Causal associations between gastroesophageal reflux disease and essential hypertension: A bidirectional Mendelian randomization study

BACKGROUND Clinical studies have reported that patients with gastroesophageal reflux disease(GERD)have a higher prevalence of hypertension.AIM To performed a bidirectional Mendelian randomization(MR)analysis to investi-gate the causal link between GERD and essential hypertension.METHODS Eligible single nucleotide polymorphisms(SNPs)were selected,and weighted median,inverse variance weighted(IVW)as well as MR egger(MR-Egger)re-gression were used to examine the potential causal association between GERD and hypertension.The MR-Pleiotropy RESidual Sum and Outlier analysis was used to detect and attempt to reduce horizontal pleiotropy by removing outliers SNPs.The MR-Egger intercept test,Cochran’s Q test and“leave-one-out”sen-sitivity analysis were performed to evaluate the horizontal pleiotropy,heterogen-eities,and stability of single instrumental variable.RESULTS IVW analysis exhibited an increased risk of hypertension(OR=1.46,95%CI:1.33-1.59,P=2.14E-16)in GERD patients.And the same result was obtained in replication practice(OR=1.002,95%CI:1.0008-1.003,P=0.000498).Meanwhile,the IVW analysis showed an increased risk of systolic blood pressure(β=0.78,95%CI:0.11-1.44,P=0.021)and hypertensive heart disease(OR=1.68,95%CI:1.36-2.08,P=0.0000016)in GERD patients.Moreover,we found an decreased risk of Barrett's esophagus(OR=0.91,95%CI:0.83-0.99,P=0.043)in essential hypertension patients.CONCLUSION We found that GERD would increase the risk of essential hypertension,which provided a novel prevent and therapeutic perspectives of essential hypertension.

Origin of Sexy Prime Numbers, Origin of Cousin Prime Numbers, Equations from Supposedly Prime Numbers, Origin of the Mersenne Number, Origin of the Fermat Number

We have found through calculations that the differences between the closest supposed prime numbers other than 2 and 3 defined in the articles are: 2;4: and 6. For those whose difference is equal to 6, we showed their origin then we classified them into two categories according to their classes, we showed in which context two prime numbers which differ from 6 are called sexy and in what context they are said real sexy prime. For those whose difference is equal to 4, we showed their origin then we showed that two prime numbers which differ from 4, that is to say two cousin prime numbers, are successive. We made an observation on the supposed prime numbers then we established two pairs of equations from this observation and deduced the origin of the Mersenne number and that of the Fermat number.

Preliminary Identification of a Prime Number Other Than 2 and 3, the Origin of Twin Prime Numbers, the Structure of the Chain of Prime Numbers and the Set of Prime Numbers Less Than a Given Integer

The application of the Euclidean division theorem for the positive integers allowed us to establish a set which contains all the prime numbers and this set we called it set of supposedly prime numbers and we noted it Esp. We subsequently established from the previous set the set of non-prime numbers (the set of numbers belonging to this set and which are not prime) denoted Enp. We then extracted from the set of supposedly prime numbers the numbers which are not prime and the set of remaining number constitutes the set of prime numbers denoted Ep. We have deduced from the previous set, the set of prime numbers between two natural numbers. We have explained during our demonstrations the origin of the twin prime numbers and the structure of the chain of prime numbers.

Understanding the educational inequalities in suicide attempts and their mediators:a Mendelian randomisation study

