The Journal of Clinical Investigation最新文献

{"title":"Complement's involvement in allergic Th2 immunity: a cross-barrier perspective.","authors":"Sarah A Thomas,Stephane Lajoie","doi":"10.1172/jci188352","DOIUrl":"https://doi.org/10.1172/jci188352","url":null,"abstract":"Type 2 (Th2) allergic diseases are chronic conditions characterized by a Th2-polarized immune response to allergens. These diseases can be categorized by affected barrier sites: skin (atopic dermatitis, allergic contact dermatitis), gut (food allergy), and respiratory tract (e.g., asthma, chronic rhinosinusitis). The global prevalence of Th2 allergic diseases has increased the need for a deeper understanding of their pathophysiology. Several associations have been identified between genetic variants in the genes encoding components of the complement system and allergic disease. Moreover, levels of several complement proteins are elevated in patients with allergy. Experimental evidence demonstrates that the complement system plays a critical role in the development of these diseases across barrier sites. While site-specific differences exist in the complement components involved, key pathways, particularly C3 and C5, are prominent across the skin, gut, and lung.","PeriodicalId":520097,"journal":{"name":"The Journal of Clinical Investigation","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143897333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The differential effects of sex hormone therapy on kidney function: insights into biological sex differences.","authors":"David Collister,Adeera Levin","doi":"10.1172/jci191907","DOIUrl":"https://doi.org/10.1172/jci191907","url":null,"abstract":"There are known sex (i.e., biological) and gender (i.e., social) differences in the epidemiology and outcomes of chronic kidney disease. In this issue of the JCI, van Eeghen et al. provide a prospective multicenter observational study of transgender individuals initiating masculinizing and feminizing hormone therapy. Testosterone and estrogen with testosterone blockade had differential effects on kidney physiology including renal plasma blood flow, measured glomerular filtration rate, tubular biomarkers, and various proteins involved in inflammatory and repair pathways. The findings suggest that estrogen is renoprotective and that testosterone may be harmful to kidney function, but requires validation in larger, more diverse cohorts. The insights gained also need to be examined in the context of both endogenous and exogenous sex hormones in individuals over the life cycle.","PeriodicalId":520097,"journal":{"name":"The Journal of Clinical Investigation","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143897335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tebentafusp elicits on-target cutaneous immune responses driven by cytotoxic T-cells in uveal melanoma patients.","authors":"Ramon Staeger,Aizhan Tastanova,Adhideb Ghosh,Nicola Winkelbeiner,Prachi Shukla,Isabel Kolm,Patrick Turko,Adel Benlahrech,Jane Harper,Anna Broomfield,Antonio Camera,Marianna Ambrosio,Veronika Haunerdinger,Phil F Cheng,Egle Ramelyte,James P Pham,Stefanie Kreutmair,Burkhard Becher,Mitchell P Levesque,Reinhard Dummer,Barbara Meier-Schiesser","doi":"10.1172/jci181464","DOIUrl":"https://doi.org/10.1172/jci181464","url":null,"abstract":"BACKGROUNDTebentafusp is the first T-cell receptor-based bispecific protein approved for clinical use in HLA-A*02:01+ adult patients with unresectable/metastatic uveal melanoma. It redirects T-cells toward gp100-expressing target cells, frequently inducing skin-related early adverse events.METHODSThis study investigated immunological and cellular responses using single-cell and spatial analysis of skin biopsies from patients with metastatic uveal melanoma treated with tebentafusp.RESULTS81.8% of patients developed acute cutaneous adverse events, which correlated with improved survival. Multimodal analysis revealed a brisk infiltration of CD4+ and