American journal of physiology. Renal physiology最新文献

{"title":"A novel automated method for comprehensive renal cast quantification from rat kidney sections using QuPath.","authors":"Lauren Yunker, Megan Cleland Harwig, Alison J Kriegel","doi":"10.1152/ajprenal.00252.2024","DOIUrl":"10.1152/ajprenal.00252.2024","url":null,"abstract":"<p><p>The presence of tubular casts within the kidney serves as an important feature when assessing the degree of renal injury. Quantification of renal tubular casts has been historically difficult due to varying cast morphologies, protein composition, and stain uptake properties, even within the same kidney. Color thresholding remains one of the most common methods of quantification in the laboratory when assessing the percentage of renal casting; however, this method is unable to account for tubule casts stained a variety of colors. We have developed a novel method of automated cast quantification using the machine learning pixel classification tool within QuPath, an open-source software designed for digital pathology. We demonstrated the usability of this method in male and female Dahl salt-sensitive rats fed either low or high salt for 2 wk and male Sprague-Dawley rats treated with podotoxin puromycin aminonucleoside (PAN). Briefly, the pixel classifier was trained to identify kidney tissue, various cast color types, and slide backgrounds. Following the development of the pixel classifier, we applied it to the sample population and compared the results with those of other methods of cast quantification, including color thresholding and manual quantification. We found that the automated pixel classifier designed in QuPath was able to comprehensively quantify metachromatic tubular casts compared with color thresholding. This novel method of cast quantification provides researchers with the ability to reliably automate cast quantification that is both comprehensive and efficient.<b>NEW & NOTEWORTHY</b> We developed a method of automated renal tubule cast quantification using a machine learning-based pixel classifier within QuPath, an open-source image analysis software. The advantages of this approach are demonstrated by rigorous comparison of quantification methods on a set of Masson's trichrome-stained kidney sections from high- and low-salt fed salt-sensitive Dahl rats. Researchers are provided with step-by-step instructions for creating and training a pixel classifier in QuPath for application to image analysis.</p>","PeriodicalId":93867,"journal":{"name":"American journal of physiology. Renal physiology","volume":" ","pages":"F230-F238"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142883824","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":"Intestinal barrier function declines during polycystic kidney disease progression.","authors":"Randee Sedaka, Caleb Lovelady, Emily Hallit, Branden Duyvestyn, Sejal Shinde, Aida Moran-Reyna, Goo Lee, Shinobu Yamaguchi, Craig L Maynard, Takamitsu Saigusa","doi":"10.1152/ajprenal.00058.2024","DOIUrl":"10.1152/ajprenal.00058.2024","url":null,"abstract":"<p><p>Most patients with autosomal dominant polycystic kidney disease (ADPKD) develop kidney cysts due to germline <i>PKD1</i> mutations. In the kidney, <i>Pkd1</i> loss impairs epithelial cell integrity and increases macrophage infiltration, contributing to cyst growth. Despite its role as the body's largest inflammatory cell reservoir, it has yet to be elucidated whether a similar phenotype presents in the intestines. We hypothesize that loss of <i>Pkd1</i> leads to a leaky intestinal epithelial barrier and increased inflammation, before rapid cystogenesis. Control and inducible, global <i>Pkd1</i> knockout (<i>Pkd1</i>KO) mice were euthanized at 3 and 6 mo of age (early and late stage) to evaluate kidney disease progression, small and large intestinal integrity, and inflammation. Early-stage <i>Pkd1</i>KO mice displayed mild cystic kidneys and tubular injury with preserved kidney function. Intestinal epithelial barrier was tighter in KO mice, which was associated with higher expression of cell-cell epithelial integrity markers. However, there was no evidence of local or systemic inflammation in either genotype. Late-stage <i>Pkd1</i>KO mice had severely cystic, impaired kidneys with increased expression of integrity markers, tubular injury, and inflammation. Intestinal epithelial barrier was leakier in late-stage <i>Pkd1</i>KO mice, accompanied by gene reduction of integrity markers, increased inflammation, and elevated water and sodium channel expression. Gut motility and fecal water excretion were increased in <i>Pkd1</i>KO compared with flox mice irrespective of age. Overall, kidney injury appears to precede intestinal injury in ADPKD, whereby the intestinal barrier becomes leaky as cystogenesis progresses.