The application of mathematical modeling to biological fluids is of utmost importance, as it has diverse applicationsin medicine. The peristaltic mechanism plays a crucial role in understanding numerous biological flo...The application of mathematical modeling to biological fluids is of utmost importance, as it has diverse applicationsin medicine. The peristaltic mechanism plays a crucial role in understanding numerous biological flows. In thispaper, we present a theoretical investigation of the double diffusion convection in the peristaltic transport of aPrandtl nanofluid through an asymmetric tapered channel under the combined action of thermal radiation andan induced magnetic field. The equations for the current flow scenario are developed, incorporating relevantassumptions, and considering the effect of viscous dissipation. The impact of thermal radiation and doublediffusion on public health is of particular interest. For instance, infrared radiation techniques have been used totreat various skin-related diseases and can also be employed as a measure of thermotherapy for some bones toenhance blood circulation, with radiation increasing blood flow by approximately 80%. To solve the governingequations, we employ a numerical method with the aid of symbolic software such as Mathematica and MATLAB.The velocity, magnetic force function, pressure rise, temperature, solute (species) concentration, and nanoparticlevolume fraction profiles are analytically derived and graphically displayed. The results outcomes are compared withthe findings of limiting situations for verification.展开更多
Background:Achilles tendinopathy(AT)is a common problem among runners.There is only limited evidence for risk factors for AT,and most studies have not defined the AT subcategories.No study has compared the incidence a...Background:Achilles tendinopathy(AT)is a common problem among runners.There is only limited evidence for risk factors for AT,and most studies have not defined the AT subcategories.No study has compared the incidence and risk factors between insertional AT and midportion AT,though they are considered distinct.This study aimed to assess incidence and risk factors of AT based on data from a large prospective cohort.The secondary aim was to explore differences in risk factors between insertional and midportion AT.Methods:Participants were recruited from among registered runners at registration for running events.Questionnaires were completed at baseline,1 month before the event,1 week before the event,and 1 month after the event.Information concerning demographics,training load,registered events,and running-related injuries were collected at baseline.The follow-up questionnaires collected information about new injuries.A pain map was used to diagnose midportion and insertional AT.The primary outcome was the incidence of AT.Multivariable logistic regression analysis was applied to identify risk factors for the onset.Results:We included 3379 participants with a mean follow-up of 20.4 weeks.The incidence of AT was 4.2%.The proportion of insertional AT was 27.7%and of midportion AT was 63.8%;the remaining proportion was a combined type of insertional and midportion AT.Men had a significantly higher incidence(5%,95%confidence interval(95%CI):4.1%-6.0%)than women(2.8%,95%CI:2.0%-3.8%).AT in the past12 months was the most predominant risk factor for new-onset AT(odds ratio(OR)=6.47,95%CI:4.27-9.81).This was similar for both subcategories of AT(insertional:OR=5.45,95%CI:2.51-11.81;midportion:OR=6.96,95%CI:4.24-11.40).Participants registering for an event with a distance of 10/10.55 km were less likely to develop a new-onset AT(OR=0.59,95%CI:0.36-0.97)or midportion AT(OR=0.47,95%CI:0.23-0.93).Higher age had a significant negative association with insertional AT(OR=0.97,95%CI:0.94-1.00).Conclusion:The incidence of new-onset AT among recreational runners was 4.2%.The proportion of insertional and midportion AT was 27.7%and 63.8%,respectively.AT in the past 12 months was the predominant risk factor for the onset of AT.Risk factors varied between insertional and midportion AT,but we could not identify clinically relevant differences between the 2 subtypes.展开更多
BACKGROUND Sport-induced injuries particularly affect young,healthy,and active individuals.Running,a popular and accessible sport,can cause a wide range of injuries,including stress fractures.Stress fractures can occu...BACKGROUND Sport-induced injuries particularly affect young,healthy,and active individuals.Running,a popular and accessible sport,can cause a wide range of injuries,including stress fractures.Stress fractures can occur during high-intensity training or competitions,especially among well-trained amateurs and professional athletes.Adequate diagnosis can be complicated by the typically young age,unremarkable medical history,and vital condition of the patient.Stress fractures present insidiously,and this is specifically the case with stress fractures of the femoral neck.Timely intervention is crucial to prevent progressive displacement,as this can damage the blood supply to the femoral head.CASE SUMMARY A 30-year-old male runner presented to our outpatient clinic with persistent pain 3 weeks after running a marathon.X-ray showed a complete lateral fracture of the left femoral neck,which was treated surgically with a dynamic hip screw.CONCLUSION It is essential for healthcare providers to be vigilant for the subtle symptoms of stress fractures to ensure timely treatment.Early recognition prevents com-plication and leads to a better prognosis.展开更多
Objective Detection and quantification of RNA synthesis in cells is a widely used technique for monitoring cell viability,health,and metabolic rate.After exposure to environmental stimuli,both the internal reference g...Objective Detection and quantification of RNA synthesis in cells is a widely used technique for monitoring cell viability,health,and metabolic rate.After exposure to environmental stimuli,both the internal reference gene and target gene would be degraded.As a result,it is imperative to consider the accurate capture of nascent RNA and the detection of transcriptional levels of RNA following environmental stimulation.This study aims to create a Click Chemistry method that utilizes its property to capture nascent RNA from total RNA that was stimulated by the environment.Methods The new RNA was labeled with 5-ethyluridine(5-EU)instead of uracil,and the azido-biotin medium ligand was connected to the magnetic sphere using a combination of“Click Chemistry”and magnetic bead screening.Then the new RNA was captured and the transcription rate of 16S rRNA was detected by fluorescence molecular beacon(M.B.)and quantitative reverse transcription PCR(qRT-PCR).Results The bacterial nascent RNA captured by“Click Chemistry”screening can be used as a reverse transcription template to form cDNA.Combined with the fluorescent molecular beacon M.B.1,the synthesis rate of rRNA at 37℃is 1.2 times higher than that at 15℃.The 16S rRNA gene and cspI gene can be detected by fluorescent quantitative PCR,it was found that the measured relative gene expression changes were significantly enhanced at 25℃and 16℃when analyzed with nascent RNA rather than total RNA,enabling accurate detection of RNA transcription rates.Conclusion Compared to other article reported experimental methods that utilize screening magnetic columns,the technical scheme employed in this study is more suitable for bacteria,and the operation steps are simple and easy to implement,making it an effective RNA capture method for researchers.展开更多
