Reproductive toxicology最新文献

{"title":"Examination of piperonyl butoxide developmental toxicity as a Sonic hedgehog pathway inhibitor targeting limb and palate morphogenesis","authors":"Kenneth S. Rivera-González ,&nbsp;Porsha M. Reynolds ,&nbsp;Robert J. Lipinski","doi":"10.1016/j.reprotox.2024.108716","DOIUrl":"10.1016/j.reprotox.2024.108716","url":null,"abstract":"<div><p>Piperonyl butoxide (PBO) is a pesticide synergist with widespread use and human exposure that was discovered to inhibit Sonic hedgehog (Shh) signaling, a pathway required for numerous developmental processes. Previous examinations of PBO’s potential for developmental toxicity have generated seemingly conflicting results. We investigated the impact of acute PBO exposure targeting Shh pathway activity during palate and limb morphogenesis. Timed-pregnant C57BL/6 J mice were exposed to a single PBO dose (67–1800 mg/kg) at gestational day (GD) 9.75, and litters were collected at GD10.25 and GD10.75 to examine Shh pathway activity or GD17 for phenotypic assessment. PBO exposure induced dose-dependent limb malformations and cleft palate in the highest dose group. Following PBO exposure, reduced expression of the Shh pathway activity markers <em>Gli1</em> and <em>Ptch1</em> was observed in the embryonic limb buds and craniofacial processes. These findings provide additional evidence that prenatal PBO exposure targeting Shh pathway activity can result in malformations in mice that parallel common etiologically complex human birth defects.</p></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"130 ","pages":"Article 108716"},"PeriodicalIF":3.3,"publicationDate":"2024-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142173879","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":"Emerging and novel technologies in reproductive and developmental toxicology","authors":"Susan E. Maier,&nbsp;Robert M. Cabrera,&nbsp;Yichang Chen,&nbsp;Neil Vargesson","doi":"10.1016/j.reprotox.2024.108705","DOIUrl":"10.1016/j.reprotox.2024.108705","url":null,"abstract":"","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"130 ","pages":"Article 108705"},"PeriodicalIF":3.3,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120508","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":"Per- and polyfluoroalkyl substances (PFAS) and hypertensive disorders of Pregnancy- integration of epidemiological and mechanistic evidence","authors":"Sri Vidya Dangudubiyyam ,&nbsp;Alissa Hofmann ,&nbsp;Pankaj Yadav ,&nbsp;Sathish Kumar","doi":"10.1016/j.reprotox.2024.108702","DOIUrl":"10.1016/j.reprotox.2024.108702","url":null,"abstract":"<div><h3>Background</h3><p>Hypertensive disorders of pregnancy (HDP) remain a significant global health burden despite medical advancements. HDP prevalence appears to be rising, leading to increased maternal and fetal complications, mortality, and substantial healthcare costs. The etiology of HDP are complex and multifaceted, influenced by factors like nutrition, obesity, stress, metabolic disorders, and genetics. Emerging evidence suggests environmental pollutants, particularly Per- and polyfluoroalkyl substances (PFAS), may contribute to HDP development.</p></div><div><h3>Objective</h3><p>This review integrates epidemiological and mechanistic data to explore the intricate relationship between PFAS exposure and HDP.</p></div><div><h3>Epidemiological evidence</h3><p>Studies show varying degrees of association between PFAS exposure and HDP, with some demonstrating positive correlations, particularly with preeclampsia. Meta-analyses suggest potential fetal sex-specific differences in these associations.</p></div><div><h3>Mechanistic insights</h3><p>Mechanistically, PFAS exposure appears to disrupt vascular hemodynamics, placental development, and critical processes like angiogenesis and sex steroid regulation. Experimental studies reveal alterations in the renin-angiotensin system, trophoblast invasion, oxidative stress, inflammation, and hormonal dysregulation – all of which contribute to HDP pathogenesis. Elucidating these mechanisms is crucial for developing preventive strategies.</p></div><div><h3>Therapeutic potential</h3><p>Targeted interventions such as AT2R agonists, caspase inhibitors, and modulation of specific microRNAs show promise in mitigating adverse outcomes associated with PFAS exposure during pregnancy.</p></div><div><h3>Knowledge gaps and future directions</h3><p>Further research is needed to comprehensively understand the full spectrum of PFAS-induced placental alterations and their long-term implications for maternal and fetal health. This knowledge will be instrumental in developing effective preventive and therapeutic strategies for HDP in a changing environmental landscape.