Coexistence of superconductivity with partially filled stripes in the Hubbard model.

The Hubbard model is an iconic model in quantum many-body physics and has been intensely studied, especially since the discovery of high-temperature cuprate superconductors. Combining the complementary capabilities of two computational methods, we found superconductivity in both the electron- and hole-doped regimes of the two-dimensional Hubbard model with next-nearest-neighbor hopping. In the electron-doped regime, superconductivity was weaker and was accompanied by antiferromagnetic Néel correlations at low doping. The strong superconductivity on the hole-doped side coexisted with stripe order, which persisted into the overdoped region with weaker hole-density modulation. These stripe orders varied in fillings between 0.6 and 0.8. Our results suggest the applicability of the Hubbard model with next-nearest hopping for describing cuprate high-transition temperature (Tc) superconductivity.

Association between Single Nucleotide Polymorphisms in Monoamine Oxidase and the Severity of Addiction to Betel Quid.

Betel quid (BQ) is the fourth most popular psychoactive substance in the world, and BQ use disorder (BUD) is prevalent in Asian countries. Although the mechanisms underlying BUD remain unclear, studies have reported influences from monoamine oxidase inhibitor. We enrolled 50 patients with BUD and assessed their BQ consumption habits, emotional conditions, and the clinical severity of addiction-assessed using the Diagnostic and Statistical Manual of Mental Disorders [Fifth Edition] (DSM-5) criteria, Substance Use Severity Rating Scale, and Yale-Brown Obsessive Compulsive Disorder Rating Scale for BQ. Patients were categorized into the severe group when showing six or more symptoms defined by DSM-5. A genome-wide association study was conducted for single nucleotide polymorphisms in BRCA1, COL9A1, NOTCH1, HSPA13, FAT1, and MAOA by using patients' blood samples. More severe BUD symptoms were associated with younger age of using BQ and poor oral hygiene and with severe craving for and more anxiety toward BQ use. The MAOA rs5953210 polymorphism was significantly associated with severe BUD (odds ratio, 6.43; 95% confidence interval, 5.12-7.74; p < 0.01) and might contribute to BQ-associated cancer risk. Further studies are required to investigate the addictive properties of BQ and the development of novel diagnostic tools and pharmacotherapeutic alternatives to BUD treatment.

Pharmacometabolomic study of drug response to antihypertensive medications for hypertension marker identification in Han Chinese individuals in Taiwan.

Various groups of antihypertensive drugs targeting different pathways have been developed; however, the pharmacometabolic responses to these drugs have rarely been compared to elucidate the common pathway of blood pressure regulation. Here, we performed a comparative multi-dimensional pharmacometabolic study on the four major lines of antihypertensive drugs, namely angiotensin-converting enzyme inhibitors (ACEis), angiotensin receptor blockers (ARBs), calcium channel blockers (CCBs), and diuretics (DIURs), through ultra-performance liquid chromatography coupled to quantum time-of-flight mass spectrometry. Two hundred fifty patients with young-onset hypertension, who were equally divided among five study groups: non-medicated, ACEi, ARB, CCB, and DIUR groups, were recruited. In a metabolome-wide association study conducted through analysis of covariance, 37 molecular features significantly associated with pharmacometabolic responses to antihypertensive drugs were identified. One-third of these features were shared by multiple medications. ACEis, ARBs, and DIURs shared more features than CCB, partially reflecting that ACEis, ARBs, and DIURs affect the renin-angiotensin-aldosterone system. Thirteen molecular features were consistently identified by all four models of the analysis of covariance. A tandem mass spectrometry (or MS/MS) experiment was performed to decipher the chemical structure of these 13 molecular features, including ARB-associated lysophosphatidylcholine (P4135), CCB-associated diacylglycerol(15:0/18:2) (P1175), and DIUR-associated oleamide (P1516). In addition, diacylglycerol(15:0/14:2) (P408) was significantly associated with the pharmacometabolic response to all four antihypertensive drugs. The identified metabolites provide insights into the mechanisms of blood pressure regulation and potential predictive markers of pharmacometabolic responses to antihypertensive drugs.

