Molecular Psychiatry最新文献

{"title":"Design and validation of novel brain-penetrant HCN channel inhibitors to ameliorate social stress-induced susceptible phenotype","authors":"Emily M. Teichman, Jianping Hu, Hsiao-yun Lin, Rachel L. Fisher-Foye, Anthony Blando, Xiaoping Hu, H. Ümit Kaniskan, Sarah E. Montgomery, Min Cai, Lyonna F. Parise, Jun Wang, Scott J. Russo, Ming-Hu Han, Jian Jin, Carole Morel","doi":"10.1038/s41380-025-02972-8","DOIUrl":"https://doi.org/10.1038/s41380-025-02972-8","url":null,"abstract":"<p>Major Depressive Disorder (MDD) is a devastating, multifactorial disease with limited pharmacological treatment options. Patients with MDD exhibit alterations in their dopamine (DA) signaling pathways through the midbrain ventral tegmental area (VTA). A similar observation is also detected in preclinical models of stress - mice exhibit behavioral and physiological impairments following chronic social defeat stress (CSDS). Prior studies demonstrate that CSDS-susceptible mice have increased VTA DA neuronal excitability, in part driven by an upregulation in hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels. Inhibiting HCN channels with known inhibitors such as Cilobradine alleviates the negative behavioral effects of CSDS. Here, we aimed to identify Cilobradine analogs with improved neural tropism and inhibitory efficacy. Two compounds, <b>MS7710</b> and <b>MS7712</b>, differing by their left-hand side moieties, have a similar, potent inhibitory effect on VTA DA <i>I</i>_h currents as compared to Cilobradine, and a greater inhibitory effect than Cilobradine on VTA DA firing rate. We demonstrate that <b>MS7710</b> and <b>MS7712</b> have superior brain/plasma concentration ratios as compared to Cilobradine. They were efficacious at inhibiting VTA DA neuron firing rate and bursting activity in CSDS-susceptible male mice at lower doses than Cilobradine, which was recapitulated in female CSDS-susceptible mice with <b>MS7710</b>. Finally, we define that a single intraperitoneal injection of <b>MS7710</b> ameliorates CSDS-induced social interaction deficits and reward-associated cognitive inflexibility for at least two weeks in male and female mice. These findings yield a novel HCN channel inhibitor with improved neural tropism and stress-alleviating effects that could provide a basis for future antidepressant drug discovery.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":"13 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143805775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter to the editor: Comments on 'Striking long-term beneficial effects of single-dose psilocybin and psychedelic mushroom extract in the SAPAP3 rodent model of OCD-like excessive self-grooming' by Brownstien et al. (2024).","authors":"James J Gattuso, Carey Wilson, Anthony J Hannan, Thibault Renoir","doi":"10.1038/s41380-025-03005-0","DOIUrl":"https://doi.org/10.1038/s41380-025-03005-0","url":null,"abstract":"","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CRISPRi-based screen of autism spectrum disorder risk genes in microglia uncovers roles of ADNP in microglia endocytosis and synaptic pruning","authors":"Olivia M. Teter, Amanda McQuade, Venus Hagan, Weiwei Liang, Nina M. Dräger, Sydney M. Sattler, Brandon B. Holmes, Vincent Cele Castillo, Vasileios Papakis, Kun Leng, Steven Boggess, Tomasz J. Nowakowski, James Wells, Martin Kampmann","doi":"10.1038/s41380-025-02997-z","DOIUrl":"https://doi.org/10.1038/s41380-025-02997-z","url":null,"abstract":"<p>Autism Spectrum Disorders (ASD) are a set of neurodevelopmental disorders with complex biology. The identification of ASD risk genes from exome-wide association studies and de novo variation analyses has enabled mechanistic investigations into how ASD-risk genes alter development. Most functional genomics studies have focused on the role of these genes in neurons and neural progenitor cells. However, roles for ASD risk genes in other cell types are largely uncharacterized. There is evidence from postmortem tissue that microglia, the resident immune cells of the brain, appear activated in ASD. Here, we used CRISPRi-based functional genomics to systematically assess the impact of ASD risk gene knockdown on microglia activation and phagocytosis. We developed an iPSC-derived microglia-neuron coculture system and high-throughput flow cytometry readout for synaptic pruning to enable parallel CRISPRi-based screening of phagocytosis of beads, synaptosomes, and synaptic pruning. Our screen identified <i>ADNP</i>, a high-confidence ASD risk genes, as a modifier of microglial synaptic pruning. We found that microglia with ADNP loss have altered endocytic trafficking, remodeled proteomes, and increased motility in coculture.