Genotype Imputation and Evaluation of Single Nucleotide Polymorphisms in 437 Women of East Asian Descent

As a result of increasing interests in discovering single nucleotide polymorphisms (SNPs) associated complex diseases and high cost of existing sequencing technology, genotype imputation is developed as a statistical method to overcome the limitations of current sequencing technology and to increase the power of the association method of Genome-Wide Association Studies (GWAS). In this paper, genotype imputation is conducted on Tianjin sample with two reference panels; the 1000 Genomes reference panel and the TOPMed reference panel. First, pre-imputation quality control is applied to remove individuals or genetic markers that may induce high error rates when conducting imputation. Principal component analysis was conducted to show the East Asian ancestry of the sample. Using Minimac3, imputation was performed on a sample of 437 individuals with 499,148 genetic variants after haplotype inference with Eagle software from Illumina 660W. Approximately 47 million and 88 million genetic variants were imputed using 1000G and TOPMed reference panels respectively. The estimated squared Pearson's correlation (R2) was used to determine which of the imputed SNPs passed the post-imputation quality control. Approximately 9.5 million imputed SNPs from the 1000G reference panel and 11 million imputed SNPs from the TOPMed reference panel exceeded the R2 threshold. To assess imputation quality, imputation was again performed on the original 437 individuals, but with 5% of the directly genotyped genetic variants randomly masked. The imputed variants for chromosomes 1, 11, and 21 were selected to calculate the true squared Pearson's correlation; and the masking results for the two reference panels were compared to determine which reference panel is more suited for this sample. Overall, the imputation provides an accurate set of genetic markers that can be used in the downstream GWAS analysis to explore SNPs associated with lung cancer.Bachelor of Science in Public Healt

A mixed integer linear programming model for minimum backbone grid

Developing a minimum backbone grid in the power system planning is beneficial to improve the power system’s resilience. To obtain a minimum backbone grid, a mixed integer linear programming (MILP) model with network connectivity constraints for a minimum backbone grid is proposed. In the model, some constraints are presented to consider the practical application requirements. Especially, to avoid islands in the minimum backbone grid, a set of linear constraints based on single-commodity flow formulations is proposed to ensure connectivity of the backbone grid. The simulations on the IEEE-39 bus system and the French 1888 bus system show that the proposed model can be solved with higher computational efficiency in only about 30 min for such a large system and the minimum backbone grid has a small scale only 52% of the original grid. Compared with the improved fireworks method, the minimum backbone grid from the proposed method has fewer lines and generators

Serum metabolomics profiles in response to n-3 fatty acids in Chinese patients with type 2 diabetes: a double-blind randomised controlled trial.

We aimed to investigate the change of serum metabolomics in response to n-3 fatty acid supplements in Chinese patients with type 2 diabetes (T2D). In a double-blind parallel randomised controlled trial, 59 Chinese T2D patients were randomised to receive either fish oil (FO), flaxseed oil (FSO) or corn oil capsules (CO, served as a control group) and followed up for 180 days. An additional 17 healthy non-T2D participants were recruited at baseline for cross-sectional comparison between cases and non-cases. A total of 296 serum metabolites were measured among healthy controls and T2D patients before and after the intervention. Serum 3-carboxy-4-methyl-5-propyl-2-furanpropanoate (CMPF) (P-interaction = 1.8 × 10(-7)) was the most significant metabolite identified by repeated-measures ANOVA, followed by eicosapentaenoate (P-interaction = 4.6 × 10(-6)), 1-eicosapentaenoylglycerophosphocholine (P-interaction = 3.4 × 10(-4)), docosahexaenoate (P-interaction = 0.001), linolenate (n-3 or n-6, P-interaction = 0.005) and docosapentaenoate (n-3, P-interaction = 0.021). CMPF level was lower in T2D patients than in the healthy controls (P = 0.014) and it was significantly increased in the FO compared with CO group (P = 1.17 × 10(-7)). Furthermore, change of CMPF during the intervention was negatively correlated with change of serum triglycerides (P = 0.016). In conclusion, furan fatty acid metabolite CMPF was the strongest biomarker of fish oil intake. The association of CMPF with metabolic markers warrants further investigation.This study was funded by the National Basic Research Program of China (973 Program: 2015CB553604); by National Natural Science Foundation of China (NSFC: 81273054); and by the Ph.D. Programs Foundation of Ministry of Education of China (20120101110107). J.-S.Z. acknowledges support from MRC Epidemiology Unit (MC_UU_12015/5) and the Cambridge Initiative – Nutrition (RG71466, SJAH/004). F.I. acknowledges support from the MRC Epidemiology Unit (MC_UU_12015/5).This is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/srep2952

