Neurotherapeutics最新文献

{"title":"Discovery of an APP-selective BACE1 inhibitor for Alzheimer's disease","authors":"Jesus Campagna ,&nbsp;Barbara Jagodzinska ,&nbsp;Dongwook Wi ,&nbsp;Chunni Zhu ,&nbsp;Jessica Lee ,&nbsp;Whitaker Cohn ,&nbsp;Michael Jun ,&nbsp;Chris Elias ,&nbsp;Samar Padder ,&nbsp;Olivier Descamps ,&nbsp;Clare Peters-Libeu ,&nbsp;Qiang Zhang ,&nbsp;Olivia Gorostiza ,&nbsp;Karen Poksay ,&nbsp;Patricia Spilman ,&nbsp;Dale Bredesen ,&nbsp;Varghese John","doi":"10.1016/j.neurot.2025.e00610","DOIUrl":"10.1016/j.neurot.2025.e00610","url":null,"abstract":"<div><div>Inhibition of amyloid precursor protein (APP) beta-site cleaving enzyme 1 (BACE1) has been a target for Alzheimer's disease (AD) therapeutic development. Here, we report our identification of APP-selective BACE1 (ASBI) inhibitors that are selective for APP as the substrate and BACE1 as the target enzyme. A known fluoro aminohydantoin (FAH) inhibitor compound was identified by screening a compound library for inhibition of BACE1 cleavage of a maltose binding protein (MBP)-conjugated-APPC125 substrate followed by optimization and IC50 determination using the P5-P5′ activity assay. Optimization of the screening hit led to candidate FAH65, which displays selectivity for inhibition of APP cleavage with little activity against other BACE1 substrates neuregulin 1 (NRG1) or p-selectin glycoprotein ligand-1 (PSGL1). FAH65 shows little inhibitory activity against other aspartyl proteases cathepsin D (Cat D) and BACE2. FAH65 reduces BACE1 cleavage products soluble APPβ (sAPPβ) and the β C-terminal fragment (βCTF), as well as amyloid-β (Aβ) 1-40 and 1-42, both <em>in vitro</em> in cells and <em>in vivo</em> in an animal model of AD. In a murine model of AD, FAH65 improved the discrimination score in the Novel Object Recognition (NOR) memory testing paradigm. The active enantiomer of racemate FAH65, FAH65E(-), displays good brain-penetrance and target engagement, meriting further pre-clinical development as an ASBI that may reduce Aβ levels and overcome the deleterious effects of the non-selective BACE1 inhibitors that have failed in the clinic. FAH65E(-) has the potential to be a first-in-class oral therapy that could be used in conjunction with an approved anti-Aβ antibody therapy for AD.</div></div>","PeriodicalId":19159,"journal":{"name":"Neurotherapeutics","volume":"22 5","pages":"Article e00610"},"PeriodicalIF":6.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144120363","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":"Enhancing working memory in MCI: Modulating alpha-gamma coupling and gamma oscillations via rTMS","authors":"Xiao Yuan ,&nbsp;Xiaochen Zhang ,&nbsp;Jingnan Sun ,&nbsp;Renren Li ,&nbsp;Jing Ma ,&nbsp;Chenxi Pan ,&nbsp;Meng Liu ,&nbsp;Hualan Yang ,&nbsp;Dan Yang ,&nbsp;Fangyun Li ,&nbsp;Zhi Bie ,&nbsp;Zhen Hu ,&nbsp;Yunxia Li","doi":"10.1016/j.neurot.2025.e00619","DOIUrl":"10.1016/j.neurot.2025.e00619","url":null,"abstract":"<div><div>Cross-frequency coupling (CFC), particularly the interaction between alpha and gamma oscillations, is a pivotal mechanism implicated in cognitive function, with potential for modulation by repetitive transcranial magnetic stimulation (rTMS). This study aimed to investigate the impact of high-frequency rTMS (HF rTMS) on CFC and visual working memory (VWM) in individuals with mild cognitive impairment (MCI). Twenty MCI patients and twenty healthy controls were administered 10Hz rTMS targeting the left dorsolateral prefrontal cortex (DLPFC). Our critical findings indicate that post-intervention, MCI patients exhibited significant enhancements in VWM performance, notably under low memory load. These improvements correlated with a reduction in occipital gamma activity, and were concurrent with strengthened phase-amplitude coupling (PAC) between frontal alpha and occipital gamma oscillations. The results underscore the capacity of alpha-band HF rTMS to modulate neural activity, offering a promising, non-invasive strategy for enhancing cognitive performance in MCI.