Software project outcomes heavily depend on natural language requirements,often causing diverse interpretations and issues like ambiguities and incomplete or faulty requirements.Researchers are exploring machine learn...Software project outcomes heavily depend on natural language requirements,often causing diverse interpretations and issues like ambiguities and incomplete or faulty requirements.Researchers are exploring machine learning to predict software bugs,but a more precise and general approach is needed.Accurate bug prediction is crucial for software evolution and user training,prompting an investigation into deep and ensemble learning methods.However,these studies are not generalized and efficient when extended to other datasets.Therefore,this paper proposed a hybrid approach combining multiple techniques to explore their effectiveness on bug identification problems.The methods involved feature selection,which is used to reduce the dimensionality and redundancy of features and select only the relevant ones;transfer learning is used to train and test the model on different datasets to analyze how much of the learning is passed to other datasets,and ensemble method is utilized to explore the increase in performance upon combining multiple classifiers in a model.Four National Aeronautics and Space Administration(NASA)and four Promise datasets are used in the study,showing an increase in the model’s performance by providing better Area Under the Receiver Operating Characteristic Curve(AUC-ROC)values when different classifiers were combined.It reveals that using an amalgam of techniques such as those used in this study,feature selection,transfer learning,and ensemble methods prove helpful in optimizing the software bug prediction models and providing high-performing,useful end mode.展开更多
BACKGROUND Angelman syndrome(AS)is caused by maternal chromosomal deletions,imprinting defects,paternal uniparental disomy involving chromosome 15 and the ubiquitin-protein ligase UBE3A gene mutations.However the gene...BACKGROUND Angelman syndrome(AS)is caused by maternal chromosomal deletions,imprinting defects,paternal uniparental disomy involving chromosome 15 and the ubiquitin-protein ligase UBE3A gene mutations.However the genetic basis remains unclear for several patients.AIM To investigate the involvement of UBE3A gene in AS and identifying new potential genes using exome sequencing.METHODS We established a cohort study in 50 patients referred to Farhat Hached University Hospital between 2006 and 2021,with a strong suspicion of AS and absence of chromosomal aberrations.The UBE3A gene was screened for mutation detection.Two unrelated patients issued from consanguineous families were subjected to exome analysis.RESULTS We describe seven UBE3A variants among them 3 none previously described including intronic variants c.2220+14T>C(intron14),c.2507+43T>A(Exon15)and insertion in Exon7:c.30-47_30-46.The exome sequencing revealed 22 potential genes that could be involved in AS-like syndromes that should be investigated further.CONCLUSION Screening for UBE3A mutations in AS patients has been proven to be useful to confirm the diagnosis.Our exome findings could rise to new potential alternative target genes for genetic counseling.展开更多
Bone metastasis secondary to breast cancer negatively impacts patient quality of life and survival.The treatment of bone metastases is challenging since many anticancer drugs are not effectively delivered to the bone ...Bone metastasis secondary to breast cancer negatively impacts patient quality of life and survival.The treatment of bone metastases is challenging since many anticancer drugs are not effectively delivered to the bone to exert a therapeutic effect.To improve the treatment efficacy,we developed Pluronic P123(P123)-based polymeric micelles dually decorated with alendronate(ALN)and cancer-specific phage protein DMPGTVLP(DP-8)for targeted drug delivery to breast cancer bone metastases.Doxorubicin(DOX)was selected as the anticancer drug and was encapsulated into the hydrophobic core of the micelles with a high drug loading capacity(3.44%).The DOX-loaded polymeric micelles were spherical,123 nm in diameter on average,and exhibited a narrow size distribution.The in vitro experiments demonstrated that a pH decrease from 7.4 to 5.0 markedly accelerated DOX release.The micelles were well internalized by cultured breast cancer cells and the cell death rate of micelle-treated breast cancer cells was increased compared to that of free DOX-treated cells.Rapid binding of the micelles to hydroxyapatite(HA)microparticles indicated their high affinity for bone.P123-ALN/DP-8@DOX inhibited tumor growth and reduced bone resorption in a 3D cancer bone metastasis model.In vivo experiments using a breast cancer bone metastasis nude model demonstrated increased accumulation of the micelles in the tumor region and considerable antitumor activity with no organ-specific histological damage and minimal systemic toxicity.In conclusion,our study provided strong evidence that these pH-sensitive dual ligand-targeted polymeric micelles may be a successful treatment strategy for breast cancer bone metastasis.展开更多
Background Cardiovascular risk burden is associated with dementia risk and neurodegeneration-related brain structure,while the role of genetics and incident cardiovascular disease(CVD)remains unclear.Aims To examine t...Background Cardiovascular risk burden is associated with dementia risk and neurodegeneration-related brain structure,while the role of genetics and incident cardiovascular disease(CVD)remains unclear.Aims To examine the association of overall cardiovascular risk burden with the risk of major dementia subtypes and volumes of related brain regions in a large sample,and to explore the role of genetics and CVD onset.Methods A prospective study among 354 654 participants free of CVD and dementia(2006-2010,mean age 56.4 years)was conducted within the UK Biobank,with brain magnetic resonance imaging(MRl)measurement availablefor 15104participants since 2014.CVD risk burden was evaluated by the Framingham General Cardiovascular Risk Score(FGCRS).Dementia diagnosis was ascertained from inpatient and death register data.Results Overamedian 12.0-yearfollow-up,3998 all-cause dementia cases were identified.Higher FGCRS was associated with increasedall-cause dementia risk after adjusting for demographic,major lifestyle,clinical factors and the polygenic risk score(PRS)of Alzheimer's disease.Comparing the high versus low tertile of FGCRS,the odds ratios(ORs)and 95%confidence intervals(Cls)were 1.26(1.12 to 1.41)for all-cause dementia,1.67(1.33 to 2.09)for Alzheimer's disease and 1.53(1.07 to 2.16)for vascular dementia(all p_(treng)<0.05).Incident stroke and coronary heart disease accounted for 14%(95%Cl:9% to 21%)of the association between FGCRS and all-cause dementia.Interactions were not detected for FGCRS and PRS on the risk of any dementia subtype.We observed an 83%(95%Cl:47%to 128%)higher all-cause dementia risk comparing the high-high versus low-low FGCRS-PRS category.For brain volumes,higher FGCRS was associated with greater log-transformed white matter hyperintensities,smaller cortical volume and smaller grey matter volume.Conclusions Our findings suggest that the positive association of cardiovascular risk burden with dementia risk also applies to major dementia subtypes.The association of cardiovascular risk burden with all-cause dementia is largely independent of CVD onset and genetic predisposition to dementia.展开更多
