsillectomy with risk of head and neck cancers.

Background: Several cancer-associated loci identified from genome-wide association studies (GWAS) have been associated with risks of multiple cancer sites, suggesting pleiotropic effects. We investigated whether GWAS-identified risk variants for other common cancers are associated with risk of esophageal adenocarcinoma (EA) or its precursor, Barrett's esophagus.Methods: We examined the associations between risks of EA and Barrett's esophagus and 387 SNPs that have been associated with risks of other cancers, by using genotype imputation data on 2,163 control participants and 3,885 (1,501 EA and 2,384 Barrett's esophagus) case patients from the Barrett's and Esophageal Adenocarcinoma Genetic Susceptibility Study, and investigated effect modification by smoking history, body mass index (BMI), and reflux/heartburn.Results: After correcting for multiple testing, none of the tested 387 SNPs were statistically significantly associated with risk of EA or Barrett's esophagus. No evidence of effect modification by smoking, BMI, or reflux/heartburn was observed.Conclusions: Genetic risk variants for common cancers identified from GWAS appear not to be associated with risks of EA or Barrett's esophagus.Impact: To our knowledge, this is the first investigation of pleiotropic genetic associations with risks of EA and Barrett's esophagus. Cancer Epidemiol Biomarkers Prev; 24(11); 1801–3. ©2015 AACR.

Supplemental Figure 2 legend: Shown are age-specific cumulative incidences of tonsillectomies during 1970-2009 in Sweden across the year of birth (i.e. birth cohort).

Figure legends

Supplementary Table 1 - Associations between LTL and pancreatic cancer risk adjusted for smoking status C-peptide and HbA1c levels

Background: The association between oral health and risk of nasopharyngeal carcinoma (NPC) is largely unknown. Further understanding could shed light on potential pathogenic mechanisms and preventive measures.Methods: We conducted a population-based case–control study in southern China between 2010 and 2014. We enrolled 2,528 incident NPC cases, aged 20–74 years, and 2,596 controls, randomly selected from the total population registers, with frequency matching to the 5-year age and sex distribution of the cases by geographic region. We interviewed subjects using a structured questionnaire inquiring about oral health indicators and potential confounding factors. We used unconditional logistic regression to estimate multivariate-adjusted ORs with 95% confidence intervals (CI).Results: A higher number of filled teeth was associated with an elevated risk of NPC. Individuals with 1 to 3 and more than 3 teeth filled versus none had adjusted ORs of 1.25 (95% CI, 1.06–1.49) and 1.55 (95% CI, 1.13–2.12), respectively (Ptrend = 0.002). Conversely, the adjusted OR for those who brushed teeth twice or more per day versus once or less per day was 0.62 (95% CI, 0.55–0.70). We detected a borderline significant positive association with earlier age at first adult tooth loss.Conclusion: Our study suggested a positive association between some indicators of poor oral health and risk of NPC. Further studies are needed to confirm whether the findings are causal and, if so, to further explain the underlying mechanisms.Impact: Improvement of oral hygiene might contribute to reducing NPC risk. Cancer Epidemiol Biomarkers Prev; 25(8); 1201–7. ©2016 AACR.

Supplementary Figure S1. NIH Roadmap Epigenome Atlas characterization of genomic regions flanking rs2687201.