Background Educational inequalities in suicide have become increasingly prominent over the past decade.Elucidating modifiable risk factors that serve as intermediaries in the impact of low educational attainment on suicide has the potential to reduce health disparities.Aims To examine the risk factors that mediate the relationship between educational attainment and suicide attempts and quantify their contributions to the mediation effect.Methods We conducted a two-sample Mendelian randomisation(MR)analysis to estimate the causal effect of educational attainment on suicide attempts,utilising genome-wide association study summary statistics from the Integrative Psychiatric Research(iPSYCH;6024 cases and 44240 controls)and FinnGen(8978 cases and 368299 controls).We systematically evaluated 42 putative mediators within the causal pathway connecting reduced educational attainment to suicide attempts and employed two-step and multivariable MR to quantify the proportion of the mediated effect.Results In the combined analysis of iPSYCH and FinnGen,each standard deviation(SD)decrease in genetically predicted educational attainment(equating to 3.4 years of education)was associated with a 105%higher risk of suicide attempts(odds ratio(OR):2.05;95%confidence interval(Cl):1.81 to 2.31).0f the 42 risk factors analysed,the two-step MR identified five factors that mediated the association between educational attainment and suicide attempts.The respective proportions of mediation were 47%(95%Cl:29%to 66%)for smoking behaviour,36%(95%Cl:0%to 84%)for chronic pain,49%(95%Cl:36%to 61%)for depression,35%(95%Cl:12%to 59%)for anxiety and 26%(95%Cl:18%to 34%)for insomnia.Multivariable MR implicated these five mediators collectively,accounting for 68%(95%Cl:40%to 96%)of the total effect.Conclusions This study identified smoking,chronic pain and mental disorders as primary intervention targets for attenuating suicide risk attributable to lower educational levels in the European population.

Different effects of 24 dietary intakes on gastroesophageal reflux disease: A mendelian randomization

BACKGROUND In observational studies,dietary intakes are associated with gastroesophageal re-flux disease(GERD).AIM To conduct a two-sample mendelian randomization(MR)analysis to determine whether those associations are causal.METHODS To explore the relationship between dietary intake and the risk of GERD,we extracted appropriate single nucleotide polymorphisms from genome-wide asso-ciation study data on 24 dietary intakes.Three methods were adopted for data analysis:Inverse variance weighting,weighted median methods,and MR-Egger's method.The odds ratio(OR)and 95%confidence interval(CI)were used to eva-luate the causal association between dietary intake and GERD.RESULTS Our univariate Mendelian randomization(UVMR)results showed significant evidence that pork intake(OR,2.83;95%CI:1.76-4.55;P=1.84×10–5),beer intake(OR,2.70,95%CI:2.00-3.64;P=6.54×10–11),non-oily fish intake(OR,2.41;95%CI:1.49-3.91;P=3.59×10–4)have a protective effect on GERD.In addition,dried fruit intake(OR,0.37;95%CI:0.27-0.50;6.27×10–11),red wine intake(OR,0.34;95%CI:0.25-0.47;P=1.90×10-11),cheese intake(OR,0.46;95%CI:0.39-0.55;P=3.73×10-19),bread intake(OR,0.72;95%CI:0.56-0.92;P=0.0009)and cereal intake(OR,0.45;95%CI:0.36-0.57;P=2.07×10-11)were negatively associated with the risk of GERD.There was a suggestive asso-ciation for genetically predicted coffee intake(OR per one SD increase,1.22,95%CI:1.03-1.44;P=0.019).Multi-variate Mendelian randomization further confirmed that dried fruit intake,red wine intake,cheese intake,and cereal intake directly affected GERD.In contrast,the impact of pork intake,beer intake,non-oily fish intake,and bread intake on GERD was partly driven by the common risk factors for GERD.However,after adjusting for all four elements,there was no longer a suggestive association between coffee intake and GERD.CONCLUSION This study provides MR evidence to support the causal relationship between a broad range of dietary intake and GERD,providing new insights for the treatment and prevention of GERD.

Theoretical and experimental study of a bi-stable piezoelectric energy harvester under hybrid galloping and band-limited random excitations

In the practical environment,it is very common for the simultaneous occurrence of base excitation and crosswind.Scavenging the combined energy of vibration and wind with a single energy harvesting structure is fascinating.For this purpose,the effects of the wind speed and random excitation level are investigated with the stochastic averaging method(SAM)based on the energy envelope.The results of the analytical prediction are verified with the Monte-Carlo method(MCM).The numerical simulation shows that the introduction of wind can reduce the critical excitation level for triggering an inter-well jump and make a bi-stable energy harvester(BEH)realize the performance enhancement for a weak base excitation.However,as the strength of the wind increases to a particular level,the influence of the random base excitation on the dynamic responses is weakened,and the system exhibits a periodic galloping response.A comparison between a BEH and a linear energy harvester(LEH)indicates that the BEH demonstrates inferior performance for high-speed wind.Relevant experiments are conducted to investigate the validity of the theoretical prediction and numerical simulation.The experimental findings also show that strong random excitation is favorable for the BEH in the range of low wind speeds.However,as the speed of the incoming wind is up to a particular level,the disadvantage of the BEH becomes clear and evident.