<b>NEW & NOTEWORTHY</b> Though autosomal dominant polycystic kidney disease (ADPKD) is a multisystem disorder, this is the first study to explore a kidney-gut contribution to disease progression. We identified a tightened intestinal epithelial barrier in early PKD, which becomes leaky as kidneys become more cystic, accompanied by a sustained loss of fecal water. Given the only approved ADPKD therapeutic yields adverse aquaretic events, this study emphasizes the need to evaluate extrarenal water loss in patients before prescribing.</p>","PeriodicalId":93867,"journal":{"name":"American journal of physiology. Renal physiology","volume":" ","pages":"F218-F229"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142856949","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 evolving concepts of KS-WNK1 effect on NCC activity.","authors":"María Chávez-Canales, Gerardo Gamba","doi":"10.1152/ajprenal.00272.2024","DOIUrl":"10.1152/ajprenal.00272.2024","url":null,"abstract":"<p><p>The field of the with-no-lysine kinases (WNKs) regulation of the thiazide-sensitive NaCl cotransporter (NCC) began at the start of the century with the discovery that mutations in two members of the family, WNK1 and WNK4, resulted in a condition known as familial hyperkalemic hypertension (FHHt). Since FHHt is the mirror image of Gitelman's syndrome that is caused by inactivating mutations of the SLC12A3 gene encoding NCC, it was expected that WNKs modulated NCC activity and that the increased function of the cotransporter is the pathophysiological mechanism of FFHt. This turned out to be the case. However, experiments over the first years generated unexpected observations that confused the field. Although most has been clarified, one issue still under a certain level of controversy is the role of an isoform of WNK1 that is only expressed in the kidney, almost entirely in the distal convoluted tubule, known as KS-WNK1. In this work, we present an overview of how the knowledge about the physiology of KS-WNK1 evolved over the years and propose explanations to understand its role in renal physiology.</p>","PeriodicalId":93867,"journal":{"name":"American journal of physiology. Renal physiology","volume":" ","pages":"F258-F269"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142907978","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":"Pax inhibition: stressing proximal tubule for successful repair.","authors":"Hiroki Kitai, Devin Mulcrone, Tomokazu Souma","doi":"10.1152/ajprenal.00368.2024","DOIUrl":"10.1152/ajprenal.00368.2024","url":null,"abstract":"","PeriodicalId":93867,"journal":{"name":"American journal of physiology. Renal physiology","volume":" ","pages":"F270-F271"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142960167","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":"Guidelines for sex-specific considerations to improve rigor in renal research and how we got there.","authors":"Daria V Ilatovskaya, Benard Ogola, Jessica L Faulkner, Mykola Mamenko, Erin B Taylor, Elena Dent, Michael J Ryan, Jennifer C Sullivan","doi":"10.1152/ajprenal.00136.2024","DOIUrl":"10.1152/ajprenal.00136.2024","url":null,"abstract":"<p><p>Biological sex significantly influences disease presentation, progression, and therapeutic outcomes in chronic kidney disease and acute kidney injury. Sex hormones, including estrogen and testosterone, modulate key renal functions, including renal blood flow, glomerular filtration, and electrolyte transport, thereby affecting disease trajectory in a sex-specific manner. It is critical for researchers to understand why and how to integrate sex as a biological variable in data collection, analysis, and reporting. Integrating a sex-based perspective in kidney research will lead to more personalized and efficacious treatment strategies, optimizing therapeutic interventions for each sex. If addressed properly, the incorporation of sex as a biological variable (SABV) in renal research not only enhances the mechanistic understanding of renal disease, but also paves the way for precision medicine, promising improved clinical outcomes, and tailored treatment protocols for all patients. This paper is designed to serve as a guideline for researchers interested in rigorously incorporating sex as a biological variable in their studies.