New complex physiological findings evolve hypothesized mechanisms of Dravet syndrome

Developmental and epileptic encephalopathies(DEEs)are neurological disorders generally involving medically intractable seizures and a diverse array of comorbid neuropsychiatric delays and deficits that may severely affect cognition,mood,sleep,social behavior,movement control,learning,and/or memory.Dravet syndrome(DS),also known as Severe Myoclonic Epilepsy of Infancy.

Association between stress hyperglycemia ratio and in-hospital outcomes:findings from the improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome(CCC-ACS)Project

BACKGROUND Stress hyperglycemia ratio(SHR)could provide accurate information on the acute status of hyperglycemia.The relationship between SHR and acute coronary syndrome(ACS)prognosis remains unclear.This study was conducted to identity the association between SHR and in-hospital outcomes in patients with ACS.METHODS A total of 12,010 patients were eventually enrolled in the study.The relationship between SHR and in-hospital major adverse cardiovascular events(MACEs)was then modeled by restricted cubic spline(RCS)curves,and all patients were divided into three groups according to the results.The multivariate logistic regression analysis was used to determine the associations between the SHR and in-hospital outcomes,described as odds ratios(ORs)and 95%confidence intervals(CIs).Subgroup analyses were also performed on different diseases.RESULTS The median age of this cohort was 63(54,71)years old,and 8942(74.5%)were male.Group 1 was defined as SHR<0.6(n=426),Group 2 was defined as SHR between 0.6 and 1(n=5821),and Group 3 was defined as SHR>1(n=5763).Compared with Group 2,Group 1(OR=1.891,95%CI:1.028-3.479,P<0.001)and Group 3(OR=1.868,95%CI:1.434-2.434,P<0.001)had higher risks of suffering from in-hospital MACEs.SHR was associated with higher risks of in-hospital MACEs in the subgroups of DM[OR=2.282,95%CI:1.477-3.524).CONCLUSIONS Both low and high SHR levels were independently associated with in-hospital MACEs.Young males with DM,hypertension,and decreased renal function had much higher risks of suffering from SHR-correlated MACEs.

Cardiovascular risk burden and disability:findings from the International Mobility in Aging Study(IMIAS)

BACKGROUND The association of cardiovascular risk burden with disability is unclear.We examined the association between trajectories of the Framingham general cardiovascular disease risk score(FGCRS)with the trajectories of limitations of physical function in older adults.METHODS A total of 1219 participants with no disabilities from the International Mobility in Aging Study(IMIAS)study who had up to three repeated measures of FGCRS between 2012–2016 and without a history of stroke or coronary heart disease at baseline and follow-up were included.FGCRS at baseline was assessed and categorized into tertiles.Physical function was evaluated with the Short Physical Performance Battery(SPPB).The data were analyzed using linear mixed-effects models.RESULTS At baseline,FGCRS ranged between 3–94(mean score:24±15.8),participants were 32(2.6%),502(41.2%)and 685(56.2%)in lowest,middle,and highest tertiles,respectively.In the trajectories of limitations of physical function,the lowest FGCRS had no differences,while the middle and highest had a decrease in physical performance between 2012–2014(P=0.0001).Age,being female,living in Andes Mountains,having middle and highest FGCRS,higher alcohol consumption,being obese,lack of exercise and cognitive impairment increase the probability of disability(P<0.05).Alternatively,living in more developed regions and having a higher educational level reduced the probability of disability during the follow-up time(P<0.05).CONCLUSIONS Higher cardiovascular risk burden is associated with decreased physical performance,especially in gait.Results suggest SPPB may provide a measure of cardiovascular health in older adults.

