PNAS nexus最新文献

{"title":"Data-driven image analysis to determine antibody-induced dissociation of cell-cell adhesion and antibody pathogenicity in pemphigus.","authors":"Amir Ostadi Moghaddam, Xiaowei Jin, Bahareh Tajvidi Safa, Kristina Seiffert-Sinha, Merced Leiker, Elijah Jones, Haiwei Zhai, Jordan Rosenbohm, Fanben Meng, Animesh A Sinha, Ruiguo Yang","doi":"10.1093/pnasnexus/pgaf218","DOIUrl":"10.1093/pnasnexus/pgaf218","url":null,"abstract":"<p><p>Pemphigus vulgaris (PV) is a blistering autoimmune disease that affects the skin and mucous membranes. The mechanisms by which PV antibodies induce loss of cohesion in keratinocytes are not fully understood. It is accepted that the process starts with antibody binding to desmosomal targets, which leads to its disassembly and subsequent structural changes to cell-cell adhesions. In vitro imaging of desmosome molecules has been used to characterize this initial phase. However, there remains an untapped potential of image analysis in providing us with more in-depth knowledge regarding biophysical changes after antibody binding. Currently, there is no quantitative framework from immunofluorescence images in PV pathology. Here, we seek to establish a correlation of biophysical changes with antibody pathogenicity by examining the effects of PV antibodies on adhesion molecules and the cytoskeletal network. Specifically, we introduced a data-driven approach to quantitatively evaluate perturbations in adhesion molecules following antibody treatment. We identify distinct imaging signatures that mark the impact of antibody binding on the remodeling of adhesion molecules and introduce a pathogenicity score to compare the relative effects of different antibodies. From this analysis, we showed that the biophysical response of keratinocytes to distinct PV antibodies is highly specific, allowing for accurate prediction of their pathogenicity. For instance, the high pathogenicity scores of the PVIgG and AK23 antibodies show strong agreement with their reported PV pathology. Our data-driven approach offers a detailed framework for the action of antibodies in pemphigus and paves the way for the development of effective diagnostic and therapeutic strategies.</p>","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"4 8","pages":"pgaf218"},"PeriodicalIF":3.8,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12314744/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144777135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A constructive framework for discovery, design, and classification of volumetric Bravais weaves.","authors":"Tolga T Yildiz, Alice C Niemeyer, Vinayak R Krishnamurthy, Ergun Akleman","doi":"10.1093/pnasnexus/pgaf219","DOIUrl":"10.1093/pnasnexus/pgaf219","url":null,"abstract":"<p><p>Woven fabrics have a long history of study across the fields of art, mathematics, and mechanics. While weaves with symmetries in <math> <msup> <mrow><mrow><mi>R</mi></mrow> </mrow> <mn>2</mn></msup> </math> have been extensively formalized, classified, and characterized, a systematic framework for representing and designing weaves in <math> <msup> <mrow><mrow><mi>R</mi></mrow> </mrow> <mn>3</mn></msup> </math> remains absent. Despite their relevance to engineering applications-particularly in composite materials-volumetric weaves are often designed in an ad hoc manner, typically by stacking planar weaves and introducing trivial thread connections along the stacking axis. In this article, we establish a formal framework for volumetric weaves by defining them through the isometries of Bravais lattices and their corresponding Voronoi cells in <math> <msup> <mrow><mrow><mi>R</mi></mrow> </mrow> <mn>3</mn></msup> </math> . This approach provides a structured description of the design space for a specific family of volumetric weaves, which we call volumetric Bravais weaves. As an example of volumetric Bravais weaves, we analyze, <i>cubic primitive weaves</i> (cP-weaves) in detail as the simplest example within the volumetric Bravais weave framework. This example demonstrates how volumetric Bravais weave structures naturally emerge from 3D lattice isometries. Furthermore, we show that all possible cP-weaves can be systematically generated using a set of cP lattice isometries and cube isometries. Our findings reveal that even just the space of cP-weaves is at least one order of magnitude larger than that of conventional two-way 2-fold weaves, highlighting the potential of our approach for expanding the design space of volumetric weaves.</p>","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"4 8","pages":"pgaf219"},"PeriodicalIF":3.8,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12311793/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144777134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modulation of immunoglobulin G oligomerization by variable domain glycans: A mechanism to regulate complement activation.","authors":"Roxane Biersteker, Leoni Abendstein, Sanne van de Bovenkamp, Hugo J van Dooren, Sebastiaan M W R Hamers, Joanneke C Kwekkeboom, Eva Maria Stork, Jan W Drijfhout, Theo Rispens, Carolien A M Koeleman, Manfred Wuhrer, Leendert A Trouw, Thomas H Sharp, René E M Toes, Theresa Kissel","doi":"10.1093/pnasnexus/pgaf216","DOIUrl":"10.1093/pnasnexus/pgaf216","url":null,"abstract":"<p><p>Immunoglobulin G (IgG) is a glycoprotein harboring