Background: Important risk factors for esophageal adenocarcinoma and its precursor, Barrett's esophagus, include gastroesophageal reflux disease, obesity, and cigarette smoking. Recently, genome-wide association studies have identified seven germline single-nucleotide polymorphisms (SNP) that are associated with risk of Barrett's esophagus and esophageal adenocarcinoma. Whether these genetic susceptibility loci modify previously identified exposure–disease associations is unclear.Methods: We analyzed exposure and genotype data from the BEACON Consortium discovery phase GWAS, which included 1,516 esophageal adenocarcinoma case patients, 2,416 Barrett's esophagus case patients, and 2,187 control participants. We examined the seven newly identified susceptibility SNPs for interactions with body mass index, smoking status, and report of weekly heartburn or reflux. Logistic regression models were used to estimate ORs for these risk factors stratified by SNP genotype, separately for Barrett's esophagus and esophageal adenocarcinoma.Results: The odds ratio for Barrett's esophagus associated with at least weekly heartburn or reflux varied significantly with the presence of at least one minor allele of rs2687201 (nominal P = 0.0005, FDR = 0.042). ORs (95% CIs) for weekly heartburn or reflux among participants with 0, 1, or 2 minor alleles of rs2687201 were 6.17 (4.91–7.56), 3.56 (2.85–4.44), and 3.97 (2.47–6.37), respectively. No statistically significant interactions were observed for smoking status and body mass index.Conclusion: Reflux symptoms are more strongly associated with Barrett's esophagus risk among persons homozygous for the major allele of rs2687201, which lies approximately 75 kb downstream of the transcription factor gene FOXP1.Impact: The novel gene–exposure interaction discovered in this study provides new insights into the etiology of esophageal adenocarcinoma. Cancer Epidemiol Biomarkers Prev; 24(11); 1739–47. ©2015 AACR.

Supplementary Table 2 - Associations between LTL and pancreatic cancer risk adjusted for Cpeptide and HbA1c levels considering only microscopically confirmed cases.

Background We aimed to investigate associations between pre-diagnostic anti-Epstein-Barr virus (EBV) antibodies, including interactions with hepatitis B virus (HBV), and risk of primary liver cancer in southern China. Methods In a population-based nested case-control study, we measured pre-diagnostic immunoglobulin A (IgA) against EBV nuclear antigen 1 (EBNA1) and viral capsid antigen (VCA) in 125 primary liver cancer cases and 2077 matched controls. We also explored the interaction between HBV surface antigen (HBsAg) and anti-EBV antibodies. Results Participants with positive EBNA1-IgA, positive VCA-IgA or single-positive anti-EBV antibodies had two-fold odds of developing liver cancer, compared with seronegative subjects. The odds ratios (ORs) between the relative optical density of EBNA1-IgA and VCA-IgA and primary cancer, controlling for age and HBsAg, were 1.59 (95% confidence interval (CI): 1.17, 2.14) and 1.60 (95% CI: 1.07, 2.41), respectively. Subjects with both HBsAg and anti-EBV antibody seropositivity were at 50-fold increased risk compared with those negative for both biomarkers (OR: 50.67, 95% CI: 18.28, 140.46), yielding a relative excess risk due to interaction of 30.81 (95% CI: 3.42, 114.93). Conclusion Pre-diagnostic seropositivity for EBNA1-IgA and/or VCA-IgA was positively associated with primary liver cancer risk, especially in combination with HBsAg positivity. EBV may interact with HBV in the development of primary liver cancer, and anti-EBV antibodies might be potential biomarkers for primary liver cancer in this high-risk population.

