The Lunar Environment heliospheric X-ray Imager(LEXI)and Solar wind Magnetosphere Ionosphere Link Explorer(SMILE)missions will image the Earth’s dayside magneto pause and cusps in soft X-rays after their respective l...The Lunar Environment heliospheric X-ray Imager(LEXI)and Solar wind Magnetosphere Ionosphere Link Explorer(SMILE)missions will image the Earth’s dayside magneto pause and cusps in soft X-rays after their respective launches in the near future,to specify glo bal magnetic reconnection modes for varying solar wind conditions.To suppo rt the success of these scientific missions,it is critical to develop techniques that extract the magnetopause locations from the observed soft X-ray images.In this research,we introduce a new geometric equation that calculates the subsolar magnetopause position(RS)from a satellite position,the look direction of the instrument,and the angle at which the X-ray emission is maximized.Two assumptions are used in this method:(1)The look direction where soft X-ray emissions are maximized lies tangent to the magnetopause,and(2)the magnetopause surface near the subsolar point is almost spherical and thus RSis nea rly equal to the radius of the magneto pause curvature.We create synthetic soft X-ray images by using the Open Geospace General Circulation Model(OpenGGCM)global magnetohydrodynamic model,the galactic background,the instrument point spread function,and Poisson noise.We then apply the fast Fourier transform and Gaussian low-pass filte rs to the synthetic images to re move noise and obtain accurate look angles for the soft X-ray pea ks.From the filte red images,we calculate RS and its accuracy for different LEXI locations,look directions,and solar wind densities by using the OpenGGCM subsolar magnetopause location as ground truth.Our method estimates RS with an accuracy of<0.3 RE when the solar wind density exceeds>10 cm-3.The accuracy improves for greater solar wind densities and during southward interplanetary magnetic fields.The method ca ptures the magnetopause motion during southwa rd interplaneta ry magnetic field turnings.Consequently,the technique will enable quantitative analysis of the magnetopause motion and help reveal the dayside reconnection modes for dynamic solar wind conditions.This technique will suppo rt the LEXI and SMILE missions in achieving their scientific o bjectives.展开更多
While we eagerly anticipate SMILE’s(Solar wind Magnetosphere Ionosphere Link Explorer)unprecedented X-ray observations of the Earth’s magnetosheath and the initiation of a new era of magnetospheric research,it seems...While we eagerly anticipate SMILE’s(Solar wind Magnetosphere Ionosphere Link Explorer)unprecedented X-ray observations of the Earth’s magnetosheath and the initiation of a new era of magnetospheric research,it seems appropriate to look ahead to the abilities of the next generation of astrophysics missions.Of these,the Line Emission Mapper(LEM),a large aperture micro-calorimeter based mission,is currently planned to be able to observe the magnetosheath at high spectral resolution(~2 eV).With a field of view of~30′,LEM will allow higher spatial resolution and higher cadence measurement of the motion of a very small portion of the magnetopause over relatively short periods of time(multiple hours),complementing SMILE’s global mapping.LEM’s strength is its spectral resolution.It will be able to measure the abundance of a broad range of elements and ionization states,many of which are inaccessible to current in situ instruments,and will be able to separate the emission from the magnetosheath from the emission from the cosmic X-ray background using the difference in their relative velocities.展开更多
Brain tissue requires high amounts of copper(Cu)for its key physiological processes,such as energy production,neurotransmitter synthesis,maturation of neuropeptides,myelination,synaptic plasticity,and radical scavengi...Brain tissue requires high amounts of copper(Cu)for its key physiological processes,such as energy production,neurotransmitter synthesis,maturation of neuropeptides,myelination,synaptic plasticity,and radical scavenging.The requirements for Cu in the brain vary depending on specific brain regions,cell types,organism age,and nutritional status.Cu imbalances cause or contribute to several life-threatening neurologic disorders including Menkes disease,Wilson disease,Alzheimer’s disease,Parkinson’s disease,and others.Despite the well-established role of Cu homeostasis in brain development and function,the mechanisms that govern Cu delivery to the brain are not well defined.This review summarizes available information on Cu transfer through the brain barriers and discusses issues that require further research.展开更多
Human dental pulp stem cell transplantation has been shown to be an effective therapeutic strategy for spinal cord injury.However,whether the human dental pulp stem cell secretome can contribute to functional recovery...Human dental pulp stem cell transplantation has been shown to be an effective therapeutic strategy for spinal cord injury.However,whether the human dental pulp stem cell secretome can contribute to functional recovery after spinal cord injury remains unclear.In the present study,we established a rat model of spinal cord injury based on impact injury from a dropped weight and then intraperitoneally injected the rats with conditioned medium from human dental pulp stem cells.We found that the conditioned medium effectively promoted the recovery of sensory and motor functions in rats with spinal cord injury,decreased expression of the microglial pyroptosis markers NLRP3,GSDMD,caspase-1,and interleukin-1β,promoted axonal and myelin regeneration,and inhibited the formation of glial scars.In addition,in a lipopolysaccharide-induced BV2 microglia model,conditioned medium from human dental pulp stem cells protected cells from pyroptosis by inhibiting the NLRP3/caspase-1/interleukin-1βpathway.These results indicate that conditioned medium from human dental pulp stem cells can reduce microglial pyroptosis by inhibiting the NLRP3/caspase-1/interleukin-1βpathway,thereby promoting the recovery of neurological function after spinal cord injury.Therefore,conditioned medium from human dental pulp stem cells may become an alternative therapy for spinal cord injury.展开更多
Traumatic brain injury(TBI)is an acquired injury of the brain caused by the impact of external forces on the brain(Maas et al.,2008).It is a major cause of death and disability among people of all ages(Maas et al.,200...Traumatic brain injury(TBI)is an acquired injury of the brain caused by the impact of external forces on the brain(Maas et al.,2008).It is a major cause of death and disability among people of all ages(Maas et al.,2008).The primary mechanical injury to the brain initiates a cascade of secondary biochemical events that lead to acute and chronic neurodegeneration and activation of inflammatory pathways(Maas et al.,2008).Both brain-resident microglia and blood-derived myeloid cells-macrophages and monocytes that infiltrate the brain due to injury-induced blood-brain barrier damage,contribute to the inflammatory responses after TBI(Morganti et al.,2015).展开更多
