Developmental Neuroscience最新文献

{"title":"The Intersection of Epigenetic Alterations and Developmental State in Pediatric Ependymomas.","authors":"Alisha Simone Kardian, Stephen Mack","doi":"10.1159/000537694","DOIUrl":"10.1159/000537694","url":null,"abstract":"<p><strong>Background: </strong>Ependymomas are the third most common brain cancer in children and have no targeted therapies. They are divided into at least 9 major subtypes based on molecular characteristics and major drivers and have few genetic mutations compared to the adult form of this disease, leading to investigation of other mechanisms.</p><p><strong>Summary: </strong>Epigenetic alterations such as transcriptional programs activated by oncofusion proteins and alterations in histone modifications play an important role in development of this disease. Evidence suggests these alterations interact with the developmental epigenetic programs in the cell of origin to initiate neoplastic transformation and later disease progression, perhaps by keeping a portion of tumor cells in a developmental, proliferative state.</p><p><strong>Key messages: </strong>To better understand this disease, research on its developmental origins and associated epigenetic states needs to be further pursued. This could lead to better treatments, which are currently lacking due to the difficult-to-drug nature of known drivers such as fusion proteins. Epigenetic and developmental states characteristic of these tumors may not just be potential therapeutic targets but used as a tool to find new avenues of treatment.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"365-372"},"PeriodicalIF":2.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11614414/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140289465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"My Life with Verne.","authors":"Richard S Nowakowski","doi":"10.1159/000531759","DOIUrl":"10.1159/000531759","url":null,"abstract":"","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"153-157"},"PeriodicalIF":2.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9748025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fetal Origins of Health Disparities: Transgenerational Consequences of Racism.","authors":"Nana Matoba, James W Collins, Maria L V Dizon","doi":"10.1159/000531462","DOIUrl":"10.1159/000531462","url":null,"abstract":"<p><p>Despite advances in perinatal medicine, racial disparity in birth outcomes remains a public health problem in the USA. The underlying mechanisms for this long-standing racial disparity are incompletely understood. This review presents transgenerational risk factors for racial disparities in preterm birth, exploring the impact of interpersonal and structural racism, theoretical models of stress, and biological markers of racial disparities.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"112-118"},"PeriodicalIF":2.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9598918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Developmental Regulation of Matrix Metalloproteinases in Response to Multifactorial, Severe Traumatic Brain Injuries during Immaturity.","authors":"Alexandra Hochstetler, George Price, Amy Baohan, Melissa Li, Frances Rodriguez Lara, Josephine Lok, Beth Costine-Bartell","doi":"10.1159/000536054","DOIUrl":"10.1159/000536054","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;A striking pattern in young children after severe TBI is when the entire cortical ribbon displays tissue damage: hemispheric hypodensity (HH). HH is often a result of abusive head trauma (AHT). We previously reported a model of HH in a gyrencephalic species where a combination of injuries consisting of (1) cortical impact, (2) midline shift, (3) subdural hematoma/subarachnoid hemorrhage, (4) traumatic seizures, and (5) brief apnea and hypoventilation resulted in extensive, hypoxic-ischemic-type injury. Importantly, this mechanism closely resembles that seen in children, with relative sparing of the contralateral cortex, thus ruling out a pure asphyxia mechanism. In this model, piglets of similar developmental stage to human toddlers (postnatal day 30, PND30) have extensive hypoxic-ischemic damage to the cortical ribbon with sparing of the contralateral hemisphere and deep gray matter areas. However, piglets of similar developmental stage to human infants (postnatal day 7, PND7) have less hypoxic-ischemic damage that is notably bilateral and patchy. We therefore sought to discover whether the extensive tissue damage observed in PND30 was due to a greater upregulation of matrix metalloproteinases (MMPs).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Materials and methods: &lt;/strong&gt;In PND7 or PND30 piglets receiving AHT injuries (cortical impact, midline shift, subdural hematoma/subarachnoid hemorrhage, traumatic seizures, and brief apnea and hypoventilation) or a sham injury, the pattern of albumin extravasation and MMP-9 upregulation throughout the brain was determined via immunohistochemistry, brain tissue adjacent to the cortical impact where the tissue damage spreads was collected for Western blots, and the gelatinase activity was determined over time in peripheral plasma. EEG was recorded, and piglets survived up to 24 h after injury administration.