Progress in Neurobiology最新文献

{"title":"Lateralization of dorsal fiber tract targeting Broca’s area concurs with language skills during development","authors":"Cornelius Eichner ,&nbsp;Philipp Berger ,&nbsp;Cheslie C. Klein ,&nbsp;Angela D. Friederici","doi":"10.1016/j.pneurobio.2024.102602","DOIUrl":"https://doi.org/10.1016/j.pneurobio.2024.102602","url":null,"abstract":"<div><p>Language is bounded to the left hemisphere in the adult brain and the functional lateralization can already be observed early during development. Here we investigate whether this is paralleled by a lateralization of the white matter structural language network. We analyze the strength and microstructural properties of language-related fiber tracts connecting temporal and frontal cortices with a separation of two dorsal tracts, one targeting the posterior Broca’s area (BA44) and one targeting the precentral gyrus (BA6). In a large sample of young children (3–6 years), we demonstrate that, in contrast to the BA6-targeting tract, the microstructural asymmetry of the BA44-targeting fiber tract significantly correlates locally with different aspects of development. While the asymmetry in its anterior segment reflects age, the asymmetry in its posterior segment is associated with the children’s language skills. These findings demonstrate a fine-grained structure-to-function mapping in the lateralized network and go beyond our current view of language-related human brain maturation.</p></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"236 ","pages":"Article 102602"},"PeriodicalIF":6.7,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0301008224000388/pdfft?md5=fd3832405d43fae881959fdf5f1be647&pid=1-s2.0-S0301008224000388-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140540744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Memory circuits in dementia: The engram, hippocampal neurogenesis and Alzheimer’s disease","authors":"Orly Lazarov,&nbsp;Muskan Gupta,&nbsp;Pavan Kumar,&nbsp;Zachery Morrissey,&nbsp;Trongha Phan","doi":"10.1016/j.pneurobio.2024.102601","DOIUrl":"10.1016/j.pneurobio.2024.102601","url":null,"abstract":"<div><p>Here, we provide an in-depth consideration of our current understanding of engrams, spanning from molecular to network levels, and hippocampal neurogenesis, in health and Alzheimer’s disease (AD). This review highlights novel findings in these emerging research fields and future research directions for novel therapeutic avenues for memory failure in dementia. Engrams, memory in AD, and hippocampal neurogenesis have each been extensively studied. The integration of these topics, however, has been relatively less deliberated, and is the focus of this review. We primarily focus on the dentate gyrus (DG) of the hippocampus, which is a key area of episodic memory formation. Episodic memory is significantly impaired in AD, and is also the site of adult hippocampal neurogenesis. Advancements in technology, especially opto- and chemogenetics, have made sophisticated manipulations of engram cells possible. Furthermore, innovative methods have emerged for monitoring neurons, even specific neuronal populations, <em>in vivo</em> while animals engage in tasks, such as calcium imaging. <em>In vivo</em> calcium imaging contributes to a more comprehensive understanding of engram cells. Critically, studies of the engram in the DG using these technologies have shown the important contribution of hippocampal neurogenesis for memory in both health and AD. Together, the discussion of these topics provides a holistic perspective that motivates questions for future research.</p></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"236 ","pages":"Article 102601"},"PeriodicalIF":6.7,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0301008224000376/pdfft?md5=bbd721eb949c6877bee74e2d0da462e3&pid=1-s2.0-S0301008224000376-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140356409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optogenetic and chemogenetic approaches for modeling neurological disorders in vivo","authors":"Viktoriya G. Krut’ ,&nbsp;Andrei L. Kalinichenko ,&nbsp;Dmitry I. Maltsev ,&nbsp;David Jappy ,&nbsp;Evgeny K. Shevchenko ,&nbsp;Oleg V. Podgorny ,&nbsp;Vsevolod V. Belousov","doi":"10.1016/j.pneurobio.2024.102600","DOIUrl":"10.1016/j.pneurobio.2024.102600","url":null,"abstract":"<div><p>Animal models of human neurological disorders provide valuable experimental tools which enable us to study various aspects of disorder pathogeneses, ranging from structural abnormalities and disrupted metabolism and signaling to motor and mental deficits, and allow us to test novel therapies in preclinical studies. To be valid, these animal models should recapitulate complex pathological features at the molecular, cellular, tissue, and behavioral levels as closely as possible to those observed in human subjects. Pathological states resembling known human neurological disorders can be induced in animal species by toxins, genetic factors, lesioning, or exposure to extreme conditions. In recent years, novel animal models recapitulating neuropathologies in humans have been introduced. These animal models are based on synthetic biology approaches: opto- and chemogenetics. In this paper, we review recent opto- and chemogenetics-based animal models of human neurological disorders. These models allow for the creation of pathological states by disrupting specific processes at the cellular level. The artificial pathological states mimic a range of human neurological disorders, such as aging-related dementia, Alzheimer’s and Parkinson’s diseases, amyotrophic lateral sclerosis, epilepsy, and ataxias. Opto- and chemogenetics provide new opportunities unavailable with other animal models of human neurological disorders. These techniques enable researchers to induce neuropathological states varying in severity and ranging from acute to chronic. We also discuss future directions for the development and application of synthetic biology approaches for modeling neurological disorders.