Bone is a mechanosensitive tissue and undergoes constant remodeling to adapt to the mechanical loading environment.However,it is unclear whether the signals of bone cells in response to mechanical stress are processed...Bone is a mechanosensitive tissue and undergoes constant remodeling to adapt to the mechanical loading environment.However,it is unclear whether the signals of bone cells in response to mechanical stress are processed and interpreted in the brain.In this study,we found that the hypothalamus of the brain regulates bone remodeling and structure by perceiving bone prostaglandin E2(PGE2)concentration in response to mechanical loading.Bone PGE2 levels are in proportion to their weight bearing.When weight bearing changes in the tail-suspension mice,the PGE2 concentrations in bones change in line with their weight bearing changes.Deletion of cyclooxygenase-2(COX2)in the osteoblast lineage cells or knockout of receptor 4(EP4)in sensory nerve blunts bone formation in response to mechanical loading.Moreover,knockout of TrkA in sensory nerve also significantly reduces mechanical load-induced bone formation.Moreover,mechanical loading induces cAMP-response element binding protein(CREB)phosphorylation in the hypothalamic arcuate nucleus(ARC)to inhibit sympathetic tyrosine hydroxylase(TH)expression in the paraventricular nucleus(PVN)for osteogenesis.Finally,we show that elevated PGE2 is associated with ankle osteoarthritis(AOA)and pain.Together,our data demonstrate that in response to mechanical loading,skeletal interoception occurs in the form of hypothalamic processing of PGE2-driven peripheral signaling to maintain physiologic bone homeostasis,while chronically elevated PGE2 can be sensed as pain during AOA and implication of potential treatment.展开更多
Traumatic spinal cord injury(SCI)is a devastating exogenous injury with long-lasting consequences and a leading cause of death and disability worldwide.Advances in assistive technology,rehabilitative interventions,and...Traumatic spinal cord injury(SCI)is a devastating exogenous injury with long-lasting consequences and a leading cause of death and disability worldwide.Advances in assistive technology,rehabilitative interventions,and the ability to identify and intervene in secondary conditions have significantly increased the long-term survival rate of SCI patients,with some people even living well into their seventh or eighth decade.These survival changes have led neurotrauma researchers to examine how SCI interacts with brain aging.Public health and epidemiological data showed that patients with long-term SCI can have a lower life expectancy and quality of life,along with a higher risk of comorbidities and complications.展开更多
BACKGROUND:Traumatic cardiac arrest(TCA)is a major contributor to mortality and morbidity in all age groups and poses a significant burden on the healthcare system.Although there have been advances in treatment modali...BACKGROUND:Traumatic cardiac arrest(TCA)is a major contributor to mortality and morbidity in all age groups and poses a significant burden on the healthcare system.Although there have been advances in treatment modalities,survival rates for TCA patients remain low.This narrative literature review critically examines the indications and eff ectiveness of current therapeutic approaches in treating TCA.METHODS:We performed a literature search in the PubMed and Scopus databases for studies published before December 31,2022.The search was refi ned by combining search terms,examining relevant study references,and restricting publications to the English language.Following the search,943 articles were retrieved,and two independent reviewers conducted a screening process.RESULTS:A review of various studies on pre-and intra-arrest prognostic factors showed that survival rates were higher when patients had an initial shockable rhythm.There were conflicting results regarding other prognostic factors,such as witnessed arrest,bystander cardiopulmonary resuscitation(CPR),and the use of prehospital or in-hospital epinephrine.Emergency thoracotomy was found to result in more favorable outcomes in cases of penetrating trauma than in those with blunt trauma.Resuscitative endovascular balloon occlusion of the aorta(REBOA)provides an advantage to emergency thoracotomy in terms of occupational safety for the operator as an alternative in managing hemorrhagic shock.When implemented in the setting of aortic occlusion,emergency thoracotomy and REBOA resulted in comparable mortality rates.Veno-venous extracorporeal life support(V-V ECLS)and veno-arterial extracorporeal life support(V-A ECLS)are viable options for treating respiratory failure and cardiogenic shock,respectively.In the context of traumatic injuries,V-V ECLS has been associated with higher rates of survival to discharge than V-A ECLS.CONCLUSION:TCA remains a signifi cant challenge for emergency medical services due to its high morbidity and mortality rates.Pre-and intra-arrest prognostic factors can help identify patients who are likely to benefit from aggressive and resource-intensive resuscitation measures.Further research is needed to enhance guidelines for the clinical use of established and emerging therapeutic approaches that can help optimize treatment effi cacy and ameliorate survival outcomes.展开更多
Neurons are highly polarized,morphologically asymmetric,and functionally compartmentalized cells that contain long axons extending from the cell body.For this reason,their maintenance relies on spatiotemporal regulati...Neurons are highly polarized,morphologically asymmetric,and functionally compartmentalized cells that contain long axons extending from the cell body.For this reason,their maintenance relies on spatiotemporal regulation of organelle distribution between the somatodendritic and axonal domains.Although some organelles,such as mitochondria and smooth endoplasmic reticulum,are widely distributed throughout the neuron,others are segregated to either the somatodendritic or axonal compartment.For example,Golgi outposts and acidified lysosomes are predominantly present in the somatodendritic domain and rarely distributed along the axon,whereas newly formed autophagosomes and synaptic vesicles are mainly distributed in the distal axon(Britt et al.,2016).展开更多
Neurological disorders are a diverse group of conditions that affect the nervous system and include neurodegenerative diseases(Alzheimer’s disease,multiple sclerosis,Parkinson’s disease,Huntington’s disease),cerebr...Neurological disorders are a diverse group of conditions that affect the nervous system and include neurodegenerative diseases(Alzheimer’s disease,multiple sclerosis,Parkinson’s disease,Huntington’s disease),cerebrovascular conditions(stroke),and neurodevelopmental disorders(autism spectrum disorder).Although they affect millions of individuals around the world,only a limited number of effective treatment options are available today.Since most neurological disorders express mitochondria-related metabolic perturbations,metformin,a biguanide type II antidiabetic drug,has attracted a lot of attention to be repurposed to treat neurological disorders by correcting their perturbed energy metabolism.However,controversial research emerges regarding the beneficial/detrimental effects of metformin on these neurological disorders.Given that most neurological disorders have complex etiology in their pathophysiology and are influenced by various risk factors such as aging,lifestyle,genetics,and environment,it is important to identify perturbed molecular functions that can be targeted by metformin in these neurological disorders.These molecules can then be used as biomarkers to stratify subpopulations of patients who show distinct molecular/pathological properties and can respond to metformin treatment,ultimately developing targeted therapy.In this review,we will discuss mitochondria-related metabolic perturbations and impaired molecular pathways in these neurological disorders and how these can be used as biomarkers to guide metformin-responsive treatment for the targeted therapy to treat neurological disorders.展开更多