An Improved Bounded Conflict-Based Search for Multi-AGV Pathfinding in Automated Container Terminals

As the number of automated guided vehicles(AGVs)within automated container terminals(ACT)continues to rise,conflicts have becomemore frequent.Addressing point and edge conflicts ofAGVs,amulti-AGVconflict-free path planning model has been formulated to minimize the total path length of AGVs between shore bridges and yards.For larger terminalmaps and complex environments,the grid method is employed to model AGVs’road networks.An improved bounded conflict-based search(IBCBS)algorithmtailored to ACT is proposed,leveraging the binary tree principle to resolve conflicts and employing focal search to expand the search range.Comparative experiments involving 60 AGVs indicate a reduction in computing time by 37.397%to 64.06%while maintaining the over cost within 1.019%.Numerical experiments validate the proposed algorithm’s efficacy in enhancing efficiency and ensuring solution quality.

Alcohol drinking triggered decrease of oxidative balance score is associated with high all-cause and cardiovascular mortality in hypertensive individuals:findings from NHANES 1999–2014

BACKGROUND Oxidative stress is closely associated with hypertensive outcomes.The oxidative balance score(OBS)measures oxidative stress exposure from dietary and lifestyle elements.The objective of this study was to investigate the association between OBS and mortality in hypertensive patients.METHODS This study included 7823 hypertensive patients from the National Health and Nutrition Examination Survey(NHA-NES)1999-2014.Several models,including Cox regression,restricted cubic splines(RCS),Kaplan-Meier survival analysis,subgroup,and sensitivity analyses,were exploited to investigate the relationship between OBS and the risk of mortality.RESULTS Controlling for all potential confounders,a significantly inverse association was observed between elevated OBS and all-cause[hazard ratio(HR)=0.90,95%CI:0.85-0.95]and cardiovascular mortality(HR=0.85,95%CI:0.75-0.95).With adjustment for covariates,significant associations between lifestyle OBS and mortality risks diminished,whereas associations between dietary OBS and these mortality risks remained robust(all-cause mortality:HR=0.91,95%CI:0.86-0.96;cardiovascular mortality:HR=0.85,95%CI:0.76-0.96).RCS demonstrated a linear relationship between OBS and all-cause and cardiovascular mortality risk(P_(nonlinear)=0.088 and P_(nonlinear)=0.447,respectively).Kaplan-Meier curves demonstrated that the mortality rate was lower with a high OBS(P<0.001).The consistency of the association was demonstrated in subgroup and sensitivity analyses.RCS after stratification showed that among current drinkers,those with higher OBS had a lower risk of mortality compared with former or never drinkers.CONCLUSIONS In hypertensive individuals,there was a negative association between OBS and all-cause and cardiovascular mortality.Encouraging hypertensive individuals,especially those currently drinking,to maintain high levels of OBS may be beneficial in improving their prognosis.

Direction finding of bistatic MIMO radar in strong impulse noise

For bistatic multiple-input multiple-output(MIMO)radar,this paper presents a robust and direction finding method in strong impulse noise environment.By means of a new lower order covariance,the method is effective in suppressing impulse noise and achieving superior direction finding performance using the maximum likelihood(ML)estimation method.A quantum equilibrium optimizer algorithm(QEOA)is devised to resolve the corresponding objective function for efficient and accurate direc-tion finding.The results of simulation reveal the capability of the presented method in success rate and root mean square error over existing direction-finding methods in different application situations,e.g.,locating coherent signal sources with very few snapshots in strong impulse noise.Other than that,the Cramér-Rao bound(CRB)under impulse noise environment has been drawn to test the capability of the presented method.

Hepatic organoids: ideal models for non-alcoholic fatty liver disease drug finding and molecular mechanism research