</p></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"235 ","pages":"Article 102600"},"PeriodicalIF":6.7,"publicationDate":"2024-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140319108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dissecting gene expression networks in the developing hippocampus through the lens of NEIL3 depletion","authors":"Anna M. Bugaj ,&nbsp;Nicolas Kunath ,&nbsp;Vidar Langseth Saasen ,&nbsp;Marion S. Fernandez-Berrocal ,&nbsp;Ana Vankova ,&nbsp;Pål Sætrom ,&nbsp;Magnar Bjørås ,&nbsp;Jing Ye","doi":"10.1016/j.pneurobio.2024.102599","DOIUrl":"10.1016/j.pneurobio.2024.102599","url":null,"abstract":"<div><p>Gene regulation in the hippocampus is fundamental for its development, synaptic plasticity, memory formation, and adaptability. Comparisons of gene expression among different developmental stages, distinct cell types, and specific experimental conditions have identified differentially expressed genes contributing to the organization and functionality of hippocampal circuits. The NEIL3 DNA glycosylase, one of the DNA repair enzymes, plays an important role in hippocampal maturation and neuron functionality by shaping transcription. While differential gene expression (DGE) analysis has identified key genes involved, broader gene expression patterns crucial for high-order hippocampal functions remain uncharted. By utilizing the weighted gene co-expression network analysis (WGCNA), we mapped gene expression networks in immature (p8-neonatal) and mature (3 m-adult) hippocampal circuits in wild-type and NEIL3-deficient mice. Our study unveiled intricate gene network structures underlying hippocampal maturation, delineated modules of co-expressed genes, and pinpointed highly interconnected hub genes specific to the maturity of hippocampal subregions. We investigated variations within distinct gene network modules following NEIL3 depletion, uncovering NEIL3-targeted hub genes that influence module connectivity and specificity. By integrating WGCNA with DGE, we delve deeper into the NEIL3-dependent molecular intricacies of hippocampal maturation. This study provides a comprehensive systems-level analysis for assessing the potential correlation between gene connectivity and functional connectivity within the hippocampal network, thus shaping hippocampal function throughout development.</p></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"235 ","pages":"Article 102599"},"PeriodicalIF":6.7,"publicationDate":"2024-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0301008224000352/pdfft?md5=f074a4b50d71eed55161043625d984cc&pid=1-s2.0-S0301008224000352-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140207480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic evoked seizures in young pre-symptomatic APP/PS1 mice induce serotonin changes and accelerate onset of Alzheimer’s disease-related neuropathology","authors":"Aaron del Pozo ,&nbsp;Kevin M. Knox ,&nbsp;Leanne M. Lehmann ,&nbsp;Stephanie Davidson ,&nbsp;Seongheon Leo Rho ,&nbsp;Suman Jayadev ,&nbsp;Melissa Barker-Haliski","doi":"10.1016/j.pneurobio.2024.102591","DOIUrl":"10.1016/j.pneurobio.2024.102591","url":null,"abstract":"<div><h3>Objective</h3><p>Hyperexcitability is intimately linked to Alzheimer's disease (AD) pathology, but the precise timing and contributions of neuronal hyperexcitability to disease progression is unclear. Seizure induction in rodent AD models can uncover new therapeutic targets. Further, investigator-evoked seizures can directly establish how hyperexcitability and AD-associated risk factors influence neuropathological hallmarks and disease course at presymptomatic stages.</p></div><div><h3>Methods</h3><p>Corneal kindling is a well-characterized preclinical epilepsy model that allows for precise control of seizure history to pair to subsequent behavioral assessments. 2–3-month-old APP/PS1, PSEN2-N141I, and transgenic control male and female mice were thus sham or corneal kindled for 2 weeks. Seizure-induced changes in glia, serotonin pathway proteins, and amyloid β levels in hippocampus and prefrontal cortex were quantified.</p></div><div><h3>Results</h3><p>APP/PS1 females were more susceptible to corneal kindling. However, regardless of sex, APP/PS1 mice experienced extensive seizure-induced mortality versus kindled Tg- controls. PSEN2-N141I mice were not negatively affected by corneal kindling. Mortality correlated with a marked downregulation of hippocampal tryptophan hydroxylase 2 and monoamine oxidase A protein expression versus controls; these changes were not detected in PSEN2-N141I mice. Kindled APP/PS1 mice also exhibited soluble amyloid β upregulation and glial reactivity without plaque deposition.