BACKGROUND The Limb Lengthening and Reconstruction Society(LLRS)is a premier orthopedic specialty organization that promotes limb reconstruction for all ages.LLRS membership characteristics,however,are poorly reported...BACKGROUND The Limb Lengthening and Reconstruction Society(LLRS)is a premier orthopedic specialty organization that promotes limb reconstruction for all ages.LLRS membership characteristics,however,are poorly reported.This study delineates orthopedic surgeon LLRS members’demographic traits,academic achievement,leadership attainment,and geographical distribution across the United States.AIM To inform aspiring orthopedic professionals,as well as to promote growth and diversity in both the LLRS organization and overarching field.METHODS This cross-sectional study examined United States LLRS members’academic,leadership,demographic,and geographical attributes.After reviewing the 2023 LLRS member directory,Google search results were matched to the listings and appended to the compiled data.Sex and ethnicity were evaluated visually utilizing retrieved images.The Hirsch index(H-index)of academic activity,residency and fellowship training,other graduate degrees,leadership positions,practice type(academic or non-academic),and spoken languages were categorized.LLRS members per state and capita determined geographic distribution.The Mann Whitney U test was applied to compare H-index between males and females,as well as to assess member differences pertaining to affiliation with academic vs non-academic practice facilities.RESULTS The study included 101 orthopedic surgeons,78(77.23%)Caucasian and 23(22.77%)non-Caucasian,79(78.22%)male and 22(21.78%)female.Surgeons with DO degrees comprised only 3.96%(4)of the cohort,while the vast majority held MDs[96.04%(97)].Mean H-index was 10.55,with male surgeons having a significantly higher score(P=0.002).Most orthopedic surgeons(88.12%,)practiced in academic centers.Of those professionals who occupied leadership positions,14%were women,while 86%were men.Additionally,19(37.25%)United States regions and the District of Columbia lacked an LLRS-member orthopedic surgeon.Total per capita rate across the United States was 0.30 LLRS orthopedic surgeons per 1 million people.CONCLUSION Over 21%of LLRS members are women,surpassing prior benchmarks noted in orthopedic faculty reporting.LLRS members’high research productivity scores imply field dedication that can refine expertise in the limb lengthening and reconstruction space.Gender disparities in leadership remain,however,necessitating greater equity efforts.A low rate of LLRS representation per capita must be addressed geographically as well,to affect improvements in regional care access.This study can serve to support aspiring orthopedic professionals,inform diversity,leadership,and field advancement strategies,and maintain the continued goal of enhanced patient care worldwide.展开更多
Glucagon-like peptide receptor agonists(GLP-1RA)are used to treat type 2 diabetes mellitus and,more recently,have garnered attention for their effect-iveness in promoting weight loss.They have been associated with sev...Glucagon-like peptide receptor agonists(GLP-1RA)are used to treat type 2 diabetes mellitus and,more recently,have garnered attention for their effect-iveness in promoting weight loss.They have been associated with several gastrointestinal adverse effects,including nausea and vomiting.These side effects are presumed to be due to increased residual gastric contents.Given the potential risk of aspiration and based on limited data,the American Society of Anesthesi-ologists updated the guidelines concerning the preoperative management of patients on GLP-1RA in 2023.They included the duration of mandated cessation of GLP-1RA before sedation and usage of“full stomach”precautions if these medications were not appropriately held before the procedure.This has led to additional challenges,such as extended waiting time,higher costs,and increased risk for patients.In this editorial,we review the current societal guidelines,clinical practice,and future directions regarding the usage of GLP-1RA in patients undergoing an endoscopic procedure.展开更多
Hepatitis E virus(HEV)is hyperendemic in South Asia and Africa accounting for half of total Global HEV burden.There are eight genotypes of HEV.Among them,the four common ones known to infect humans,genotypes 1 and 2 a...Hepatitis E virus(HEV)is hyperendemic in South Asia and Africa accounting for half of total Global HEV burden.There are eight genotypes of HEV.Among them,the four common ones known to infect humans,genotypes 1 and 2 are prevalent in the developing world and genotypes 3 and 4 are causing challenge in the industrialized world.Asymptomatic HEV viremia in the general population,especially among blood donors,has been reported in the literature worldwide.The clinical implications related to this asymptomatic viremia are unclear and need further exploration.Detection of viremia due to HEV genotype 1 infection,apparently among healthy blood donors is also reported without much knowledge about its infection rate.Similarly,while HEV genotype 3 is known to be transmitted via blood transfusion in humans and has been subjected to screening in many European nations,instances of transmission have also been documented albeit without significant clinical consequences.Epidemiology of HEV genotype 1 in endemic areas often show waxing and waning pattern.Occasional sporadic occurrence of HEV infection interrupted by outbreaks have been frequently seen.In absence of known animal reservoir,where HEV exists in between outbreak is a mystery that needs further exploration.However,occurrence of asymptomatic HEV viremia due to HEV genotype 1 during epidemiologically quiescent period may explain that this phenomenon may act as a dynamic reservoir.Since HEV genotype 1 infection cannot cause chronicity,subclinical transient infection and transmission of virus might be the reason it sustains in interepidemic period.This might be the similar phenomenon with SARS COVID-19 corona virus infection which is circulating worldwide in distinct phases with peaks and plateaus despite vaccination against it.In view of existing evidence,we propose the concept of“Dynamic Human Reservoir.”Quiescent subclinical infection of HEV without any clinical consequences and subsequent transmission may contribute to the existence of the virus in a community.The potential for transmitting HEV infection by asymptomatic HEV infected individuals by fecal shedding of virus has not been reported in literature.This missing link may be a key to Pandora's box in understanding epidemiology of HEV infection in genotype 1 predominant region.展开更多
Background Little is known about the association between stressors(especially positive stressors)during pregnancy and postpartum depression and anxiety.Aims We investigated the association between positive and negativ...Background Little is known about the association between stressors(especially positive stressors)during pregnancy and postpartum depression and anxiety.Aims We investigated the association between positive and negative stress events during different stages of pregnancy and postpartum mental health outcomes among low-income pregnant women with symptoms of anxiety in Pakistan and evaluated whether an intervention based on cognitive behavioural therapy(CBT)had a regulatory effect.Methods Participants were 621 pregnant Pakistani women with mild anxiety.Using the Pregnancy Experience Scale-Brief Version,six scores were created to assess positive and negative stressors.We performed a multivariate linear regression to examine whether these six scores,measured both at baseline and in the third trimester,were associated with postpartum anxiety and depressive symptoms.The effect of the intervention on this relationship was examined by adding an interaction term to the regression model.Results Hassles frequency measured in the third trimester was positively associated with depression(B=0.22,95%confidence interval(Cl):0.09 to 0.36)and anxiety(B=0.19,95%Cl:0.08to 0.30).At the same timepoint,uplifts intensity was negatively associated with symptoms of depression(B=-0.82,95%Cl:1.46 to-0.18)and anxiety(B=-0.70,95%Cl:-1.25 to-0.15),whereas hassles intensity was positively related to symptoms of depression(B=1.02,95%Cl:0.36 to 1.67)and anxiety(B=0.90,95%Cl:0.34 to 1.47).The intensity ratio of hassles to uplifts reported in the third trimester was positively related to both depression(B=1.40,95%Cl:0.59 to 2.20)and anxiety(B=1.26,95%Cl:0.57 to 1.96).The intervention strengthened the overall positive effects of uplfts and the negative effects of hassles.Pregnancy experiences at baseline during early pregnancy to mid-pregnancy were not associated with mental health outcomes.Conclusions Stressors in the third trimester but not earlier in pregnancy were associated with postpartum symptoms of anxiety and depression.The CBT intervention modified the association between pregnancy stressors and postpartum mental health outcomes.Programmes that promote positive experiences and reduce negative experiences,especially in late pregnancy,may mitigate postpartum mental health consequences.展开更多