SLC12A3 Variation and Renal Function in Chinese Patients With Hypertension.

Objective: SLC12A3 (solute carrier family 12 member 3) gene variants are associated with diabetic nephropathy; however, their association with hypertensive nephropathy remains unknown. We aimed to investigate the association between SLC12A3 gene polymorphisms and renal function in patients with hypertension. Methods: Participants from three non-diabetic hypertensive cohorts, including young-onset hypertension (cohort 1, n = 882), treatment-naïve hypertension (cohort 2, n = 90), and follow-up cohort (cohort 3, n = 166), underwent genotyping for single nucleotide polymorphisms in SLC12A3. Renal events were defined as a >25 and >50% decline in estimated glomerular filtration rate (eGFR). Results: In cohort 1, SLC12A3 rs16963397 C/C or C/G (P = 0.005), rs13334864 C/C or C/T (P = 0.020), and rs7187932 A/A or A/G polymorphisms (P = 0.014) had higher eGFRs compared to their counterparts, with similar findings observed in cohort 2. In cohort 3, over a mean follow-up of 5.8 ± 1.7 years, participants with either SLC12A3 rs16963397 C/C or rs13334864 C/C polymorphisms had more >25 and >50% eGFR decline than their counterparts (log-rank test, P = 0.058 and P = 0.038, respectively). Cox regression analysis revealed that SLC12A3 rs16963397 C/C and rs13334864 C/C polymorphisms were significantly associated with an increased risk of >25% [hazard ratio (HR), 3.294; 95% confidence interval (CI), 1.158-9.368; P = 0.025] and >50% decline in eGFR (HR, 18.630; 95% CI, 1.529-227.005, P = 0.022) than their counterparts. Conclusion: SLC12A3 polymorphisms are associated with renal function in Chinese patients with hypertension.

Emergency department visits among people with predementia highly predicts conversion to dementia.

Emergency department visits (EDV) are common among older adults with and without dementia. The risk factors and demands of EDVs for people with dementia have been well studied; however, the association between EDVs and conversion to dementia among people with predementia has not been thoroughly explored. To study the predictive value of EDVs in predementia's progression to dementia. The baseline predementia cohort registered from September 2015 to August 2017, with longitudinal follow-up in the History-based Artificial Intelligent Clinical Dementia Diagnostic System database, was retrospectively analyzed. The rates of conversion among the different EDVs were compared. Multivariate logistic regression and Cox proportional hazards analyses were applied to study the influence of EDVs on progression. Age, education, sex, neuropsychological tests, activities of daily living, neuropsychiatric symptoms, parkinsonism, and multiple vascular risk factors were adjusted for. A total of 512 participants were analyzed, including 339 (66.2%) non-converters and 173 (33.8%) converters with a mean follow-up of 3.3 (range 0.4-6.1) and 2.8 (range 0.5-5.9) years, respectively. Compared to people without EDV (EDV 0), the hazard ratios for conversion to dementia were 3.6, 5.9, and 6.9 in those with EDV once (EDV 1), twice (EDV 2), and more than twice (EDV >2), respectively. In addition, older age, lower education, poorer cognition, poorer ADL performance, and longer follow-up periods also increased the conversion rates. EDVs in the predementia stages highly predict progression to dementia. Therefore, a sound public health as well as primary healthcare system that provide strategies for better management of mental and physical condition might help prevention of EDVs among older people in the predementia stages.

Reduction in and Preventive Effects for Oral-Cancer Risk with Antidepressant Treatment.