How Prime Numbers Are Interconnected and Built with Two Equations: Addition and Subtraction Rules the Function (6µ)

Are all prime numbers linked by four simple functions? Can we predict when a prime will appear in a sequence of primes? If we classify primes into two groups, Group 1 for all primes that appear before ζ (such that , for instance 5, ), an even number divisible by 3 and 2, and Group 2 for all primes that are after ζ (such that , for instance 7), then we find a simple function: for each prime in each group, , where n is any natural number. If we start a sequence of primes with 5 for Group 1 and 7 for Group 2, we can attribute a μ value for each prime. The μ value can be attributed to every prime greater than 7. Thus for Group 1, and . Using this formula, all the primes appear for , where μ is any natural number.

Strong invariance principle for a counterbalanced random walk

We study a counterbalanced random walkS_(n)=X_(1)+…+X_(n),which is a discrete time non-Markovian process andX_(n) are given recursively as follows.For n≥2,X_(n) is a new independent sample from some fixed law̸=0 with a fixed probability p,andX_(n)=−X_(v(n))with probability 1−p,where v(n)is a uniform random variable on{1;…;n−1}.We apply martingale method to obtain a strong invariance principle forS_(n).

OFDMA-Based Unsourced Random Access in LEO Satellite Internet of Things

This paper investigates the low earth orbit(LEO)satellite-enabled coded compressed sensing(CCS)unsourced random access(URA)in orthogonal frequency division multiple access(OFDMA)framework,where a massive uniform planar array(UPA)is equipped on the satellite.In LEO satellite communications,unavoidable timing and frequency offsets cause phase shifts in the transmitted signals,substantially diminishing the decoding performance of current terrestrial CCS URA receiver.To cope with this issue,we expand the inner codebook with predefined timing and frequency offsets and formulate the inner decoding as a tractable compressed sensing(CS)problem.Additionally,we leverage the inherent sparsity of the UPA-equipped LEO satellite angular domain channels,thereby enabling the outer decoder to support more active devices.Furthermore,the outputs of the outer decoder are used to reduce the search space of the inner decoder,which cuts down the computational complexity and accelerates the convergence of the inner decoding.Simulation results verify the effectiveness of the proposed scheme.

How completely are randomized controlled trials of non-pharmacological interventions following concussion reported? A systematic review

Purpose:The study aimed to examine the reporting completeness of randomized controlled trials(RCTs)of non-pharmacological interventions following concussion.Methods:We searched MEDLINE,Embase,PsycInfo,CINAHL,and Web of Science up to May 2022.Two reviewers independently screened studies and assessed reporting completeness using the Template for Intervention Description and Replication(TIDieR),Consensus on Exercise Reporting Template(CERT),and international Consensus on Therapeutic Exercise aNd Training(i-CONTENT)checklists.Additional information was sought my study authors where reporting was incomplete.Risk of bias(ROB)was assessed with the Cochrane ROB-2 Tool.RCTs examining non-pharmacological interventions following concussion.Results:We included 89 RCTs(n=53 high ROB)examining 11 different interventions for concussion:sub-symptom threshold aerobic exercise,cervicovestibular therapy,physical/cognitive rest,vision therapy,education,psychotherapy,hyperbaric oxygen therapy,transcranial magnetic stimulation,blue light therapy,osteopathic manipulation,and head/neck cooling.Median scores were:TIDieR 9/12(75%;interquartile range(IQR)=5;range:5-12),CERT 17/19(89%;IQR=2;range:10-19),and i-CONTENT 6/7(86%;IQR=1;range:5-7).Percentage of studies completely reporting all items was TIDieR 35%(31/89),CERT 24%(5/21),and i-CONTENT 10%(2/21).Studies were more completely reported after publication of TIDieR(t_(87)=2.08;p=0.04)and CERT(t_(19)=2.72;p=0.01).Reporting completeness was not strongly associated with journal impact factor(TIDieR:rs=0.27;p=0.01;CERT:r_(s)=-0.44;p=0.06;i-CONTENT:r_(s)=-0.17;p=0.48)or ROB(TIDieR:rs=0.11;p=0.31;CERT:rs=0.04;p=0.86;i-CONTENT:rs=0.12;p=0.60).Conclusion:RCTs of non-pharmacological interventions following concussion demonstrate moderate to good reporting completeness,but are often missing key components,particularly modifications,motivational strategies,and qualified supervisor.Reporting completeness improved after TIDieR and CERT publication,but publication in highly cited journals and low ROB do not guarantee reporting completeness.