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The pattern of albumin extravasation, indicating vasogenic edema, as well as increase in MMP-9, were both present at the same areas of hypoxic-ischemic tissue damage. Evidence from immunohistochemistry, Western blot, and zymogens demonstrate that MMP-2, -3, or -9 are constitutively expressed during immaturity and are not different between developmental stages; however, active forms are upregulated in PND30 but not PND7 after in response to AHT model injuries. Furthermore, peripheral active MMP-9 was downregulated after model injuries in PND7.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;This differential response to AHT model injuries might confer protection to the PND7 brain. Additionally, we find that immature gyrencephalic species have a greater baseline and array of MMPs than previously demonstrated in rodent species. Treatment with an oral or intravenous broad-spectrum matrix metalloproteinase inhibitor might reduce the extensive spread of injury in PND30, but the exposure to metalloproteinase inhibitors must be acute as to not interfere with the homeostatic role of ma","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"319-332"},"PeriodicalIF":2.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11228128/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139405092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Does Perinatal Intermittent Hypoxia Affect Cerebrovascular Network Development?","authors":"Vanessa Coelho-Santos, Anne-Jolene N Cruz, Andy Y Shih","doi":"10.1159/000530957","DOIUrl":"10.1159/000530957","url":null,"abstract":"<p><p>Perinatal hypoxia is an inadequate delivery of oxygen to the fetus in the period immediately before, during, or after the birth process. The most frequent form of hypoxia occurring in human development is chronic intermittent hypoxia (CIH) due to sleep-disordered breathing (apnea) or bradycardia events. CIH incidence is particularly high with premature infants. During CIH, repetitive cycles of hypoxia and reoxygenation initiate oxidative stress and inflammatory cascades in the brain. A dense microvascular network of arterioles, capillaries, and venules is required to support the constant metabolic demands of the adult brain. The development and refinement of this microvasculature is orchestrated throughout gestation and in the initial weeks after birth, at a critical juncture when CIH can occur. There is little knowledge on how CIH affects the development of the cerebrovasculature. However, since CIH (and its treatments) can cause profound abnormalities in tissue oxygen content and neural activity, there is reason to believe that it can induce lasting abnormalities in vascular structure and function at the microvascular level contributing to neurodevelopmental disorders. This mini-review discusses the hypothesis that CIH induces a positive feedback loop to perpetuate metabolic insufficiency through derailment of normal cerebrovascular development, leading to long-term deficiencies in cerebrovascular function.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"44-54"},"PeriodicalIF":2.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9521911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fluoxetine Can Cause Epileptogenesis and Aberrant Neurogenesis in Male Wild-Type Mice.","authors":"Ksenia Musaelyan, Mark A Horowitz, Stephen McHugh, Francis G Szele","doi":"10.1159/000531478","DOIUrl":"10.1159/000531478","url":null,"abstract":"<p><p>Antidepressants in general, and fluoxetine in particular, increase adult hippocampal neurogenesis (AHN) in mice. Here we asked how the antidepressant fluoxetine affects behavior and AHN in a corticosterone model of depression. In three groups of adult male C57BL/6j mice, we administered either vehicle (VEH), corticosterone (CORT) treatment to induce a depression-like state, or corticosterone plus a standard dose of fluoxetine (CORT+FLX). Following treatment, mice performed the open field test, the novelty suppressed feeding (NSF) test, and the splash test. Neurogenesis was assessed by means of immunohistochemistry using BrdU and neuronal maturation markers. Unexpectedly, 42% of the CORT+FLX-treated mice exhibited severe weight loss, seizures, and sudden death. As expected, the CORT-treated group had altered behaviors compared to the VEH group, but the CORT+FLX mice that survived did not show any behavioral improvement compared to the CORT group. Antidepressants generally increase neurogenesis and here we also found that compared to CORT mice, CORT+FLX mice that survived had a significantly greater density of BrdU+, BrdU+DCX+, and BrdU+NeuN+ cells, suggesting increased neurogenesis. Moreover, the density of BrdU+NeuN+ cells was increased in an aberrant location, the hilus, of CORT+FLX mice, similar to previous studies describing aberrant neurogenesis following seizures. In conclusion, fluoxetine could induce considerable adverse effects in wild-type mice, including seizure-like activity. Fluoxetine-induced neurogenesis increases could be related to this activity; therefore, proneurogenic effects of fluoxetine and other antidepressants, especially in the absence of any behavioral therapeutic effects, should be interpreted with caution.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"158-166"},"PeriodicalIF":2.