Cationic Polystyrene Resolves Nonalcoholic Steatohepatitis, Obesity, and Metabolic Disorders by Promoting Eubiosis of Gut Microbiota and Decreasing Endotoxemia.

A pandemic of metabolic diseases, consisting of type 2 diabetes, nonalcoholic fatty liver disease, and obesity, has imposed critical challenges for societies worldwide, prompting investigation of underlying mechanisms and exploration of low-cost and effective treatment. In this report, we demonstrate that metabolic disorders in mice generated by feeding with a high-fat diet without dietary vitamin D can be prevented by oral administration of polycationic amine resin. Oral administration of cholestyramine, but not the control uncharged polystyrene, was able to sequester negatively charged bacterial endotoxin in the gut, leading to 1) reduced plasma endotoxin levels, 2) resolved systemic inflammation and hepatic steatohepatitis, and 3) improved insulin sensitivity. Gut dysbiosis, characterized as an increase of the phylum Firmicutes and a decrease of Bacteroidetes and Akkermansia muciniphila, was fully corrected by cholestyramine, indicating that the negatively charged components in the gut are critical for the dysbiosis. Furthermore, fecal bacteria transplant, derived from cholestyramine-treated animals, was sufficient to antagonize the metabolic disorders of the recipient mice. These results indicate that the negatively charged components produced by dysbiosis are critical for biogenesis of metabolic disorders and also show a potential application of cationic polystyrene to treat metabolic disorders through promoting gut eubiosis

The Functions of Effector Proteins in Yersinia Virulence

Yersinia species are bacterial pathogens that can cause plague and intestinal diseases after invading into human cells through the Three Secre­tion System (TTSS). The effect of pathogenesis is mediated by Yersinia outer proteins (Yop) and manifested as down-regulation of the cytokine genes expression by inhibiting nuclear factor-κ-gene binding (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. In addition, its pathogenesis can also manipulate the disorder of host innate immune system and cell death such as apoptosis, pyroptosis, and autophagy. Among the Yersinia effector proteins, YopB and YopD assist the injection of other virulence effectors into the host cytoplasm, while YopE, YopH, YopJ, YopO, and YopT target on disrupting host cell signaling pathways in the host cytosols. Many efforts have been applied to reveal that intracellular proteins such as Rho-GTPase, and transmembrane receptors such as Toll-like receptors (TLRs) both play critical roles in Yersinia pathogenesis, establishing a connection between the pathogenic process and the signaling response. This review will mainly focus on how the effector proteins of Yersinia modulate the intrinsic signals in host cells and disturb the innate immunity of hosts through TTSS

Psychometric property study of the Affective Lability Scale-short form in Chinese patients with mood disorders

IntroductionThis study aimed to investigate the psychometric properties of the Affective Lability Scale-short form (ALS-SF) among Chinese patients with mood disorders, and to compare ALS-SF subscale scores between patients with major depressive disorder (MDD) and patients with bipolar disorder (BD) depression.MethodsA total of 344 patients with mood disorders were included in our study. Participants were measured through a set of questionnaires including the Chinese version of ALS-SF, Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder 7-item (GAD-7), and NEO-Five Factor Inventory (NEO-FFI). Exploratory factor analysis and confirmatory factor analysis were applied to examine the psychometric properties of ALS-SF. Besides, correlation and regression analyses were performed to explore the relationship between affective lability and depression, anxiety, and neuroticism. Independent samples t-tests were used to compare the subscale scores of ALS-SF between the MDD and BD depression groups.ResultsResults of factor analysis indicated that the model of ALS-SF was consistent with ALS-SF. The ALS-SF showed a solid validity and high internal consistency (Cronbach’s alpha = 0.861). In addition, each subscale of ALS-SF was significantly correlated with PHQ-9, GAD-7, and NEO-FFI neuroticism subscale, except for the anger subscale showed no significant correlation with PHQ-9. Besides, the depression/elation and anger factor scores in patients with BD depression were higher than in patients with MDD.ConclusionOur study suggests that the Chinese version of ALS-SF has good reliability and validity for measuring affective lability in Chinese patients with mood disorders. Assessing affective lability would assist clinicians to distinguish between MDD and BP depression and may decrease the risks of misdiagnosis