conserved fragment crystallizable domain glycans, but it can also express variable domain glycans (VDGs). Elevated levels of VDGs are a hallmark of the autoantibodies most specific to rheumatoid arthritis and are also associated with other autoimmune diseases. Nonetheless, the effect of VDGs on IgG function remains poorly understood. This study investigates the impact of VDGs on the ability of antibodies to activate the complement system, a key immune effector mechanism. We demonstrate that VDGs on IgG inhibit the initiation of the classical complement pathway, as evidenced by complement activation assays with IgG displaying varying degrees of VDGs. Structure-function analyses show that VDGs reduce classical complement activation by impeding IgG oligomer formation on antigenic surfaces. As IgG oligomerization is essential for effective C1q binding, VDG-mediated interference with this process lowers IgG's complement activation potential. This impaired ability to recruit complement was further substantiated through direct visualization of IgG oligomer-C1q complexes on antigen-coated vesicles by cryoelectron tomography. Together, these data reveal that VDGs increase the functional diversity of IgG and identify a novel regulatory mechanism that modulates the ability of antibodies to activate one of their main immune effector mechanisms.</p>","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"4 7","pages":"pgaf216"},"PeriodicalIF":3.8,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12305304/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144746407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: Functional connectivity signatures of political ideology.","authors":"","doi":"10.1093/pnasnexus/pgaf212","DOIUrl":"https://doi.org/10.1093/pnasnexus/pgaf212","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1093/pnasnexus/pgac066.].</p>","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"4 7","pages":"pgaf212"},"PeriodicalIF":2.2,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12264739/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144651459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reordered hierarchical complexity in ecosystems with delayed interactions.","authors":"Bo-Wei Qin, Wenbo Sheng, Xuzhe Qian, Jürgen Kurths, Alan Hastings, Ying Cheng Lai, Wei Lin","doi":"10.1093/pnasnexus/pgaf214","DOIUrl":"10.1093/pnasnexus/pgaf214","url":null,"abstract":"<p><p>It was once believed that large ecosystems with random interactions are unstable, limiting their complexity. Thus, large community size or numerous interactions are rare in nature. Later, a strict hierarchical complexity was revealed: competitive and mutualistic communities have the least complexity, followed by random ones, and then predator-prey communities. Recently, a hierarchy of recovery times for ecosystems with identical complexity was found, influenced by discrete time delays. A key question is whether this hierarchical complexity holds under noninstantaneous interactions. We surprisingly show that it does not. Specifically, the complexity of predator-prey communities is significantly affected by time delays, reordering the hierarchy at a critical threshold. These changes exhibit nonmonotonic behavior with continuous time delays, another realistic interaction type. We validated our findings in various realistic ecosystems. Our results indicate that incorporating factors like time delays and their appropriate forms can lead to correct and even deeper understanding about complexity of large ecosystems and other biophysical systems.</p>","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"4 7","pages":"pgaf214"},"PeriodicalIF":2.2,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12280872/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144692722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Noncanonical sustained actions of propofol reverse surgery-induced microglial activation and cognitive impairment in aged mice.","authors":"Rajasekar Nagarajan, Jinrui Lyu, Maltesh Kambali, Muxiao Wang, Robert A Pearce, Uwe Rudolph","doi":"10.1093/pnasnexus/pgaf213","DOIUrl":"10.1093/pnasnexus/pgaf213","url":null,"abstract":"<p><p>Perioperative neurocognitive disorder is a major concern in aged individuals, and currently, treatment options are limited. Chronic intermittent propofol (CIP) has been shown to have neuroprotective effects in aged mice and in a mouse model of Alzheimer's disease. Here, we investigated whether CIP could reverse surgery-induced cognitive deficits and propose a mechanism of action. Male and female mice (21-24 months old) underwent exploratory laparotomy under isoflurane anesthesia. Animals were administered either CIP (75 mg/kg i.p.) or vehicle every fifth day throughout the experiment. Cognitive function was assessed using a battery of behavioral tests: the Y-maze test (spatial working memory), the novel object recognition test (recognition memory), the Morris water maze (spatial learning and memory), and trace and contextual fear conditioning (nondeclarative associative memory). Expression of α5-GABA_A receptors, markers of apoptosis, and a microglial activation marker were assessed in the hippocampus using western blotting. The amount of α5-GABA_A receptor subunits in cell-surface membranes was determined by biotinylation followed by western blotting. CIP induced a sustained redistribution of α5-GABA_A receptors to the cell-surface membranes. Laparotomy led to an increased expression of the microglial activation marker Iba-1 and of proapoptotic markers, and impaired cognitive functions. CIP prevented these molecular and cognitive changes. Perioperative CIP redistributes α5-GABA_A receptors to cell-surface membranes and thus prevents or reverses surgery-induced increases in markers of microglial activation, apoptosis, and cognitive dysfunction. Increasing the number or activity of α5-GABA_A receptors on cell-surface membranes may be an effective therapeutic strategy to reduce postoperative morbidity in elderly patients.