Areca nut (AN) was identified as carcinogenic to humans. Around 600 million people globally use AN in some form, yet no effective therapeutic drug is available to overcome AN addiction. This preclinical study examines the effects of antidepressants on AN use with animal models. We produced AN powder and dissolved it into drinking water, training 55 C57BL/6 mice in free self-selection to drink AN water or normal water. Then, the mice were randomly divided into four groups. Selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs), and tricyclic antidepressants (TCAs) were given as three treatment groups and one placebo group for four weeks. In the follow-up period, the preference and amount of free selection of AN and normal water, and oral pathological change were evaluated. There was a significant decrease in preference for AN drinking during the first four weeks, and the 36th week after drug withdrawal in the MAOI and SSRI groups (all p < 0.05). The drug-reducing effect of AN water in the 1-4-week period was significant in the MAOI group (p < 0.0001) and was also significant in the 3-4-week period in the SSRI group (p = 0.03). The TCA group did not show a decrease effect. At the endpoint (60 weeks), oral mucosal fibrosis (OSF) levels and risk in the SSRI (p = 0.0081) and MAOI (p = 0.01) groups were significantly lower than those in the control group. Antidepressant drugs MAOIs and SSRIs could reduce the amount of AN use and decrease the early stage of oral fibrosis in mice, but SSRIs may need to be boosted again.

Risk Assessment for Heroin Use and Craving Score Using Polygenic Risk Score.

Addiction is characterized by drug-craving, compulsive drug-taking, and relapse, and results from the interaction between multiple genetic and environmental factors. Reward pathways play an important role in mediating drug-seeking and drug-taking behaviors, and relapse. The objective of this study was to identify heroin addicts who carry specific genetic variants in their dopaminergic reward systems. A total of 326 heroin-dependent patients undergoing methadone maintenance therapy (MMT) were recruited from the Addiction Center of the China Medical University Hospital. A heroin-use and craving questionnaire was used to evaluate the urge for heroin, the daily or weekly frequency of heroin usage, daily life disturbance, anxiety, and the ability to overcome heroin use. A general linear regression model was used to assess the associations of genetic polymorphisms in one's dopaminergic reward system with heroin-use and craving scores. Results: The most significant results were obtained for rs2240158 in GRIN3B (p = 0.021), rs3983721 in GRIN3A (p = 0.00326), rs2129575 in TPH2 (p = 0.033), rs6583954 in CYP2C19 (p = 0.033), and rs174699 in COMT (p = 0.036). These were all associated with heroin-using and craving scores with and without adjustments for age, sex, and body mass index. We combined five variants, and the ensuing dose-response effect indicated that heroin-craving scores increased with the numbers of risk alleles (p for trend = 0.0008). These findings will likely help us to understand the genetic mechanism of craving, which will help in predicting the risk of relapse in clinical practice and the potential for therapies to target craving in heroin addiction.

Anti-TROVE2 Antibody Determined by Immune-Related Array May Serve as a Predictive Marker for Adalimumab Immunogenicity and Effectiveness in RA.

Anti-drug antibody (ADAb) development is associated with secondary therapeutic failure in biologic-treated rheumatoid arthritis (RA) patients. With a treat-to-target goal, we aimed to identify biomarkers for predicting ADAb development and therapeutic response in adalimumab-treated patients. Three independent cohorts were enrolled. In Cohort-1, 24 plasma samples (6 ADAb-positive and 6 ADAb-negative patients at baseline and week 24 of adalimumab therapy, respectively) were assayed with immune-related microarray containing 1,636 correctly folded functional proteins. Next, we executed statistically powered autoantibody profiling analysis of 50 samples in Cohort-2 (24 ADAb-positive and 26 ADAb-negative patients). Subsequently, immunofluorescence assay was performed on 48 samples in Cohort-3 to correlate with ADAb titers and drug levels. The biomarkers were identified for predicting ADAb development and therapeutic response using the immune-related microarray and machine learning approach. ADAb-positive patients had lower drug levels at week 24 (median = 0.024 µg/ml) compared with ADAb-negative patients (median = 6.38 µg/ml, p < 0.001). ROC analysis based on the ADAb status revealed the top 20 autoantibodies with AUC ≥ 0.7 in differentiating both groups in Cohort-1. Analysis of Cohort-2 dataset identified a panel of 8 biomarkers (TROVE2, SSB, NDE1, ZHX2, SH3GL1, CARD9, PTPN20, and KLHL12) with 80.6% specificity, 77.4% sensitivity, and 79.0% accuracy in discriminating poor from EULAR responders. Immunofluorescence assay validated that anti-TROVE2 antibody could highly predict ADAb development and poor EULAR response (AUC 0.79 and 0.89, respectively). Multivariate regression analysis proved anti-TROVE2 antibody to be an independent predictor for developing ADAb. Immune-related protein microarray and replication analysis identified anti-TROVE2 antibody as a useful biomarker for predicting ADAb development and therapeutic response in adalimumab-treated patients.