</p></div><div><h3>Significance</h3><p>Evoked convulsive seizures and neuronal hyperexcitability in pre-symptomatic APP/PS1 mice promoted premature mortality without pathological Aβ plaque deposition, whereas PSEN2-N141I mice were unaffected. Disruptions in serotonin pathway metabolism in APP/PS1 mice was associated with increased glial reactivity without Aβ plaque deposition, demonstrating that neuronal hyperexcitability in early AD causes pathological Aβ overexpression and worsens long-term outcomes through a serotonin-related mechanism.</p></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"235 ","pages":"Article 102591"},"PeriodicalIF":6.7,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140132428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The unconditioned fear response in vertebrates deficient in dystrophin","authors":"Saba Gharibi ,&nbsp;Cyrille Vaillend ,&nbsp;Angus Lindsay","doi":"10.1016/j.pneurobio.2024.102590","DOIUrl":"10.1016/j.pneurobio.2024.102590","url":null,"abstract":"<div><p>Dystrophin loss due to mutations in the Duchenne muscular dystrophy (DMD) gene is associated with a wide spectrum of neurocognitive comorbidities, including an aberrant unconditioned fear response to stressful/threat stimuli. Dystrophin-deficient animal models of DMD demonstrate enhanced stress reactivity that manifests as sustained periods of immobility. When the threat is repetitive or severe in nature, dystrophinopathy phenotypes can be exacerbated and even cause sudden death. Thus, it is apparent that enhanced sensitivity to stressful/threat stimuli in dystrophin-deficient vertebrates is a legitimate cause of concern for patients with DMD that could impact neurocognition and pathophysiology. This review discusses our current understanding of the mechanisms and consequences of the hypersensitive fear response in preclinical models of DMD and the potential challenges facing clinical translatability.</p></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"235 ","pages":"Article 102590"},"PeriodicalIF":6.7,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0301008224000261/pdfft?md5=8c89744ca34fc843b8fd9ccaf61922b7&pid=1-s2.0-S0301008224000261-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140125651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Contralateral delay activity and alpha lateralization reflect retinotopic and screen-centered reference frames in visual memory","authors":"Wanja A. Mössing ,&nbsp;Svea C.Y. Schroeder ,&nbsp;Anna Lena Biel ,&nbsp;Niko A. Busch","doi":"10.1016/j.pneurobio.2024.102576","DOIUrl":"10.1016/j.pneurobio.2024.102576","url":null,"abstract":"<div><p>The visual system represents objects in a lateralized manner, with contralateral cortical hemispheres responsible for left and right visual hemifields. This organization extends to visual short-term memory (VSTM), as evidenced by electrophysiological indices of VSTM maintenance: contralateral delay activity (CDA) and alpha-band lateralization. However, it remains unclear if VSTM represents object locations in gaze-centered (retinotopic) or screen-centered (spatiotopic) coordinates, especially after eye movements. In two experiments, participants encoded the colors of target objects and made a lateral saccade during the maintenance interval, thereby shifting the object’s location on the retina. A non-lateralized probe stimulus was then presented at the new fixation for a change detection task. The CDA maintained lateralization towards the target’s original retinotopic location, unaffected by subsequent saccades, and did not invert polarity even when a saccade brought that location into the opposite hemifield. We also found conventional alpha lateralization towards the target’s location before a saccade. After a saccade, however, alpha was lateralized towards the screen center regardless of the target’s original location, even in a control condition without any memory requirements. This suggests that post-saccadic alpha-band lateralization reflects attentional processes unrelated to memory, while pre- and post-saccade CDA reflect VSTM maintenance in a retinotopic reference frame.</p></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"234 ","pages":"Article 102576"},"PeriodicalIF":6.7,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0301008224000121/pdfft?md5=7c9a19b9f8c8e9cd6a1fdf61990aa92b&pid=1-s2.0-S0301008224000121-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139662822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A cytoskeleton symphony: Actin and microtubules in microglia dynamics and aging","authors":"Renato Socodato ,&nbsp;João B. Relvas","doi":"10.1016/j.pneurobio.2024.102586","DOIUrl":"10.1016/j.pneurobio.2024.102586","url":null,"abstract":"<div><p>Microglia dynamically reorganize their cytoskeleton to perform essential functions such as phagocytosis of toxic protein aggregates, surveillance of the brain parenchyma, and regulation of synaptic plasticity during neuronal activity bursts. Recent studies have shed light on the critical role of the microtubule cytoskeleton in microglial reactivity and function, revealing key regulators like cyclin-dependent kinase 1 and centrosomal nucleation in the remodeling of microtubules in activated microglia. Concurrently, the role of the actin cytoskeleton is also pivotal, particularly in the context of small GTPases like RhoA, Rac1, and Cdc42 and