Brain, Behavior, and Immunity最新文献

{"title":"Decreased neutrophil-to-lymphocyte ratio predicted cognitive improvement in late-life depression treated with vortioxetine: Findings from an eight-week randomized controlled trial","authors":"Lingfeng Xue ,&nbsp;Elin Lewis ,&nbsp;Mariia Bocharova ,&nbsp;Allan H. Young ,&nbsp;Dag Aarsland","doi":"10.1016/j.bbi.2025.01.029","DOIUrl":"10.1016/j.bbi.2025.01.029","url":null,"abstract":"<div><h3>Background</h3><div>Elevated neutrophil-to-lymphocyte ratio, a marker of inflammation, has been reported in adult and late-life depression. Vortioxetine has shown efficacy in treatment of late-life depression, yet little is known regarding its immunomodulatory role in clinical trials.</div></div><div><h3>Methods</h3><div>This is a post-hoc analysis of an eight-week randomized controlled trial. Depressed patients aged 65 or above were treated by vortioxetine, duloxetine or placebo. 321 patients that have taken blood tests at baseline and endpoint were included in the analysis. Neutrophil-to-lymphocyte ratio (NLR) was calculated using the absolute counts of each cell type. Cognitive performance was assessed by composite score of Digit Symbol Substitution Test (DSST) and the Rey Auditory Verbal Learning Test (RAVLT) tasks, while depressive symptoms were assessed by Montgomery–Åsberg Depression Rating Scale (MADRS) and Geriatric Depression Scale (GDS).</div></div><div><h3>Results</h3><div>NLR levels decreased significantly in the entire analysis set (<em>t</em>₍₃₂₀₎ = 2.64, <em>p</em> = 0.008) and in the vortioxetine group (M = −0.186, <em>t</em>₍₁₀₅₎ = 2.070, <em>p</em> = 0.041, Cohen’s d = 0.20), but not in the two other groups. This decrease was not significantly different compared to placebo (<em>F</em>_{(1, 213)} = 0.420, <em>p</em> = 0.517). Furthermore, larger NLR changes in vortioxetine arm predicted significant cognitive improvement (<em>β</em> = −4.03, <em>p</em> = 0.03), specifically regarding the DSST correct symbols (<em>β</em> = −1.97, <em>p</em> = 0.04) and RAVLT delayed recall (<em>β</em> = −1.87, <em>p</em> = 0.02) tasks. Additionally, decreased NLR significantly predicted reduced GDS score (<em>β</em> = 1.82, <em>p</em> = 0.02), yet not MADRS score.</div></div><div><h3>Conclusion</h3><div>Vortioxetine treatment was associated with decreased NLR levels in late-life depression, and reductions in NLR predicted improvements in cognitive function and depressive symptoms, suggesting a potential link between inflammation and clinical outcomes.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"126 ","pages":"Pages 53-58"},"PeriodicalIF":8.8,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143373876","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":"Association between hospital-treated infectious diseases and risk of neurodegenerative disease among patients with prediabetes and diabetes: A prospective cohort study in UK Biobank","authors":"Jing Wang ,&nbsp;Yifang Huang ,&nbsp;Qiuli Zhu ,&nbsp;Chen Huang ,&nbsp;Ruilang Lin ,&nbsp;Yuwei Peng ,&nbsp;Zixuan Jiang ,&nbsp;Dongxu Tang ,&nbsp;Ye Yao ,&nbsp;Xueying Zheng ,&nbsp;Guoyou Qin ,&nbsp;Jiaohua Chen","doi":"10.1016/j.bbi.2025.01.027","DOIUrl":"10.1016/j.bbi.2025.01.027","url":null,"abstract":"<div><h3>Background</h3><div>Previous evidence suggests that infectious diseases may contribute to the development of neurodegenerative diseases (NDDs) while individuals with hyperglycemia may be at increased risk for both infection and NDDs due to dysregulated inflammation levels. This study aimed to examine the association between hospital-treated infectious diseases and the risk of NDDs among patients with prediabetes and diabetes and whether the associations differed by the number of infections and potential effect modifiers.