Effects of n-3 fatty acid supplements on glycemic traits in Chinese type 2 diabetic patients: A double-blind randomized controlled trial.

SCOPE: To investigate the effects of n-3 fatty acid supplements, both marine and plant-based, on glycemic traits in Chinese type 2 diabetes patients. METHOD AND RESULTS: In a double-blind randomized controlled trial, 185 recruited Chinese type 2 diabetes patients were randomized to either fish oil (FO, n = 63), flaxseed oil (FSO, n = 61), or corn oil group (served as control group, n = 61) for 180 days. The patients were asked to take corresponding oil capsules (four capsules/day), which totally provided 2 g/day of eicosapentaenoic acid + docosahexaenoic acid in FO group and 2.5 g/day of alpha-linolenic acid in FSO group. No group × time interaction was observed for homeostatic model assessment of insulin resistance, fasting insulin, or glucose. Significant group × time interaction (P = 0.035) was observed for glycated hemoglobin A1c (HbA1c), with HbA1c decreased in FO group compared with corn oil group (P = 0.037). We also found significant group × time interactions for lipid traits, including LDL cholesterol (P = 0.043), total cholesterol (P = 0.021), total cholesterol/HDL cholesterol (P = 0.009), and triacylglycerol (P = 0.003), with the lipid profiles improved in FO group. No significant effects of FSO on glycemic traits or blood lipids were observed. CONCLUSIONS: Marine n-3 PUFA supplements may improve glycemic control and lipid profiles among Chinese type 2 diabetic patients.National Basic Research Program of China (973 Program: 2015CB553604)This is the author accepted manuscript. The final version is available from Wiley via http://dx.doi.org/10.1002/mnfr.20160023

Physico-chemistry of bacterial transmission versus adhesion

Bacterial adhesion is a main problem in many biomedical, domestic, natural and industrial environments and forms the onset of the formation of a biofilm, in which adhering bacteria grow into a multi-layered film while embedding themselves in a matrix of extracellular polymeric substances. It is usually assumed that bacterial adhesion occurs from air or by convective-diffusion from a liquid suspension, but often bacteria adhere by transmission from a bacterially contaminated donor to a receiver surface. Therewith bacterial transmission is mechanistically different from adhesion, as it involves bacterial detachment from a donor surface followed by adhesion to a receiver one. Transmission is further complicated when the donor surface is not covered with a single layer of adhering bacteria but with a multi-layered biofilm, in which case bacteria can be transmitted either by interfacial failure at the biofilm-donor surface or through cohesive failure in the biofilm. Transmission through cohesive failure in a biofilm is more common than interfacial failure. The aim of this review is to oppose surface thermodynamics and adhesion force analyses, as can both be applied towards bacterial adhesion, with their appropriate extensions towards transmission. Opposition of surface thermodynamics and adhesion force analyses, will allow to distinguish between transmission of bacteria from a donor covered with a (sub)monolayer of adhering bacteria or a multi layered biofilm. Contact angle measurements required for surface thermodynamic analyses of transmission are of an entirely different nature than analyses of adhesion forces, usually measured through atomic force microscopy. Nevertheless, transmission probabilities based on Weibull analyses of adhesion forces between bacteria and donor and receiver surfaces, correspond with the surface thermodynamic preferences of bacteria for either the donor or receiver surface. Surfaces with low adhesion forces such as polymer-brush coated or nanostructured surfaces are thus preferable for use as non-adhesive receiver surfaces, but at the same time should be avoided for use as a donor surface. Since bacterial transmission occurs under a contact pressure between two surfaces, followed by their separation under tensile or shear pressure and ultimately detachment, this will affect biofilm structure. During the compression phase of transmission, biofilms are compacted into a more dense film. After transmission, and depending on the ability of the bacterial strain involved to produce extracellular polymeric substances, biofilm left-behind on a donor or transmitted to a receiver surface will relax to its original, pre-transmission structure owing to the viscoelasticity of the extracellular polymeric substances matrix, when present. Apart from mechanistic differences between bacterial adhesion and transmission, the low numbers of bacteria generally transmitted require careful selection of suitably sensitive enumeration methods, for which culturing and optical coherence tomography are suggested. Opposing adhesion and transmission as done in this review, not only yields a better understanding of bacterial transmission, but may stimulate researchers to more carefully consider whether an adhesion or transmission model is most appropriate in the specific area of application aimed for, rather than routinely relying on adhesion models