Objective: To analyze outcomes and complications of cytoreductive prostatectomy (CRP) for oligometastatic prostate cancer (PCa) in order to elucidate its role in this space.Methods: We performed a systematic literatur...Objective: To analyze outcomes and complications of cytoreductive prostatectomy (CRP) for oligometastatic prostate cancer (PCa) in order to elucidate its role in this space.Methods: We performed a systematic literature search using three databases (Medline, Scopus, and Web of Science). The primary endpoints were oncologic outcomes. The secondary endpoints were complication rates and functional results.Results: In all studies, overall survival was better or at least comparable variable in the groups with CRP compared to no local treatment. The greatest benefit from CRP in 5-year overall survival in one study was 67.4% for CRP versus 22.5% for no local treatment. Cancer-specific survival (CSS) showed the same trend. Several authors found significant benefits from CSS in the CRP group: from 79% vs. 46% to 100% vs. 61%. CRP was a predictor of better CSS (hazard ratio 0.264, p=0.004). Positive surgical margin rates differed widely from 28.6% to 100.0%. Urinary continence in CRP versus RP for localized PCa was significantly lower (57.4% vs. 90.8%, p<0.0001). Severe incontinence occurred seldom (2.5%-18.6%). Total complication rates after CRP differed widely, from 7.0% to 43.6%. Rates of grades 1 and 2 events prevailed. Patients on ADT alone also showed a considerable number of complications varying from 5.9% to 57.7%.Conclusion: CRP improves medium-term cancer control in patients with oligometastatic PCa. The morbidity and complication rates of this surgery are comparable with other approaches, but postoperative incontinence rate is higher compared with RP for localized disease.展开更多
BACKGROUND Despite advances in detection and treatments,biliary tract cancers continue to have poor survival outcomes.Currently,there is limited data investigating the significance of socioeconomic status,race/ethnici...BACKGROUND Despite advances in detection and treatments,biliary tract cancers continue to have poor survival outcomes.Currently,there is limited data investigating the significance of socioeconomic status,race/ethnicity,and environmental factors in biliary tract cancer survival.Data from the Surveillance,Epidemiology,and End Results database for biliary and gallbladder adenocarcinomas were extracted from 1975 to 2016.Socioe-conomic data included smoking,poverty level,education,adjusted household income,and percentage of foreign-born persons and urban population.Survival was calculated with Cox proportional hazards models for death in the 5-year period following diagnosis.RESULTS Our study included 15883 gallbladder,11466 intrahepatic biliary,12869 extrahepatic biliary and 7268 ampulla of Vater adenocarcinoma cases.When analyzing county-specific demographics,patients from counties with higher incomes were associated with higher survival rates[hazard ratio(HR)=0.97,P<0.05].Similarly,counties with a higher percentage of patients with a college level education and counties with a higher urban population had higher 5-year survival rates(HR=0.96,P=0.002 and HR=0.97,P=0.004,respectively).CONCLUSION Worse survival outcomes were observed in lower income counties while higher income and education level were associated with higher 5-year overall survival among gallbladder and biliary malignancies.展开更多
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(RAN...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.展开更多
AIM:To explore the usage of choroidal thickness measured by swept-source optical coherence tomography(SS-OCT)to detect myopic macular degeneration(MMD)in high myopic participants.METHODS:Participants with bilateral hi...AIM:To explore the usage of choroidal thickness measured by swept-source optical coherence tomography(SS-OCT)to detect myopic macular degeneration(MMD)in high myopic participants.METHODS:Participants with bilateral high myopia(≤−6 diopters)were recruited from a subset of the Guangzhou Zhongshan Ophthalmic Center-Brien Holden Vision Institute High Myopia Cohort Study.SS-OCT was performed to determine the choroidal thickness,and myopic maculopathy was graded by the International Meta-Analysis for Pathologic Myopia(META-PM)Classification.Presence of MMD was defined as META-PM category 2 or above.RESULTS:A total of 568 right eyes were included for analysis.Eyes with MMD(n=106,18.7%)were found to have older age,longer axial lengths(AL),higher myopic spherical equivalents(SE),and reduced choroidal thickness in each Early Treatment Diabetic Retinopathy Study(ETDRS)grid sector(P<0.001).The area under the receiver operating characteristic(ROC)curves(AUC)for subfoveal choroidal thickness(0.907)was greater than that of the model,including age,AL,and SE at 0.6249,0.8208,and 0.8205,respectively.The choroidal thickness of the inner and outer nasal sectors was the most accurate indicator of MMD(AUC of 0.928 and 0.923,respectively).An outer nasal sector choroidal thickness of less than 74μm demonstrated the highest odds of predicting MMD(OR=33.8).CONCLUSION:Choroidal thickness detects the presence of MMD with high agreement,particularly of the inner and outer nasal sectors of the posterior pole,which appears to be a biometric parameter more precise than age,AL,or SE.展开更多
This paper explains various factors that contribute to saltwater intrusion, including overexploitation of freshwater resources and climate change as well as the different techniques essential for effective saltwater i...This paper explains various factors that contribute to saltwater intrusion, including overexploitation of freshwater resources and climate change as well as the different techniques essential for effective saltwater intrusion management. The impact of saltwater intrusion along coastal regions and its impact on the environment, hydrogeology and groundwater contamination. It suggests potential solutions to mitigate the impact of saltwater intrusion, including effective water management and techniques for managing SWI. The application of A.I (assessment index) serves as a guideline to correctly identify wells with SWI ranging from no intrusion, slight intrusion and strong intrusion. The challenges of saltwater intrusion in Lagos and the salinization of wells were investigated using the hydro-chemical parameters. The study identifies four wells (“AA”, “CMS”, “OBA” and “VIL”) as having high electric conductivities, indicating saline water intrusion, while other wells (“EBM”, “IKJ, and “IKO”) with lower electric conductivities, indicate little or no salt-water intrusion, and “AJ” well shows slight intrusion. The elevation of the wells also played a vital role in the SWI across coastal regions of Lagos. The study recommends continuous monitoring of coastal wells to help sustain and reduce saline intrusion. The findings of the study are important for policymakers, researchers, and practitioners who are interested in addressing the challenges of saltwater intrusion along coastal regions. We assessed the SWI across the eight (8) wells using the Assessment Index to identify wells with SWI. Wells in “CMS” and “VIL” has strong intrusions. A proposed classification system based on specific ion ratios categorizes water quality from good (+) to highly (-) contaminated (refer to Table 4). These findings underscore the need for attention and effective management strategies to address groundwater unsuitability for various purposes.展开更多