</div></div><div><h3>Study Design and Method</h3><div>Using data from the UK Biobank, we conducted a prospective study involving 69,731 individuals, consisting of 48,149 participants with prediabetes and 21,582 participants with diabetes. Hospital-treated infectious diseases and NDDs were identified through record linkage to Health Episode Statistics and the Scottish Morbidity Records. Cox regression models were applied to assess the association between hospital-treated infectious diseases and the risk of developing NDDs, and to evaluate the trend of this association in relation to the number of infections. The modification effects by age, sex, smoking status, alcohol consumption, sleep duration, body mass index (BMI), glycated hemoglobin (HbA_1c) levels, comorbidities, and diabetes medication use were investigated.</div></div><div><h3>Results</h3><div>Over a median follow-up of 10.75 years, 1,867 participants (2.57 per 1,000 person­years) were diagnosed with NDDs. We found hospital-treated infectious diseases were significantly associated with an increased risk of NDDs among both individuals with prediabetes or diabetes (adjusted HR [aHR] 3.11, 95 % CI 2.83–3.42). Specifically, hospital-treated infectious diseases were associated with a higher risk of developing Alzheimer’s disease, vascular dementia, all-cause dementia, Parkinson’s disease, and multiple sclerosis. Moreover, a greater number of infection diagnoses was associated with a higher risk of NDDs. Consistent associations between infection and an increased risk of NDDs were observed, regardless of factors representing age, sex, lifestyle, and diabetes severity.</div></div><div><h3>Conclusions</h3><div>Hospital-treated infectious diseases were significantly associated with the risk of NDDs in individuals with diabetes and prediabetes, with similar associations observed for bacterial and viral infections. These findings emphasize the importance of implementing infection prevention strategies and monitoring of infectious comorbidities in the management of NDDs among patients with prediabetes and diabetes.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"126 ","pages":"Pages 30-37"},"PeriodicalIF":8.8,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143349696","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":"Increased LPS-induced fever and sickness behavior in adult male and female rats perinatally exposed to morphine","authors":"Hannah J. Harder ,&nbsp;Morgan G. Gomez,&nbsp;Christopher T. Searles,&nbsp;Meghan E. Vogt,&nbsp;Anne Z. Murphy","doi":"10.1016/j.bbi.2025.01.019","DOIUrl":"10.1016/j.bbi.2025.01.019","url":null,"abstract":"<div><div>As a result of the current opioid crisis, the rate of children born exposed to opioids has skyrocketed. Later in life, these children have an increased risk for hospitalization and infection, raising concerns about potential immunocompromise, as is common with chronic opioid use. Opioids can act directly on immune cells or indirectly via the central nervous system to decrease immune system activity, leading to increased susceptibility, morbidity, and mortality to infection. However, it is currently unknown how perinatal opioid exposure (POE) alters immune function. Using a clinically relevant and translatable model of POE, we have investigated how baseline immune function and the reaction to an immune stimulator, lipopolysaccharide, is influenced by <em>in utero</em> opioid exposure in adult male and female rats. We report here that POE potentiates the febrile and neuroinflammatory response to lipopolysaccharide, likely due to suppressed immune function at baseline. This suggests that POE increases susceptibility to infection by manipulating immune system development, consistent with the clinical literature. Investigation of the mechanisms whereby POE increases susceptibility to pathogens is critical for the development of potential interventions for immunosuppressed children exposed to opioids <em>in utero</em>.