Arecoline N-oxide initiates oral carcinogenesis and arecoline N-oxide mercapturic acid attenuates the cancer risk.

Arecoline N-oxide (ANO), an oxidative metabolite of the areca nut, is a predictable initiator in carcinogenesis. The mechanisms of arecoline metabolites in human cancer specimens is still limited. This present study aims to estimate the oral squamous cell carcinoma (OSCC) inductive activity between arecoline metabolites in human cancer specimens/OSCC cells. We have collected 22 pairs (tumor and non-tumor part) of patient's specimens and checked for clinical characteristics. The identification of arecoline and its metabolites levels by using LC-MS/MS. The NOD/SCID mice model was used to check the OSCC inductive activity. The tumor part of OSCC samples exhibited higher levels of arecoline and ANO. Besides, ANO treated mice accelerates the NOTCH1, IL-17a and IL-1ß expressions compared to the control mice. ANO exhibited higher cytotoxicity, intracellular ROS levels and decline in antioxidant enzyme levels in OC-3 cells. The protein expression of NOTCH1 and proliferation marker levels are significantly lower in NOM treated cells. Overall, ANO induced initial stage carcinogenesis in the oral cavity via inflammation, ROS and depletion of antioxidant enzymes. Arecoline N-oxide mercapturic acid (NOM) attenuates the initiation of oral carcinogenesis.

Sex difference in sympathetic nervous system activity and blood pressure in hypertensive patients.

Increased sympathetic nervous system (SNS) activity leads to increased risk of cardiovascular morbidity and mortality. This study investigated whether there were sex differences in SNS activity among Chinese patients with hypertension. Ethnic Chinese non-diabetic hypertensive patients aged 20-50 years were enrolled in Taiwan. A total of 970 hypertensive patients (41.0 ± 7.2 years) completed the study, 664 men and 306 women. They received comprehensive evaluations including office blood pressure (BP) measurement, 24-h ambulatory BP monitoring, and 24-h urine sampling assayed for catecholamine excretion. Compared to women, men were younger, had higher body mass index (BMI), office systolic BP (SBP), office diastolic BP (DBP), 24-h ambulatory BP, and 24-h urine catecholamine excretion. In men, 24-h urine total catecholamine levels were correlated with 24-h SBP (r = 0.103, p = .008) and 24-h DBP (r = 0.083, p = .033). In women, however, there was no correlation between 24-h urine total catecholamine levels and 24-h ambulatory BP. Multivariate linear regression indicated that being male (ß = 1.65, 95% confidence interval [CI] 0.01-3.29, p = .048) and 24-h urine total catecholamine (ß = 5.03, 95% CI 0.62-9.44, p = .025) were both independently associated with 24-h SBP; being male was independently associated with 24-h DBP (ß = 3.55, 95% CI 2.26-4.85, p < .001). In conclusion, Chinese men with hypertension had higher SNS activity than women, and SNS activity was independently associated with 24-h ambulatory BP in men rather than in women. These findings suggest that different hypertensive treatment strategies should be considered according to patient sex.

24-h ambulatory blood pressure variability and hypertensive nephropathy in Han Chinese hypertensive patients.

