Journal of Applied Toxicology最新文献

{"title":"Acute and Subacute Toxicity Study of α-Arbutin: An In Vivo Evidence.","authors":"Pooja Mishra, Farogh Ahsan, Tarique Mahmood, Shahzadi Bano, Vaseem Ahamad Ansari, Jyoti Yadav, Jamal Akhtar Ansari, Mohd Masih Uzzaman Khan","doi":"10.1002/jat.4822","DOIUrl":"https://doi.org/10.1002/jat.4822","url":null,"abstract":"<p><p>α-Arbutin, a glucoside of hydroquinone, is utilized as a skin-lightening agent that inhibits human tyrosinase activity. Although it exhibits antioxidant and anti-inflammatory properties, limited research exists on its toxicological effects. This research investigates the oral toxicity of α-arbutin in both acute and subacute settings using Sprague-Dawley rats as test subjects. Female Sprague-Dawley rats underwent acute oral toxicity testing in accordance with OECD TG 425 guidelines. The rats received oral doses of 175, 550, 1750, and 2000 mg/kg. Additionally, a subacute oral toxicity study following OECD TG 407 protocols was performed on both male and female rats. In this study, the animals were given daily oral doses of 250, 500, 1000, and 2000 mg/kg for 28 days. During acute and subacute oral toxicity assessments, no deaths or observable changes in behavior were noted at the administered doses. Examination of gross anatomy showed a significant decrease in the relative spleen weight of rats given α-arbutin at 250 mg/kg compared to the control group. Male rats treated with α-arbutin exhibited markedly non-significantly increased levels of AST, ALT, and chloride ions. In contrast, mean corpuscular hemoglobin concentration levels notably decreased at lower α-arbutin doses relative to the control group. Brain histopathology of male rats revealed moderate inflammation with pyknotic nuclei, whereas the cortex showed extensive epithelial cell necrosis following the administration of 2000 mg/kg of α-arbutin. The results showed that when given for a short time, α-arbutin is nontoxic till 2000 mg/kg. The median lethal dose (LD₅₀) of α-arbutin is more than 2000 mg/kg. A long-term toxicity study may be performed to validate the result. This study evaluated the acute and subacute oral toxicity of α-arbutin in Sprague-Dawley rats. No mortality or significant behavioral changes were observed up to 2000 mg/kg. However, at higher doses, male rats exhibited elevated liver enzymes and chloride ions, along with brain inflammation and cortical necrosis. Overall, α-arbutin showed no remarkable toxicity at tested doses, with an LD₅₀ exceeding 2000 mg/kg, warranting further long-term safety assessments.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144179897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unravelling the Mechanistic Approach of Aflatoxin Contaminated Food on Neurodegenerative Diseases-A Novel Approach.","authors":"Ajay Elangovan, Arya Singh, Mahalaxmi Iyer, Sindduja Muthu Kumar, Masako Kinoshita, Jayalakshmi Krishnan, Jyoti Parkash, Neelakshi Verma, Mukesh Kumar Yadav, Arvinder Wander, Dibbanti HariKrishna Reddy, Balachandar Vellingiri","doi":"10.1002/jat.4817","DOIUrl":"https://doi.org/10.1002/jat.4817","url":null,"abstract":"<p><p>Aflatoxins (AFs) are a group of toxic secondary metabolites and a dietary toxin produced predominantly by Aspergillus species such as Aspergillus flavus and Aspergillus parasiticus. The four most common and harmful forms of AFs include Aflatoxin B1 (AFB1), Aflatoxin B2 (AFB2), Aflatoxin G1 (AFG1), and Aflatoxin G2 (AFG2), which pose a significant health threat due to their widespread contamination of food and feed products. Particularly, AFB1 has raised a major global health concern. Noxious neurological outcomes have been associated with chronic exposure to AF-contaminated food, contributing to development of neuropathies, demyelinating diseases, and cognitive decline. Disrupted tight junctions of blood-brain barrier (BBB) said to have implicated by AFs toxicity by directly damaging brain endothelial cells. Compromised BBB leads to the formation of DNA adducts, mitochondrial dysfunction, and impaired oxidative phosphorylation, contributing to oxidative stress in neuronal cells. AFs disrupt neuronal signaling pathways by generating reactive oxygen species (ROS) and initiating chronic inflammation, impairing cognitive function and motor control. Mounting evidences suggests that these factors trigger neurological disorders especially neurodegenerative disorders. Neuroprotective compounds, such as hesperetin, N-acetylcysteine (NAC), curcumin, and artichoke extract, have shown promise in counteracting AF-induced neurotoxicity. These compounds could reduce oxidative stress, attenuate inflammation, and support mitochondrial function, offering potential therapeutic strategies to mitigate AF-induced neurodegeneration. This review focuses on the molecular pathways through which AFs exert neurotoxic effects, highlighting their role in the onset of neurodegenerative diseases and potential neuroprotective compounds for therapies have been highlighted.