With the improvement of living standards and changes in dietary habits,the non-alcoholic fatty liver disease(NAFLD)has become one of the most common metabolic diseases clinically,with a global prevalence exceeding 25%.NAFLD often presents as a multisystem disease characterized by excessive deposition of triglycerides within hepatocytes,with over 5%of hepatocytes exhibiting steatosis.The clinical progression of NAFLD can mainly be divided into two stages:non-alcoholic fatty liver(NAFL)and non-alcoholic steatohepatitis(NASH).NAFL represents the early stage,primarily characterized by hepatocellular steatosis(which can be reversed with early intervention)and further progression leading to NASH.Besides hepatocellular steatosis,NASH also exhibits hepatocyte inflammation,injury,and fibrosis.Research indicates that 25%of NAFL patients may progress to NASH,and 35%to 50%of NASH patients further develop into liver cirrhosis or even liver cancer.Additionally,NAFLD is closely associated with various chronic diseases and tumors,such as obesity,hyperlipidemia,diabetes,breast cancer,and colorectal cancer.Despite the high and rising incidence of NAFLD,there are currently no clinically proven safe and effective drugs specifically targeting each stage of NAFLD.

Community Caregivers’ Experiences and Programmatic Strategies to Improve Active Case Finding in Community Tuberculosis Care in Botswana 2016-2021

Background: The community tuberculosis care program was started to reduce the impact of TB and increase successful treatment outcomes, thus contributing to meeting WHO targets on TB. According to the Botswana Ministry of Health, community tuberculosis care was introduced with the main goal of reducing tuberculosis-related morbidity and mortality among communities through the expansion of direct observed therapy and community involvement to community settings. The community caregivers were to support tuberculosis patients throughout their treatment period until they were cured or had completed their treatment. Settings: Two major cities of Botswana, Francistown and Gaborone, with more than twenty-two health clinics offering tuberculosis care. Objective: To investigate community caregivers’ experiences and identify programmatic strategies to improve active TB case findings under the community TB care (CTBC) program in Botswana during 2016-2021. Methods: We adopted a descriptive qualitative research design, followed by convenience purposive sampling. We obtained consent and interviewed 40 participants who met the inclusion criteria, 16 out of 73 in Gaborone and 24 out of 38 from Francistown. Results: We interviewed 40 caregivers with a mean age of 43.4 years. Accepting the caregiving role was identified as the main experience by more than two thirds of the caregivers. While at least more than two-fifth felt obligated to care for the patient at home due to personal relations. More than half of the respondents found caregiving difficult or frustrating due to some challenges encountered during the caregiving role. Behavioral modifications were suggested under different subthemes as strategies to improve active case finding. [-rId13-]Conclusion: Acceptance was the major experience in CTBC. Intensification of known programmatic strategies was suggested by caregivers to improve tuberculosis active case finding in CTBC.

Why caution should be applied when interpreting and promoting findings from Mendelian randomisation studies

Introduction In their article entitled‘Investigating genetic causal relationships between blood pressure and anxiety,depressive symptoms,neuroticism and subjective well-being’,Cai and colleagues1 presented the results of a two-sample Mendelian randomisation2(MR)study examining associations between blood pressure traits(systolic,diastolic,hypertension and pulse pressure)and psychological traits(anxiety,depression,neuroticism and subjective well-being).After correction for multiple testing.

The dynamic relaxation form finding method aided with advanced recurrent neural network

How to establish a self‐equilibrium configuration is vital for further kinematics and dynamics analyses of tensegrity mechanism.In this study,for investigating tensegrity form‐finding problems,a concise and efficient dynamic relaxation‐noise tolerant zeroing neural network(DR‐NTZNN)form‐finding algorithm is established through analysing the physical properties of tensegrity structures.In addition,the non‐linear constrained opti-misation problem which transformed from the form‐finding problem is solved by a sequential quadratic programming algorithm.Moreover,the noise may produce in the form‐finding process that includes the round‐off errors which are brought by the approximate matrix and restart point calculating course,disturbance caused by external force and manufacturing error when constructing a tensegrity structure.Hence,for the purpose of suppressing the noise,a noise tolerant zeroing neural network is presented to solve the search direction,which can endow the anti‐noise capability to the form‐finding model and enhance the calculation capability.Besides,the dynamic relaxation method is contributed to seek the nodal coordinates rapidly when the search direction is acquired.The numerical results show the form‐finding model has a huge capability for high‐dimensional free form cable‐strut mechanisms with complicated topology.Eventually,comparing with other existing form‐finding methods,the contrast simulations reveal the excellent anti‐noise performance and calculation capacity of DR‐NTZNN form‐finding algorithm.