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":"25 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143784671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Striatal dopamine tone is positively associated with adiposity in humans as determined by PET using dual dopamine type-2 receptor antagonist tracers","authors":"Valerie L. Darcey, Juen Guo, Meible Chi, Stephanie T. Chung, Amber B. Courville, Isabelle Gallagher, Peter Herscovitch, Rebecca Howard, Melissa La Noire, Lauren Milley, Alex Schick, Michael Stagliano, Sara Turner, Nicholas Urbanski, Shanna Yang, Eunha Yim, Nan Zhai, Megan S. Zhou, Kevin D. Hall","doi":"10.1038/s41380-025-02960-y","DOIUrl":"https://doi.org/10.1038/s41380-025-02960-y","url":null,"abstract":"<p>The relationship between adiposity and dopamine type-2 receptor binding potential (D2BP) in the human brain has been repeatedly studied for &gt;20 years with highly discrepant results, likely due to variable methodologies and differing study populations. We conducted a controlled inpatient feeding study to measure D2BP in the striatum using positron emission tomography with both [¹⁸F]fallypride and [¹¹C]raclopride in pseudo-random order in 54 young adults with a wide range of body mass index (BMI 20–44 kg/m²). Within-subject D2BP measurements using the two tracers were moderately correlated (r = 0.47, <i>p</i> &lt; 0.001). D2BP was negatively correlated with BMI as measured by [¹¹C]raclopride (r = −0.51; <i>p</i> &lt; 0.0001) but not [¹⁸F]fallypride (r = −0.01; <i>p</i> = 0.92) and these correlation coefficients were significantly different from each other (<i>p</i> &lt; 0.001). Given that [¹⁸F]fallypride has greater binding affinity to dopamine type-2 receptors than [¹¹C]raclopride, which is more easily displaced by endogenous dopamine, our results suggest that adiposity is positively associated with increased striatal dopamine tone.ClinicalTrials.gov Identifier: NCT03648892</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":"59 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143784712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deconstructing a common pathway concept for Deep Brain Stimulation in the case of Obsessive-Compulsive Disorder","authors":"Volker A. Coenen, Mircea Polosan, Thomas E. Schläpfer, Stephan Chabardes, Dora M. Meyer-Doll, Manuel Czornik, Oskan Sürücü, Juan Carlos Baldermann, Dominique Endres, Horst Urbach, Peter C. Reinacher, Alexander Rau, Máté D. Döbrössy, Bastian E. A. Sajonz, Marco Reisert","doi":"10.1038/s41380-025-03008-x","DOIUrl":"https://doi.org/10.1038/s41380-025-03008-x","url":null,"abstract":"<p>Deep Brain Stimulation (DBS) is a therapeutic option for treatment resistant (TR) obsessive-compulsive disorder (OCD). The OCD network comprises different sub-networks with homeostatic functions, altered under disease and modifiable with DBS. Connectomic analyses of DBS data sets have defined fiber selections explaining anti-OCD efficacy. This is a retrospective stimulation and outcome derived anatomical overlay analysis of 26 TR-OCD patients who received DBS at two academic centers. Grenoble, 14 anteromedial subthalamic nucleus (amSTN); Freiburg, 12 superolateral medial forebrain bundle (slMFB). Yale-Brown Obsessive Compulsive Scale improvement at 24 months served as outcome parameter. Structural proximity and outcomes were correlated using individual volumes of activated tissue for STN, slMFB, ORT (average OCD response tract) and further structures based on atlases or established connectomes. Connectomes (slMFB, ORT) were inspected for structural congruences. Normative connectomic data served to investigate cortical fiber penetration for the two target regions. Cortical sub-network conjugations were evaluated as peak levels. Our analyses revealed that ORT represents a fiber selection from the slMFB. DBS of amSTN and slMFB each address distinctive sub-networks while deep amSTN DBS can also address slMFB. Sub-network conjugations project amongst other regions onto the dorsomedial prefrontal cortex (dmPFC). The average ORT fiber selection is an integral part of the generic slMFB. Anti-OCD effects of amSTN DBS are not entirely explained by ORT overlay. The slMFB is dispersed and encompasses all OCD sub-networks and might qualify as a common DBS target when stimulated close to the ventral tegmental area. The dmPFC emerges as an interesting conjugation/hub between OCD sub-networks.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":"4 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143784672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression of SARS-CoV-2 entry receptor ACE2 in human brain and its association with Alzheimer’s disease and COVID-19","authors":"Sijie Li, Jingyi Sun, He Li, Zhifa Han, Tao Wang, Shan Gao, Ping Zhu, Yan Chen, Peiguang Yan, Mingxin Wang, Guiyou Liu","doi":"10.1038/s41380-025-03006-z","DOIUrl":"https://doi.org/10.1038/s41380-025-03006-z","url":null,"abstract":"<p>It is known that infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cause coronavirus disease 2019 (COVID-19). It is widely reported that Alzheimer’s disease (AD) is associated with the highest risk of COVID-19 infection, hospitalization and mortality. However, it remains largely unclear about the link between AD and COVID-19. ACE2 is an entry receptor for SARS-CoV-2. We consider that there may be a link between AD and COVID-19 through the expression of ACE2. Here, we summarize recent findings about the ACE2 expression especially in AD and