Socioeconomic traits and the risk of Barrett’s esophagus and gastroesophageal reflux disease: A Mendelian randomization study

BACKGROUND Previous observational studies have shown that the prevalence of gastroesophageal reflux disease(GERD)and Barrett’s esophagus(BE)is associated with socioeconomic status.However,due to the methodological limitations of traditional observational studies,it is challenging to definitively establish causality.AIM To explore the causal relationship between the prevalence of these conditions and socioeconomic status using Mendelian randomization(MR).METHODS We initially screened single nucleotide polymorphisms(SNPs)to serve as proxies for eight socioeconomic status phenotypes for univariate MR analysis.The inverse variance weighted(IVW)method was used as the primary analytical method to estimate the causal relationship between the eight socioeconomic status phenotypes and the risk of GERD and BE.We then collected combinations of SNPs as composite proxies for the eight socioeconomic phenotypes to perform multivariate MR(MVMR)analyses based on the IVW MVMR model.Furthermore,a two-step MR mediation analysis was used to examine the potential mediation of the associations by body mass index,major depressive disorder(MDD),smoking,alcohol consumption,and sleep duration.RESULTS The study identified three socioeconomic statuses that had a significant impact on GERD.These included household income[odds ratio(OR):0.46;95% confidence interval(95%CI):0.31-0.70],education attainment(OR:0.23;95%CI:0.18-0.29),and the Townsend Deprivation Index at recruitment(OR:1.57;95%CI:1.04-2.37).These factors were found to independently and predominantly influence the genetic causal effect of GERD.Furthermore,the mediating effect of educational attainment on GERD was found to be mediated by MDD(proportion mediated:10.83%).Similarly,the effect of educational attainment on BE was mediated by MDD(proportion mediated:10.58%)and the number of cigarettes smoked per day(proportion mediated:3.50%).Additionally,the mediating effect of household income on GERD was observed to be mediated by sleep duration(proportion mediated:9.75%)CONCLUSION This MR study shed light on the link between socioeconomic status and GERD or BE,providing insights for the prevention of esophageal cancer and precancerous lesions.

The study of lithographic variation in resistive random access memory

Reducing the process variation is a significant concern for resistive random access memory(RRAM).Due to its ultrahigh integration density,RRAM arrays are prone to lithographic variation during the lithography process,introducing electrical variation among different RRAM devices.In this work,an optical physical verification methodology for the RRAM array is developed,and the effects of different layout parameters on important electrical characteristics are systematically investigated.The results indicate that the RRAM devices can be categorized into three clusters according to their locations and lithography environments.The read resistance is more sensitive to the locations in the array(~30%)than SET/RESET voltage(<10%).The increase in the RRAM device length and the application of the optical proximity correction technique can help to reduce the variation to less than 10%,whereas it reduces RRAM read resistance by 4×,resulting in a higher power and area consumption.As such,we provide design guidelines to minimize the electrical variation of RRAM arrays due to the lithography process.

An Interpolation Method for Karhunen-Loève Expansion of Random Field Discretization

In the context of global mean square error concerning the number of random variables in the representation,the Karhunen–Loève(KL)expansion is the optimal series expansion method for random field discretization.The computational efficiency and accuracy of the KL expansion are contingent upon the accurate resolution of the Fredholm integral eigenvalue problem(IEVP).The paper proposes an interpolation method based on different interpolation basis functions such as moving least squares(MLS),least squares(LS),and finite element method(FEM)to solve the IEVP.Compared with the Galerkin method based on finite element or Legendre polynomials,the main advantage of the interpolation method is that,in the calculation of eigenvalues and eigenfunctions in one-dimensional random fields,the integral matrix containing covariance function only requires a single integral,which is less than a two-folded integral by the Galerkin method.The effectiveness and computational efficiency of the proposed interpolation method are verified through various one-dimensional examples.Furthermore,based on theKL expansion and polynomial chaos expansion,the stochastic analysis of two-dimensional regular and irregular domains is conducted,and the basis function of the extended finite element method(XFEM)is introduced as the interpolation basis function in two-dimensional irregular domains to solve the IEVP.