To overcome the limitation in formability at room temperature,manufacturers have developed magnesium alloys with remarkable properties by adding rare-earth elements.The rare-earth magnesium alloys behave differently f...To overcome the limitation in formability at room temperature,manufacturers have developed magnesium alloys with remarkable properties by adding rare-earth elements.The rare-earth magnesium alloys behave differently from the conventional alloys,especially with respect to their coupled anisotropic and strain rate sensitive behavior.In the current work,such behavior of the rare-earth Mg alloy ZEK100 sheet at room temperature is investigated with the aid of the elastic viscoplastic self-consistent polycrystal plasticity model.Different strain rate sensitivities(SRSs)for various deformation modes are employed by the model to simulate the strain rate sensitive behaviors under different loading directions and loading rates.Good agreement between the experiments and simulations reveals the importance and necessity of using different SRSs for each deformation mode in hexagonal close-packed metals.Furthermore,the relative activities of each deformation mode and the texture evolution during different loadings are discussed.The anisotropic and strain rate sensitive behavior is ascribed to the various operating deformation modes with different SRSs during loading along different directions.展开更多
In the synovial joint,mechanical force creates an important signal that influences chondrocyte behavior.The conversion of mechanical signals into biochemical cues relies on different elements in mechanotransduction pa...In the synovial joint,mechanical force creates an important signal that influences chondrocyte behavior.The conversion of mechanical signals into biochemical cues relies on different elements in mechanotransduction pathways and culminates in changes in chondrocyte phenotype and extracellular matrix composition/structure.Recently,several mechanosensors,the first responders to mechanical force,have been discovered.However,we still have limited knowledge about the downstream molecules that enact alterations in the gene expression profile during mechanotransduction signaling.Recently,estrogen receptorα(ERα)has been shown to modulate the chondrocyte response to mechanical loading through a ligand-independent mechanism,in line with previous research showing that ERαexerts important mechanotransduction effects on other cell types,such as osteoblasts.In consideration of these recent discoveries,the goal of this review is to position ERαinto the mechanotransduction pathways known to date.Specifically,we first summarize our most recent understanding of the mechanotransduction pathways in chondrocytes on the basis of three categories of actors,namely mechanosensors,mechanotransducers,and mechanoimpactors.Then,the specific roles played by ERαin mediating the chondrocyte response to mechanical loading are discussed,and the potential interactions of ERαwith other molecules in mechanotransduction pathways are explored.Finally,we propose several future research directions that may advance our understanding of the roles played by ERαin mediating biomechanical cues under physiological and pathological conditions.展开更多
We present a Gaussian process(GP)approach,called Gaussian process hydrodynamics(GPH)for approximating the solution to the Euler and Navier-Stokes(NS)equations.Similar to smoothed particle hydrodynamics(SPH),GPH is a L...We present a Gaussian process(GP)approach,called Gaussian process hydrodynamics(GPH)for approximating the solution to the Euler and Navier-Stokes(NS)equations.Similar to smoothed particle hydrodynamics(SPH),GPH is a Lagrangian particle-based approach that involves the tracking of a finite number of particles transported by a flow.However,these particles do not represent mollified particles of matter but carry discrete/partial information about the continuous flow.Closure is achieved by placing a divergence-free GP priorξon the velocity field and conditioning it on the vorticity at the particle locations.Known physics(e.g.,the Richardson cascade and velocityincrement power laws)is incorporated into the GP prior by using physics-informed additive kernels.This is equivalent to expressingξas a sum of independent GPsξl,which we call modes,acting at different scales(each modeξlself-activates to represent the formation of eddies at the corresponding scales).This approach enables a quantitative analysis of the Richardson cascade through the analysis of the activation of these modes,and enables us to analyze coarse-grain turbulence statistically rather than deterministically.Because GPH is formulated by using the vorticity equations,it does not require solving a pressure equation.By enforcing incompressibility and fluid-structure boundary conditions through the selection of a kernel,GPH requires significantly fewer particles than SPH.Because GPH has a natural probabilistic interpretation,the numerical results come with uncertainty estimates,enabling their incorporation into an uncertainty quantification(UQ)pipeline and adding/removing particles(quanta of information)in an adapted manner.The proposed approach is suitable for analysis because it inherits the complexity of state-of-the-art solvers for dense kernel matrices and results in a natural definition of turbulence as information loss.Numerical experiments support the importance of selecting physics-informed kernels and illustrate the major impact of such kernels on the accuracy and stability.Because the proposed approach uses a Bayesian interpretation,it naturally enables data assimilation and predictions and estimations by mixing simulation data and experimental data.展开更多
This paper presents a comprehensive study that includes the sizing and power flow by series and parallel inverters in a distributed generation system(DGs)that integrates the system of hybrid wind photovoltaic with a u...This paper presents a comprehensive study that includes the sizing and power flow by series and parallel inverters in a distributed generation system(DGs)that integrates the system of hybrid wind photovoltaic with a unified power quality conditioner(UPQC).In addition to supplying active power to the utility grid,the system of hybrid wind photovoltaic functions as a UPQC,compensating reactive power and suppressing the harmonic load currents.Additionally,the load is supplied with harmonic-free,balanced and regulated output voltages.Since PVWind-UPQC is established on a dual compensation scheme,the series inverter works like a sinusoidal current source,while the parallel inverter works like a sinusoidal voltage source.Consequently,a smooth alteration from interconnected operating modes to island operating modes and vice versa can be achieved without load voltage transients.Since PV-Wind-UPQC inverters handle the energy generated through the hybrid wind photovoltaic system and the energy demanded through the load,the converters should be sized cautiously.A detailed study of the flow of power via the PV-Wind-UPQC is imperative to gain a complete understanding of the system operation and the proper design of the converters.Thus,curves that allow the sizing of the power converters according to the power flow via the converters are presented and discussed.Simulation results are presented to assess both steady state and dynamic performances of the grid connected hybrid system of PV-Wind-UPQC.This investigation is verified by simulating and analyzing the results with Matlab/Simulink.展开更多