Gesture detection is the primary and most significant step for sign language detection and sign language is the communication medium for people with speaking and hearing disabilities. This paper presents a novel metho...Gesture detection is the primary and most significant step for sign language detection and sign language is the communication medium for people with speaking and hearing disabilities. This paper presents a novel method for dynamic hand gesture detection using Hidden Markov Models (HMMs) where we detect different English alphabet letters by tracing hand movements. The process involves skin color-based segmentation for hand isolation in video frames, followed by morphological operations to enhance image trajectories. Our system employs hand tracking and trajectory smoothing techniques, such as the Kalman filter, to monitor hand movements and refine gesture paths. Quantized sequences are then analyzed using the Baum-Welch Re-estimation Algorithm, an HMM-based approach. A maximum likelihood classifier is used to identify the most probable letter from the test sequences. Our method demonstrates significant improvements over traditional recognition techniques in real-time, automatic hand gesture recognition, particularly in its ability to distinguish complex gestures. The experimental results confirm the effectiveness of our approach in enhancing gesture-based sign language detection to alleviate the barrier between the deaf and hard-of-hearing community and general people.展开更多
基金supported by NASA(Grant Nos.80NSSC19K0844,80NSSC20K1670,80MSFC20C0019,and 80GSFC21M0002)support from NASA Goddard Space Flight Center internal funding programs(HIF,Internal Scientist Funding Model,and Internal Research and Development)。
文摘The Lunar Environment heliospheric X-ray Imager(LEXI)and Solar wind Magnetosphere Ionosphere Link Explorer(SMILE)missions will image the Earth’s dayside magneto pause and cusps in soft X-rays after their respective launches in the near future,to specify glo bal magnetic reconnection modes for varying solar wind conditions.To suppo rt the success of these scientific missions,it is critical to develop techniques that extract the magnetopause locations from the observed soft X-ray images.In this research,we introduce a new geometric equation that calculates the subsolar magnetopause position(RS)from a satellite position,the look direction of the instrument,and the angle at which the X-ray emission is maximized.Two assumptions are used in this method:(1)The look direction where soft X-ray emissions are maximized lies tangent to the magnetopause,and(2)the magnetopause surface near the subsolar point is almost spherical and thus RSis nea rly equal to the radius of the magneto pause curvature.We create synthetic soft X-ray images by using the Open Geospace General Circulation Model(OpenGGCM)global magnetohydrodynamic model,the galactic background,the instrument point spread function,and Poisson noise.We then apply the fast Fourier transform and Gaussian low-pass filte rs to the synthetic images to re move noise and obtain accurate look angles for the soft X-ray pea ks.From the filte red images,we calculate RS and its accuracy for different LEXI locations,look directions,and solar wind densities by using the OpenGGCM subsolar magnetopause location as ground truth.Our method estimates RS with an accuracy of<0.3 RE when the solar wind density exceeds>10 cm-3.The accuracy improves for greater solar wind densities and during southward interplanetary magnetic fields.The method ca ptures the magnetopause motion during southwa rd interplaneta ry magnetic field turnings.Consequently,the technique will enable quantitative analysis of the magnetopause motion and help reveal the dayside reconnection modes for dynamic solar wind conditions.This technique will suppo rt the LEXI and SMILE missions in achieving their scientific o bjectives.
基金financial support from CNES via its Sun-Heliosphere-Magnetosphere(SHM)programsupport from NASA grant#80NSSC20K1709。
文摘While we eagerly anticipate SMILE’s(Solar wind Magnetosphere Ionosphere Link Explorer)unprecedented X-ray observations of the Earth’s magnetosheath and the initiation of a new era of magnetospheric research,it seems appropriate to look ahead to the abilities of the next generation of astrophysics missions.Of these,the Line Emission Mapper(LEM),a large aperture micro-calorimeter based mission,is currently planned to be able to observe the magnetosheath at high spectral resolution(~2 eV).With a field of view of~30′,LEM will allow higher spatial resolution and higher cadence measurement of the motion of a very small portion of the magnetopause over relatively short periods of time(multiple hours),complementing SMILE’s global mapping.LEM’s strength is its spectral resolution.It will be able to measure the abundance of a broad range of elements and ionization states,many of which are inaccessible to current in situ instruments,and will be able to separate the emission from the magnetosheath from the emission from the cosmic X-ray background using the difference in their relative velocities.
基金supported by the National Institute of Health grant R01 GM101502(to SL).
文摘Brain tissue requires high amounts of copper(Cu)for its key physiological processes,such as energy production,neurotransmitter synthesis,maturation of neuropeptides,myelination,synaptic plasticity,and radical scavenging.The requirements for Cu in the brain vary depending on specific brain regions,cell types,organism age,and nutritional status.Cu imbalances cause or contribute to several life-threatening neurologic disorders including Menkes disease,Wilson disease,Alzheimer’s disease,Parkinson’s disease,and others.Despite the well-established role of Cu homeostasis in brain development and function,the mechanisms that govern Cu delivery to the brain are not well defined.This review summarizes available information on Cu transfer through the brain barriers and discusses issues that require further research.
基金supported by the Research Foundation of Technology Committee of Tongzhou District,No.KJ2019CX001(to SX).
文摘Human dental pulp stem cell transplantation has been shown to be an effective therapeutic strategy for spinal cord injury.However,whether the human dental pulp stem cell secretome can contribute to functional recovery after spinal cord injury remains unclear.In the present study,we established a rat model of spinal cord injury based on impact injury from a dropped weight and then intraperitoneally injected the rats with conditioned medium from human dental pulp stem cells.We found that the conditioned medium effectively promoted the recovery of sensory and motor functions in rats with spinal cord injury,decreased expression of the microglial pyroptosis markers NLRP3,GSDMD,caspase-1,and interleukin-1β,promoted axonal and myelin regeneration,and inhibited the formation of glial scars.In addition,in a lipopolysaccharide-induced BV2 microglia model,conditioned medium from human dental pulp stem cells protected cells from pyroptosis by inhibiting the NLRP3/caspase-1/interleukin-1βpathway.These results indicate that conditioned medium from human dental pulp stem cells can reduce microglial pyroptosis by inhibiting the NLRP3/caspase-1/interleukin-1βpathway,thereby promoting the recovery of neurological function after spinal cord injury.Therefore,conditioned medium from human dental pulp stem cells may become an alternative therapy for spinal cord injury.
基金supported by NIH funding(R01NS091218 and R01NS115876)to MML.
文摘Traumatic brain injury(TBI)is an acquired injury of the brain caused by the impact of external forces on the brain(Maas et al.,2008).It is a major cause of death and disability among people of all ages(Maas et al.,2008).The primary mechanical injury to the brain initiates a cascade of secondary biochemical events that lead to acute and chronic neurodegeneration and activation of inflammatory pathways(Maas et al.,2008).Both brain-resident microglia and blood-derived myeloid cells-macrophages and monocytes that infiltrate the brain due to injury-induced blood-brain barrier damage,contribute to the inflammatory responses after TBI(Morganti et al.,2015).