Random Forest-Based Fatigue Reliability-Based Design Optimization for Aeroengine Structures

Fatigue reliability-based design optimization of aeroengine structures involves multiple repeated calculations of reliability degree and large-scale calls of implicit high-nonlinearity limit state function,leading to the traditional direct Monte Claro and surrogate methods prone to unacceptable computing efficiency and accuracy.In this case,by fusing the random subspace strategy and weight allocation technology into bagging ensemble theory,a random forest(RF)model is presented to enhance the computing efficiency of reliability degree;moreover,by embedding the RF model into multilevel optimization model,an efficient RF-assisted fatigue reliability-based design optimization framework is developed.Regarding the low-cycle fatigue reliability-based design optimization of aeroengine turbine disc as a case,the effectiveness of the presented framework is validated.The reliabilitybased design optimization results exhibit that the proposed framework holds high computing accuracy and computing efficiency.The current efforts shed a light on the theory/method development of reliability-based design optimization of complex engineering structures.

Complex Decision Modeling Framework with Fairly Operators and Quaternion Numbers under Intuitionistic Fuzzy Rough Context

The main goal of informal computing is to overcome the limitations of hypersensitivity to defects and uncertainty while maintaining a balance between high accuracy,accessibility,and cost-effectiveness.This paper investigates the potential applications of intuitionistic fuzzy sets(IFS)with rough sets in the context of sparse data.When it comes to capture uncertain information emanating fromboth upper and lower approximations,these intuitionistic fuzzy rough numbers(IFRNs)are superior to intuitionistic fuzzy sets and pythagorean fuzzy sets,respectively.We use rough sets in conjunction with IFSs to develop several fairly aggregation operators and analyze their underlying properties.We present numerous impartial laws that incorporate the idea of proportionate dispersion in order to ensure that the membership and non-membership activities of IFRNs are treated equally within these principles.These operations lead to the development of the intuitionistic fuzzy rough weighted fairly aggregation operator(IFRWFA)and intuitionistic fuzzy rough ordered weighted fairly aggregation operator(IFRFOWA).These operators successfully adjust to membership and non-membership categories with fairness and subtlety.We highlight the unique qualities of these suggested aggregation operators and investigate their use in the multiattribute decision-making field.We use the intuitionistic fuzzy rough environment’s architecture to create a novel strategy in situation involving several decision-makers and non-weighted data.Additionally,we developed a novel technique by combining the IFSs with quaternion numbers.We establish a unique connection between alternatives and qualities by using intuitionistic fuzzy quaternion numbers(IFQNs).With the help of this framework,we can simulate uncertainty in real-world situations and address a number of decision-making problems.Using the examples we have released,we offer a sophisticated and systematically constructed illustrative scenario that is intricately woven with the complexity ofmedical evaluation in order to thoroughly assess the relevance and efficacy of the suggested methodology.

Risk Factors of Depression Screened by Two-Sample Mendelian Randomization Analysis:A Systematic Review

Objective This study explored the potentially modifiable factors for depression and major depressive disorder(MDD)from the MR-Base database and further evaluated the associations between drug targets with MDD.Methods We analyzed two-sample of Mendelian randomization(2SMR)using genetic variant depression(n=113,154)and MDD(n=208,811)from Genome-Wide Association Studies(GWAS).Separate calculations were performed with modifiable risk factors from MR-Base for 1,001 genomes.The MR analysis was performed by screening drug targets with MDD in the DrugBank database to explore the therapeutic targets for MDD.Inverse variance weighted(IVW),fixed-effect inverse variance weighted(FE-IVW),MR-Egger,weighted median,and weighted mode were used for complementary calculation.Results The potential causal relationship between modifiable risk factors and depression contained 459 results for depression and 424 for MDD.Also,the associations between drug targets and MDD showed that SLC6A4,GRIN2A,GRIN2C,SCN10A,and IL1B expression are associated with an increased risk of depression.In contrast,ADRB1,CHRNA3,HTR3A,GSTP1,and GABRG2 genes are candidate protective factors against depression.Conclusion This study identified the risk factors causally associated with depression and MDD,and estimated 10 drug targets with significant impact on MDD,providing essential information for formulating strategies to prevent and treat depression.