BackgroundLow-density lipoprotein cholesterol (LDLc) and body mass index (BMI) are not always correlated and their relationship is probably dependent on age, indicating differential age-specific effects of these two factors on health outcomes. We thus aimed to discriminate the effects of LDLc and BMI on the risk of coronary heart disease (CHD) across different age groups.MethodsThis is a prospective cohort study of 368,274 participants aged 38-73 years and free of CHD at baseline. LDLc and BMI were measured at baseline, and incident CHD was the main outcome. Cox proportional hazards model and restricted cubic spline (RCS) regression were used to estimate hazard ratio (HR) and 95% confidence interval (CI) of exposure on CHD.ResultsSimilar relationships of LDLc and BMI with CHD risk were observed in overall population but in differential age-specific patterns. Across the age groups of =65 years, the LDLc-CHD association diminished with the adjusted HRs decreasing from 1.35, 1.26, 1.19, 1.11 to 1.08; while no declining trend was found in BMI-CHD relationship with the adjusted HRs of 1.15, 1.11, 1.12, 1.13 and 1.15, respectively. The interaction and mediation between LDLc and BMI on CHD risk were only present at young-age groups. And the LDLc-CHD but not BMI-CHD association was dependent on sex, metabolic syndrome and lipid-lowering drugs use.ConclusionThere were differential age-specific effects of LDLc and BMI on the risk of developing CHD, calling for future efforts to discriminate the age-different benefits from lipids management or weight control on the primary prevention for CHD.Clinical PerspectiveWhat Is New?This study shows, for the first time, that there were differential age-specific effects of LDLc and BMI on the risk of developing coronary heart disease (CHD), in which the LDLc-CHD association diminished with increasing age while no declining trend was found in BMI-CHD relationship.The interaction and mediation between LDLc and BMI on the risk of coronary heart disease were only present in young adults.What Are the Clinical Implications?Future efforts are called to discriminate the age-different benefits from lipids management or weight control on the primary prevention for CHD.Findings from this study highlighted that lipids management at young age was expected to have a much more favorable benefit in CHD prevention; and weight control shouldn’t be overlooked, especially for elderly adults, as lipid-lowering therapy might not contribute to the reduction of obesity-related CHD.

EBV is classified as the group I human carcinogen and is associated with multiple cancers, including NPC. The interplays between the microbiota and oncovirus in cancer development remain largely unknown.

There is emerging evidence that spouses of patients with cancer may have a higher prevalence of mental illness, but these studies have been limited by pre-post designs, focus on a single mental illness, and short follow-up periods.To assess the overall burden of psychiatric disorders among spouses of patients with cancer vs spouses of individuals without cancer and to describe possible changes in this burden over time.This population based cohort study included spouses of patients with cancer (diagnosed 1986-2016 in Denmark and 1973-2014 in Sweden; exposed group) and spouses of individuals without cancer (unexposed group). Members of the unexposed group were individually matched to individuals in the exposed group on the year of birth, sex, and country. Spouses with and without preexisting psychiatric morbidity were analyzed separately. Data analysis was performed between May 2021 and January 2022.Being spouse to a patient with cancer.The main outcome was a clinical diagnosis of psychiatric disorders through hospital-based inpatient or outpatient care. Flexible parametric models and Cox models were fitted to estimate hazard ratios (HRs) with 95% CIs, adjusted for sex, age and year at cohort entry, country, household income, and cancer history.Among 546 321 spouses in the exposed group and 2 731 574 in the unexposed group who had no preexisting psychiatry morbidity, 46.0% were male participants, with a median (IQR) age at cohort entry of 60 (51-68) years. During follow-up (median, 8.4 vs 7.6 years), the incidence rate of first-onset psychiatric disorders was 6.8 and 5.9 per 1000 person-years for the exposed and unexposed groups, respectively (37 830 spouses of patients with cancer [6.9%]; 153 607 of spouses of individuals without cancer [5.6%]). Risk of first-onset psychiatric disorders increased by 30% (adjusted HR, 1.30; 95% CI, 1.25-1.34) during the first year after cancer diagnosis, especially for depression (adjusted HR, 1.38; 95% CI, 1.30-1.47) and stress-related disorders (adjusted HR, 2.04; 95% CI, 1.88-2.22). Risk of first-onset psychiatric disorders increased by 14% (adjusted HR, 1.14; 95% CI, 1.13-1.16) during the entire follow-up, which was similar for substance abuse, depression, and stress-related disorders. The risk increase was more prominent among spouses of patients diagnosed with a cancer with poor prognosis (eg, pancreatic cancer: adjusted HR, 1.41; 95% CI, 1.32-1.51) or at an advanced stage (adjusted HR, 1.31; 95% CI, 1.26-1.36) and when the patient died during follow-up (adjusted HR, 1.29; 95% CI, 1.27-1.31). Among spouses with preexisting psychiatric morbidity, the risk of psychiatric disorders (first-onset or recurrent) increased by 23% during the entire follow-up (adjusted HR, 1.23; 95% CI, 1.20-1.25).In this cohort study of 2 populations in Denmark and Sweden, spouses of patients with cancer experienced increased risk of several psychiatric disorders that required hospital-based specialist care. Our results support the need for clinical awareness to prevent potential mental illness among the spouses of patients with cancer.