Cost-benefit and discriminant validity of a stepwise dementia case-finding approach in an Asian older adult community

Background Case-finding is a recommended approach for dementia early detection in the community.Aims To investigate the discriminant validity and cost-effectiveness of a stepwise dementia case-finding approach in a Singaporean older adult community.Methods The two-phase study was conducted in the community from 2009 to 2015 in Singapore.A total of 3780 participants(age≥60 years)completed phase I(a brief cognitive screening);918 completed phase II and were included in the final analysis.In phase I,all participants were administered the Abbreviated Mental Test(AMT)and the Progressive Forgetfulness Question(PFQ).Those who screened positive on either test were invited to phase II,whereby the Mini-Mental State Examination(MMSE),Montreal Cognitive Assessment(MoCA)and a formal neuropsychological battery were administered,followed by the research diagnosis of no cognitive impairment,cognitive impairment no dementia(CIND)-Mild(≤2 impaired cognitive domains),CIND-Moderate(>2 impaired domains)or dementia.Receiver operating characteristic curve analyses were conducted for the different cognitive instruments.All discriminant indices were calculated,including sensitivity,specificity,positive and negative predictive values(NPV)and accuracy.Cost-effectiveness analysis was conducted by estimating the amount of screening time needed and the number of older adults requiring re-evaluation in two case-finding scenarios,ie,with or without preselection by the PFQ.Results The stepwise case-finding approach(preselection by the PFQ,then MMSE or MoCA or AMT)showed an excellent NPV(>99%)and accuracy(>86%)for excluding dementia-free cases.Without preselection by the PFQ,screening time for the three cognitive tools were 317.5,317.5 and 254 hours,with 159,302 and 175 screen-positive older adults involved in further evaluation.By adopting the stepwise case-finding approach,total screening time were 156.5,156.5 and 126.2 hours,which decreased by 50.7%,50.7% and 50.3% as compared with those without preselection.Furthermore,after preselection,only 98,167 and 145 screen-positive older adults required further evaluation,corresponding to a reduction of 38.4%,44.7% and 17.1% in the numbers compared with those without preselection.Conclusions A stepwise approach for dementia case-finding should be implemented in the community to minimise the time and resources needed for large-scale early detection of dementia.

A perspective on recent findings and future strategies for reactive aldehyde removal in spinal cord injury

Acrolein in spinal cord injury:The propensity of reactive aldehydes such as acrolein to both initiate and perpetuate tissue damage after spinal cord injury (SCI) is well established.Formed primarily from lipid peroxidation,acrolein is known to be one of the most reactive aldehydes.Acrolein will quickly overwhelm endogenous clearance mechanisms and antioxidants,and form adductswith lipids,proteins,and DNA.

A step towards zero leprosy: Active case finding through community-based approach

Leprosy with multidrug therapy and treatment in the early stages can prevent disability,but it still represents a significant health problem,mainly in vulnerable populations[1].However,if left untreated,leprosy can cause progressive and permanent damage to the skin,nerves,limbs,and eyes.With the constant efforts of the National Leprosy Elimination Programme in India,the implementation of multidrug therapy has lowered the prevalence rate to 0.66/10000 in 2016[1].

Visual Analysis of Research Hotspots and Trends of Benefit Finding in China Based on Citespace

[Objectives]Based on the related literature of benefit finding in China National Knowledge Infrastructure(CNKI),this paper analyzes the research status,hot spots and trends in this field.[Methods]To search for the related literature on benefit finding in China National Knowledge Infrastructure(CNKI),and use Citespace software to visually analyze the number of papers,authors,institutions and keywords.[Results]A total of 204 related papers were obtained,and the annual number of published papers showed a gradual increasing trend.The authors of published papers were represented by Zhang Fenglan,Liu Zhunzhun and Zhang Ting,and the Nursing College of Anhui Medical University published the most papers.The research focus was on social support,coping method and other influencing factors,and qualitative research was the main research type.The key population was breast cancer,stroke patients and their caregivers,and the development trend focused on reliability and validity test and correlation analysis.[Conclusions]The field of benefit finding in China is in the initial exploration stage,and there is little cooperation and exchange between authors and institutions.In the future,academic exchanges and multidisciplinary assistance should be strengthened to promote the rapid development of this field.