</p></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"130 ","pages":"Article 108702"},"PeriodicalIF":3.3,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120509","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":"DNAJA1 regulates protein ubiquitination and is essential for spermatogenesis in the testes of mice and rats","authors":"Jing-jing Mao ,&nbsp;Xiao-yu Dai ,&nbsp;Yun-zi Liu ,&nbsp;Li-jun Ren ,&nbsp;Ji-qian-zhu Zhang ,&nbsp;Lang Yan ,&nbsp;Jin-feng Li ,&nbsp;Yi-jun Tian ,&nbsp;Jiang-bo Zhu ,&nbsp;Ji-kuai Chen","doi":"10.1016/j.reprotox.2024.108701","DOIUrl":"10.1016/j.reprotox.2024.108701","url":null,"abstract":"<div><p>DNAJA1 is a member of type I DnaJ proteins, which is essential for spermatogenesis and male fertility. However, its expression pattern in the testes and its impact on spermatogenesis remains unclear. Our study aimed to elucidate the mechanism of action of DNAJA1. We employed DNAJA1 knockout mice in this study. Western blotting and immunofluorescence analysis were conducted to determine the protein abundance of DNAJA1 in testes at various developmental stages. Our results revealed that DNAJA1 is predominantly expressed in the testes, and its knockout leads to complete infertility in male mice. We observed that DNAJA1 protein levels increased on postnatal days 14, 21, and 28, peaking on postnatal day 35 in mice. Immunofluorescence staining indicated that DNAJA1 expression varies across different stages of the spermatogenesis cycle. Additionally, DNAJA1 was absent in epididymal sperm. In early- and mid-stage tubules, DNAJA1 protein distribution was co-localized with residual bodies in elongating spermatids. Furthermore, we found that DNAJA1 knockout significantly reduced protein polyubiquitination in the testis. Analysis of the GEO database showed that DNAJA1 levels were significantly decreased in semen samples from subjects with teratozoospermia, asthenozoospermia, and impaired spermatogenesis. Our findings suggest that DNAJA1 is an essential protein for spermatogenesis, and its deletion reduces protein polyubiquitination in the testis, ultimately resulting in infertility and spermatogenesis defects.</p></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"130 ","pages":"Article 108701"},"PeriodicalIF":3.3,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142111463","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":"Expression and localization of Cyclin D1/Nanog and NF-κB/Bax protein in dysplastic testicles of mice","authors":"Penggang Liu ,&nbsp;Xiaoxiang Pan ,&nbsp;Luxian Wu ,&nbsp;Seth Yaw Afedo ,&nbsp;Xinwei Feng ,&nbsp;Jin Yang","doi":"10.1016/j.reprotox.2024.108704","DOIUrl":"10.1016/j.reprotox.2024.108704","url":null,"abstract":"<div><p>Testicular dysplasia significantly impairs male reproductive capacity. This study investigated the expression of Cyclin D1/Nanog and NF-κB/Bax in dysplastic testes of mice using histological staining, Western blotting, and immunohistochemistry. The results showed that Nanog and Bax expression were significantly higher in dysplastic testicular tissue than in normal tissue (P &lt; 0.01). Cyclin D1 protein expression was higher in normal testis tissue than in dysplastic testis (P &lt; 0.01). NF-κB was highly expressed in cryptorchid and normal testis with no significant difference (P &gt; 0.05). Immunolocalization revealed that Nanog, NF-κB, and Bax were expressed in the cytoplasm of Leydig and spermatogenic cells. Cyclin D1 primarily expressed in the nucleus of Sertoli cells. These findings suggest that altered expression of Nanog, Cyclin D1, and Bax may contribute to testicular dysplasia. This study provides a scientific foundation for detecting testicular dysplasia and selecting appropriate animal models, ultimately informing strategies to improve male reproductive health.</p></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"130 ","pages":"Article 108704"},"PeriodicalIF":3.3,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142111464","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":"Male premating treatment in FEED studies: Length is not everything","authors":"Paul Barrow","doi":"10.1016/j.reprotox.2024.108703","DOIUrl":"10.1016/j.reprotox.2024.108703","url":null,"abstract":"<div><p>The ICH S5(R3) guideline recommends that male rodents in a FEED study are treated for ≥2 weeks before mating, which has frequently been criticized as being too short for the detection of all effects on sperm maturation, mating behavior and male fertility. In a FEED study, males generally continue for ≥5 weeks after the start of cohabitation. This review determines how often a 2-week premating treatment period for males was used in FEED studies of novel drugs approved by the FDA in 2022 and 2023. The male premating treatment duration was specified for 44 drugs. Only 16 % of these had a 2-week male premating treatment period. 52 % of drugs had a 4-week period. No examples were found in the literature of drugs for which male-mediated reproductive toxicity could have been detected using a 4-week, but not a 2-week, premating treatment period. Repeat dose studies in 2 species, with a duration of treatment at least equivalent to that in patients, are generally completed before the FEED study is planned. Providing no effects on male reproductive organs are detected in the repeat dose studies, a 2-week premating treatment period appears sufficient for the detection of effects on male mating performance. If toxic effects on spermatogenesis are detected in the repeat dose studies, a male FEED study serves little regulatory purpose. Even in the absence of effects on mating performance and fertility in the FEED study, a drug-related disruption of spermatogenesis would likely be considered pertinent to the human.