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9617661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ultrasound-Induced Prenatal Stress: New Possibilities for Modeling Mental Disorders.","authors":"Olga Abramova, Anna Morozova, Eugene Zubkov, Valeria Ushakova, Yana Zorkina, Andrey T Proshin, Zinaida Storozheva, Olga Gurina, Vladimir Chekhonin","doi":"10.1159/000534687","DOIUrl":"10.1159/000534687","url":null,"abstract":"<p><p>The development of animal models of mental disorders is an important task since such models are useful for studying the neurobiological mechanisms of psychopathologies and for trial of new therapeutic drugs. One way to model pathologies of the nervous system is to impair fetal neurodevelopment through stress of the pregnant future mother, or prenatal stress (PS). The use of variable frequency ultrasound (US) in rodents is a promising method of imitating psychological stress, to which women in modern society are most often subjected. The aim of our study was to investigate the effect of PS induced by exposure to variable frequency ultrasound (US PS) throughout the gestational period on the adult rat offspring, namely, to identify features of behavioral alterations and neurochemical brain parameters that can be associated with certain mental disorders in humans, to determine the possibility of creating a new model of psychopathology. Our study included a study of some behavioral characteristics of male and female rats in the elevated plus maze, open-field test, object recognition test, social interaction test, sucrose preference test, latent inhibition test, Morris water maze, forced swimming test, acoustic startle reflex, and prepulse inhibition tests. We also determined the activity of the serotonergic, dopaminergic, and noradrenergic neurotransmitter systems in the hippocampus and frontal cortex by HPLC-ED. Concentration of norepinephrine, dopamine, DOPAC, serotonin, and HIAA, as well as DOPAC/dopamine and HIAA/serotonin ratios were determined. A correlation analysis of behavioral and neurochemical parameters in male and female rats was performed based on the data obtained. The results of the study showed that US PS altered the behavioral phenotype of the rat offspring. US PS increased the level of anxious behavior, impaired orientation-research behavior, increased grooming activity, decreased the desire for social contacts, shifted behavioral reactions from social interaction to interaction with inanimate objects, impaired latent inhibition, and decreased the startle reflex. US PS activated the serotonergic, dopaminergic, and noradrenergic neurotransmitter systems of the rat frontal cortex and hippocampus. A correlation between neurochemical and behavioral parameters was revealed. Our study showed that US PS leads to a certain dysfunction on behavioral and neurochemical levels in rats that is most closely associated with symptoms of schizophrenia or autism. We hypothesize that this could potentially be an indicator of face validity for a model of psychopathology based on neurodevelopmental impairment.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"237-261"},"PeriodicalIF":2.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11251674/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49684538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pain/Stress, Mitochondrial Dysfunction, and Neurodevelopment in Preterm Infants.","authors":"Tingting Zhao, Xiaolin Chang, Subrata Kumar Biswas, Jeremy L Balsbaugh, Jennifer Liddle, Ming-Hui Chen, Adam P Matson, Nathan N Alder, Xiaomei Cong","doi":"10.1159/000536509","DOIUrl":"10.1159/000536509","url":null,"abstract":"<p><strong>Introduction: </strong>Preterm infants experience tremendous early life pain/stress during their neonatal intensive care unit (NICU) hospitalization, which impacts their neurodevelopmental outcomes. Mitochondrial function/dysfunction may interface between perinatal stress events and neurodevelopment. Nevertheless, the specific proteins or pathways linking mitochondrial functions to pain-induced neurodevelopmental outcomes in infants remain unidentified. Our study aims to investigate the associations among pain/stress, proteins associated with mitochondrial function/dysfunction, and neurobehavioral responses in preterm infants.</p><p><strong>Methods: </strong>We conducted a prospective cohort study, enrolling 33 preterm infants between September 2017 and July 2022 at two affiliated NICUs located in Hartford and Farmington, CT. NICU Network Neurobehavioral Scale (NNNS) datasets were evaluated to explore potential association with neurobehavioral outcomes. The daily pain/stress experienced by infant's during their NICU stay was documented. At 36-38 weeks post-menstrual age (PMA), neurobehavioral outcomes were evaluated using the NNNS and buccal swabs were collected for further analysis. Mass spectrometry-based proteomics was conducted on epithelial cells obtained from buccal swabs to evaluate protein expression level. Lasso statistical methods were conducted to study the association between protein abundance and infants' NNNS summary scores. Multiple linear regression and Gene Ontology (GO) enrichment analyses were performed to examine how clinical characteristics and neurodevelopmental outcomes may be associated with protein levels and underlying molecular pathways.</p><p><strong>Results: </strong>During NICU hospitalization, preterm premature rupture of membrane (PPROM) was negatively associated with neurobehavioral outcomes. The protein functions including leptin receptor binding activity, glutathione disulfide oxidoreductase activity and response to oxidative stress, lipid metabolism, and phosphate and proton transmembrane transporter activity were negatively associated with neurobehavioral outcomes; in contrast, cytoskeletal regulation, epithelial barrier, and protection function were found to be associated with the optimal neurodevelopmental outcomes. In addition, mitochondrial function-associated proteins including SPRR2A, PAIP1, S100A3, MT-CO2, PiC, GLRX, PHB2, and BNIPL-2 demonstrated positive association with favorable neurodevelopmental outcomes, while proteins of ABLIM1, UNC45A, keratins, MUC1, and CYB5B showed positive association with adverse neurodevelopmental outcomes.