The human immunodeficiency viruses are two species of Lentivirus that infect humans.Over time,they cause acquired immunodeficiency syndrome,a condition in which progressive immune system failure allows life-threatening ...The human immunodeficiency viruses are two species of Lentivirus that infect humans.Over time,they cause acquired immunodeficiency syndrome,a condition in which progressive immune system failure allows life-threatening opportunistic infections and cancers to thrive.Human immunodeficiency virus infection came from a type of chimpanzee in Central Africa.Studies show that immunodeficiency viruses may have jumped from chimpanzees to humans as far back as the late 1800s.Over decades,human immunodeficiency viruses slowly spread across Africa and later into other parts of the world.The Susceptible-Infected-Recovered(SIR)models are significant in studying disease dynamics.In this paper,we have studied the effect of irresponsible immigrants on HIV/AIDS dynamics by formulating and considering different methods.Euler,Runge Kutta,and a Non-standardfinite difference(NSFD)method are developed for the same problem.Numerical experiments are performed at disease-free and endemic equilibria points at different time step sizes‘ℎ’.The results reveal that,unlike Euler and Runge Kutta,which fail for large time step sizes,the proposed Non-standardfinite difference(NSFD)method gives a convergence solution for any time step size.Our proposed numerical method is bounded,dynamically con-sistent,and preserves the positivity of the continuous solution,which are essential requirements when modeling a prevalent disease.展开更多
The mechanisms underlying the bone disease induced by diabetes are complex and not fully understood;and antiresorptive agents,the current standard of care,do not restore the weakened bone architecture.Herein,we reveal...The mechanisms underlying the bone disease induced by diabetes are complex and not fully understood;and antiresorptive agents,the current standard of care,do not restore the weakened bone architecture.Herein,we reveal the diabetic bone signature in mice at the tissue,cell,and transcriptome levels and demonstrate that three FDA-approved bone-anabolic agents correct it.Diabetes decreased bone mineral density(BMD)and bone formation,damaged microarchitecture,increased porosity of cortical bone,and compromised bone strength.Teriparatide(PTH),abaloparatide(ABL),and romosozumab/anti-sclerostin antibody(Scl-Ab)all restored BMD and corrected the deteriorated bone architecture.Mechanistically,PTH and more potently ABL induced similar responses at the tissue and gene signature levels,increasing both formation and resorption with positive balance towards bone gain.In contrast,Scl-Ab increased formation but decreased resorption.All agents restored bone architecture,corrected cortical porosity,and improved mechanical properties of diabetic bone;and ABL and Scl-Ab increased toughness,a fracture resistance index.Remarkably,all agents increased bone strength over the healthy controls even in the presence of severe hyperglycemia.These findings demonstrate the therapeutic value of bone anabolic agents to treat diabetes-induced bone disease and suggest the need for revisiting the approaches for the treatment of bone fragility in diabetes.展开更多
THE rapid growth of new energy vehicles is accelerating the low-carbon transition in the global transportation sector. According to the international energy agency report, more than 10 million electric vehicles(EVs) i...THE rapid growth of new energy vehicles is accelerating the low-carbon transition in the global transportation sector. According to the international energy agency report, more than 10 million electric vehicles(EVs) including pure electric and hybrid models were sold worldwide in 2022, which means that the global share of electric vehicles in the overall automotive market has risen from less than 5% in 2020 to 14% in 2022.展开更多
Background In China's Mainland,patients with neovascular age-related macular degeneration(nAMD)have approximately an 40%prevalence of polypoidal choroidal vasculopathy(PCV).This disease leads to recurrent retinal ...Background In China's Mainland,patients with neovascular age-related macular degeneration(nAMD)have approximately an 40%prevalence of polypoidal choroidal vasculopathy(PCV).This disease leads to recurrent retinal pigment epithelium detachment(PED),extensive subretinal or vitreous hemorrhages,and severe vision loss.China has introduced various treatment modalities in the past years and gained comprehensive experience in treating PCV.Methods A total of 14 retinal specialists nationwide with expertise in PCV were empaneled to prioritize six questions and address their corresponding outcomes,regarding opinions on inactive PCV,choices of anti-vascular endothelial growth factor(anti-VEGF)monotherapy,photodynamic therapy(PDT)monotherapy or combined therapy,patients with persistent subretinal fluid(SRF)or intraretinal fluid(IRF)after loading dose anti-VEGF,and patients with massive subretinal hemorrhage.An evidence synthesis team conducted systematic reviews,which informed the recommendations that address these questions.This guideline used the GRADE(Grading of Recommendations,Assessment,Development,and Evaluation)approach to assess the certainty of evidence and grade the strengths of recommendations.Results The panel proposed the following six conditional recommendations regarding treatment choices.(1)For patients with inactive PCV,we suggest observation over treatment.(2)For treatment-na?ve PCV patients,we suggest either anti-VEGF monotherapy or combined anti-VEGF and PDT rather than PDT monotherapy.(3)For patients with PCV who plan to initiate combined anti-VEGF and PDT treatment,we suggest later/rescue PDT over initiate PDT.(4)For PCV patients who plan to initiate anti-VEGF monotherapy,we suggest the treat and extend(TE)regimen rather than the pro re nata(PRN)regimen following three monthly loading doses.(5)For patients with persistent SRF or IRF on optical coherence tomography(OCT)after three monthly anti-VEGF treatments,we suggest proceeding with anti-VEGF treatment rather than observation.(6)For PCV patients with massive subretinal hemorrhage(equal to or more than four optic disc areas)involving the central macula,we suggest surgery(vitrectomy in combination with tissue-plasminogen activator(tPA)intraocular injection and gas tamponade)rather than anti-VEGF monotherapy.Conclusions Six evidence-based recommendations support optimal care for PCV patients'management.展开更多
基金Institutional Fund Projects under No.(IFP-A-2022-2-5-24)by Ministry of Education and University of Hafr Al Batin,Saudi Arabia.