Blood pressure (BP) is characterized by spontaneous oscillation over time, which is described as BP variability (BPV). The current study aimed to investigate whether short-term BPV was correlated with hypertensive nephropathy in Han Chinese individuals with hypertension. A single-center prospective cohort study of 300 Han Chinese participants with hypertension was conducted in Taiwan. Five different BPV parameters were derived from ambulatory BP monitoring (ABPM), including standard deviation (SD), weighted SD (wSD), coefficient of variation (CoV), successive variation (SV), and average real variability (ARV). Renal event was defined as > 50% reduction in baseline estimated glomerular filtration rate (eGFR). The average age of the participants was 63.5 years. The baseline eGFR was 84.5 mL/min/1.73 m2 . The participants were divided into two groups according to the wSD of systolic BP (SBP). Survival was assessed via a Kaplan-Meier analysis. During the 4.2-year follow-up, the participants with the highest SBP wSD tertile had a greater number of renal events (6.0%) than their counterparts (0.5%) (log-rank test, p = .007). The Cox proportional hazard regression model was used to assess the independent effects of BPV, and results showed that 24-h SBP (HR = 1.105; 95% CI = 1.020-1.197, p = .015) and 24-h DBP (HR = 1.162; 95% CI = 1.004-1.344, p = .044) were independently associated with renal events. However, BPV parameters were only associated with renal events univariately, but not after adjusting for baseline characteristics, 24-h mean BP, and office BP. Therefore, the risk of hypertensive nephropathy was independently associated with 24-h mean BP, but not with ambulatory BPV, in Han Chinese participants with hypertension.

CYP26A1 Is a Novel Biomarker for Betel Quid-Related Oral and Pharyngeal Cancers.

Betel quid (BQ) has been classified as a Group I human carcinogen in light of evidence demonstrating an association with an elevated risk of oral and pharyngeal cancers. To date, the incidence rate of oral and pharynx cancers among Taiwanese men ranks the highest worldwide. However, no study has yet confirmed variants of CYP26A1 was associated with the risks of oral and pharyngeal cancers. A case-control study was conducted (n = 339). CYP26A1 polymorphism was performed using SNP assay. Real-time qRT-PCR and Western blotting were used to determine the levels of CYP26A1 expression. The cancer cell model involved treatment with arecoline. Our findings showed that the downregulation of CYP26A1 mRNA and protein expression are more frequently observed in cancerous tissues than adjacent normal tissues in patients with oral and pharynx cancers (p < 0.01). We found that CYP26A1 was downregulated as the arecoline dose increased. We hypothesized that lower levels of CYP26A1 mRNA expression can be utilized a clinically biomarker causes oral and pharynx cancers. Arecoline appears to modulate CYP26A1 expression through specific pathways. Carriers of CYP26A1 SNP, rs2068888 (G/G)/rs4418728 (G/G) and who have lower levels of CYP26A1 expression are associated with an increased risk of oral and pharyngeal cancers.

Entanglement Renyi Negativity across a Finite Temperature Transition: A Monte Carlo Study.

Quantum entanglement is fragile to thermal fluctuations, which raises the question whether finite temperature phase transitions support long-range entanglement similar to their zero temperature counterparts. Here we use quantum Monte Carlo simulations to study the third Renyi negativity, a generalization of entanglement negativity, as a proxy of mixed-state entanglement in the 2D transverse field Ising model across its finite temperature phase transition. We find that the area-law coefficient of the Renyi negativity is singular across the transition, while its subleading constant is zero within the statistical error. This indicates that the entanglement is short-range at the critical point despite a divergent correlation length. Renyi negativity in several exactly solvable models also shows qualitative similarities to that in the 2D transverse field Ising model.

Increased Expression of p-GSK3ß Predicts Poor Survival in T -III/IV Stage OSCC Patients.