Radio Direction Finding Method to Mitigate Tsunami Risk in Sierra Leone

In this study,the Radio Direction Finding method is proposed for the detection of electromagnetic signals,in the VLF band,to try to anticipate the occurrence of potentially destructive geophysical events.The experimentation concerns the interception of electromagnetic anomalies in Sierra Leone,in the five-day time window,associated with seismic events that could potentially generate tsunamis.The area of investigation is Sierra Leone,whose coastline is subjected to tidal wave hazards triggered by earthquakes generated in the Mid-Atlantic Ridge.Although Sierra Leone is not affected by recurrent earthquakes,there is nevertheless a low probability,estimated at 2 percent,of the occurrence of destructive earthquakes in the next 50 years.Also in estimates,the risk of rogue and potentially damaging waves is estimated to strike the Sierra Leone coast at least once in the next 10 years.The Radio Direction Finding experiment carried out continuously 24/7,has shown a close relationship between increased radio-anomalies,in the frequencies of 6,000 Hz,a time window between electromagnetic anomaly detection and the imminence of an earthquake,and higher frequency times for the risk of earthquake occurrence in the Mid-Atlantic Ridge.

Optimal path finding algorithms based on SLSD road network model

A solution to compute the optimal path based on a single-line-single-directional（SLSD）road network model is proposed.Unlike the traditional road network model,in the SLSD conceptual model,being single-directional and single-line style,a road is no longer a linkage of road nodes but abstracted as a network node.Similarly,a road node is abstracted as the linkage of two ordered single-directional roads.This model can describe turn restrictions,circular roads,and other real scenarios usually described using a super-graph.Then a computing framework for optimal path finding（OPF）is presented.It is proved that classical Dijkstra and A algorithms can be directly used for OPF computing of any real-world road networks by transferring a super-graph to an SLSD network.Finally,using Singapore road network data,the proposed conceptual model and its corresponding optimal path finding algorithms are validated using a two-step optimal path finding algorithm with a pre-computing strategy based on the SLSD road network.

Clinical manifestation,lifestyle,and treatment patterns of chronic erosive gastritis:A multicenter real-world study in China

BACKGROUND Although chronic erosive gastritis(CEG)is common,its clinical characteristics have not been fully elucidated.The lack of consensus regarding its treatment has resulted in varied treatment regimens.AIM To explore the clinical characteristics,treatment patterns,and short-term outcomes in CEG patients in China.METHODS We recruited patients with chronic non-atrophic or mild-to-moderate atrophic gastritis with erosion based on endoscopy and pathology.Patients and treating physicians completed a questionnaire regarding history,endoscopic findings,and treatment plans as well as a follow-up questionnaire to investigate changes in symptoms after 4 wk of treatment.RESULTS Three thousand five hundred sixty-three patients from 42 centers across 24 cities in China were included.Epigastric pain(68.0%),abdominal distension(62.6%),and postprandial fullness(47.5%)were the most common presenting symptoms.Gastritis was classified as chronic non-atrophic in 69.9%of patients.Among those with erosive lesions,72.1%of patients had lesions in the antrum,51.0%had multiple lesions,and 67.3%had superficial flat lesions.In patients with epigastric pain,the combination of a mucosal protective agent(MPA)and proton pump inhibitor was more effective.For those with postprandial fullness,acid regurgitation,early satiety,or nausea,a MPA appeared more promising.CONCLUSION CEG is a multifactorial disease which is common in Asian patients and has non-specific symptoms.Gastroscopy may play a major role in its detection and diagnosis.Treatment should be individualized based on symptom profile.