文摘The application of mathematical modeling to biological fluids is of utmost importance, as it has diverse applicationsin medicine. The peristaltic mechanism plays a crucial role in understanding numerous biological flows. In thispaper, we present a theoretical investigation of the double diffusion convection in the peristaltic transport of aPrandtl nanofluid through an asymmetric tapered channel under the combined action of thermal radiation andan induced magnetic field. The equations for the current flow scenario are developed, incorporating relevantassumptions, and considering the effect of viscous dissipation. The impact of thermal radiation and doublediffusion on public health is of particular interest. For instance, infrared radiation techniques have been used totreat various skin-related diseases and can also be employed as a measure of thermotherapy for some bones toenhance blood circulation, with radiation increasing blood flow by approximately 80%. To solve the governingequations, we employ a numerical method with the aid of symbolic software such as Mathematica and MATLAB.The velocity, magnetic force function, pressure rise, temperature, solute (species) concentration, and nanoparticlevolume fraction profiles are analytically derived and graphically displayed. The results outcomes are compared withthe findings of limiting situations for verification.
基金supported by the Netherlands Organisation for Health Research and Development(ZonMW)(Grant No.50-53600-98-104)China Scholarship Council(CSC)(Grant No.202106100138)。
文摘Background:Achilles tendinopathy(AT)is a common problem among runners.There is only limited evidence for risk factors for AT,and most studies have not defined the AT subcategories.No study has compared the incidence and risk factors between insertional AT and midportion AT,though they are considered distinct.This study aimed to assess incidence and risk factors of AT based on data from a large prospective cohort.The secondary aim was to explore differences in risk factors between insertional and midportion AT.Methods:Participants were recruited from among registered runners at registration for running events.Questionnaires were completed at baseline,1 month before the event,1 week before the event,and 1 month after the event.Information concerning demographics,training load,registered events,and running-related injuries were collected at baseline.The follow-up questionnaires collected information about new injuries.A pain map was used to diagnose midportion and insertional AT.The primary outcome was the incidence of AT.Multivariable logistic regression analysis was applied to identify risk factors for the onset.Results:We included 3379 participants with a mean follow-up of 20.4 weeks.The incidence of AT was 4.2%.The proportion of insertional AT was 27.7%and of midportion AT was 63.8%;the remaining proportion was a combined type of insertional and midportion AT.Men had a significantly higher incidence(5%,95%confidence interval(95%CI):4.1%-6.0%)than women(2.8%,95%CI:2.0%-3.8%).AT in the past12 months was the most predominant risk factor for new-onset AT(odds ratio(OR)=6.47,95%CI:4.27-9.81).This was similar for both subcategories of AT(insertional:OR=5.45,95%CI:2.51-11.81;midportion:OR=6.96,95%CI:4.24-11.40).Participants registering for an event with a distance of 10/10.55 km were less likely to develop a new-onset AT(OR=0.59,95%CI:0.36-0.97)or midportion AT(OR=0.47,95%CI:0.23-0.93).Higher age had a significant negative association with insertional AT(OR=0.97,95%CI:0.94-1.00).Conclusion:The incidence of new-onset AT among recreational runners was 4.2%.The proportion of insertional and midportion AT was 27.7%and 63.8%,respectively.AT in the past 12 months was the predominant risk factor for the onset of AT.Risk factors varied between insertional and midportion AT,but we could not identify clinically relevant differences between the 2 subtypes.
文摘BACKGROUND Sport-induced injuries particularly affect young,healthy,and active individuals.Running,a popular and accessible sport,can cause a wide range of injuries,including stress fractures.Stress fractures can occur during high-intensity training or competitions,especially among well-trained amateurs and professional athletes.Adequate diagnosis can be complicated by the typically young age,unremarkable medical history,and vital condition of the patient.Stress fractures present insidiously,and this is specifically the case with stress fractures of the femoral neck.Timely intervention is crucial to prevent progressive displacement,as this can damage the blood supply to the femoral head.CASE SUMMARY A 30-year-old male runner presented to our outpatient clinic with persistent pain 3 weeks after running a marathon.X-ray showed a complete lateral fracture of the left femoral neck,which was treated surgically with a dynamic hip screw.CONCLUSION It is essential for healthcare providers to be vigilant for the subtle symptoms of stress fractures to ensure timely treatment.Early recognition prevents com-plication and leads to a better prognosis.
文摘Objective Detection and quantification of RNA synthesis in cells is a widely used technique for monitoring cell viability,health,and metabolic rate.After exposure to environmental stimuli,both the internal reference gene and target gene would be degraded.As a result,it is imperative to consider the accurate capture of nascent RNA and the detection of transcriptional levels of RNA following environmental stimulation.This study aims to create a Click Chemistry method that utilizes its property to capture nascent RNA from total RNA that was stimulated by the environment.Methods The new RNA was labeled with 5-ethyluridine(5-EU)instead of uracil,and the azido-biotin medium ligand was connected to the magnetic sphere using a combination of“Click Chemistry”and magnetic bead screening.Then the new RNA was captured and the transcription rate of 16S rRNA was detected by fluorescence molecular beacon(M.B.)and quantitative reverse transcription PCR(qRT-PCR).Results The bacterial nascent RNA captured by“Click Chemistry”screening can be used as a reverse transcription template to form cDNA.Combined with the fluorescent molecular beacon M.B.1,the synthesis rate of rRNA at 37℃is 1.2 times higher than that at 15℃.The 16S rRNA gene and cspI gene can be detected by fluorescent quantitative PCR,it was found that the measured relative gene expression changes were significantly enhanced at 25℃and 16℃when analyzed with nascent RNA rather than total RNA,enabling accurate detection of RNA transcription rates.Conclusion Compared to other article reported experimental methods that utilize screening magnetic columns,the technical scheme employed in this study is more suitable for bacteria,and the operation steps are simple and easy to implement,making it an effective RNA capture method for researchers.
基金This Research is funded by Researchers Supporting Project Number(RSPD2024R947),King Saud University,Riyadh,Saudi Arabia.