基金This research was supported by NIH National Institute on Aging under Award Number R01 AG076783,R01 AG068997 and P01 AG066603(to X.C.).
文摘Bone is a mechanosensitive tissue and undergoes constant remodeling to adapt to the mechanical loading environment.However,it is unclear whether the signals of bone cells in response to mechanical stress are processed and interpreted in the brain.In this study,we found that the hypothalamus of the brain regulates bone remodeling and structure by perceiving bone prostaglandin E2(PGE2)concentration in response to mechanical loading.Bone PGE2 levels are in proportion to their weight bearing.When weight bearing changes in the tail-suspension mice,the PGE2 concentrations in bones change in line with their weight bearing changes.Deletion of cyclooxygenase-2(COX2)in the osteoblast lineage cells or knockout of receptor 4(EP4)in sensory nerve blunts bone formation in response to mechanical loading.Moreover,knockout of TrkA in sensory nerve also significantly reduces mechanical load-induced bone formation.Moreover,mechanical loading induces cAMP-response element binding protein(CREB)phosphorylation in the hypothalamic arcuate nucleus(ARC)to inhibit sympathetic tyrosine hydroxylase(TH)expression in the paraventricular nucleus(PVN)for osteogenesis.Finally,we show that elevated PGE2 is associated with ankle osteoarthritis(AOA)and pain.Together,our data demonstrate that in response to mechanical loading,skeletal interoception occurs in the form of hypothalamic processing of PGE2-driven peripheral signaling to maintain physiologic bone homeostasis,while chronically elevated PGE2 can be sensed as pain during AOA and implication of potential treatment.
基金supported by NIH funding(RF1NS110637,2RF1NS094527,R01NS110635)to JW.
文摘Traumatic spinal cord injury(SCI)is a devastating exogenous injury with long-lasting consequences and a leading cause of death and disability worldwide.Advances in assistive technology,rehabilitative interventions,and the ability to identify and intervene in secondary conditions have significantly increased the long-term survival rate of SCI patients,with some people even living well into their seventh or eighth decade.These survival changes have led neurotrauma researchers to examine how SCI interacts with brain aging.Public health and epidemiological data showed that patients with long-term SCI can have a lower life expectancy and quality of life,along with a higher risk of comorbidities and complications.
文摘BACKGROUND:Traumatic cardiac arrest(TCA)is a major contributor to mortality and morbidity in all age groups and poses a significant burden on the healthcare system.Although there have been advances in treatment modalities,survival rates for TCA patients remain low.This narrative literature review critically examines the indications and eff ectiveness of current therapeutic approaches in treating TCA.METHODS:We performed a literature search in the PubMed and Scopus databases for studies published before December 31,2022.The search was refi ned by combining search terms,examining relevant study references,and restricting publications to the English language.Following the search,943 articles were retrieved,and two independent reviewers conducted a screening process.RESULTS:A review of various studies on pre-and intra-arrest prognostic factors showed that survival rates were higher when patients had an initial shockable rhythm.There were conflicting results regarding other prognostic factors,such as witnessed arrest,bystander cardiopulmonary resuscitation(CPR),and the use of prehospital or in-hospital epinephrine.Emergency thoracotomy was found to result in more favorable outcomes in cases of penetrating trauma than in those with blunt trauma.Resuscitative endovascular balloon occlusion of the aorta(REBOA)provides an advantage to emergency thoracotomy in terms of occupational safety for the operator as an alternative in managing hemorrhagic shock.When implemented in the setting of aortic occlusion,emergency thoracotomy and REBOA resulted in comparable mortality rates.Veno-venous extracorporeal life support(V-V ECLS)and veno-arterial extracorporeal life support(V-A ECLS)are viable options for treating respiratory failure and cardiogenic shock,respectively.In the context of traumatic injuries,V-V ECLS has been associated with higher rates of survival to discharge than V-A ECLS.CONCLUSION:TCA remains a signifi cant challenge for emergency medical services due to its high morbidity and mortality rates.Pre-and intra-arrest prognostic factors can help identify patients who are likely to benefit from aggressive and resource-intensive resuscitation measures.Further research is needed to enhance guidelines for the clinical use of established and emerging therapeutic approaches that can help optimize treatment effi cacy and ameliorate survival outcomes.
基金supported by the Merkin PNNR Center(23-DF/C2/261)(to HS).
文摘Neurons are highly polarized,morphologically asymmetric,and functionally compartmentalized cells that contain long axons extending from the cell body.For this reason,their maintenance relies on spatiotemporal regulation of organelle distribution between the somatodendritic and axonal domains.Although some organelles,such as mitochondria and smooth endoplasmic reticulum,are widely distributed throughout the neuron,others are segregated to either the somatodendritic or axonal compartment.For example,Golgi outposts and acidified lysosomes are predominantly present in the somatodendritic domain and rarely distributed along the axon,whereas newly formed autophagosomes and synaptic vesicles are mainly distributed in the distal axon(Britt et al.,2016).
文摘Neurological disorders are a diverse group of conditions that affect the nervous system and include neurodegenerative diseases(Alzheimer’s disease,multiple sclerosis,Parkinson’s disease,Huntington’s disease),cerebrovascular conditions(stroke),and neurodevelopmental disorders(autism spectrum disorder).Although they affect millions of individuals around the world,only a limited number of effective treatment options are available today.Since most neurological disorders express mitochondria-related metabolic perturbations,metformin,a biguanide type II antidiabetic drug,has attracted a lot of attention to be repurposed to treat neurological disorders by correcting their perturbed energy metabolism.However,controversial research emerges regarding the beneficial/detrimental effects of metformin on these neurological disorders.Given that most neurological disorders have complex etiology in their pathophysiology and are influenced by various risk factors such as aging,lifestyle,genetics,and environment,it is important to identify perturbed molecular functions that can be targeted by metformin in these neurological disorders.These molecules can then be used as biomarkers to stratify subpopulations of patients who show distinct molecular/pathological properties and can respond to metformin treatment,ultimately developing targeted therapy.In this review,we will discuss mitochondria-related metabolic perturbations and impaired molecular pathways in these neurological disorders and how these can be used as biomarkers to guide metformin-responsive treatment for the targeted therapy to treat neurological disorders.