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144180506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Do Gadolinium-Based Contrasts Represent a High Risk for Genotoxicity in Mammalian Cells? A Systematic Review.","authors":"Thiago Guedes Pinto, Rogerio Aparecido Dedivits, Daniel Araki Ribeiro","doi":"10.1002/jat.4814","DOIUrl":"https://doi.org/10.1002/jat.4814","url":null,"abstract":"<p><p>The scientific rationale for this review stems from the increasing global use of gadolinium-based contrast agents in medical imaging and the concerns over the long-term environmental accumulation of gadolinium waste, which may pose biological risks. The primary objective was to determine whether gadolinium exposure induces genetic damage in mammalian cells, regardless of the assay method used, and to assess the quality of the studies available in the literature. Genotoxicity was measured through assays such as the micronucleus test, comet assay, chromosomal aberration, and sister chromatid exchange. A total of 17 studies were included being 11 studies (out of 17) with positive genotoxic effects, suggesting that gadolinium can induce DNA damage. Most of the studies (12 out of 17) were rated as \"strong\" or \"moderate\" in quality, providing reliable evidence for these findings. This review advances the current understanding of gadolinium's potential health risks by highlighting its genotoxic effects.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144173945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute and Subacute Toxicity of Synthetic Pyridone Analogs in Albino Rats: Analysis of Basic Parameters.","authors":"Vaishali Singh, Lalhruaizela, Ranjeet Maurya, Ved Prakash Singh, Rajesh Kumar Kharwar","doi":"10.1002/jat.4819","DOIUrl":"https://doi.org/10.1002/jat.4819","url":null,"abstract":"<p><p>1,4-Dihydropyridones and its derivatives possess biological and pharmacological activities. However, at present there is no information regarding toxicity and biological as well as pharmacological potentials of Compound 1 [Ethyl-5-cyano-2-methyl-4-(2-nitrophenyl)-6-oxo-1,4,5,6-tetrahydropyridine-3-carboxylate], Compound 2 [Ethyl 4-(4-chlorophenyl)-5-cyano-2-methyl-6-oxo-1,6-dihydropyridine-3-carboxylate], and Compound 3 [Ethyl-5-cyano-2-methyl-6-oxo-4-phenyl-1,6-dihydropyridine-3-carboxylate]. We evaluated acute and subacute toxicity of Compounds 1, 2, and 3. To achieve the proposed objective, rats were orally administrated with different doses of 1, 2, and 3. For acute oral toxicity animals were administered single oral dose of 10, 20, 50, and 100 mg/100 g bw and for subacute oral toxicity animals were administered oral dose of 1 and 10 mg/100 g bw for 28 days. Common physiological endpoints such as food and water consumption, stool weight and mortality were observed up to 14 and 28 days. Variation in bw, food and water consumption, stool weight, hematological, biochemical, organ weight, and histopathology was observed. In acute study, administration of Compound 2 lead to the mortality of one female rat. However, no mortality was noted in males. Normal physiological endpoints were noted in males as well as female rats. No significant change was noted in any parameters after treatment with acute and subacute doses. After oral administration of Compound 1 and Compound 3 no significant variation was noted in any groups of the animals. All compounds showed no toxic potential for either acute or subacute dose. Further studies are required to check biological and pharmacological efficiency of the compounds.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144159207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Application of a 3D Human Cornea-Like Epithelium for Eye Irritation Assessment of Contact Lens Solutions.","authors":"Xian He, Li Fang, Xianhua Chen, Ziyang Zhang, Senting Zhou, Danning Qi, Xu Weng, Xinyi Lin, Nana Gao, Fei Hu, Xin Lu","doi":"10.1002/jat.4820","DOIUrl":"https://doi.org/10.1002/jat.4820","url":null,"abstract":"<p><p>Currently, medical device eye irritation testing relies on the Draize eye test in rabbits, which presents significant challenges regarding animal welfare and variations across laboratories. This research explores the application of the commercially available three-dimensional reconstructed human corneal epithelial tissue (Skinovo-Ocular) in eye irritation evaluation. The model is developed by culturing immortalized human corneal epithelial cells at a liquid-air interface, resembling the morphology and induction of biological indicators found in human corneal tissue. We evaluated the eye irritation effect of 30 minimum reference chemicals according to OECD Performance Standards. The results revealed a sensitivity of 100%, specificity of 66.7%, and accuracy of 83.3%, indicating predictive performance comparable to other reference methods. Furthermore, we conducted analyses including trans-epithelial electrical resistance, cytokine secretion, and histology, thereby enhancing our understanding of the mechanisms underlying eye irritation assessment in this model. Additionally, we tested various contact lens solutions and compared the results with rabbit in vivo experiments, demonstrating the model's potential for analyzing the eye irritation of mixtures. This model shows promise as an alternative for eye irritation analysis of medical devices, further reducing the reliance on experimental animals.