actin-binding molecules such as profilin-1 and cofilin. This article delves into the intricate molecular landscape of actin and microtubules, exploring their synergistic roles in driving microglial cytoskeletal dynamics. We propose a more integrated view of actin and microtubule cooperation, which is fundamental to understanding the functional coherence of the microglial cytoskeleton and its pivotal role in propelling brain homeostasis. Furthermore, we discuss how alterations in microglial cytoskeleton dynamics during aging and in disease states could have far-reaching implications for brain function. By unraveling the complexities of microglia cytoskeletal dynamics, we can deepen our understanding of microglial functional states and their implications in health and disease, offering insights into potential therapeutic interventions for neurologic disorders.</p></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"234 ","pages":"Article 102586"},"PeriodicalIF":6.7,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0301008224000224/pdfft?md5=b05641ae124b63732693c80fcc59db08&pid=1-s2.0-S0301008224000224-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139773986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epilepsy and demyelination: Towards a bidirectional relationship","authors":"Jiayi Li ,&nbsp;Honggang Qi ,&nbsp;Yuzhou Chen ,&nbsp;Xinjian Zhu","doi":"10.1016/j.pneurobio.2024.102588","DOIUrl":"10.1016/j.pneurobio.2024.102588","url":null,"abstract":"<div><p>Demyelination stands out as a prominent feature in individuals with specific types of epilepsy. Concurrently, individuals with demyelinating diseases, such as multiple sclerosis (MS) are at a greater risk of developing epilepsy compared to non-MS individuals. These bidirectional connections raise the question of whether both pathological conditions share common pathogenic mechanisms. This review focuses on the reciprocal relationship between epilepsy and demyelination diseases. We commence with an overview of the neurological basis of epilepsy and demyelination diseases, followed by an exploration of how our comprehension of these two disorders has evolved in tandem. Additionally, we discuss the potential pathogenic mechanisms contributing to the interactive relationship between these two diseases. A more nuanced understanding of the interplay between epilepsy and demyelination diseases has the potential to unveiling the molecular intricacies of their pathological relationships, paving the way for innovative directions in future clinical management and treatment strategies for these diseases.</p></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"234 ","pages":"Article 102588"},"PeriodicalIF":6.7,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139913359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fundamentals of sleep regulation: Model and benchmark values for fractal and oscillatory neurodynamics","authors":"Róbert Bódizs ,&nbsp;Bence Schneider ,&nbsp;Péter P. Ujma ,&nbsp;Csenge G. Horváth ,&nbsp;Martin Dresler ,&nbsp;Yevgenia Rosenblum","doi":"10.1016/j.pneurobio.2024.102589","DOIUrl":"10.1016/j.pneurobio.2024.102589","url":null,"abstract":"<div><p>Homeostatic, circadian and ultradian mechanisms play crucial roles in the regulation of sleep. Evidence suggests that ratios of low-to-high frequency power in the electroencephalogram (EEG) spectrum indicate the instantaneous level of sleep pressure, influenced by factors such as individual sleep-wake history, current sleep stage, age-related differences and brain topography characteristics. These effects are well captured and reflected in the spectral exponent, a composite measure of the constant low-to-high frequency ratio in the periodogram, which is scale-free and exhibits lower interindividual variability compared to slow wave activity, potentially serving as a suitable standardization and reference measure. Here we propose an index of sleep homeostasis based on the spectral exponent, reflecting the level of membrane hyperpolarization and/or network bistability in the central nervous system in humans. In addition, we advance the idea that the U-shaped overnight deceleration of oscillatory slow and fast sleep spindle frequencies marks the biological night, providing somnologists with an EEG-index of circadian sleep regulation. Evidence supporting this assertion comes from studies based on sleep replacement, forced desynchrony protocols and high-resolution analyses of sleep spindles. Finally, ultradian sleep regulatory mechanisms are indicated by the recurrent, abrupt shifts in dominant oscillatory frequencies, with spindle ranges signifying non-rapid eye movement and non-spindle oscillations – rapid eye movement phases of the sleep cycles. Reconsidering the indicators of fundamental sleep regulatory processes in the framework of the new Fractal and Oscillatory Adjustment Model (FOAM) offers an appealing opportunity to bridge the gap between the two-process model of sleep regulation and clinical somnology.</p></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"234 ","pages":"Article 102589"},"PeriodicalIF":6.7,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S030100822400025X/pdfft?md5=845c93808f88289d0d973cca899ab38d&pid=1-s2.0-S030100822400025X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140065794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}