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"126 ","pages":"Pages 38-52"},"PeriodicalIF":8.8,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254467","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":"Effects of kynurenine pathway metabolites on choroid plexus volume, hemodynamic response, and spontaneous neural activity: A new mechanism for disrupted neurovascular communication and impaired cognition in mood disorders","authors":"Beatrice Bravi ,&nbsp;Chiara Verga ,&nbsp;Mariagrazia Palladini ,&nbsp;Sara Poletti ,&nbsp;Camilla Buticchi ,&nbsp;Sut Stefania ,&nbsp;Dall’Acqua Stefano ,&nbsp;Cristina Colombo ,&nbsp;Stefano Comai ,&nbsp;Francesco Benedetti","doi":"10.1016/j.bbi.2025.01.025","DOIUrl":"10.1016/j.bbi.2025.01.025","url":null,"abstract":"<div><div>Major Depressive Disorder (MDD) and Bipolar Disorder (BD) involve alterations of immune-inflammatory setpoints that activate the kynurenine pathway (KP), affecting serotoninergic and glutamatergic neurotransmission through indoleamine-2,3-dioxygenase (IDO) activity. This process produces metabolites like Kynurenine (Kyn), 3-Hydroxykynurenine (3-HK), Quinolinic acid (QuinA), and Kynurenic acid (KynA), these last two acting as agonist and antagonist at glutamatergic N-methyl-D-aspartate receptors (NMDARs), respectively. NMDARs, expressed in the choroid plexus (ChP) and arteriolar smooth muscle cells, regulate blood–brain-barrier permeability and cerebral artery dilation, suggesting that KP may influence neurovascular coupling, aligning blood flow with neural energy demand. KP’s role in modulating vascular tone supports this hypothesis. Altered fractional amplitude of low-frequency fluctuations (fALFF) and disrupted default mode network (DMN) activity in mood disorders are linked to cognitive deficits possibly through neurovascular uncoupling like in neurological diseases. This makes fALFF and hemodynamic response function (HRF) potential indicators of these changes. We investigated KP associations with ChP volumes, functional-MRI at rest measures like spontaneous neural activity (fALFF) and hemodynamic response function (HRF) parameters within the default mode network (DMN), and cognitive performance in 42 MDD and 36 BD inpatients experiencing a depressive episode.</div><div>Results revealed that lower QuinA/KynA ratios and higher KynA levels predict larger ChP volumes. Higher KYN and 3-HK levels, along with lower KynA levels, were associated with increased DMN fALFF and shorter time-to-peak (TTP) in HRF, suggesting altered neurovascular coupling. Mediation analyses indicated that KP metabolites influenced cognitive performance through their effects on resting state measures, affecting global cognitive functioning score, verbal fluency, and psychomotor coordination. These findings suggest that KP metabolites modulate brain function and structure via NMDAR-mediated pathways and vascular-based mechanisms, offering insights into the cognitive impairments observed in mood disorders and identifying potential therapeutic targets.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"125 ","pages":"Pages 414-427"},"PeriodicalIF":8.8,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143136663","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":"No rest, no stress: Rethinking sleep disturbances in adolescence","authors":"Kiersten S. Bell,&nbsp;Laura K. Fonken","doi":"10.1016/j.bbi.2025.02.001","DOIUrl":"10.1016/j.bbi.2025.02.001","url":null,"abstract":"","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"126 ","pages":"Pages 1-2"},"PeriodicalIF":8.8,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143215887","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":"Chipping away at the iceberg: Uncovering immune complexity in schizophrenia","authors":"Fabiana Corsi-Zuelli","doi":"10.1016/j.bbi.2025.01.023","DOIUrl":"10.1016/j.bbi.2025.01.023","url":null,"abstract":"","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"125 ","pages":"Pages 410-412"},"PeriodicalIF":8.8,"publicationDate":"2025-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143136664","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 language we speak amid COVID-19","authors":"Zhaohui Su ,&nbsp;Francis Mungai Kaburu ,&nbsp;Abdulswabul Kudiza ,&nbsp;Ruijie Zhang ,&nbsp;Chaojun Tong ,&nbsp;Mehak Intizar ,&nbsp;Jianlin Jiang ,&nbsp;Xin Yu ,&nbsp;Qiang Kuang ,&nbsp;Ruru Chen ,&nbsp;Dean McDonnell ,&nbsp;Junaid Ahmed ,&nbsp;Barry L. Bentley ,&nbsp;Ali Cheshmehzangi ,&nbsp;Sabina Šegalo ,&nbsp;Jing-Bao Nie ,&nbsp;Claudimar Pereira da Veiga ,&nbsp;Yu-Tao Xiang","doi":"10.1016/j.bbi.2025.02.004","DOIUrl":"10.1016/j.bbi.2025.02.004","url":null,"abstract":"<div><div>The language we speak shapes our perceptions of reality. In this paper, we shed light on the fact that by inventing and normalizing phrases such as the “UK variant”, “Chinese virus”, or the “Spanish flu”, along with the widespread use of war metaphors, we are not only endorsing narratives that could undermine international collaborations and deepen divisions within society, harming people’s mental health, but also distracting the public’s attention from the most important issue amid pandemics—how to stall or stem transmission in a timely matter. Furthermore, we also make a call to action for media professionals, health experts, and government officials to stop creating and popularizing discriminative terms related to COVID-19 and future outbreaks, so that we can reduce the divisions between societies and better focus on controlling pandemics.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"126 ","pages":"Pages 356-360"},"PeriodicalIF":8.8,"publicationDate":"2025-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188249","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":"Regional skull translocator protein elevation in autistic adults detected by PET-MRI","authors":"Chieh-En Jane Tseng ,&nbsp;Elisa Guma ,&nbsp;Christopher J. McDougle ,&nbsp;Jacob M. Hooker ,&nbsp;Nicole R. Zürcher","doi":"10.1016/j.bbi.2025.02.002","DOIUrl":"10.1016/j.bbi.2025.02.002","url":null,"abstract":"<div><div>Immune processes have been implicated in the pathophysiology of autism spectrum disorder (ASD). Brain borders, such as the skull, have recently been highlighted as sites where neuro-immune interactions occur with key consequences for brain immunity. Translocator protein (TSPO), a mitochondrial protein involved in immune functions, was measured in the skull using [¹¹C]PBR28 positron emission tomography-magnetic resonance imaging (PET-MRI) in 38 autistic adults (26 males, 12 females) and 29 age-and sex-matched healthy controls (19 males, 10 females). [¹¹C]PBR28 uptake relative to a pseudo-reference region assessed using standardized uptake value ratio (SUVR) revealed elevated TSPO in autistic adults in frontal and temporal skull. We did not observe an association between [¹¹C]PBR28 uptake in total or regional skull areas and autism symptom severity. C-reactive protein levels were positively associated with [¹¹C]PBR28 uptake in the total skull across participants. Lastly, [¹¹C]PBR28 uptake in the total skull was stable across a 4-month period. This work indicates regional TSPO elevations in the skull in autistic adults, which may suggest immune involvement.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"126 ","pages":"Pages 70-79"},"PeriodicalIF":8.8,"publicationDate":"2025-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188237","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":"Evidence of microglial involvement in the childhood abuse-associated increase in perineuronal nets in the ventromedial prefrontal cortex","authors":"Claudia Belliveau ,&nbsp;Reza Rahimian ,&nbsp;Gohar Fakhfouri ,&nbsp;Clémentine Hosdey ,&nbsp;Sophie Simard ,&nbsp;Maria Antonietta Davoli ,&nbsp;Dominique Mirault ,&nbsp;Bruno Giros ,&nbsp;Gustavo Turecki ,&nbsp;Naguib Mechawar","doi":"10.1016/j.bbi.2024.12.013","DOIUrl":"10.1016/j.bbi.2024.12.013","url":null,"abstract":"<div><div>Microglia, known for their diverse roles in the central nervous system, have recently been recognized for their involvement in degrading the extracellular matrix. Perineuronal nets (PNNs), a specialized form of this matrix, are crucial for stabilizing neuronal connections and constraining plasticity. Our group recently reported increased PNN densities in the ventromedial prefrontal cortex (vmPFC) of depressed individuals that died by suicide in adulthood after experiencing childhood abuse (DS-CA) compared to matched controls. To explore potential underlying mechanisms, we employed a comprehensive approach in similar postmortem vmPFC samples, combining a human matrix metalloproteinase and chemokine array, isolation of CD11b-positive microglia and enzyme-linked immunosorbent assays (ELISA). Our findings indicate a significant downregulation of matrix metalloproteinase (MMP)-9 and tissue inhibitors of metalloproteinases (TIMP)-2 in both whole vmPFC grey matter and isolated microglial cells from DS-CA samples. Furthermore, our experiments reveal that a history of child abuse is associated with diminished levels of microglial CX3CR1 and IL33R in both vmPFC whole lysate and CD11b⁺ isolated cells. However, levels of the CX3CR1 ligand, CX3CL1 (Fractalkine), did not differ between groups. While these data suggest potential long-lasting alterations in microglial markers in the vmPFC of individuals exposed to severe childhood adversity, direct functional assessments were not conducted. Nonetheless, these findings offer insight into how childhood abuse may contribute to PNN alterations via microglial-related mechanisms.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"124 ","pages":"Pages 321-334"},"PeriodicalIF":8.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142821783","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":"Transcriptional signature of a hypersensitive glucocorticoid receptor variant in the neuroendocrine system suggests enhanced vulnerability to brain disorders","authors":"Eduard Murani,&nbsp;Nares Trakooljul,&nbsp;Frieder Hadlich,&nbsp;Klaus Wimmers","doi":"10.1016/j.bbi.2024.12.004","DOIUrl":"10.1016/j.bbi.2024.12.004","url":null,"abstract":"<div><div>The natural substitution Ala610Val in the porcine glucocorticoid receptor (GR_Ala610Val) leads to a profound compensatory downregulation of the hypothalamic–pituitary–adrenal (HPA) axis in early ontogeny. In this study, we leveraged this unique animal model to explore mechanisms of HPA axis regulation and consequences of its genetically-based persistent hypoactivity. To this end, we examined transcriptional signature of GR_Ala610Val in the hypothalamus, hippocampus, amygdala and adrenal gland in resting conditions (i.e. baseline glucocorticoid level) using mRNA sequencing. In addition, we studied transcriptome responses to two different doses of dexamethasone in the hypothalamus and hippocampus, depending on GR_Ala610Val. Across tissues, GR_Ala610Val consistently influenced the expression of several clustered protocadherins, particularly <em>PCDHB7</em>. Clustered protocadherins play an important role in neuronal connectivity and are implicated in different neurobiological disorders. Moreover, in line with our previous findings in blood immune cells, we found higher expression of pro-inflammatory genes, including canonical members of the TLR4 signaling pathway, in the brain of Val carriers. While the pro-inflammatory priming occurs already at resting conditions in the amygdala, in hypothalamus and hippocampus this seems to be associated with a stronger downregulation of several marker genes of homeostatic microglia, such as <em>SALL1</em>, by dexamethasone in Val carriers. Regarding the regulation of the HPA axis, GR_Ala610Val showed a dose-dependent effect on the central regulator of the axis, <em>CRH</em>, suggesting a dynamic adaptation to the glucocorticoid hypersensitivity of the Val variant. In the adrenal gland, GR_Ala610Val appears to downregulate cortisol production by impairing mitochondrial function. Overall, the transcriptional signature of GR_Ala610Val provides strong evidence that GR hypersensitivity leads to increased susceptibility to brain disorders.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"124 ","pages":"Pages 335-346"},"PeriodicalIF":8.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142823673","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}