CD8+ T-cells, while melanocyte numbers declined. Single-cell RNA-sequencing revealed T-cell activation, proliferation, and IFN-γ/cytotoxic gene upregulation. CD8+ T-cells co-localized with melanocytes and upregulated LAG3, suggesting potential for combination therapies with tebentafusp. Melanocytes upregulated antigen presentation and apoptotic pathways, while pigmentation gene expression decreased. However, gp100 remained stably expressed.CONCLUSIONSequential skin biopsies enable in vivo pharmacodynamic modeling of tebentafusp, offering insights into immune activation, toxicity, and treatment response. Examining the on-target effects of bispecifics in tissues amenable to longitudinal sampling enhances our understanding of toxicity and therapeutic escape mechanisms, guiding strategies for treatment optimization.","PeriodicalId":520097,"journal":{"name":"The Journal of Clinical Investigation","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143902965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA demethylating agents suppress preclinical models of synovial sarcoma.","authors":"Nobuhiko Hasegawa,Nezha S Benabdallah,Kyllie Smith-Fry,Li Li,Sarah McCollum,Jinxiu Li,Caelen A Jones,Lena Wagner,Vineet Dalal,Viola Golde,Anastasija Pejkovska,Lara Carroll,Malay Haldar,Seth M Pollack,Scott W Lowe,Torsten O Nielsen,Ana Banito,Kevin B Jones","doi":"10.1172/jci190855","DOIUrl":"https://doi.org/10.1172/jci190855","url":null,"abstract":"Synovial sarcoma is an aggressive soft tissue cancer driven by the chimeric SS18::SSX fusion oncoprotein, which disrupts chromatin remodeling by combining two antagonistic transcriptional regulators. SS18 participates in BAF complexes that open chromatin, while the SSX genes are cancer-testis antigens that interface with chromatin decorated with monoubiquitinated histone H2A placed by Polycomb repressive complexes (PRCs) activity. Because KDM2B brings PRC to unmethylated CpG islands, it is plausible that methylation directly determines the distribution of SS18::SSX to target loci. Given that synovial sarcoma is also characterized by a peculiarly low DNA hypomethylation profile, we hypothesized that further disturbance of DNA methylation would have a negative impact on synovial sarcoma growth. DNMT1 disruption by CRISPR/Cas9 targeting or pharmacologic inhibition with cytidine analogs 5-aza-2'-deoxycytidine (decitabine) and 5-azacytidine led to decreased genome-wide methylation, redistribution of SS18::SSX, and altered gene expression profiles, most prominently including upregulation of tumor suppressor genes, immune-related genes, and mesenchymal differentiation-related genes. These drugs suppressed growth of synovial sarcoma cell lines and drove cytoreduction in mouse genetic models. DNMT1 inhibitors, already approved for treating myelodysplastic syndromes, warrant further clinical investigation for synovial sarcoma as repurposed, targeted treatments exploiting a vulnerability in the intrinsic biology of this cancer.","PeriodicalId":520097,"journal":{"name":"The Journal of Clinical Investigation","volume":"132 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143893404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Kinesin-like protein KIFC2 stabilizes CDK4 to accelerate growth and confer resistance in HR+/HER2- breast cancer.","authors":"Shao-Ying Yang,Ming-Liang Jin,Lisa Andriani,Qian Zhao,Yun-Xiao Ling,Cai-Jin Lin,Min-Ying Huang,Jia-Yang Cai,Yin-Ling Zhang,Xin Hu,Zhi-Ming Shao,Fang-Lin Zhang,Xi Jin,A Yong Cao,Da-Qiang Li","doi":"10.1172/jci183531","DOIUrl":"https://doi.org/10.1172/jci183531","url":null,"abstract":"Hormone receptor-positive and human epidermal growth factor receptor 2-negative breast cancer (HR+/HER2- BC) is the most common subtype, with high risk of long-term recurrence and metastasis. Endocrine therapy (ET) combined with cyclin-dependent kinase 4/6 (CDK4/6) inhibitors is a standard treatment for advanced/metastatic HR+/HER2- BC, but resistance remains a