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.

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.

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.

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.

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 subspace expanding technique for global zero finding of multi-degree-of-freedom nonlinear systems

A subspace expanding technique(SET) is proposed to efficiently discover and find all zeros of nonlinear functions in multi-degree-of-freedom(MDOF) engineering systems by discretizing the space into smaller subdomains, which are called cells. The covering set of the cells is identified by parallel calculations with the root bracketing method. The covering set can be found first in a low-dimensional subspace, and then gradually extended to higher dimensional spaces with the introduction of more equations and variables into the calculations. The results show that the proposed SET is highlyefficient for finding zeros in high-dimensional spaces. The subdivision technique of the cell mapping method is further used to refine the covering set, and the obtained numerical results of zeros are accurate. Three examples are further carried out to verify the applicability of the proposed method, and very good results are achieved. It is believed that the proposed method will significantly enhance the ability to study the stability, bifurcation,and optimization problems in complex MDOF nonlinear dynamic systems.

Test research and computer simulation analysis of construction state during form finding for suspen-dome system

A novel construction method without scaffold work called as assembly-prestressing form finding loop by loop is presented.Based on the theory of finite displacement,the cycle-forward analysis method is presented for its construction calculation,which adopts the finite element method of generalized geometric nonlinearity combined with the application in the real construction process.By means of the combination of the forward analysis according to real construction sequence and the cycle iteration according to the initial strain increment method of cable force adjustment,the influence of the structural geometric nonlinearity and the loss of prestress are taken into account due to prestressing of tendons in turn and so on.If the initial cable forces derived from the method were used for construction,expected cable forces and shape could be assured easily.Simulation analysis achieved real-time tracking and controlling of the construction status.Finally,according to the procedure and parameters in simulating,a model experimental research on the stage of form finding(namely prestressing)was carried out for suspen-dome structure.The feasibility on the assembly-prestressing form finding method loop by loop was testified.The cycle-forward analysis method was established and numerical simulation was performed,and the results show that it was useful for the design and the construction of similar suspen-dome structure.

Combining User-Driven Social Marketing with System-Driven Personalized Recommendation for Student Finding

Student selection is of crucial importance for supervisors who are choosing students for postgraduate studies or research projects.Due to the challenge of asymmetric information,it is difficult for them to find suitable candidates.The existing methods do not work so well in the web 2.0 context which is inundated with vast online information.In order to overcome the deficiency,a research social network enhanced approach is proposed to provide decision support.It appeals to supervisors to adopt the proposed user-driven social marketing strategy.Meanwhile,this study mainly presents a system-driven personalized recommendation approach to support supervisors'decisions of student selection.The proposed method distinguishes supervisors based on their co-author networks to extract their potential preferences of collaboration styles.Subsequently,corresponding recommendation strategies are employed to provide personalized student recommendation services for targeted supervisors.A prototype is implemented on ScholarMate which provides online communication channels for researchers.A user study is conducted to verify the effectiveness of the proposed approach.The results enlighten designers to consider the differences among different users when designing recommendation strategies.

System Vulnerability Analysis Using Graph Pathfinding Strategies in Partitioned Networks

In this paper, a new method has been introduced to find the most vulnerable lines in the system dynamically in an interconnected power system to help with the security and load flow analysis in these networks. Using the localization of power networks, the power grid can be divided into several divisions of sub-networks in which, the connection of the elements is stronger than the elements outside of that division. By using our proposed method, the probable important lines in the network can be identified to do the placement of the protection apparatus and planning for the extra extensions in the system. In this paper, we have studied the pathfinding strategies in most vulnerable line detection in a partitioned network. The method has been tested on IEEE39-bus system which is partitioned using hierarchical spectral clustering to show the feasibility of the proposed method.

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.

Hybrid Algorithm-Driven Smart Logistics Optimization in IoT-Based Cyber-Physical Systems

Effectively managing complex logistics data is essential for development sustainability and growth,especially in optimizing distribution routes.This article addresses the limitations of current logistics path optimization methods,such as inefficiencies and high operational costs.To overcome these drawbacks,we introduce the Hybrid Firefly-Spotted Hyena Optimization(HFSHO)algorithm,a novel approach that combines the rapid exploration and global search abilities of the Firefly Algorithm(FO)with the localized search and region-exploitation skills of the Spotted Hyena Optimization Algorithm(SHO).HFSHO aims to improve logistics path optimization and reduce operational costs.The algorithm’s effectiveness is systematically assessed through rigorous comparative analyses with established algorithms like the Ant Colony Algorithm(ACO),Cuckoo Search Algorithm(CSA)and Jaya Algo-rithm(JA).The evaluation also employs benchmarking methodologies using standardized function sets covering diverse objective functions,including Schwefel’s,Rastrigin,Ackley,Sphere and the ZDT and DTLZ Function suite.HFSHO outperforms these algorithms,achieving a minimum path distance of 546 units,highlighting its prowess in logistics path optimization.This comprehensive evaluation authenticates HFSHO’s exceptional performance across various logistic optimization scenarios.These findings emphasize the critical significance of selecting an appropriate algorithm for logistics path navigation,with HFSHO emerging as an efficient choice.Through the synergistic use of FO and SHO,HFSHO achieves a 15%improvement in convergence,heightened operational efficiency and substantial cost reductions in logistics operations.It presents a promising solution for optimizing logistics paths,offering logistics planners and decision-makers valuable insights and contributing substantively to sustainable sectoral growth.

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.

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.

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.

RANKL inhibition reduces lesional cellularity and Gαs variant expression and enables osteogenic maturation in fibrous dysplasia

Fibrous dysplasia(FD)is a rare,disabling skeletal disease for which there are no established treatments.Growing evidence supports inhibiting the osteoclastogenic factor receptor activator of nuclear kappa-B ligand(RANKL)as a potential treatment strategy.In this study,we investigated the mechanisms underlying RANKL inhibition in FD tissue and its likely indirect effects on osteoprogenitors by evaluating human FD tissue pre-and post-treatment in a phase 2 clinical trial of denosumab(NCT03571191)and in murine in vivo and ex vivo preclinical models.Histological analysis of human and mouse tissue demonstrated increased osteogenic maturation,reduced cellularity,and reduced expression of the pathogenic Gαs variant in FD lesions after RANKL inhibition.RNA sequencing of human and mouse tissue supported these findings.The interaction between osteoclasts and mutant osteoprogenitors was further assessed in an ex vivo lesion model,which indicated that the proliferation of abnormal FD osteoprogenitors was dependent on osteoclasts.The results from this study demonstrated that,in addition to its expected antiosteoclastic effect,denosumab reduces FD lesion activity by decreasing FD cell proliferation and increasing osteogenic maturation,leading to increased bone formation within lesions.These findings highlight the unappreciated role of cellular crosstalk between osteoclasts and preosteoblasts/osteoblasts as a driver of FD pathology and demonstrate a novel mechanism of action of denosumab in the treatment of bone disease.

Call for Papers from Food Science of Animal Products

Food Science of Animal Products (ISSN:2958-4124,e-ISSN:2958-3780)is a peer-reviewed,open access international journal that publishes the latest research findings in the field of animal-origin foods,involving food materials such as meat,aquatic products,milk,eggs,animal offals and edible insects.

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.