文摘BACKGROUND The Limb Lengthening and Reconstruction Society(LLRS)is a premier orthopedic specialty organization that promotes limb reconstruction for all ages.LLRS membership characteristics,however,are poorly reported.This study delineates orthopedic surgeon LLRS members’demographic traits,academic achievement,leadership attainment,and geographical distribution across the United States.AIM To inform aspiring orthopedic professionals,as well as to promote growth and diversity in both the LLRS organization and overarching field.METHODS This cross-sectional study examined United States LLRS members’academic,leadership,demographic,and geographical attributes.After reviewing the 2023 LLRS member directory,Google search results were matched to the listings and appended to the compiled data.Sex and ethnicity were evaluated visually utilizing retrieved images.The Hirsch index(H-index)of academic activity,residency and fellowship training,other graduate degrees,leadership positions,practice type(academic or non-academic),and spoken languages were categorized.LLRS members per state and capita determined geographic distribution.The Mann Whitney U test was applied to compare H-index between males and females,as well as to assess member differences pertaining to affiliation with academic vs non-academic practice facilities.RESULTS The study included 101 orthopedic surgeons,78(77.23%)Caucasian and 23(22.77%)non-Caucasian,79(78.22%)male and 22(21.78%)female.Surgeons with DO degrees comprised only 3.96%(4)of the cohort,while the vast majority held MDs[96.04%(97)].Mean H-index was 10.55,with male surgeons having a significantly higher score(P=0.002).Most orthopedic surgeons(88.12%,)practiced in academic centers.Of those professionals who occupied leadership positions,14%were women,while 86%were men.Additionally,19(37.25%)United States regions and the District of Columbia lacked an LLRS-member orthopedic surgeon.Total per capita rate across the United States was 0.30 LLRS orthopedic surgeons per 1 million people.CONCLUSION Over 21%of LLRS members are women,surpassing prior benchmarks noted in orthopedic faculty reporting.LLRS members’high research productivity scores imply field dedication that can refine expertise in the limb lengthening and reconstruction space.Gender disparities in leadership remain,however,necessitating greater equity efforts.A low rate of LLRS representation per capita must be addressed geographically as well,to affect improvements in regional care access.This study can serve to support aspiring orthopedic professionals,inform diversity,leadership,and field advancement strategies,and maintain the continued goal of enhanced patient care worldwide.
文摘Glucagon-like peptide receptor agonists(GLP-1RA)are used to treat type 2 diabetes mellitus and,more recently,have garnered attention for their effect-iveness in promoting weight loss.They have been associated with several gastrointestinal adverse effects,including nausea and vomiting.These side effects are presumed to be due to increased residual gastric contents.Given the potential risk of aspiration and based on limited data,the American Society of Anesthesi-ologists updated the guidelines concerning the preoperative management of patients on GLP-1RA in 2023.They included the duration of mandated cessation of GLP-1RA before sedation and usage of“full stomach”precautions if these medications were not appropriately held before the procedure.This has led to additional challenges,such as extended waiting time,higher costs,and increased risk for patients.In this editorial,we review the current societal guidelines,clinical practice,and future directions regarding the usage of GLP-1RA in patients undergoing an endoscopic procedure.
文摘Hepatitis E virus(HEV)is hyperendemic in South Asia and Africa accounting for half of total Global HEV burden.There are eight genotypes of HEV.Among them,the four common ones known to infect humans,genotypes 1 and 2 are prevalent in the developing world and genotypes 3 and 4 are causing challenge in the industrialized world.Asymptomatic HEV viremia in the general population,especially among blood donors,has been reported in the literature worldwide.The clinical implications related to this asymptomatic viremia are unclear and need further exploration.Detection of viremia due to HEV genotype 1 infection,apparently among healthy blood donors is also reported without much knowledge about its infection rate.Similarly,while HEV genotype 3 is known to be transmitted via blood transfusion in humans and has been subjected to screening in many European nations,instances of transmission have also been documented albeit without significant clinical consequences.Epidemiology of HEV genotype 1 in endemic areas often show waxing and waning pattern.Occasional sporadic occurrence of HEV infection interrupted by outbreaks have been frequently seen.In absence of known animal reservoir,where HEV exists in between outbreak is a mystery that needs further exploration.However,occurrence of asymptomatic HEV viremia due to HEV genotype 1 during epidemiologically quiescent period may explain that this phenomenon may act as a dynamic reservoir.Since HEV genotype 1 infection cannot cause chronicity,subclinical transient infection and transmission of virus might be the reason it sustains in interepidemic period.This might be the similar phenomenon with SARS COVID-19 corona virus infection which is circulating worldwide in distinct phases with peaks and plateaus despite vaccination against it.In view of existing evidence,we propose the concept of“Dynamic Human Reservoir.”Quiescent subclinical infection of HEV without any clinical consequences and subsequent transmission may contribute to the existence of the virus in a community.The potential for transmitting HEV infection by asymptomatic HEV infected individuals by fecal shedding of virus has not been reported in literature.This missing link may be a key to Pandora's box in understanding epidemiology of HEV infection in genotype 1 predominant region.
基金the National Institute of Mental Health at the US National Institutes of Health(grant number:R01 MH111859).
文摘Background Little is known about the association between stressors(especially positive stressors)during pregnancy and postpartum depression and anxiety.Aims We investigated the association between positive and negative stress events during different stages of pregnancy and postpartum mental health outcomes among low-income pregnant women with symptoms of anxiety in Pakistan and evaluated whether an intervention based on cognitive behavioural therapy(CBT)had a regulatory effect.Methods Participants were 621 pregnant Pakistani women with mild anxiety.Using the Pregnancy Experience Scale-Brief Version,six scores were created to assess positive and negative stressors.We performed a multivariate linear regression to examine whether these six scores,measured both at baseline and in the third trimester,were associated with postpartum anxiety and depressive symptoms.The effect of the intervention on this relationship was examined by adding an interaction term to the regression model.Results Hassles frequency measured in the third trimester was positively associated with depression(B=0.22,95%confidence interval(Cl):0.09 to 0.36)and anxiety(B=0.19,95%Cl:0.08to 0.30).At the same timepoint,uplifts intensity was negatively associated with symptoms of depression(B=-0.82,95%Cl:1.46 to-0.18)and anxiety(B=-0.70,95%Cl:-1.25 to-0.15),whereas hassles intensity was positively related to symptoms of depression(B=1.02,95%Cl:0.36 to 1.67)and anxiety(B=0.90,95%Cl:0.34 to 1.47).The intensity ratio of hassles to uplifts reported in the third trimester was positively related to both depression(B=1.40,95%Cl:0.59 to 2.20)and anxiety(B=1.26,95%Cl:0.57 to 1.96).The intervention strengthened the overall positive effects of uplfts and the negative effects of hassles.Pregnancy experiences at baseline during early pregnancy to mid-pregnancy were not associated with mental health outcomes.Conclusions Stressors in the third trimester but not earlier in pregnancy were associated with postpartum symptoms of anxiety and depression.The CBT intervention modified the association between pregnancy stressors and postpartum mental health outcomes.Programmes that promote positive experiences and reduce negative experiences,especially in late pregnancy,may mitigate postpartum mental health consequences.