major clinical challenge. We report that kinesin family member C2 (KIFC2) was amplified in approximately 50% HR+/HER2- BC, and its high expression was associated with poor disease outcome, increased tumor protein p53 (TP53) somatic mutation, and active pyrimidine metabolism. Function assays revealed that depletion of KIFC2 suppressed growth and enhanced sensitivity of HR+/HER2- BC cells to tamoxifen and CDK4/6 inhibitors. Mechanistically, KIFC2 stabilized CDK4 by enhancing its interaction with ubiquitin specific peptidase 9 X-linked (USP9X). Importantly, re-expression of CDK4 in KIFC2-depleted cells partially rescued the decreased growth and increased sensitivity to tamoxifen and CDK4/6 inhibitors caused by KIFC2 depletion. Clinically, high KIFC2 mRNA expression was negatively associated with survival rate of HR+/HER2- BC patients received adjuvant ET alone or in combination with CDK4/6 inhibitors. Collectively, these findings identify an important role for KIFC2 in HR+/HER2- BC growth and therapeutic resistance, and support its potential as a therapeutic target and predictive biomarker.","PeriodicalId":520097,"journal":{"name":"The Journal of Clinical Investigation","volume":"69 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143893176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A gain-of-function mutation in ATP6V0A4 drives primary distal renal tubular alkalosis with enhanced V-ATPase activity.","authors":"Si-Qi Peng,Qian-Qian Wu,Wan-Yi Wang,Yi-Lin Zhang,Rui-Ning Zhou,Jun Liao,Jin-Xuan Wei,Yan Yang,Wen Shi,Jun-Lan Yang,Xiao-Xu Wang,Zhi-Yuan Wei,Jia-Xuan Sun,Lu Huang,Hong Fan,Hui Cai,Cheng-Kun Wang,Xin-Hua Li,Ting-Song Li,Bi-Cheng Liu,Xiao-Liang Zhang,Bin Wang","doi":"10.1172/jci188807","DOIUrl":"https://doi.org/10.1172/jci188807","url":null,"abstract":"The ATP6V0A4 gene encodes the a4 subunit of Vacuolar H+-ATPase (V-ATPase), which mediates hydrogen ion transport across the membrane. Previous studies have suggested that mutations in ATP6V0A4 consistently result in a loss of function (LOF), impairing the hydrogen ion transport efficacy of V-ATPase and leading to distal renal tubular acidosis (dRTA) and sensorineural hearing loss. Here, we identified a 32-year-old male patient and his father, both of whom harbored a heterozygous ATP6V0A4 p.V512L mutation, and both exhibited with hypochloremic metabolic alkalosis, acidic urine and hypokalemia. Through a series of protein structural analyses and functional experiments, the V512L mutation was confirmed as a gain-of-function (GOF) mutation in the ATP6V0A4 gene. V512-a4 increased a4 subunit expression abundance by enhancing V512L-a4 stability and reducing its degradation, which in turn potentiated V-ATPase's capacity to acidify the tubular lumen, leading to acidic urine and metabolic alkalosis. Through mutant V512L-a4 subunit structure-based virtual and experimental screening, we discovered F351 (C25H26FN3O2S), a small-molecule inhibitor specifically targeting the V512L-a4 mutant. In conclusion, we identify a GOF mutation in the ATP6V0A4 gene, broadening its phenotypic and mutational spectrum, and provide valuable insights into potential therapeutic approaches for diseases associated with ATP6V0A4 mutations.","PeriodicalId":520097,"journal":{"name":"The Journal of Clinical Investigation","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143893403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ketogenesis mitigates metabolic dysfunction-associated steatotic liver disease through mechanisms that extend beyond fat oxidation.","authors":"Eric D Queathem,David B Stagg,Alisa B Nelson,Alec B Chaves,Scott B Crown,Kyle Fulghum,D Andre d'Avignon,Justin R Ryder,Patrick J Bolan,Abdirahman Hayir,Jacob R Gillingham,Shannon Jannatpour,Ferrol I Rome,Ashley S Williams,Deborah M Muoio,Sayeed Ikramuddin,Curtis C Hughey,Patrycja Puchalska,Peter A Crawford","doi":"10.1172/jci191021","DOIUrl":"https://doi.org/10.1172/jci191021","url":null,"abstract":"The progression of