BACKGROUND/AIM: Glycogen synthase kinase 3 beta (GSK3-ß) acts either as a tumor suppressor or an oncogene in various human cancers. The present study aimed to investigate the expression and activity of p-GSK3-ß (Ser9) in oral cancer patients. MATERIALS AND METHODS: We investigated the levels of p-GSK3ß in 152 oral cancer tissues by immunohistochemistry, and explored their prognostic impact. RESULTS: To investigate the role of p-GSK3ß (Ser9) in OSCC progression, we first analyzed the expression levels of protein p-GSK3ß in normal and oral cancer tissues using immunohistochemical staining. p-GSK3ß immunostaining was detected in 32 of 152 (21.1%) oral cancer specimens. High p-GSK3ß expression was significantly associated with T (III/IV) stage. Kaplan-Meier survival analysis revealed that high levels of p-GSK3ß were correlated with poor survival (p=0.001) in T stage (III/IV) OSCC patients. Multivariate analyses indicated that TN stage, AJCC tumor stage, tumor differentiation status and clinical therapy, but not p-GSK3ß levels, were independent prognostic factors. Significant mortality risk was found in T stage (III/IV) oral cancer patients with high levels of p-GSK3ß (p=0.0006). CONCLUSION: GSK3ß inactivation is a key event in oral cancer patients and targeting GSK3ß might be valuable in treating oral cancer patients.

Spin-lattice Coupling and the Emergence of the Trimerized Phase in the S=1 Kagome Antiferromagnet Na_{2}Ti_{3}Cl_{8}.

Spin-1 antiferromagnets are abundant in nature, but few theories exist to understand their properties and behavior when geometric frustration is present. Here we study the S=1 kagome compound Na_{2}Ti_{3}Cl_{8} using a combination of density functional theory, exact diagonalization, and density matrix renormalization group approaches to achieve a first principles supported explanation of its exotic magnetic phases. We find that the effective magnetic Hamiltonian includes essential non-Heisenberg terms that do not stem from spin-orbit coupling, and both trimerized and spin-nematic magnetic phases are relevant. The experimentally observed structural transition to a breathing kagome phase is driven by spin-lattice coupling, which favors the trimerized magnetic phase against the quadrupolar one. We thus show that lattice effects can be necessary to understand the magnetism in frustrated magnetic compounds and surmise that Na_{2}Ti_{3}Cl_{8} is a compound that cannot be understood from only electronic or only lattice Hamiltonians, very much like VO_{2}.

Antidepressant-induced reduction in betel-quid use in patients with depression: A pioneer clinical study.

Betel-quid is commonly used around the world and is listed as a Group I carcinogen. Prior research has suggested a possible association between antidepressants and betel-quid use. We aimed to clarify the effects of antidepressant therapy in betel-quid chewers in the population of patients with depression.We enrolled 204 patients with depressive disorders, collected their demographic information, and administered the Substance Use Severity Rating Scale for alcohol, cigarettes, and betel-quid and the Hamilton Depression Rating Scale. We compared betel-quid and non-betel-quid chewers and examined the effects of antidepressant therapy on betel-quid abstinence after previous exposure to betel-quid.Patients with depression were reported a higher prevalence of 26% betel-quid chewing habits and patients who chewed betel-quid showed more severe depressive symptoms. After antidepressant therapy, the addictiveness of betel-quid was significantly reduced by 4 times.This was a pioneering study showing that antidepressants could be a candidate for betel-quid cessation therapy. Future clinical trials are needed to verify their efficacy in reducing consumption for betel-quid addiction treatment.

Combination of celecoxib and calyculin-A inhibits epithelial-mesenchymal transition in human oral cancer cells.