文摘Software project outcomes heavily depend on natural language requirements,often causing diverse interpretations and issues like ambiguities and incomplete or faulty requirements.Researchers are exploring machine learning to predict software bugs,but a more precise and general approach is needed.Accurate bug prediction is crucial for software evolution and user training,prompting an investigation into deep and ensemble learning methods.However,these studies are not generalized and efficient when extended to other datasets.Therefore,this paper proposed a hybrid approach combining multiple techniques to explore their effectiveness on bug identification problems.The methods involved feature selection,which is used to reduce the dimensionality and redundancy of features and select only the relevant ones;transfer learning is used to train and test the model on different datasets to analyze how much of the learning is passed to other datasets,and ensemble method is utilized to explore the increase in performance upon combining multiple classifiers in a model.Four National Aeronautics and Space Administration(NASA)and four Promise datasets are used in the study,showing an increase in the model’s performance by providing better Area Under the Receiver Operating Characteristic Curve(AUC-ROC)values when different classifiers were combined.It reveals that using an amalgam of techniques such as those used in this study,feature selection,transfer learning,and ensemble methods prove helpful in optimizing the software bug prediction models and providing high-performing,useful end mode.
文摘BACKGROUND Angelman syndrome(AS)is caused by maternal chromosomal deletions,imprinting defects,paternal uniparental disomy involving chromosome 15 and the ubiquitin-protein ligase UBE3A gene mutations.However the genetic basis remains unclear for several patients.AIM To investigate the involvement of UBE3A gene in AS and identifying new potential genes using exome sequencing.METHODS We established a cohort study in 50 patients referred to Farhat Hached University Hospital between 2006 and 2021,with a strong suspicion of AS and absence of chromosomal aberrations.The UBE3A gene was screened for mutation detection.Two unrelated patients issued from consanguineous families were subjected to exome analysis.RESULTS We describe seven UBE3A variants among them 3 none previously described including intronic variants c.2220+14T>C(intron14),c.2507+43T>A(Exon15)and insertion in Exon7:c.30-47_30-46.The exome sequencing revealed 22 potential genes that could be involved in AS-like syndromes that should be investigated further.CONCLUSION Screening for UBE3A mutations in AS patients has been proven to be useful to confirm the diagnosis.Our exome findings could rise to new potential alternative target genes for genetic counseling.
基金supported by the National Natural Science Foundation of China(#81872220 and#81703437)Xinjiang Uygur Autonomous Region Science and Technology Support Project(#2020E0290)+4 种基金Basic Public Welfare Research Project of Zhejiang Province(#LGF18H160034,LGC21B050011 and#LGF20H300012),Science and Technology Bureau of Jiaxing(2020AY10021)Key Research and Development and Transformation project of Qinghai Province(2021-SF-C20)Dutch Cancer Foundation(KWF project#10666)a Zhejiang Provincial Foreign Expert Program Grant,Zhejiang Provincial Key Natural Science Foundation of China(#Z20H160031)and Jiaxing Key Laboratory of Oncological Photodynamic Therapy and Targeted Drug Research,and“Innovative Jiaxing·Excellent Talent Support Program”-Top Talents in Technological Innovation.
文摘Bone metastasis secondary to breast cancer negatively impacts patient quality of life and survival.The treatment of bone metastases is challenging since many anticancer drugs are not effectively delivered to the bone to exert a therapeutic effect.To improve the treatment efficacy,we developed Pluronic P123(P123)-based polymeric micelles dually decorated with alendronate(ALN)and cancer-specific phage protein DMPGTVLP(DP-8)for targeted drug delivery to breast cancer bone metastases.Doxorubicin(DOX)was selected as the anticancer drug and was encapsulated into the hydrophobic core of the micelles with a high drug loading capacity(3.44%).The DOX-loaded polymeric micelles were spherical,123 nm in diameter on average,and exhibited a narrow size distribution.The in vitro experiments demonstrated that a pH decrease from 7.4 to 5.0 markedly accelerated DOX release.The micelles were well internalized by cultured breast cancer cells and the cell death rate of micelle-treated breast cancer cells was increased compared to that of free DOX-treated cells.Rapid binding of the micelles to hydroxyapatite(HA)microparticles indicated their high affinity for bone.P123-ALN/DP-8@DOX inhibited tumor growth and reduced bone resorption in a 3D cancer bone metastasis model.In vivo experiments using a breast cancer bone metastasis nude model demonstrated increased accumulation of the micelles in the tumor region and considerable antitumor activity with no organ-specific histological damage and minimal systemic toxicity.In conclusion,our study provided strong evidence that these pH-sensitive dual ligand-targeted polymeric micelles may be a successful treatment strategy for breast cancer bone metastasis.
基金grants from the National Key R&D Program of China(2023YFF1104301)(by Geng Zong)National Natural Science Foundation of China(82373576)(by Geng Zong)+2 种基金National Science Fund for Excellent Young Scholars(81922060)(by Geng Zong)Strategic Priority CAS Project(XDB38010300)(by Geng Zong)the Zhejiang University Education Foundation Global Partnership Fund(by Changzheng Yuan).
文摘Background Cardiovascular risk burden is associated with dementia risk and neurodegeneration-related brain structure,while the role of genetics and incident cardiovascular disease(CVD)remains unclear.Aims To examine the association of overall cardiovascular risk burden with the risk of major dementia subtypes and volumes of related brain regions in a large sample,and to explore the role of genetics and CVD onset.Methods A prospective study among 354 654 participants free of CVD and dementia(2006-2010,mean age 56.4 years)was conducted within the UK Biobank,with brain magnetic resonance imaging(MRl)measurement availablefor 15104participants since 2014.CVD risk burden was evaluated by the Framingham General Cardiovascular Risk Score(FGCRS).Dementia diagnosis was ascertained from inpatient and death register data.Results Overamedian 12.0-yearfollow-up,3998 all-cause dementia cases were identified.Higher FGCRS was associated with increasedall-cause dementia risk after adjusting for demographic,major lifestyle,clinical factors and the polygenic risk score(PRS)of Alzheimer's disease.Comparing the high versus low tertile of FGCRS,the odds ratios(ORs)and 95%confidence intervals(Cls)were 1.26(1.12 to 1.41)for all-cause dementia,1.67(1.33 to 2.09)for Alzheimer's disease and 1.53(1.07 to 2.16)for vascular dementia(all p_(treng)<0.05).Incident stroke and coronary heart disease accounted for 14%(95%Cl:9% to 21%)of the association between FGCRS and all-cause dementia.Interactions were not detected for FGCRS and PRS on the risk of any dementia subtype.We observed an 83%(95%Cl:47%to 128%)higher all-cause dementia risk comparing the high-high versus low-low FGCRS-PRS category.For brain volumes,higher FGCRS was associated with greater log-transformed white matter hyperintensities,smaller cortical volume and smaller grey matter volume.Conclusions Our findings suggest that the positive association of cardiovascular risk burden with dementia risk also applies to major dementia subtypes.The association of cardiovascular risk burden with all-cause dementia is largely independent of CVD onset and genetic predisposition to dementia.