metabolic dysfunction-associated steatotic liver disease (MASLD) to metabolic dysfunction-associated steatohepatitis (MASH) involves alterations in both liver-autonomous and systemic metabolism that influence the liver's balance of fat accretion and disposal. Here, we quantify the contributions of hepatic oxidative pathways to liver injury in MASLD-MASH. Using NMR spectroscopy, UHPLC-MS, and GC-MS, we performed stable-isotope tracing and formal flux modeling to quantify hepatic oxidative fluxes in humans across the spectrum of MASLD-MASH, and in mouse models of impaired ketogenesis. In humans with MASH, liver injury correlated positively with ketogenesis and total fat oxidation, but not with turnover of the tricarboxylic acid cycle. Loss-of-function mouse models demonstrated that disruption of mitochondrial HMG-CoA synthase (HMGCS2), the rate-limiting step of ketogenesis, impairs overall hepatic fat oxidation and induces a MASLD-MASH-like phenotype. Disruption of mitochondrial β-hydroxybutyrate dehydrogenase (BDH1), the terminal step of ketogenesis, also impaired fat oxidation, but surprisingly did not exacerbate steatotic liver injury. Taken together, these findings suggest that quantifiable variations in overall hepatic fat oxidation may not be a primary determinant of MASLD-to-MASH progression, but rather, that maintenance of ketogenesis could serve a protective role through additional mechanisms that extend beyond overall rates of fat oxidation.","PeriodicalId":520097,"journal":{"name":"The Journal of Clinical Investigation","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143876421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Colistin exerts potent activity against mcr+ Enterobacteriaceae via synergistic interactions with the host defense.","authors":"Monika Kumaraswamy,Angelica Riestra,Anabel Flores,Samira Dahesh,Fatemeh Askarian,Satoshi Uchiyama,Jonathan Monk,Sean Jung,Gunnar Bondsäter,Victoria Nilsson,Melanie Chang,Jürgen B Bulitta,Yinzhi Lang,Armin Kousha,Elisabet Bjånes,Natalie Chavarria,Ty'Tianna Clark,Hideya Seo,George Sakoulas,Victor Nizet","doi":"10.1172/jci170690","DOIUrl":"https://doi.org/10.1172/jci170690","url":null,"abstract":"Colistin (COL) is a cationic cyclic peptide that disrupts negatively-charged Gram-negative bacterial cell membranes and frequently serves as an antibiotic of last resort to combat multidrug-resistant Gram-negative bacterial infections. Emergence of the horizontally transferable plasmid-borne mobilized colistin resistance (mcr) determinant and its spread to Gram-negative strains harboring extended-spectrum β-lactamase and carbapenemase resistance genes threatens futility of our chemotherapeutic arsenal. COL is widely regarded to have zero activity against mcr+ strains based on standard antimicrobial susceptibility testing (AST) performed in enriched bacteriological growth media; consequently, the drug is withheld from patients with mcr+ infections. However, these standard testing media poorly mimic in vivo physiology and omit host immune factors. Here we observed that COL exhibits bactericidal activities against mcr+ isolates of Escherichia coli, Klebsiella pneumoniae, and Salmonella enterica in tissue culture media containing the physiological buffer bicarbonate. Moreover, COL promoted serum complement deposition on the mcr-1+ Gram-negative bacterial surface and synergized potently with active human serum in pathogen killing. At COL concentrations readily achievable with standard dosing, the peptide antibiotic killed mcr-1+ E. coli, K. pneumoniae, and S. enterica in freshly isolated human blood and proved effective as monotherapy in a murine model of E. coli bacteremia. Our results suggest that COL, currently ignored as a treatment option based on traditional AST, may in fact benefit patients with mcr-1+ Gram negative infections based on evaluations performed in a more physiologic context. These concepts warrant careful consideration in the clinical microbiology