</p>","PeriodicalId":93867,"journal":{"name":"American journal of physiology. Renal physiology","volume":" ","pages":"F204-F217"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142869792","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":"Excess dietary sodium restores electrolyte and water homeostasis caused by loss of the endoplasmic reticulum molecular chaperone, GRP170, in the mouse nephron.","authors":"Aidan W Porter, Hannah E Vorndran, Allison Marciszyn, Stephanie M Mutchler, Arohan R Subramanya, Thomas R Kleyman, Linda M Hendershot, Jeffrey L Brodsky, Teresa M Buck","doi":"10.1152/ajprenal.00192.2024","DOIUrl":"10.1152/ajprenal.00192.2024","url":null,"abstract":"<p><p>The maintenance of fluid and electrolyte homeostasis by the kidney requires proper folding and trafficking of ion channels and transporters in kidney epithelia. Each of these processes requires a specific subset of a diverse class of proteins termed molecular chaperones. One such chaperone is GRP170, which is an Hsp70-like, endoplasmic reticulum (ER)-localized chaperone that plays roles in protein quality control and protein folding in the ER. We previously determined that loss of GRP170 in the mouse nephron leads to hypovolemia, electrolyte imbalance, and rapid weight loss. In addition, GRP170-deficient mice develop an acute kidney injury (AKI)-like phenotype, typified by tubular injury, elevation of kidney injury markers, and induction of the unfolded protein response (UPR). By using an inducible GRP170 knockout cellular model, we confirmed that GRP170 depletion induces the UPR, triggers apoptosis, and disrupts protein homeostasis. Based on these data, we hypothesized that UPR induction underlies hyponatremia and volume depletion in these rodents and that these and other phenotypes might be rectified by sodium supplementation. To test this hypothesis, control and GRP170 tubule-specific knockout mice were provided a diet containing 8% sodium chloride. We discovered that sodium supplementation improved electrolyte imbalance and kidney injury markers in a sex-specific manner but was unable to restore weight or tubule integrity. These results are consistent with UPR induction contributing to the kidney injury phenotype in the nephron-specific GR170 knockout model and indicate that GRP170 function in kidney epithelia is essential to both maintain electrolyte balance and ER homeostasis.<b>NEW & NOTEWORTHY</b> Loss of the endoplasmic reticulum chaperone, GRP170, results in widespread kidney injury and induction of the unfolded protein response (UPR). We now show that sodium supplementation is able to at least partially restore electrolyte imbalance and reduce kidney injury markers in a sex-dependent manner.</p>","PeriodicalId":93867,"journal":{"name":"American journal of physiology. Renal physiology","volume":" ","pages":"F173-F189"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142670080","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":"Remote organ cancer induces kidney injury, inflammation, and fibrosis and adversely alters renal function.","authors":"Dana Hammouri, Andrew Orwick, Mark A Doll, Dianet Sanchez Vega, Parag P Shah, Christopher J Clarke, Brian Clem, Levi J Beverly, Leah J Siskind","doi":"10.1152/ajprenal.00264.2024","DOIUrl":"10.1152/ajprenal.00264.2024","url":null,"abstract":"<p><p>Approximately 30% of the patients with cancer experience kidney complications, which hinder optimal cancer management, imposing a burden on patients' quality of life and the healthcare system. The etiology of kidney complications in patients with cancer is often attributed to oncological therapies. However, the direct impact of cancer on kidney health is underestimated. Our previous study demonstrated that metastatic lung cancer adversely alters the kidney and exacerbates chemotherapy-induced nephrotoxicity, indicating lung cancer-kidney crosstalk. The current study examines whether this phenomenon is