基金supported by the National Natural Science Foundation of China(No.51975365)the Shanghai Pujiang Program(18PJ1405000)+1 种基金supported by the Natural Sciences and Engineering Research Council of Canada(NSERC)the Province of Ontario
文摘To overcome the limitation in formability at room temperature,manufacturers have developed magnesium alloys with remarkable properties by adding rare-earth elements.The rare-earth magnesium alloys behave differently from the conventional alloys,especially with respect to their coupled anisotropic and strain rate sensitive behavior.In the current work,such behavior of the rare-earth Mg alloy ZEK100 sheet at room temperature is investigated with the aid of the elastic viscoplastic self-consistent polycrystal plasticity model.Different strain rate sensitivities(SRSs)for various deformation modes are employed by the model to simulate the strain rate sensitive behaviors under different loading directions and loading rates.Good agreement between the experiments and simulations reveals the importance and necessity of using different SRSs for each deformation mode in hexagonal close-packed metals.Furthermore,the relative activities of each deformation mode and the texture evolution during different loadings are discussed.The anisotropic and strain rate sensitive behavior is ascribed to the various operating deformation modes with different SRSs during loading along different directions.
基金supported by the Department of Orthopaedic Surgery at the University of Pittsburghthe Department of Orthopaedic Surgery at Xiangya Hospital,Central South Universitypartially supported by the Pennsylvania Department of Health。
文摘In the synovial joint,mechanical force creates an important signal that influences chondrocyte behavior.The conversion of mechanical signals into biochemical cues relies on different elements in mechanotransduction pathways and culminates in changes in chondrocyte phenotype and extracellular matrix composition/structure.Recently,several mechanosensors,the first responders to mechanical force,have been discovered.However,we still have limited knowledge about the downstream molecules that enact alterations in the gene expression profile during mechanotransduction signaling.Recently,estrogen receptorα(ERα)has been shown to modulate the chondrocyte response to mechanical loading through a ligand-independent mechanism,in line with previous research showing that ERαexerts important mechanotransduction effects on other cell types,such as osteoblasts.In consideration of these recent discoveries,the goal of this review is to position ERαinto the mechanotransduction pathways known to date.Specifically,we first summarize our most recent understanding of the mechanotransduction pathways in chondrocytes on the basis of three categories of actors,namely mechanosensors,mechanotransducers,and mechanoimpactors.Then,the specific roles played by ERαin mediating the chondrocyte response to mechanical loading are discussed,and the potential interactions of ERαwith other molecules in mechanotransduction pathways are explored.Finally,we propose several future research directions that may advance our understanding of the roles played by ERαin mediating biomechanical cues under physiological and pathological conditions.
基金supported by the Air Force Office of Scientific Research under the MURI award number FA9550-20-1-0358(Machine Learning and Physics-Based Modeling and Simulation)by the Department of Energy under the award number DE-SC0023163(SEA-CROGS:Scalable,Efficient,and Accelerated Causal Reasoning Operators,Graphs and Spikes for Earth and Embedded Systems)。
文摘We present a Gaussian process(GP)approach,called Gaussian process hydrodynamics(GPH)for approximating the solution to the Euler and Navier-Stokes(NS)equations.Similar to smoothed particle hydrodynamics(SPH),GPH is a Lagrangian particle-based approach that involves the tracking of a finite number of particles transported by a flow.However,these particles do not represent mollified particles of matter but carry discrete/partial information about the continuous flow.Closure is achieved by placing a divergence-free GP priorξon the velocity field and conditioning it on the vorticity at the particle locations.Known physics(e.g.,the Richardson cascade and velocityincrement power laws)is incorporated into the GP prior by using physics-informed additive kernels.This is equivalent to expressingξas a sum of independent GPsξl,which we call modes,acting at different scales(each modeξlself-activates to represent the formation of eddies at the corresponding scales).This approach enables a quantitative analysis of the Richardson cascade through the analysis of the activation of these modes,and enables us to analyze coarse-grain turbulence statistically rather than deterministically.Because GPH is formulated by using the vorticity equations,it does not require solving a pressure equation.By enforcing incompressibility and fluid-structure boundary conditions through the selection of a kernel,GPH requires significantly fewer particles than SPH.Because GPH has a natural probabilistic interpretation,the numerical results come with uncertainty estimates,enabling their incorporation into an uncertainty quantification(UQ)pipeline and adding/removing particles(quanta of information)in an adapted manner.The proposed approach is suitable for analysis because it inherits the complexity of state-of-the-art solvers for dense kernel matrices and results in a natural definition of turbulence as information loss.Numerical experiments support the importance of selecting physics-informed kernels and illustrate the major impact of such kernels on the accuracy and stability.Because the proposed approach uses a Bayesian interpretation,it naturally enables data assimilation and predictions and estimations by mixing simulation data and experimental data.