Intrusion/erosion will cause mass loss of bentonite, resulting in endangering the operation safety of the repository for disposal of high-level radioactive waste. In this work, intrusion/erosion tests were conducted on GMZ bentonite specimens with a fracture aperture of 0.1, 0.5, 0.75 and 1.0 mm, as well as a duration of 60 days. Images were regularly captured with a digital camera. The intrusion distance and width of accessory-mineral ring were obtained. The erosion rate was determined by a turbidimeter. Meanwhile, parallel tests with a fracture aperture of 0.5 and 1.0 mm were repeated with a duration of 5, 15 and 30 days. After tests stopped, dry weight of specimens was measured. Results show that the intrusion distance increased with increasing fracture apertures, resulting in the increase of accessory-mineral-ring width, which will in turn restrict intrusion and erosion. Actually, the erosion rate in the early period decreased obviously with increasing accessory-mineral-ring widths, due to its filtration effects. However, when erosion reached stabilization, the erosion rate increased with increasing fracture apertures and intrusion distances but not independent of the accessory-mineral ring. The majority part of specimen mass loss ratio in the early period was from intrusion. But when intrusion reached stabilization, the mass loss ratio of specimen will be mainly contributed by erosion and would keep on increasing. Moreover, the mass loss ratios of specimens after 60 days by intrusion and erosion both increased with increasing fracture apertures. Meanwhile, the difference between the mass loss ratio by intrusion and erosion increased with increasing fracture apertures.

Background There is continued uncertainty regarding the risks of hepato-pancreato-biliary cancers in patients with inflammatory bowel disease (IBD) with or without concomitant primary sclerosing cholangitis (PSC). Objective To give updated estimates on risk of hepato-pancreato-biliary cancers in patients with IBD, including pancreatic cancer, hepatocellular carcinoma, gall bladder cancer, and intra – and extrahepatic cholangiocarcinoma. Methods In a population-based cohort study, we included all patients diagnosed with IBD in Norway and Sweden from 1987 to 2016. The cohort comprised of 141,960 patients, identified through hospital databases and the National Patient Register. Participants were followed through linkage to national cancer, cause of death, and population registries. We calculated absolute risk and standardized incidence ratios (SIRs) of hepato-pancreato-biliary cancers by PSC and other clinical characteristics. Results Of the 141,960 IBD patients, 3.2% were diagnosed with PSC. During a median follow-up of 10.0 years, we identified 443 biliary tract cancers (SIR 5.2, 95% confidence interval [CI] 4.8–5.7), 161 hepatocellular carcinomas (SIR 2.4, 95% CI 2.0–2.7) and 282 pancreatic cancers (SIR 1.3, 95% CI 1.2–1.5). The relative risks were considerably higher in PSC-IBD patients, with SIR of 140 (95% CI 123–159) for biliary tract, 38.6 (95% CI 29.2–50.0) for hepatocellular, and 9.0 (95% CI 6.3–12.6) for pancreatic cancer. The SIRs were still slightly increased in non-PSC-IBD patients, compared to the general population. For biliary tract cancer, the cumulative probability at 25 years was 15.6% in PSC-IBD patients, and 0.4% in non-PSC-IBD patients. Conclusions The dramatically increased risks of hepato-pancreato-biliary cancers in PSC-IBD patients support periodic surveillance for these malignancies. While much lower, the excess relative risks in non-PSC-IBD patients were not trivial compared to non-IBD related risk factors.