specific to the employed cancer model. Female and male mice of various strains were injected with different cell lines of remote organ cancer, and their kidney tissues were analyzed for toxicity and fibrosis. The impact of cancer on the kidney varied by cancer type. Breast cancer and specific subtypes of lung cancer, including KRAS- and epidermal growth factor receptor (EGFR)-mutant cancer, pathologically altered kidney physiology and function in a manner dependent on the metastatic potential of the cell line. This was independent of mouse strain, sex, and cancer cell line origin. Moreover, tumor DNA was not detected in the renal tissue, excluding metastases to the kidney as a causative factor for the observed pathological alterations. Lewis lung carcinoma and B16 melanoma did not cause nephrotoxicity, regardless of the tumor size. Our results confirm cancer-kidney crosstalk in specific cancer types. In the era of precision medicine, further research is essential to identify at-risk oncology populations, enabling early detection and management of renal complications.<b>NEW & NOTEWORTHY</b> Patients with cancer frequently experience kidney complications, often attributed to antineoplastic therapies. This emphasis on therapy-induced nephrotoxicity has led to the underestimation of the impact of cancer on the kidney. Our study demonstrates that distant organ cancer is sufficient to induce nephrotoxicity, highlighting the existence of cancer-kidney crosstalk. Our findings underscore a gap in our understanding of renal complications in patients with cancer and provide a rationale for identifying the underlying mechanisms for the development of nephroprotective agents.</p>","PeriodicalId":93867,"journal":{"name":"American journal of physiology. Renal physiology","volume":" ","pages":"F272-F288"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142840556","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":"Glycerol-3-phosphate contributes to the increase in FGF23 production in chronic kidney disease.","authors":"Petra Simic, Han Xie, Qian Zhang, Wen Zhou, Rohan Cherukuru, Michael A Adams, Mandy E Turner, Eugene P Rhee","doi":"10.1152/ajprenal.00311.2024","DOIUrl":"10.1152/ajprenal.00311.2024","url":null,"abstract":"<p><p>Why fibroblast growth factor 23 (FGF23) levels increase markedly in chronic kidney disease (CKD) is unknown. Recently, we found that phosphate stimulates renal production of glycerol-3-phosphate (G-3-P), which circulates to the bone to trigger FGF23 production. To assess the impact of G-3-P on FGF23 production in CKD, we compared the effect of adenine-induced CKD in mice deficient in glycerol-3-phosphate dehydrogenase 1 (Gpd1), an enzyme that synthesizes G-3-P, along with wild-type littermates. We found that an adenine diet causes a similar degree of renal insufficiency across genotypes and that adenine-induced CKD increases blood G-3-P and FGF23 levels in wild-type mice. Furthermore, we found that the increases in both G-3-P and FGF23 are significantly attenuated, but not fully abrogated, in <i>Gpd1</i>^-/- compared with <i>Gpd1</i>^+/+ mice with CKD. There is no difference in blood phosphate or parathyroid hormone between <i>Gpd1</i>^-/- and <i>Gpd1</i>^+/+ mice on an adenine diet, but adenine-induced CKD causes greater cortical bone loss in <i>Gpd1</i>^-/- mice. In a separate cohort of rats fed an adenine or control diet, we confirmed that CKD causes an increase in blood G-3-P levels. Importantly, an acute phosphate load increases G-3-P production in both CKD and non-CKD rats, with a significant correlation between measured kidney phosphate uptake and blood G-3-P levels. Together, these findings establish a key role for G-3-P in mineral metabolism in CKD, although more work is required to parse the factors that regulate both Gpd1-dependent and Gpd1-independent G-3-P production in this context.<b>NEW & NOTEWORTHY</b> This study shows that glycerol-3-phosphate, a glycolytic by-product recently implicated in a kidney-to-bone signaling axis that regulates FGF23 production, increases in mice and rats with CKD. Furthermore, mice deficient in a key enzyme that synthesizes glycerol-3-phosphate have attenuated increases in both glycerol-3-phosphate and FGF23 in CKD, along with enhanced cortical bone loss. These studies identify glycerol-3-phosphate as a novel regulator of FGF23 and mineral metabolism in CKD.