</div></div>","PeriodicalId":19159,"journal":{"name":"Neurotherapeutics","volume":"22 5","pages":"Article e00619"},"PeriodicalIF":6.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144275457","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":"Clinical experience implanting a miniature externally powered vagus nerve stimulator","authors":"Joseph D. Epperson ,&nbsp;Michael L. Foreman ,&nbsp;Richard C. Naftalis ,&nbsp;Rita G. Hamilton ,&nbsp;Mark B. Powers ,&nbsp;Holle L. Gallaway ,&nbsp;Gregory dePrisco ,&nbsp;Seth A. Hays ,&nbsp;Michael P. Kilgard ,&nbsp;Robert L. Rennaker II ,&nbsp;Jane G. Wigginton","doi":"10.1016/j.neurot.2025.e00625","DOIUrl":"10.1016/j.neurot.2025.e00625","url":null,"abstract":"<div><div>Vagus nerve stimulation (VNS) is widely used to treat various neurological and psychiatric conditions, including epilepsy and treatment-resistant depression, as well as to enhance motor rehabilitation following stroke. Conventional VNS devices have demonstrated reliability over decades of use, though recent advancements in technology offer new opportunities to further enhance the device. Many emerging indications require only intermittent stimulation, allowing for the development of a miniature externally powered implantable stimulator (MEPS) that is approximately 50 times smaller than conventional devices, is implanted with a single incision, has no battery or leads, and enables paired stimulation. Our observations compiled from three clinical trials with the MEPS device tested the hypotheses that removing the implanted battery and reducing device size would (1) shorten the surgical procedure and (2) maintain or improve safety outcomes. Data were collected from individuals with stroke, spinal cord injury, or post-traumatic stress disorder. Operative time was significantly reduced, averaging 38 ​± ​1 ​min compared to 76 ​± ​3 ​min for conventional VNS, with no significant intraoperative complications and no revision surgeries. The MEPS device successfully delivered 481,995 stimulations during 2205 ​h of therapy. One participant underwent an MRI outside the study, indicating compatibility with standard imaging protocols. Device-related adverse events occurred at a low rate; all were mild and resolved before study end. Overall, the MEPS device demonstrated a favorable safety and performance profile in a select population, with fewer occurrences of certain adverse events, extending the strong safety record of conventional VNS systems.</div></div>","PeriodicalId":19159,"journal":{"name":"Neurotherapeutics","volume":"22 5","pages":"Article e00625"},"PeriodicalIF":6.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144512190","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":"Early versus Delayed Drug-Coated Balloons for Symptomatic Intracranial Atherosclerotic Stenosis","authors":"Xiaofei Sun ,&nbsp;Yayue Liu ,&nbsp;Lucynda Pham ,&nbsp;Guangwen Li","doi":"10.1016/j.neurot.2025.e00689","DOIUrl":"10.1016/j.neurot.2025.e00689","url":null,"abstract":"<div><div>In recent years, drug-coated balloons (DCB) have been increasingly used for intervention therapy of intracranial atherosclerotic stenosis (ICAS) with significant efficacy. However, the timing of DCB intervention therapy remains controversial, and there are few published studies that further investigated this. This study aimed to evaluate the clinical outcomes of early (≤21 days) versus delayed (21–42 days) DCB treatment in patients with ICAS. Symptomatic ICAS (sICAS) patients who underwent DCB angioplasty between August 2021 and March 2024 were included in the study. Based on the time from the last qualifying event (QE) to the procedure, patients were divided into an early group (≤21 days) and a delayed group (21–42 days). The efficacy and safety of DCB angioplasty, including perioperative complications and restenosis, were recorded and