</p>","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"4 7","pages":"pgaf213"},"PeriodicalIF":3.8,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12287697/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144710173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rapid adaptation to a globally introduced virulent pathogen in a keystone species.","authors":"Loren Cassin-Sackett, Mirian T N Tsuchiya, Rebecca B Dikow","doi":"10.1093/pnasnexus/pgaf199","DOIUrl":"10.1093/pnasnexus/pgaf199","url":null,"abstract":"<p><p>Emerging infectious diseases are one of the foremost contemporary threats to biodiversity conservation. Outbreaks of novel pathogens can lead to the extinction of host populations, loss of gene flow due to extirpation, and bottlenecks in host populations with surviving individuals. In outbreaks with survivors, pathogens can exert strong selection on hosts, in some cases leading to the evolution of resistance or tolerance in the host population. The pathogen causing sylvatic plague, <i>Yersinia pestis</i>, was introduced to North America in the early 1900s and caused widespread population declines in prairie dogs (genus <i>Cynomys</i>), which experience >95% mortality during epizootics. Recently, survival from plague was documented in a small number of black-tailed prairie dogs (<i>Cynomys ludovicianus</i>) in natural populations in Colorado (United States). We performed whole-genome sequencing on all seven individuals that survived infection with plague and seven individuals that likely died. Using genome-wide association tests, <i>F</i> _ST outlier tests, and other inferences of selection, we detected single nucleotide polymorphisms (SNPs) on five scaffolds that were strongly associated with survivorship from plague in nature. One candidate gene, inducible T-cell stimulator (<i>ICOS</i>), was also associated with survival in humans during the Black Death in London (United Kingdom), suggesting conservation of gene function across taxonomically diverse lineages. In addition, three candidate genes (<i>TMEM198</i>, <i>PCDHB12/15</i>, and <i>KIAA1191</i>) are different from but in the same gene classes (transmembrane proteins, protocadherins, and Kasuza protein-binding genes) as candidate genes for plague resistance in great gerbils, providing support for the hypothesis that parallel evolution may occur at the level of gene classes in addition to individual genes. Understanding the genomic basis of immunity can enable genetically informed management actions, such as targeted relocation to protect grassland species. Moreover, understanding how rapid adaptation to pathogens occurs can help us predict the time frame and spatial scale at which adaptation may occur, during which other interventions are needed.</p>","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"4 7","pages":"pgaf199"},"PeriodicalIF":2.2,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12235602/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144593149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From transcripts to trajectories: A framework for studying academic pathways through college.","authors":"Jai K Malik, Fred M Feinberg, Elizabeth E Bruch","doi":"10.1093/pnasnexus/pgaf210","DOIUrl":"https://doi.org/10.1093/pnasnexus/pgaf210","url":null,"abstract":"<p><p>Educational institutions face pressing challenges regarding student persistence, time to graduation, and underrepresentation of women and minorities in STEM fields. Developing targeted and effective solutions to these problems requires a concrete understanding of how diverse student groups progress through academic programs. In light of this, there are growing calls for a new science of educational pathways, but this idea remains more metaphor than methodology. Transcript data hold the promise of revealing the paths students take through a curriculum, but existing frameworks do not provide a fine-grained, processual account of how students arrive at their academic destinations. In this study, we present a theoretically grounded, data-driven framework for translating transcript data into academic pathways. Our framework delivers information about students' movements both through the space of possible majors and within a particular program. This information is remarkably detailed, but its richness creates statistical challenges in that the analyst must allow for temporal dynamics, diverse pathways, and the possibility that the most likely path for a given type of student differs across contexts (e.g. fields of study, colleges, or universities). We develop a question- and data-driven statistical model that leverages the richness of pathways data, with each level tuned to nonparametrically extract a different kind of information about trajectories, student demographics, and how their relationship varies across contexts. We apply this framework to data from a large public university to reveal how students of varying backgrounds, including historically underrepresented groups, enter and exit fields of study.