Analysis of pseudo-random number generators in QMC-SSE method

In the quantum Monte Carlo(QMC)method,the pseudo-random number generator(PRNG)plays a crucial role in determining the computation time.However,the hidden structure of the PRNG may lead to serious issues such as the breakdown of the Markov process.Here,we systematically analyze the performance of different PRNGs on the widely used QMC method known as the stochastic series expansion(SSE)algorithm.To quantitatively compare them,we introduce a quantity called QMC efficiency that can effectively reflect the efficiency of the algorithms.After testing several representative observables of the Heisenberg model in one and two dimensions,we recommend the linear congruential generator as the best choice of PRNG.Our work not only helps improve the performance of the SSE method but also sheds light on the other Markov-chain-based numerical algorithms.

Three- and Four-Dimensional Generalized Pythagorean Numbers

The Pythagorean triples (a, b | c) of planar geometry which satisfy the equation a2+b2=c2 with integers (a, b, c) are generalized to 3D-Pythagorean quadruples (a, b, c | d) of spatial geometry which satisfy the equation a2+b2+c2=d2 with integers (a, b, c, d). Rules for a parametrization of the numbers (a, b, c, d) are derived and a list of all possible nonequivalent cases without common divisors up to d2 is established. The 3D-Pythagorean quadruples are then generalized to 4D-Pythagorean quintuples (a, b, c, d | e) which satisfy the equation a2+b2+c2+d2=e2 and a parametrization is derived. Relations to the 4-square identity are discussed which leads also to the N-dimensional case. The initial 3D- and 4D-Pythagorean numbers are explicitly calculated up to d2, respectively, e2.

An efficient method for constructing a random insertional mutant library for forward genetics in Nannochloropsis oceanica

Insertional mutation,phenotypic evaluation,and mutated gene cloning are widely used to clone genes from scratch.Exogenous genes can be integrated into the genome during non-homologous end joining(NHEJ)of the double-strand breaks of DNA,causing insertional mutation.The random insertional mutant library constructed using this method has become a method of forward genetics for gene cloning.However,the establishment of a random insertional mutant library requires a high transformation efficiency of exogenous genes.Many microalgal species show a low transformation efficiency,making constructing random insertional mutant libraries difficult.In this study,we established a highly efficient transformation method for constructing a random insertional mutant library of Nannochloropsis oceanica,and tentatively tried to isolate its genes to prove the feasibility of the method.A gene that may control the growth rate and cell size was identified.This method will facilitate the genetic studies of N.oceanica,which should also be a reference for other microalgal species.

Causal relationship between circulating vitamin C and 25-hydroxyvitamin D concentrations and common mental disorders-a Mendelian randomization study

Mental disorders seriously affect people’s health and social stability.This Mendelian randomization(MR)study was designed to investigate the causal relationship between circulating vitamin C(VC)or 25-hydroxyvitamin D(25(OH)D)levels and mental disorders.The data used for the MR analysis were derived from the summary genome-wide association studies(GWAS)database for VC and 25(OH)D and from the Finn Gen consortium for fourteen mental disorders.Based on the inverse variance weighted(IVW)method,we found a potential causal association between circulating VC and anxiety disorders(IVW:OR=1.139,95%CI:1.023-1.269,P=0.018).However,no causal association was found between VC or 25(OH)D and other mental disorders(P>0.05).In the reverse MR analysis,individuals with Alzheimer’s disease was causally associated with higher concentrations of circulating VC(P=0.012),while individuals with anxiety disorders had a negative association between the concentrations of 25(OH)D(P=0.012).However,the current evidence does not support a causal relationship between VC or 25(OH)D and other mental disorders.In addition,there was no causal association between circulating VC and 25(OH)D(P>0.05).Future studies are needed to confirm these findings and to elucidate the mechanisms of potential causality.