compared between the two groups. A total of 186 patients were enrolled, with 75 in the early group and 111 in the delayed group where all patients underwent DCB angioplasty successfully. The delayed group showed significantly lower postoperative residual stenosis (10 ​% vs. 20 ​%, P ​= ​0.041) and restenosis rates (10.81 ​% vs. 22.67 ​%, P ​= ​0.029) at the 12-month follow-up compared to the early group. The delayed group also had numerically lower perioperative complication rates (5.41 ​% vs. 9.33 ​%, P ​= ​0.303) and recurrence rates (7.21 ​% vs. 9.33 ​%, P ​= ​0.601), however these differences were not statistically significant. Our study concludes that in patients with sICAS, performing DCB angioplasty within 21 days may carry a higher degree of residual stenosis and an increased long-term risk of restenosis.</div></div>","PeriodicalId":19159,"journal":{"name":"Neurotherapeutics","volume":"22 5","pages":"Article e00689"},"PeriodicalIF":6.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144601069","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":"Flickers of awareness: Cerebellar stimulation in disorders of consciousness","authors":"David Fischer","doi":"10.1016/j.neurot.2025.e00636","DOIUrl":"10.1016/j.neurot.2025.e00636","url":null,"abstract":"","PeriodicalId":19159,"journal":{"name":"Neurotherapeutics","volume":"22 5","pages":"Article e00636"},"PeriodicalIF":6.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144591800","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":"Erratum to ‘Utilization of precision medicine digital twins for drug discovery in Alzheimer's disease’, Neurotherapeutics, 22(3), e00553","authors":"Yunxiao Ren ,&nbsp;Andrew A. Pieper ,&nbsp;Feixiong Cheng","doi":"10.1016/j.neurot.2025.e00628","DOIUrl":"10.1016/j.neurot.2025.e00628","url":null,"abstract":"","PeriodicalId":19159,"journal":{"name":"Neurotherapeutics","volume":"22 5","pages":"Article e00628"},"PeriodicalIF":6.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336759","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":"Integrating perfusion imaging derived venous outflow and tissue-level collateral parameters in a comprehensive clinical model enhances prognostication in large vessel occlusion stroke","authors":"Janet Mei ,&nbsp;Hamza Adel Salim ,&nbsp;Dhairya A. Lakhani ,&nbsp;Aneri Balar ,&nbsp;Vaibhav Vagal ,&nbsp;Manisha Koneru ,&nbsp;Dylan Wolman ,&nbsp;Risheng Xu ,&nbsp;Victor Urrutia ,&nbsp;Elisabeth Breese Marsh ,&nbsp;Benjamin Pulli ,&nbsp;Meisam Hoseinyazdi ,&nbsp;Licia Luna ,&nbsp;Francis Deng ,&nbsp;Nathan Z. Hyson ,&nbsp;Mona Shahriari ,&nbsp;Adam A. Dmytriw ,&nbsp;Adrien Guenego ,&nbsp;Gregory W. Albers ,&nbsp;Hanzhang Lu ,&nbsp;Vivek Yedavalli","doi":"10.1016/j.neurot.2025.e00632","DOIUrl":"10.1016/j.neurot.2025.e00632","url":null,"abstract":"<div><div>Arterial inflow restoration and collateral status have been significantly correlated with functional outcomes in AIS-LVO patients undergoing mechanical thrombectomy (MT). CT perfusion imaging biomarkers, including prolonged venous transit (PVT), cerebral blood volume (CBV) index, and hypoperfusion intensity ratio (HIR), have emerged as reliable pretreatment adjunct parameters of comprehensive flow assessment. However, their absolute and comparative effectiveness in improving prognostic prediction remains unclear when used in conjunction with clinical and arterial inflow parameters. In our prospectively maintained database, we retrospectively reviewed and analyzed 149 patients with anterior circulation AIS-LVO who underwent MT. PVT was defined as Tmax ≥10 ​s timing within the superior sagittal sinus, torcula, or both, where PVT-was considered favorable. CBV index and HIR were derived from automated CTP software and analyzed in both continuous and dichotomized forms (HIR &lt;0.4 and CBV index ≥0.8 represented favorable collaterals). A baseline logistic regression model incorporating significant clinical parameters and arterial