Construction of a Nomogram predictive model for post-discharge psychosomatic review of psychiatric liaison consultation patients based on medical record data

Epidemiological studies have shown that almost all physical illnesses coexist with psychiatric disorders or psychological problems, and the severity of mental illness is positively correlated with the duration and severity of physical illness. Liaison consultations are valuable in identifying and treating psychiatric disorders, but the rate of psychiatric follow-up after consultation is low in outpatients. This study aimed to investigate the factors influencing post-discharge psychosomatic follow-up visits in patients undergoing psychiatric liaison consultation in general hospitals and construct a Nomogram prediction model for patients’ post-discharge psychosomatic follow-up visits. Medical record data of inpatients who received psychiatric liaison consultations at Xi’an International Medical Center Hospital in China from September 2019 to September 2020 were analyzed. Lasso regression and multivariate logistic regression analyses were conducted to screen independent influences on the occurrence of post-discharge psychosomatic follow-ups in patients undergoing psychiatric liaison consultations. Risk prediction column line graphs were constructed using R software, and the models were evaluated. Of the 494 inpatients who received psychiatric liaison consultations, 115 patients (23.279%) (mean age = 54.8 years) went for post-discharge psychosomatic follow-up, while 379 patients (mean age = 59.3 years) had no record of psychosomatic follow-up. Furthermore, occupation, interval.time, diagnosis, out.antipsychotics, and recommendations.followup were independent factors influencing post-discharge psychosomatic follow-up. The model accurately predicted post-discharge psychosomatic follow-up behavior of inpatients who received psychiatric liaison consultations. Lastly, the clinical decision curve analysis showed that the model had good validity for clinical application. Patients who received a psychiatric liaison consultation with a ≤ 10-day interval between admission to the hospital and application for consultation, were discharged with prescribed medication, and had a clear written medical order for a follow-up consultation had an increased probability of psychosomatic follow-up after discharge

Transmission prevention behaviors in US households with SARS-CoV-2 cases in 2020

Introduction Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) transmission frequently occurs within households, yet few studies describe which household contacts and household units are most likely to engage in transmission-interrupting behaviors. Methods We analyzed a COVID-19 prospective household transmission cohort in North Carolina (April to October 2020) to quantify changes in physical distancing behaviors among household contacts over 14 days. We evaluated which household contacts were most likely to ever mask at home and to ever share a bedroom with the index case between days 7–14. Results In the presence of a household COVID-19 infection, 24% of household contacts reported ever masking at home during the week before study entry. Masking in the home between days 7–14 was reported by 26% of household contacts and was more likely for participants who observed their household index case wearing a mask. Participants of color and participants in high-density households were more likely to mask at home. After adjusting for race/ethnicity, living density was not as clearly associated with masking. Symptomatic household contacts were more likely to share a bedroom with the index case. Working individuals and those with comorbidities avoided sharing a bedroom with the index case.DiscussionIn-home masking during household exposure to COVID-19 was infrequent in 2020. In light of the ongoing transmission of SARS-CoV-2, these findings underscore a need for health campaigns to increase the feasibility and social desirability of in-home masking among exposed household members. Joint messaging on social responsibility and prevention of breakthrough infections, reinfections, and long COVID-19 may help motivate transmission-interruption behaviors