A multi-platform analysis of human gingival crevicular fluid reveals ferroptosis as a relevant regulated cell death mechanism during the clinical progression of periodontitis

Ferroptosis is implicated in the pathogenesis of numerous chronic-inflammatory diseases,yet its association with progressive periodontitis remains unexplored.To investigate the involvement and significance of ferroptosis in periodontitis progression,we assessed sixteen periodontitis-diagnosed patients.Disease progression was clinically monitored over twelve weeks via weekly clinical evaluations and gingival crevicular fluid(GCF)collection was performed for further analyses.Clinical metrics,proteomic data,in silico methods,and bioinformatics tools were combined to identify protein profiles linked to periodontitis progression and to explore their potential connection with ferroptosis.Subsequent western blot analyses validated key findings.Finally,a single-cell RNA sequencing(scRNA-seq)dataset(GSE164241)for gingival tissues was analyzed to elucidate cellular dynamics during periodontitis progression.Periodontitis progression was identified as occurring at a faster rate than traditionally thought.GCF samples from progressing and non-progressing periodontal sites showed quantitative and qualitatively distinct proteomic profiles.In addition,specific biological processes and molecular functions during progressive periodontitis were revealed and a set of hub proteins,including SNCA,CA1,HBB,SLC4A1,and ANK1 was strongly associated with the clinical progression status of periodontitis.Moreover,we found specific proteins-drivers or suppressors-associated with ferroptosis(SNCA,FTH1,HSPB1,CD44,and GCLC),revealing the co-occurrence of this specific type of regulated cell death during the clinical progression of periodontitis.Additionally,the integration of quantitative proteomic data with scRNA-seq analysis suggested the susceptibility of fibroblasts to ferroptosis.Our analyses reveal proteins and processes linked to ferroptosis for the first time in periodontal patients,which offer new insights into the molecular mechanisms of progressive periodontal disease.These findings may lead to novel diagnostic and therapeutic strategies.

New immune regulators of sciatic nerve regeneration?Lessons from the neighborhood

For decades,the immune system has been associated with host protection against infectious pathogens or tumors,while also contributing to autoimmunity.Notwithstanding,this paradigm is now changing,with recent studies highlighting novel roles for immune mediators in the maintenance of steady-state tissue homeostasis.In this perspective,we review some of the latest findings featuring immune modulators of the nervous system pathophysiology,with a special focus on interleukin(IL)-17.

Deciphering TADF Mechanisms in Metal-Free Organic Emitters BrA-HBI:Utilizing Optimally Tuned Range-Separated Functionals for Insight

Metal-free organic emitters,characterized by their thermally activated delayed fluorescence(TADF)properties,offer considerable promise for the creation of highly efficient organic light-emitting diodes(OLEDs).Recently,Shao et al.presented a novel excited state intramolecular proton transfer(ESIPT)system BrA-HBI,demonstrating an emission quantum yield of up to 50%[Adv.Funct.Mater.32,2201256(2022)].However,many open issues cannot be answered solely by experimental means only and require detailed theoretical investigations.For instance,what causes the activation of TADF from the Keto*tautomer and leads to fluorescence quenching in the Enol^(*)form?Herein,we provide a theoretical investigation on the TADF mechanism of the BrA-HBI molecule by optimally tuned range-separated functionals.Our findings reveal that ESIPT occurs in the BrA-HBI molecule.Moreover,we have disclosed the reason for the fluorescence quenching of the Enol^(*)form and determined that the T_(2)state plays a dominant role in the TADF phenomenon.In addition,double hybrid density functionals method was utilized to verify the reliability of optimally tuned range separation functionals on the calculation of the TADF mechanism in BrA-HBI.These findings not only provide a theoretical reference for development of highly efficient organic light-emitting diodes,but also demonstrate the effectiveness of the optimally tuned range-separated functionals in predicting the luminescence properties of TADF molecules.