laboratory and for future clinical investigation of their merits in high-risk patients with limited therapeutic options.","PeriodicalId":520097,"journal":{"name":"The Journal of Clinical Investigation","volume":"138 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143866430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Widespread distribution of transcriptionally active, clonally expanded, HIV-1 proviruses despite suppressive antiretroviral therapy.","authors":"Hiromi Imamichi,Ven Natarajan,Francesca Scrimieri,Mindy Smith,Yunden Badralmaa,Marjorie Bosche,Jack M Hensien,Thomas Buerkert,Weizhong Chang,Brad T Sherman,Kanal Singh,H Clifford Lane","doi":"10.1172/jci190824","DOIUrl":"https://doi.org/10.1172/jci190824","url":null,"abstract":"The rapid viral rebound observed following treatment interruption, despite prolonged time on antiretroviral therapy with plasma HIV-RNA levels <40 copies/mL, suggests persistent HIV-1 reservoir(s) outside of the blood. Studies of HIV-1 proviruses in autopsy tissue samples have hinted at their persistence. However, their distribution across different anatomical compartments and their transcriptional activity within tissues remains unclear. The present study has examined molecular DNA and RNA reservoirs of HIV-1 in autopsy samples from 13 individuals with HIV-1 infection. Of the 13, 5 had detectable levels of HIV-1 RNA in plasma while 8 did not. Cell associated HIV-RNA was detected in 12 out of 13 donors and in 27 of the 30 different tissues examined. HIV-specific DNA and RNA were widely distributed and predominantly associated with clonal expansions. No significant differences were noted between the groups and no tissues were preferentially affected. These data imply that a substantial seeding of tissues with cells harboring transcriptionally active proviral DNA can be seen in the setting of HIV-1 infection despite ART and highlight one of the challenges in achieving an HIV-1 cure.","PeriodicalId":520097,"journal":{"name":"The Journal of Clinical Investigation","volume":"138 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143893405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antimicrobial Peptide Developed with Machine Learning Sequence Optimization Targets Drug Resistant Staphylococcus aureus in Mice.","authors":"Biswajit Mishra,Anindya Basu,Fadi Shehadeh,LewisOscar Felix,Sai Sundeep Kollala,Yashpal Singh Chhonker,Mandar T Naik,Charilaos Dellis,Liyang Zhang,Narchonai Ganesan,Daryl J Murry,Jianhua Gu,Michael B Sherman,Frederick M Ausubel,Paul P Sotiriadis,Eleftherios Mylonakis","doi":"10.1172/jci185430","DOIUrl":"https://doi.org/10.1172/jci185430","url":null,"abstract":"As antimicrobial resistance rises, new antibacterial candidates are urgently needed. Using sequence space information from over 14,743 functional antimicrobial peptides (AMPs), we improved the antimicrobial properties of citropin 1.1, an AMP with weak anti-methicillin resistant Staphylococcus aureus (MRSA) activity, producing a short and potent anti-staphylococcal peptide, CIT-8 (13 residues). At 40 μg/ml, CIT-8 eradicated 1 × 108 drug-resistant MRSA and VRSA (vancomycin resistant S. aureus) persister cells within 30 mins of exposure and reduced the number of viable biofilm cells of MRSA and VRSA by 3 log10 and 4 log10 in established biofilms, respectively. CIT-8 (at 32 μg/ml) depolarized and permeated the S. aureus MW2 membrane. In a mouse model of MRSA skin infection, CIT-8 (2% w/w in petroleum jelly) significantly reduced the bacterial burden by 2.3 log10 (p < 0.0001). Our methodology accelerates AMP design by combining traditional peptide design strategies, such as truncation, substitution, and structure-guided alteration, with machine learning (ML)-backed sequence optimization.","PeriodicalId":520097,"journal":{"name":"The Journal of Clinical Investigation","volume":"172 4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143866388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}