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144159210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"How Permethrin Affects Freshwater Mussels: Physiological, Biochemical, and Histopathological Analyses?","authors":"Reyhan Gençer, Pınar Arslan Yüce, Aysel Çağlan Günal","doi":"10.1002/jat.4821","DOIUrl":"https://doi.org/10.1002/jat.4821","url":null,"abstract":"<p><p>Freshwater mussel Unio delicatus is a species found in aquatic ecosystems in countries bordering the Mediterranean Sea. Permethrin is a synthetic pyrethroid and a widely used chemical in domestic, industrial, and agricultural areas due to its insecticidal properties. Therefore, it is one of the substances that inevitably contaminate aquatic ecosystems and is a chemical whose effects on different types of nontarget aquatic organisms are investigated. In the present study, the sublethal effects of permethrin on the physiological, biochemical, and histological properties of U. delicatus were investigated with two different exposure times. Permethrin was less toxic than other commonly used insecticides against U. delicatus, and its 96-h LC₅₀ value was 119.4430 μg/L. In 96-h and 7-day exposure to permethrin with ¹/₁₀, ¹/₅₀, and ¹/₁₀₀ concentrations, a decrease in total hemocyte count occurred compared to control groups, whereas hemolymph fluid biochemical parameters showed an increase in total antioxidant and total oxidant levels depending on the concentration. In addition to these biochemical results, there were changes in total glutathione, advanced oxidative protein products, and malondialdehyde levels in the gill and digestive gland tissues compared to the control groups. In the gill, digestive gland, connective tissue, and ovaries, ¹/₁₀ and ¹/₅₀ concentrations of LC₅₀ caused pathological findings in both exposure periods. All these data showed that permethrin has significant sublethal effects on U. delicatus. The results of this study provided a comprehensive understanding of the effects of permethrin on nontarget organisms such as U. delicatus.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144159213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptome Analysis Suggests Chronic Toxic Effects of 1-Ethyl-3-(3-Dimethylaminopropyl)carbodiimide in Daphnia magna via Induction of Endoplasmic Reticulum Stress.","authors":"Haruka Ito, Megumi Matsumoto, Keisuke Mitsukuni, Tomohiro Suzuki, Hitoshi Miyakawa","doi":"10.1002/jat.4816","DOIUrl":"https://doi.org/10.1002/jat.4816","url":null,"abstract":"<p><p>Plastics have revolutionized modern life, yet their persistence in the environment poses a growing ecological threat. Biodegradable plastics, like polycaprolactone (PCL), offer a promising alternative, but their degradation can release toxic byproducts. In this study, we evaluated the ecotoxicological impact of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC), a carbodiimide-based additive used to stabilize PCL, using Daphnia magna as a model organism. Chronic toxicity assays revealed that EDC exposure at concentrations as low as 1 mg/L significantly impaired reproduction, and concentrations above 7.5 mg/L caused complete lethality. To clarify the underlying molecular mechanisms, RNA-seq analysis was conducted using four developmental stages. Surprisingly, the highest number of differentially expressed genes appeared at Day 2, prior to visible phenotypic changes. Gene ontology and pathway analysis revealed that EDC exposure induced endoplasmic reticulum (ER) stress, indicated by suppressed ribosomal gene expression and enhanced protein folding and degradation pathways. Concurrently, sphingolipid metabolism and glutathione metabolism were altered, suggesting adaptive responses to maintain cellular homeostasis. These findings suggest that EDC leaching from degrading plastics can cause profound cellular and organismal toxicity, even at environmentally relevant concentrations. Our study highlights the need to assess the toxicity of not only intact polymers, but also their degradation byproducts, offering essential insights for safer plastic chemistry and for environmental risk evaluation.