文摘This paper presents a comprehensive study that includes the sizing and power flow by series and parallel inverters in a distributed generation system(DGs)that integrates the system of hybrid wind photovoltaic with a unified power quality conditioner(UPQC).In addition to supplying active power to the utility grid,the system of hybrid wind photovoltaic functions as a UPQC,compensating reactive power and suppressing the harmonic load currents.Additionally,the load is supplied with harmonic-free,balanced and regulated output voltages.Since PVWind-UPQC is established on a dual compensation scheme,the series inverter works like a sinusoidal current source,while the parallel inverter works like a sinusoidal voltage source.Consequently,a smooth alteration from interconnected operating modes to island operating modes and vice versa can be achieved without load voltage transients.Since PV-Wind-UPQC inverters handle the energy generated through the hybrid wind photovoltaic system and the energy demanded through the load,the converters should be sized cautiously.A detailed study of the flow of power via the PV-Wind-UPQC is imperative to gain a complete understanding of the system operation and the proper design of the converters.Thus,curves that allow the sizing of the power converters according to the power flow via the converters are presented and discussed.Simulation results are presented to assess both steady state and dynamic performances of the grid connected hybrid system of PV-Wind-UPQC.This investigation is verified by simulating and analyzing the results with Matlab/Simulink.
文摘The human immunodeficiency viruses are two species of Lentivirus that infect humans.Over time,they cause acquired immunodeficiency syndrome,a condition in which progressive immune system failure allows life-threatening opportunistic infections and cancers to thrive.Human immunodeficiency virus infection came from a type of chimpanzee in Central Africa.Studies show that immunodeficiency viruses may have jumped from chimpanzees to humans as far back as the late 1800s.Over decades,human immunodeficiency viruses slowly spread across Africa and later into other parts of the world.The Susceptible-Infected-Recovered(SIR)models are significant in studying disease dynamics.In this paper,we have studied the effect of irresponsible immigrants on HIV/AIDS dynamics by formulating and considering different methods.Euler,Runge Kutta,and a Non-standardfinite difference(NSFD)method are developed for the same problem.Numerical experiments are performed at disease-free and endemic equilibria points at different time step sizes‘ℎ’.The results reveal that,unlike Euler and Runge Kutta,which fail for large time step sizes,the proposed Non-standardfinite difference(NSFD)method gives a convergence solution for any time step size.Our proposed numerical method is bounded,dynamically con-sistent,and preserves the positivity of the continuous solution,which are essential requirements when modeling a prevalent disease.
基金This research was supported by the Veterans Administration I01 BX002104 and IK6BX004596 to T.B.R01-AR059357 to T.B.+3 种基金UAMS College of Medicine Sturgis Endowment Grant to T.B.ASH scholar award to S.M.National Center for Advancing Translational Sciences of the National Institutes of Health KL2TR003108 and UL1TR003107 to A.Y.S.National Institute of General Medical Sciences of the National Institutes of Health P20GM125503 to I.N.
文摘The mechanisms underlying the bone disease induced by diabetes are complex and not fully understood;and antiresorptive agents,the current standard of care,do not restore the weakened bone architecture.Herein,we reveal the diabetic bone signature in mice at the tissue,cell,and transcriptome levels and demonstrate that three FDA-approved bone-anabolic agents correct it.Diabetes decreased bone mineral density(BMD)and bone formation,damaged microarchitecture,increased porosity of cortical bone,and compromised bone strength.Teriparatide(PTH),abaloparatide(ABL),and romosozumab/anti-sclerostin antibody(Scl-Ab)all restored BMD and corrected the deteriorated bone architecture.Mechanistically,PTH and more potently ABL induced similar responses at the tissue and gene signature levels,increasing both formation and resorption with positive balance towards bone gain.In contrast,Scl-Ab increased formation but decreased resorption.All agents restored bone architecture,corrected cortical porosity,and improved mechanical properties of diabetic bone;and ABL and Scl-Ab increased toughness,a fracture resistance index.Remarkably,all agents increased bone strength over the healthy controls even in the presence of severe hyperglycemia.These findings demonstrate the therapeutic value of bone anabolic agents to treat diabetes-induced bone disease and suggest the need for revisiting the approaches for the treatment of bone fragility in diabetes.
文摘THE rapid growth of new energy vehicles is accelerating the low-carbon transition in the global transportation sector. According to the international energy agency report, more than 10 million electric vehicles(EVs) including pure electric and hybrid models were sold worldwide in 2022, which means that the global share of electric vehicles in the overall automotive market has risen from less than 5% in 2020 to 14% in 2022.
文摘Background In China's Mainland,patients with neovascular age-related macular degeneration(nAMD)have approximately an 40%prevalence of polypoidal choroidal vasculopathy(PCV).This disease leads to recurrent retinal pigment epithelium detachment(PED),extensive subretinal or vitreous hemorrhages,and severe vision loss.China has introduced various treatment modalities in the past years and gained comprehensive experience in treating PCV.Methods A total of 14 retinal specialists nationwide with expertise in PCV were empaneled to prioritize six questions and address their corresponding outcomes,regarding opinions on inactive PCV,choices of anti-vascular endothelial growth factor(anti-VEGF)monotherapy,photodynamic therapy(PDT)monotherapy or combined therapy,patients with persistent subretinal fluid(SRF)or intraretinal fluid(IRF)after loading dose anti-VEGF,and patients with massive subretinal hemorrhage.An evidence synthesis team conducted systematic reviews,which informed the recommendations that address these questions.This guideline used the GRADE(Grading of Recommendations,Assessment,Development,and Evaluation)approach to assess the certainty of evidence and grade the strengths of recommendations.Results The panel proposed the following six conditional recommendations regarding treatment choices.(1)For patients with inactive PCV,we suggest observation over treatment.(2)For treatment-na?ve PCV patients,we suggest either anti-VEGF monotherapy or combined anti-VEGF and PDT rather than PDT monotherapy.(3)For patients with PCV who plan to initiate combined anti-VEGF and PDT treatment,we suggest later/rescue PDT over initiate PDT.(4)For PCV patients who plan to initiate anti-VEGF monotherapy,we suggest the treat and extend(TE)regimen rather than the pro re nata(PRN)regimen following three monthly loading doses.(5)For patients with persistent SRF or IRF on optical coherence tomography(OCT)after three monthly anti-VEGF treatments,we suggest proceeding with anti-VEGF treatment rather than observation.(6)For PCV patients with massive subretinal hemorrhage(equal to or more than four optic disc areas)involving the central macula,we suggest surgery(vitrectomy in combination with tissue-plasminogen activator(tPA)intraocular injection and gas tamponade)rather than anti-VEGF monotherapy.Conclusions Six evidence-based recommendations support optimal care for PCV patients'management.