</p>","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"4 10","pages":"pgaf210"},"PeriodicalIF":3.8,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12501848/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145254050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"VX-445 (elexacaftor) inhibits chloride secretion across human bronchial epithelial cells by directly blocking KCa3.1 channels.","authors":"Aaron Kolski-Andreaco, Corina M Balut, Matthew D Green, John Sembrat, Robert J Bridges, Ashvani K Singh, Chris Tse, Michael B Butterworth, Daniel C Devor","doi":"10.1093/pnasnexus/pgaf211","DOIUrl":"10.1093/pnasnexus/pgaf211","url":null,"abstract":"<p><p>Cystic fibrosis (CF) is a genetic disorder resulting from mutations to the CF transmembrane regulator (CFTR) anion channel. CFTR correctors partially restore the folding and trafficking of mutant CFTR. We recently demonstrated that the correctors VX-445 and VX-121 directly potentiate large-conductance Ca²⁺-activated (BK_Ca) channels. We postulated that this could enhance the therapeutic potential of these drugs in the lung by increasing the driving force for transepithelial Cl^- secretion. Herein, we evaluated the effect of acute addition of VX-445 on forskolin- and 5,6-dichloro-1-ethyl-1,3-dihydro-2H-benzimidazol-2-one-mediated Cl^- secretion across primary human bronchial epithelial cells (HBEs) from wild type (WT) and F508del donors. Surprisingly, VX-445 (10 µM) induced a significant inhibition of forskolin-stimulated Cl^- secretion in WT and F508del donor HBEs with corrected CFTR. We hypothesized that this was due to inhibition of the basolateral membrane Ca²⁺-activated K⁺ channel, KCa3.1 that maintains the driving force for Cl^- secretion. Thus, we utilized patch-clamp techniques to evaluate VX-445 effects on isolated KCa3.1 currents. We demonstrate that VX-445 directly inhibits KCa3.1, as do similar molecules VX-659 and VX-121; however, only VX-659 inhibited KCa2.3 and KCa2.2 with a similar affinity to KCa3.1. To summarize, acute addition of CFTR correctors to HBEs reduces transepithelial Cl^- secretion due to inhibition of KCa3.1.</p>","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"4 7","pages":"pgaf211"},"PeriodicalIF":2.2,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12275099/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144676801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic score omics regression and multitrait meta-analysis detect widespread <i>cis</i>-regulatory effects shaping bovine complex traits.","authors":"Ruidong Xiang, Lingzhao Fang, Shuli Liu, George E Liu, Albert Tenesa, Yahui Gao, Brett A Mason, Amanda J Chamberlain, Michael E Goddard","doi":"10.1093/pnasnexus/pgaf208","DOIUrl":"10.1093/pnasnexus/pgaf208","url":null,"abstract":"<p><p>To complete the genome-to-phenome map, transcriptome-wide association studies (TWAS) are performed to correlate genetically predicted gene expression with observed phenotypic measurements. However, the relatively small training population assayed with gene expression could limit the accuracy of TWAS. We propose genetic score omics regression (GSOR) correlating observed gene expression with genetically predicted phenotype, i.e. estimated breeding values (EBVs) in agriculture or polygenic score (PGS) in medicine. The score, calculated using variants near genes with assayed expression (<i>cis</i>-EBV or <i>cis</i>-PGS), provides a powerful association test between <i>cis-</i>effects on gene expression and the trait. In simulated and real data, GSOR outperforms TWAS in detecting causal/informative genes. We applied GSOR to transcriptomes of 16 tissues (<i>N</i> ∼ 5,000) and 37 traits in ∼120,000 cattle and conducted multitrait meta-analyses of omics-associations (MTAO). We found that, on average, each significant gene expression and splicing mediates <i>cis</i>-genetic effects on 8-10 traits. Many prioritized genes by GSOR and MTAO can be verified by Mendelian randomization analysis and show significantly reduced d<i>N</i>/d<i>S</i>, suggesting elevated evolutionary constraint for these genes. Using multiple methods, we detect expression levels of genes and/or RNA splicing events underlying previously thought single-gene loci to influence multiple traits. For example, the expression and RNA splicing of <i>DGAT1</i> from multiple tissues regulated milk production, mastitis, gestation length, temperament, and stature. Also, gene expression and splicing of <i>ABO</i> (Histo-blood group) and <i>ACHE</i> (acetylcholinesterase, Cartwright blood group) affected protein concentration and mastitis, respectively. Taken together, our work provides new methods and biological insights for prioritizing informative omics-phenotype associations in mammals.</p>","PeriodicalId":74468,"journal":{"name":"PNAS nexus","volume":"4 7","pages":"pgaf208"},"PeriodicalIF":2.2,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12275098/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144676800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}