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144127453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Oxidative Stress on Reproductive Toxicity Induced by Alpha-Terpineol in Male Sprague-Dawley Rats.","authors":"Pakkiresha Goravara, Vijaykumar B Malashetty","doi":"10.1002/jat.4815","DOIUrl":"https://doi.org/10.1002/jat.4815","url":null,"abstract":"<p><p>α-Terpineol, a monoterpene found in essential oils and fragrances, has been reported to exhibit reproductive toxicity. The present study investigates the impact of oxidative stress on reproductive toxicity induced by α-Terpineol in male rats. α-Terpineol was administered to rats at various doses (0, 75, 150, and 300 mg/kg/day) via oral gavage for 28 days. Endpoints assessed included sperm parameters, testicular histopathology, morphology, and the expression of Nrf2 a key regulator of cellular antioxidant defense, using immunohistochemistry, serum hormone analysis, and markers of oxidative stress in the testes malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), ferric reducing antioxidant power (FRAP) assay, and protein carbonyl content (PC) assay. Results demonstrated that α-Terpineol significantly induced oxidative stress as evidenced by increased MDA levels and decreased SOD, GSH, CAT, activities, and FRAP level. Furthermore, α-Terpineol exposure resulted in a dose-dependent reduction in sperm motility and concentration, increased abnormal sperm morphology, decreased serum testosterone, FSH and LH levels, and histopathological alterations in the testes indicating disruption of the hypothalamic-pituitary-gonadal axis. These findings suggest that oxidative stress plays a crucial role in α-Terpineol-induced reproductive toxicity in male rats, potentially through disruption of antioxidant defense mechanisms and subsequent damage to testicular tissues and sperm.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144127351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toxicological Evaluation of the Sweet Protein Brazzein Derived From Komagataella phaffii for Use as a Sweetener in Foods and Beverages.","authors":"Jwar Meetro, Labiba Nahian, Kirt R Phipps, Trung Duc Vo, Irina Dahms, Minal Lalpuria, Hadi Omrani","doi":"10.1002/jat.4811","DOIUrl":"https://doi.org/10.1002/jat.4811","url":null,"abstract":"<p><p>Brazzein is a promising new protein sweetener that has gained significant attention by the food and beverage industry in recent years. Brazzein has a sweetness intensity significantly greater than that of other low- and no-calorie sweeteners currently on the global market and can provide a comparable sweetness at lower use levels within food and beverage products. In this study, a safety assessment of the sweet protein brazzein, produced from the fermentation of Komagataella phaffii, was undertaken in an in vitro digestibility study, an in silico allergenicity assessment, an in vitro reverse mutation assay, an in vitro mammalian micronucleus assay, and a 90-day oral toxicity study in rats. The results of the in silico and in vitro studies indicate that brazzein is not readily digestible, does not have allergenic potential, and does not have genotoxic or mutagenic potential. In the 90-day toxicity study, brazzein was not associated with any adverse systemic effects at up to 2000 mg/kg body weight/day, the highest dose tested. The dose of 2000 mg/kg body weight/day was concluded to be the no observed adverse effect level. The findings from the current safety assessment demonstrate that brazzein is safe for use as a sweetener in foods and beverages for human consumption.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144119736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toxic Effects of CdTe Quantum Dots on Locomotor Behavior, Neurodevelopment, and Axon Growth in Zebrafish Larvae.","authors":"Changcun Bai, Meng Tang","doi":"10.1002/jat.4809","DOIUrl":"https://doi.org/10.1002/jat.4809","url":null,"abstract":"<p><p>The nervous system is very sensitive to CdTe quantum dots (CdTe QDs), and an understanding of the effects of CdTe QDs on the nervous system is indispensable for their use in biomedical applications, especially in clinical medicine. This research explored the possible neurotoxic effects of CdTe QDs on the peripheral nervous system of zebrafish, including motor neuron damage, altered mobility and motor behavior of zebrafish larvae. The mechanism of peripheral neurotoxicity induced by CdTe QDs was also investigated by qRT-PCR in this study. The experimental results showed that 100 nM and above quantum dot exposure induced shortening of axon length of motor neurons and reduced the length and number of neurogenesis as well as motor nerve branching in 24-120-hpf zebrafish. The toxic effects of 100 nM and above CdTe QDs on motor neurons were further manifested as a decrease in the overall activity level of the 144-hpf zebrafish larvae including decreased locomotor velocity and shortened movement time. The average swimming velocity and total movement time of zebrafish in the 400-nM CdTe QDs-treated group were 24.7% and 17.1% of those of the control group, respectively. Molecular toxicology studies showed that genes related to neurogenesis (nrd) and axonal growth (mbp, gfap, and gap43) were significantly affected by CdTe QDs exposure. Their expressions all tended to decrease in zebrafish larvae at 72 hpf after exposure to 400-nM CdTe QDs. In conclusion, the present study demonstrates that exposure of zebrafish to CdTe QDs at early life stages leads to adverse neural outcomes through inhibition of neural development and motor neuron axon growth.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144110674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}