</p>","PeriodicalId":93867,"journal":{"name":"American journal of physiology. Renal physiology","volume":" ","pages":"F165-F172"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142883790","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":"Soluble (pro)renin receptor as a novel regulator of renal medullary Na⁺ reabsorption.","authors":"Tianxin Yang, Zhong-Xiuzi Gao, Zi-Hui Mao, Peng Wu","doi":"10.1152/ajprenal.00156.2024","DOIUrl":"10.1152/ajprenal.00156.2024","url":null,"abstract":"<p><p>Epithelial sodium channel (ENaC) represents a major route of Na⁺ reabsorption in the aldosterone-sensitive distal nephron where the bulk of ENaC activity is considered to occur in the cortical collecting duct (CCD). Relatively, ENaC activity in the medulla, especially the inner medulla, is often neglected. (Pro)renin receptor (PRR), also termed ATP6ap2, a newly characterized member of the renin-angiotensin system, has emerged as an important regulator of ENaC in the distal nephron. The ENaC regulatory action of PRR is largely mediated by the 28 kDa soluble PRR (sPRR). Although all three subunits of ENaC are under the control of aldosterone, sPRR only mediates the upregulation of α-ENaC but not the other two subunits. Furthermore, sPRR-dependent regulation of α-ENaC only occurs in the renal inner medulla but not in the cortex. sPRR also rapidly upregulates ENaC activity via Nox4-derived H₂O₂. Overall, sPRR has emerged as an important regulator of renal medullary Na⁺ reabsorption in the context of overactivation of the renin-angiotensin-aldosterone system.</p>","PeriodicalId":93867,"journal":{"name":"American journal of physiology. Renal physiology","volume":" ","pages":"F239-F247"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142605111","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":"Induction of plasmalemmal vesicle-associated protein exacerbates glomerular endothelial injury in thrombotic microangiopathy.","authors":"Chelsea C Estrada, Craig Wilson, Nehaben Gujarati, Sumaya Ahmed, Robert Bronstein, Ilse S Daehn, Monica P Revelo, Yiqing Guo, Sandeep K Mallipattu","doi":"10.1152/ajprenal.00283.2024","DOIUrl":"10.1152/ajprenal.00283.2024","url":null,"abstract":"<p><p>Glomerular endothelial cell (GEnC) injury is a common feature across the wide spectrum of glomerular diseases. We recently reported that the endothelial-specific knockout of <i>Krüppel-like factor 4 (Klf4)</i> increases the susceptibility to GEnC injury and subsequent development of subacute thrombotic microangiopathy (TMA). However, the mechanism(s) mediating GEnCs response to injury in TMA are poorly understood. Single-nucleus RNA-sequencing demonstrated enrichment in pathways involved in angiogenesis, permeability, focal adhesion, dedifferentiation, and cytoskeletal organization in the endothelial cluster in mice with TMA. <i>Plasmalemmal vesicle-associated protein (Plvap)</i>, a structural component of fenestral diaphragms, was highly enriched specifically in injured GEnCs. Induction of <i>Plvap</i> in cultured GEnCs increased proliferation, migration, and cell permeability with an accompanying loss of mature GEnC markers. Immunostaining for PLVAP in human kidney biopsies confirmed the increase in glomerular PLVAP in TMA, which correlated with a higher grade of glomerular injury. To date, this is the first study to show that the induction of <i>Plvap</i> in GEnCs shifts the cells to an immature state, which might exacerbate glomerular injury in TMA.<b>NEW & NOTEWORTHY</b> This study investigated the mechanism(s) underlying glomerular endothelial cell (GEnC) injury in thrombotic microangiopathy (TMA). We identified plasmalemmal vesicle-associated protein (PLVAP) as specifically upregulated in injured GEnCs in TMA, which was accompanied by pathways involved in angiogenesis and loss of differentiation. Induction of <i>Plvap</i> increased proliferation and migration of GEnCs. Human kidney biopsies with TMA demonstrated an increase in glomerular PLVAP, which correlated with histological markers of GEnC injury, confirming its pathologic role in TMA.</p>","PeriodicalId":93867,"journal":{"name":"American journal of physiology. Renal physiology","volume":" ","pages":"F190-F203"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873634","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}