文摘Objective: To analyze outcomes and complications of cytoreductive prostatectomy (CRP) for oligometastatic prostate cancer (PCa) in order to elucidate its role in this space.Methods: We performed a systematic literature search using three databases (Medline, Scopus, and Web of Science). The primary endpoints were oncologic outcomes. The secondary endpoints were complication rates and functional results.Results: In all studies, overall survival was better or at least comparable variable in the groups with CRP compared to no local treatment. The greatest benefit from CRP in 5-year overall survival in one study was 67.4% for CRP versus 22.5% for no local treatment. Cancer-specific survival (CSS) showed the same trend. Several authors found significant benefits from CSS in the CRP group: from 79% vs. 46% to 100% vs. 61%. CRP was a predictor of better CSS (hazard ratio 0.264, p=0.004). Positive surgical margin rates differed widely from 28.6% to 100.0%. Urinary continence in CRP versus RP for localized PCa was significantly lower (57.4% vs. 90.8%, p<0.0001). Severe incontinence occurred seldom (2.5%-18.6%). Total complication rates after CRP differed widely, from 7.0% to 43.6%. Rates of grades 1 and 2 events prevailed. Patients on ADT alone also showed a considerable number of complications varying from 5.9% to 57.7%.Conclusion: CRP improves medium-term cancer control in patients with oligometastatic PCa. The morbidity and complication rates of this surgery are comparable with other approaches, but postoperative incontinence rate is higher compared with RP for localized disease.
文摘BACKGROUND Despite advances in detection and treatments,biliary tract cancers continue to have poor survival outcomes.Currently,there is limited data investigating the significance of socioeconomic status,race/ethnicity,and environmental factors in biliary tract cancer survival.Data from the Surveillance,Epidemiology,and End Results database for biliary and gallbladder adenocarcinomas were extracted from 1975 to 2016.Socioe-conomic data included smoking,poverty level,education,adjusted household income,and percentage of foreign-born persons and urban population.Survival was calculated with Cox proportional hazards models for death in the 5-year period following diagnosis.RESULTS Our study included 15883 gallbladder,11466 intrahepatic biliary,12869 extrahepatic biliary and 7268 ampulla of Vater adenocarcinoma cases.When analyzing county-specific demographics,patients from counties with higher incomes were associated with higher survival rates[hazard ratio(HR)=0.97,P<0.05].Similarly,counties with a higher percentage of patients with a college level education and counties with a higher urban population had higher 5-year survival rates(HR=0.96,P=0.002 and HR=0.97,P=0.004,respectively).CONCLUSION Worse survival outcomes were observed in lower income counties while higher income and education level were associated with higher 5-year overall survival among gallbladder and biliary malignancies.
基金supported by the Intramural Research Program of the NIDCR, NICHD,and Clinical Center, National Institutes of Healthsupported by Amgen, Inc.+2 种基金supported in part by the NIDCR Genomics and Computational Biology Core:ZIC DC000086Veterinary Resources Core:ZIC DE000740-05supported by the Research on Women’s Health(ORWH)through the Bench to Bedside Program award#884515.
文摘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.
基金Supported by the National Natural Science Foundation of China(No.82301249,No.82371086)the Science and Technology Projects in Guangzhou(No.SL2024A04J01756)the Fundamental Research Funds of the State Key Laboratory of Ophthalmology(No.83000-32030003).
文摘AIM:To explore the usage of choroidal thickness measured by swept-source optical coherence tomography(SS-OCT)to detect myopic macular degeneration(MMD)in high myopic participants.METHODS:Participants with bilateral high myopia(≤−6 diopters)were recruited from a subset of the Guangzhou Zhongshan Ophthalmic Center-Brien Holden Vision Institute High Myopia Cohort Study.SS-OCT was performed to determine the choroidal thickness,and myopic maculopathy was graded by the International Meta-Analysis for Pathologic Myopia(META-PM)Classification.Presence of MMD was defined as META-PM category 2 or above.RESULTS:A total of 568 right eyes were included for analysis.Eyes with MMD(n=106,18.7%)were found to have older age,longer axial lengths(AL),higher myopic spherical equivalents(SE),and reduced choroidal thickness in each Early Treatment Diabetic Retinopathy Study(ETDRS)grid sector(P<0.001).The area under the receiver operating characteristic(ROC)curves(AUC)for subfoveal choroidal thickness(0.907)was greater than that of the model,including age,AL,and SE at 0.6249,0.8208,and 0.8205,respectively.The choroidal thickness of the inner and outer nasal sectors was the most accurate indicator of MMD(AUC of 0.928 and 0.923,respectively).An outer nasal sector choroidal thickness of less than 74μm demonstrated the highest odds of predicting MMD(OR=33.8).CONCLUSION:Choroidal thickness detects the presence of MMD with high agreement,particularly of the inner and outer nasal sectors of the posterior pole,which appears to be a biometric parameter more precise than age,AL,or SE.
文摘This paper explains various factors that contribute to saltwater intrusion, including overexploitation of freshwater resources and climate change as well as the different techniques essential for effective saltwater intrusion management. The impact of saltwater intrusion along coastal regions and its impact on the environment, hydrogeology and groundwater contamination. It suggests potential solutions to mitigate the impact of saltwater intrusion, including effective water management and techniques for managing SWI. The application of A.I (assessment index) serves as a guideline to correctly identify wells with SWI ranging from no intrusion, slight intrusion and strong intrusion. The challenges of saltwater intrusion in Lagos and the salinization of wells were investigated using the hydro-chemical parameters. The study identifies four wells (“AA”, “CMS”, “OBA” and “VIL”) as having high electric conductivities, indicating saline water intrusion, while other wells (“EBM”, “IKJ, and “IKO”) with lower electric conductivities, indicate little or no salt-water intrusion, and “AJ” well shows slight intrusion. The elevation of the wells also played a vital role in the SWI across coastal regions of Lagos. The study recommends continuous monitoring of coastal wells to help sustain and reduce saline intrusion. The findings of the study are important for policymakers, researchers, and practitioners who are interested in addressing the challenges of saltwater intrusion along coastal regions. We assessed the SWI across the eight (8) wells using the Assessment Index to identify wells with SWI. Wells in “CMS” and “VIL” has strong intrusions. A proposed classification system based on specific ion ratios categorizes water quality from good (+) to highly (-) contaminated (refer to Table 4). These findings underscore the need for attention and effective management strategies to address groundwater unsuitability for various purposes.
文摘Gesture detection is the primary and most significant step for sign language detection and sign language is the communication medium for people with speaking and hearing disabilities. This paper presents a novel method for dynamic hand gesture detection using Hidden Markov Models (HMMs) where we detect different English alphabet letters by tracing hand movements. The process involves skin color-based segmentation for hand isolation in video frames, followed by morphological operations to enhance image trajectories. Our system employs hand tracking and trajectory smoothing techniques, such as the Kalman filter, to monitor hand movements and refine gesture paths. Quantized sequences are then analyzed using the Baum-Welch Re-estimation Algorithm, an HMM-based approach. A maximum likelihood classifier is used to identify the most probable letter from the test sequences. Our method demonstrates significant improvements over traditional recognition techniques in real-time, automatic hand gesture recognition, particularly in its ability to distinguish complex gestures. The experimental results confirm the effectiveness of our approach in enhancing gesture-based sign language detection to alleviate the barrier between the deaf and hard-of-hearing community and general people.