COVID-19, and shows that (1) ACE2 shows mRNA and protein expression in human brain tissues, especially in neurons and non-neuron cells; (2) low ACE2 mRNA and protein expression are sufficient for SARS-CoV-2 entry into the human brain through the neural route (olfactory and/or vagal) and the hematogenous route; (3) SARS-CoV-2 RNA and protein were detected in brains of COVID-19 patients; (4) SARS-CoV-2 infects and replicates in human brain dependent on ACE2; (5) SARS-CoV-2 viral RNA load shows a positive association with ACE2 mRNA levels and COVID-19 severity; (6) ACE2 shows increased expression in AD compared with controls in human brain; (7) ACE2 shows increased expression in COVID-19 compared with controls in human brain; (8) ACE2 expression levels affect COVID-19 outcomes. Together, ACE2 shows significantly increased mRNA and protein expression in AD compared with controls in human brain. Consequently, the increased expression of ACE2 would facilitate infection with SARS-CoV-2, and play a role in the context of COVID-19. These findings suggest that the expression of ACE2 may partly explain the link of AD with COVID-19 infection, hospitalization and mortality.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":"59 8 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143784673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Maternal prenatal stress induces sex-dependent changes in tRNA fragment families and cholinergic pathways in newborns","authors":"Shani Vaknine Treidel, Silvia M. Lobmaier, Ritika Sharma, Nimrod Madrer, Serafima Dubnov, Dana Shulman, Pnina Greenberg, Estelle R. Bennett, David S. Greenberg, Adi Turjeman, Camilla Zelgert, Peter Zimmermann, Martin G. Frasch, Liran Carmel, Marta C. Antonelli, Hermona Soreq","doi":"10.1038/s41380-025-03011-2","DOIUrl":"https://doi.org/10.1038/s41380-025-03011-2","url":null,"abstract":"<p>Maternal perceived prenatal stress (PPS) is a known risk factor for diverse developmental impairments in newborns, but the underlying molecular processes are incompletely understood. Here, we report that maternal PPS altered the birth profiles of blood transfer RNA fragments (tRFs), 16–50 nt long non-random cleavage products of tRNAs, in a sex-dependent manner. Importantly, comparing stressed versus control maternal and umbilical cord blood serum presented alterations that were not limited to individual tRFs, but rather reflected selective changes in particular tRF families grouped by their mitochondrial or nuclear genome origin, parental tRNA coded amino acid, and cleavage type. Specifically, tRF families that show stress- and sex-specific effects, revealed shared length and expression patterns which were strongest in the female newborns. Several of these tRFs carry complementary motifs to particular cholinergic mRNAs, suggesting possible translational regulation similar to microRNAs. Compatible with the cholinergic regulation of stress reactions, those “CholinotRFs” achieved an AUC of 95% when classifying female newborns according to maternal PPS. Moreover, we found altered catalytic activity of serum acetylcholinesterase, which was particularly elevated in male newborns, marking a second sex-specific effect. Our findings demonstrate an association of tRF families’ patterns with newborns’ sex-specific stress response to PPS and may lead to better diagnosis and therapeutic tools for these and other stressors.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":"63 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143782537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The functional role of locus coeruleus microglia in the female stress response","authors":"Cora E. Smiley, Brittany S. Pate, Samantha J. Bouknight, Evelynn N. Harrington, Aaron M. Jasnow, Susan K. Wood","doi":"10.1038/s41380-025-02971-9","DOIUrl":"https://doi.org/10.1038/s41380-025-02971-9","url":null,"abstract":"<p>Neuropsychiatric disorders that result from stress exposure are highly associated with central inflammation. Our previous work established that females selectively exhibit heightened proinflammatory cytokine production within the noradrenergic locus coeruleus (LC) along with a hypervigilant behavioral phenotype in response to witnessing social stress. Notably, ablation of microglia using pharmacological techniques prevents this behavioral response. These studies were designed to further investigate the impact of stress-induced neuroimmune signaling on the long-term behavioral and neuronal consequences of social stress exposure in females using chemogenetics. We first characterized the use of an AAV-CD68-G_i-DREADD virus targeted to microglia within the LC and confirmed viral transduction, selectivity, and efficacy. Clozapine-n-oxide (CNO) was used for the suppression of microglial reactivity during acute and chronic exposure to vicarious/witness social defeat in female rats. Chemogenetic-mediated inhibition of microglial reactivity during stress blunted the neuroimmune response to stress and prevented both acute and long-term hypervigilant behavioral responses. Further, a history of microglial suppression during stress prevented the heightened LC activity typically observed in response to stress cues. These studies are among the first to use a chemogenetic approach to inhibit central microglia in vivo and establish LC microglia as a key driver of the behavioral and neuronal responses to social stress in females.