Expression of cyclo-oxygenase-2 (COX-2) and protein phosphatase 2A (PP2A) deactivation occurs frequently in oral squamous cell carcinoma (OSCC). We initially assessed COX-2 and PP2A protein expression in OSCC specimens using immunohistochemical (IHC) staining and western blot analysis. We found strong COX-2 and phosphorylated PP2A (p-PP2A) expression in OSCC samples. No significant difference in total PP2A expression was observed between cancer and nontumor tissues. The effect of combining COX-2 inhibitor and celecoxib (CXB) with the PP2A inhibitor, calyculin-A (CLA) on the OSCC cell line, HSC3, was evaluated in vitro. We found that a combination of 1 nM CLA and 50 µM CXB significantly inhibited cell viability, and migration and invasion of HSC3 cells. Western blots for AKT, p-AKT, ERK, p-ERK, E-cadherin, vimentin and ß-catenin were conducted after treatment with CXB and/or CLA. Increased E-cadherin and decreased ß-catenin expression were found in CXB or CLA treated hsc-3 cells, whereas the combined CXB and CLA treatment showed no difference in E-cadherin or ß-catenin expression. Our findings suggest that CLA alone was more effective than CXB alone, but not in the combined drug treatment.

The Mediterranean diet reduces the genetic risk of chromosome 9p21 for myocardial infarction in an Asian population community cohort.

The interaction of genetic susceptibility and dietary habits in cardiovascular disease (CVD) remains undetermined. The purpose of this study was to investigate whether a Mediterranean dietary style modified the genetic risk of developing CVD in a Chinese cohort. A total of 2098 subjects with dietary information from a Chinese community cohort (CVDFACTS) were enrolled. Candidate genes, including SNP markers rs1333049 (CDKN2B, 9p21.3), rs17465637 (MIA3, 1q41) and rs501120 (CXCL12, 10q11.21), were genotyped to analyze the association with future CVD. The impact of dietary pattern was also analyzed according to adherence to the diet using the Mediterranean Diet Score (MDS). After an average follow-up of 7.8 years, only the C risk allele of rs1333049 at chromosome 9p21.3 was associated with a higher risk of MI with either an additive [HR = 1.78, 95% CI:1.23-2.5] or a recessive model [HR = 2.40, 95% CI: 1.42-4.04], and the CC genotype had a higher risk of developing MI (p = 0.009, log-rank test). There was no significant difference in the association of the lipid profile with future CV outcomes among the MDS tertiles. However, the high MI risk of the CC genotype in individuals consuming a less healthy diet (MDS1) (HR: 6.39, 95% CI: 1.74-23.43) significantly decreased to 2.38 (95% CI: 0.57-10.04) in individuals consuming a healthier diet (MDS3), indicating that a healthier dietary pattern (higher MDS) modified the risk of developing MI in carriers of variants in CDKN2B. In conclusion, genetic variants of CDKN2B at 9p21 were significantly associated with future MI risk in a Chinese cohort, and the genetic risk of MI could be modified by a healthier diet.

c-MYC expression in T (III/IV) stage oral squamous cell carcinoma (OSCC) patients.

Purpose: c-MYC has been noted in many tumor types, but its functional significance and clinical utility in oral squamous cell carcinoma (OSCC) are not well known. Here we studied the expression of c-MYC in correlation to clinical outcome in patients with oral squamous cell carcinoma. Methods: The current study, using immunohistochemical staining, first examined c-MYC expression in OSCC patients and further correlated its expression with clinicopathological parameters. Results: c-MYC was expressed in the majority of OSCC patients (n=133). The c-MYC expression is associated with histological grade (P=0.0205) of patients with oral squamous cell carcinoma. Multivariate Cox regression analysis revealed that TN stage (P<0.001), American Joint Committee on Cancer (AJCC) stage (P<0.0001), and tumor differentiation (P=0.0025) were independent factors for overall survival in patients with OSCC except for c-MYC expression (P>0.05). Multiplicative-scale interaction between T stage (III/IV) and low c-MYC expression on mortality risk was identified (P=0.0233). Kaplan-Meier survival analysis demonstrated that oral cancer patients (T III/IV stage) with high c-MYC expression had better survival than those with low and medium c-MYC expression (P=0.0270). Conclusion: Our data indicate that c-MYC is a potential biomarker that can be used as a therapeutic target for treating OSCC patients with T stage (III/IV).