</p><p><strong>Conclusion: </strong>Mitochondrial function-related proteins were observed to be associated with early life pain/stress and neurodevelopmental outcomes in infants. Large-scale studies with longitudinal datasets are warranted. Buccal proteins could be used to predict potential neurobehavioral outcomes.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"341-352"},"PeriodicalIF":2.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11284246/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139577102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex-Specific Behavioural Deficits in Adulthood following Acute Activation of the GABAA Receptor in the Neonatal Mouse.","authors":"Ane Goikolea-Vives, Cathy Fernandes, Michael S C Thomas, Claire Thornton, Helen B Stolp","doi":"10.1159/000536641","DOIUrl":"10.1159/000536641","url":null,"abstract":"<p><strong>Introduction: </strong>Sex differences exist in the prevalence of neurodevelopmental disorders (NDDs). Part of the aetiology of NDDs has been proposed to be alterations in the balance between excitatory and inhibitory neurotransmission, leading to the question of whether males and females respond differently to altered neurotransmitter balance. We investigated whether pharmacological alteration of GABAA signalling in early development results in sex-dependent changes in adult behaviours associated with NDDs.</p><p><strong>Methods: </strong>Male and female C57BL/6J mice received intraperitoneal injections of 0.5 mg/kg muscimol or saline on postnatal days (P) 3-5 and were subjected to behavioural testing, specifically open field, light/dark box, marble-burying, sucralose preference, social interaction, and olfactory habituation/dishabituation tests between P60 and P90.</p><p><strong>Results: </strong>Early postnatal administration of muscimol resulted in reduced anxiety in the light/dark box test in both male and female adult mice. Muscimol reduced sucralose preference in males, but not females, whereas female mice showed reduced social behaviours. Regional alterations in cortical thickness were observed in the weeks following GABAA receptor activation, pointing to an evolving structural difference in the brain underlying adult behaviour.</p><p><strong>Conclusions: </strong>We conclude that activation of the GABAA receptor in the first week of life resulted in long-lasting changes in a range of behaviours in adulthood following altered neurodevelopment. Sex of the individual affected the nature and severity of these abnormalities, explaining part of the varied pathophysiology and neurodevelopmental diagnosis that derive from excitatory/inhibitory imbalance.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"386-400"},"PeriodicalIF":2.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139703904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of Gene Regulatory Elements in Human Fetal Cortical Development: Enhancing Our Understanding of Neurodevelopmental Disorders and Evolution.","authors":"Qiuyu Guo, Sarah Wu, Daniel H Geschwind","doi":"10.1159/000530929","DOIUrl":"10.1159/000530929","url":null,"abstract":"<p><p>The neocortex is the region that most distinguishes human brain from other mammals and primates [Annu Rev Genet. 2021 Nov;55(1):555-81]. Studying the development of human cortex is important in understanding the evolutionary changes occurring in humans relative to other primates, as well as in elucidating mechanisms underlying neurodevelopmental disorders. Cortical development is a highly regulated process, spatially and temporally coordinated by expression of essential transcriptional factors in response to signaling pathways [Neuron. 2019 Sep;103(6):980-1004]. Enhancers are the most well-understood cis-acting, non-protein-coding regulatory elements that regulate gene expression [Nat Rev Genet. 2014 Apr;15(4):272-86]. Importantly, given the conservation of both DNA sequence and molecular function of the majority of proteins across mammals [Genome Res. 2003 Dec;13(12):2507-18], enhancers [Science. 2015 Mar;347(6226):1155-9], which are far more divergent at the sequence level, likely account for the phenotypes that distinguish the human brain by changing the regulation of gene expression. In this review, we will revisit the conceptual framework of gene regulation during human brain development, as well as the evolution of technologies to study transcriptional regulation, with recent advances in genome biology that open a window allowing us to systematically characterize cis-regulatory elements in developing human brain [Hum Mol Genet. 2022 Oct;31(R1):R84-96]. We provide an update on work to characterize the suite of all enhancers in the developing human brain and the implications for understanding neuropsychiatric disorders. Finally, we discuss emerging therapeutic ideas that utilize our emerging knowledge of enhancer function.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"69-83"},"PeriodicalIF":2.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9876673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}