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":"23 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143782539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cocaine and morphine induce shared and divergent transcriptional regulation in nucleus accumbens D1 and D2 medium spiny neurons","authors":"Caleb J. Browne, Philipp Mews, Molly Estill, Xianxiao Zhou, Leanne M. Holt, Rita Futamura, Li Shen, Bin Zhang, Eric J. Nestler","doi":"10.1038/s41380-025-03004-1","DOIUrl":"https://doi.org/10.1038/s41380-025-03004-1","url":null,"abstract":"<p>Substance use disorders (SUDs) induce widespread molecular dysregulation in nucleus accumbens (NAc), a brain region pivotal for coordinating motivation and reward, which is linked to neural and behavioral disturbances promoting addiction. Despite the overlapping symptomatology of SUDs, different drug classes exert partly unique influences on neural circuits, cell types, physiology, and gene expression. To better understand common and divergent molecular mechanisms governing SUD pathology, we characterized the cell-type-specific restructuring of the NAc transcriptional landscape after psychostimulant or opioid exposure. We combined fluorescence-activated nuclei sorting and deep RNA sequencing to profile NAc D1 and D2 medium spiny neurons (MSNs) across cocaine and morphine exposure paradigms, including initial exposure, prolonged withdrawal after repeated exposure, and re-exposure post-withdrawal. Our analyses reveal that D1 MSNs display many convergent transcriptional responses between the two drug classes, whereas D2 MSNs manifest highly divergent responses, with morphine causing more adaptations in this cell type. Utilizing multiscale embedded gene co-expression network analysis (MEGENA), we discerned transcriptional regulatory networks subserving biological functions altered by cocaine vs. morphine. We observed largely integrative engagement of overlapping gene networks across drug classes in D1 MSNs, but opposite regulation of key D2 networks, highlighting potential therapeutic gene network targets within MSNs. Analysis of gene regulatory systems at the level of enhancers revealed that morphine engages a unique enhancer landscape in D2 MSNs compared to cocaine. Our findings, and future work leveraging this dataset, will open avenues for the development of targeted therapeutic interventions, addressing the urgent need for more effective treatments for SUDs.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":"37 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143784713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Directed exploration is reduced by an aversive interoceptive state induction in healthy individuals but not in those with affective disorders","authors":"Ning Li, Claire A. Lavalley, Ko-Ping Chou, Anne E. Chuning, Samuel Taylor, Carter M. Goldman, Taylor Torres, Rowan Hodson, Robert C. Wilson, Jennifer L. Stewart, Sahib S. Khalsa, Martin P. Paulus, Ryan Smith","doi":"10.1038/s41380-025-02980-8","DOIUrl":"https://doi.org/10.1038/s41380-025-02980-8","url":null,"abstract":"<p>Elevated anxiety and uncertainty avoidance are known to exacerbate maladaptive choice in individuals with affective disorders. However, the differential roles of state vs. trait anxiety remain unclear, and underlying computational mechanisms have not been thoroughly characterized. In the present study, we investigated how a somatic (interoceptive) state anxiety induction influences learning and decision-making under uncertainty in individuals with clinically significant levels of trait anxiety. A sample of 58 healthy comparisons (HCs) and 61 individuals with affective disorders displaying elevated anxiety symptoms (iADs; i.e., anxiety and/or depression) completed a previously validated explore-exploit decision task, with and without an added breathing resistance manipulation designed to induce state anxiety. Computational modeling revealed a significant group-by-condition interaction, such that information-seeking (i.e., directed exploration) in HCs was reduced by the anxiety induction (Cohen’s <i>d</i> = 0.47, <i>p</i> = 0.013), while no change was observed in iADs. The iADs also showed slower learning rates than HCs across conditions (Cohen’s <i>d</i> = 0.52, <i>p</i> = 0.003), suggesting their uncertainty decreased more slowly over time. These findings highlight a complex interplay between trait anxiety and state anxiety. Specifically, state anxiety may attenuate reflection on uncertainty in healthy individuals, while familiarity with anxious states in those with high trait anxiety may create an insensitivity to this effect.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":"108 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143782538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}