inflow information was built first. PVT, CBV index, and HIR were subsequently incorporated individually and then in combination. Model performance was assessed using receiver operating characteristic analysis and compared by Delong's tests.PVT+ was associated with a significantly higher likelihood of unfavorable 90-day modified Rankin Scale outcomes (47.9 ​% vs. 16.7 ​%, p ​&lt; ​0.01). Incorporating PVT into a baseline model comprised of significant clinical and arterial inflow parameters (age, hypertension, NIHSS, and mTICI score) improved outcome prediction (AUC: 0.821 [95%CI 0.749–0.879]), outperforming models incorporating CBV index (AUC: 0.792 [95%CI 0.718–0.854] and 0.799 [95%CI 0.725–0.860] in continuous and dichotomized forms, respectively) or HIR (AUC: 0.789 [95%CI 0.715–0.852] and 0.789 [95%CI 0.714–0.851] in continuous and dichotomized forms, respectively). The highest predictive accuracy was achieved by combining PVT with dichotomized CBV index, significantly outperforming the baseline model (AUC: 0.831 [95%CI 0.761–0.887] vs. 0.780 [95%CI 0.705–0.843], p ​= ​0.04).The combination of PVT and CBV index in conjunction with well-established clinical and interventional parameters significantly enhances predictive accuracy. This comprehensive imaging and clinical model offers potential utility for outcome stratification and clinical decision-making. Furthermore, PVT is a stronger predictor of functional outcomes in AIS-LVO patients than CBV index or HIR, highlighting the importance of VO assessment in stroke prognosis. However, prospective studies are necessary for further evaluation of the strength of these findings.</div></div>","PeriodicalId":19159,"journal":{"name":"Neurotherapeutics","volume":"22 5","pages":"Article e00632"},"PeriodicalIF":6.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575931","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":"From metabolism to mind: The expanding role of the GLP-1 receptor in neurotherapeutics","authors":"Akash Roy ,&nbsp;Valina L. Dawson ,&nbsp;Ted M. Dawson","doi":"10.1016/j.neurot.2025.e00712","DOIUrl":"10.1016/j.neurot.2025.e00712","url":null,"abstract":"<div><div>GLP-1 receptor agonists (GLP-1RAs), initially approved for diabetes and obesity, are now under investigation for neuroprotective effects in a range of neurological disorders. These agents, whose receptors are widely expressed in brain regions involved in cognition and metabolism, modulate neurotransmitter release and promote neurogenesis. While preclinical studies consistently demonstrate benefits in models of Alzheimer's disease, Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis (ALS), clinical trial outcomes have been variable, largely owing to heterogeneity in study populations and trial design. Newer agents, such as NLY01 and tirzepatide, are under development to enhance central nervous system penetration and efficacy. Although GLP-1RAs are generally safe in metabolic conditions, their use in neurological diseases requires careful monitoring and patient selection. Future directions include developing reliable biomarkers, implementing precision medicine strategies, and exploring the use of combination therapies to maximize therapeutic potential.</div></div>","PeriodicalId":19159,"journal":{"name":"Neurotherapeutics","volume":"22 5","pages":"Article e00712"},"PeriodicalIF":6.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144753897","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":"Multi-tracer PET and MR imaging visualize distinct metabolic and inflammatory profiles in the white matter of NMOSD and MOGAD.","authors":"Shuwei Bai, Hongda Shao, Hong Yang, Kan Wang, Chenpeng Zhang, Qiuju Li, Jie Ding, Chong Xie, Tao Xue, Yong Hao, Jianjun Liu, Yangtai Guan","doi":"10.1016/j.neurot.2025.e00720","DOIUrl":"https://doi.org/10.1016/j.neurot.2025.e00720","url":null,"abstract":"<p><p>This study investigates distinct neuroinflammatory patterns in neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody disease (MOGAD) using multi-tracer PET and MR imaging. Eight NMOSD (5F/3M; median age 36.5) and six MOGAD patients (2F/4M; median age 34.0) underwent PET scans with [¹⁸F]FDG (glucose metabolism), the translocator protein (TSPO) ligand [¹⁸F]PBR06 (glial activation), and [¹¹C]acetate (astrocyte metabolism), integrated with synchronous 3T MRI sequences. Standardized uptake value ratios (SUVRs) referenced to contralateral white matter (WM) or whole brain were statistically compared across specific anatomic regions: active lesions, normal-appearing WM (NAWM), and periventricular zones. Both groups exhibited elevated [¹⁸F]PBR06 SUVR within lesions compared to contralateral WM, marking microgliosis. Crucially, NMOSD lesions showed significantly lower [¹⁸F]FDG SUVR (p ​= ​0.01; metabolic impairment) and [¹¹C]acetate SUVR (astrocyte dysfunction) than MOGAD lesions. Lesional [¹⁸F]PBR06 uptake correlated significantly with [¹⁸F]FDG uptake. Beyond lesions, NMOSD patients had higher [¹⁸F]FDG SUVR in cerebellar WM (p ​< ​0.01) and periventricular regions near the fourth ventricle (p ​= ​0.01), and higher [¹⁸F]PBR06 SUVR in cerebral WM (p ​= ​0.03), contrasted with MOGAD. With lesions in both disorders demonstrating microgliosis, NMOSD exhibited more severe lesion-specific metabolic suppression and astrocyte dysfunction, reflected in reduced [¹¹C]acetate uptake, coupled with regional inflammation (microgliosis) and hypermetabolism. These differential multi-tracer PET patterns, especially the combined reduction in lesional astrocytic ([¹¹C]acetate) and metabolic ([¹⁸F]FDG) markers in NMOSD versus MOGAD, highlight multimodal PET/MRI as a powerful tool for differentiating NMOSD and MOGAD pathophysiology.</p>","PeriodicalId":19159,"journal":{"name":"Neurotherapeutics","volume":" ","pages":"e00720"},"PeriodicalIF":6.9,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144962533","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":"Profiling the landscape of cysteine posttranslational modifications in brain aging and neurodegeneration.","authors":"Milos R Filipovic","doi":"10.1016/j.neurot.2025.e00726","DOIUrl":"https://doi.org/10.1016/j.neurot.2025.e00726","url":null,"abstract":"<p><p>Cysteine residues occupy a unique position in the proteome: their thiolate side chain combines high nucleophilicity with redox sensitivity, making them prime targets for a diverse and ever-expanding array of post-translational modifications (PTMs). This review provides an overview of recent methodological developments for chemoselective site-specific detection and quantitation of the major cysteine PTMs-sulfenylation (RSOH), sulfinylation (RSO₂H), sulfonylation (RSO₃H), persulfidation (RSSH), S-nitrosylation (RSNO), and S-palmitoylation-emphasizing applications in brain aging and neurodegeneration. In neural tissues, these approaches have begun to map age-dependent increases in sulfenylation and sulfonylation, declines in persulfidation, and aberrant S-nitrosylation and palmitoylation linked to Alzheimer's, Parkinson's, and Huntington's disease. However, significant challenges remain. Further improvements in sensitivity, specificity, and quantitative accuracy are essential to capture low-abundance and labile modifications in complex neural tissues. These attempts should be coupled to more detailed anatomical dissection of these modifications in different parts of the brain, enabling region- and cell-type-specific insights. Advancing analytical workflows, integrating multi-dimensional data, and linking chemical modifications to biological outcomes will pave the way for innovative therapeutic strategies targeting cysteine chemistry in neurological disease.</p>","PeriodicalId":19159,"journal":{"name":"Neurotherapeutics","volume":" ","pages":"e00726"},"PeriodicalIF":6.9,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144962530","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}