</p></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"130 ","pages":"Article 108703"},"PeriodicalIF":3.3,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142111465","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":"Altered mitochondrial homeostasis on bisphenol-A exposure and its association in developing polycystic ovary syndrome: A comprehensive review","authors":"Supraja M. Kodanch ,&nbsp;Sayantani Mukherjee ,&nbsp;Navya B. Prabhu ,&nbsp;Shama Prasada Kabekkodu ,&nbsp;Shashikala K. Bhat ,&nbsp;Padmalatha S. Rai","doi":"10.1016/j.reprotox.2024.108700","DOIUrl":"10.1016/j.reprotox.2024.108700","url":null,"abstract":"<div><p>Polycystic ovary syndrome (PCOS) is a heterogeneous endocrinopathy that is known to be one of the most common reproductive pathologies observed in premenopausal women around the globe and is particularly complex as it affects various endocrine and reproductive metabolic pathways. Endocrine-disrupting chemicals (EDCs) are considered to be environmental toxicants as they have hazardous health effects on the functioning of the human endocrine system. Among various classes of EDCs, bisphenol A (BPA) has been under meticulous investigation due to its ability to alter the endocrine processes. As there is emerging evidence suggesting that BPA-induced mitochondrial homeostasis dysfunction in various pathophysiological conditions, this review aims to provide a detailed review of how various pathways associated with ovarian mitochondrial homeostasis are impaired on BPA exposure and its mirroring effects on the PCOS phenotype. BPA exposure might cause significant damage to the mitochondrial morphology and functions through the generation of reactive oxygen species (ROS) and simultaneously downregulates the total antioxidant capacity, thereby leading to oxidative stress. BPA disrupts the mitochondrial dynamics in human cells by altering the expressions of mitochondrial fission and fusion genes, increases the senescence marker proteins, along with significant alterations in the mTOR/AMPK pathway, upregulates the expression of autophagy mediating factors, and downregulates the autophagic suppressor. Furthermore, an increase in apoptosis of the ovarian granulosa cells indicates impaired folliculogenesis. As all these key features are associated with the pathogenesis of PCOS, this review can provide a better insight into the possible associations between BPA-induced dysregulation of mitochondrial homeostasis and PCOS.</p></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"130 ","pages":"Article 108700"},"PeriodicalIF":3.3,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0890623824001679/pdfft?md5=c7a3b3ce1a3040142a14a5f15a9df035&pid=1-s2.0-S0890623824001679-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142056342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of Bisphenol S (BPS) toxicity on the reproductive system of Channa striatus: Insights for environmental risk assessment","authors":"Sini Mohan ,&nbsp;Siju Surendran ,&nbsp;N.A. Malini ,&nbsp;K. Roy George","doi":"10.1016/j.reprotox.2024.108690","DOIUrl":"10.1016/j.reprotox.2024.108690","url":null,"abstract":"<div><p>Aquatic ecosystems face significant exposure to endocrine-disrupting chemicals (EDCs), which can mimic, block, or alter the synthesis of endogenous hormones. Bisphenol A (BPA), a widely known EDC, has been phased out from consumer products due to concerns about its potential impacts on human health. In its place, bisphenol S (BPS), an organic compound, has been increasingly used in the production of polycarbonate plastics, epoxy resins, thermal receipt papers, and currency. Vitellogenin (<em>Vtg</em>), a yolk precursor protein synthesized in the liver and present in oviparous fish, particularly males, serves as a pertinent biomarker for studying the effects of estrogenic EDCs on fish. This study aimed to assess the impact of BPS on reproductive parameters and hepatic vitellogenin expression in <em>Channa striatus</em>. The LC50 of BPS was determined to be 128.8 mg/L. Experimental groups included control and BPS-exposed fish, with sub-lethal concentrations of BPS (1 mg/L, 4 mg/L, and 12 mg/L) administered and effects monitored at seven- and twenty-one-day intervals. Significant decreases in gonadosomatic index (GSI), ova diameter, and fecundity were observed in BPS-exposed <em>Channa striatus</em>. Hepatic <em>Vtg</em> mRNA expression was downregulated in female and upregulated in male following BPS exposure. Serum hormone analysis confirmed the estrogenic activity of BPS. These findings underscore BPS's ability as an endocrine disruptor to interfere with hormone synthesis and disrupt spermatogenesis and oogenesis processes in <em>Channa striatus</em>. This research contributes to understanding the endocrine-disrupting effects of BPS on aquatic organisms, highlighting potential ecological implications and the need for continued monitoring and regulatory considerations.</p></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"130 ","pages":"Article 108690"},"PeriodicalIF":3.3,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142047068","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":"Extended one-generation reproductive toxicity study of food-grade titanium dioxide E171 with emphasis on reproductive and endocrine endpoints","authors":"Rodger V. Battersby ,&nbsp;Janine Adam ,&nbsp;Amy L. Williams ,&nbsp;John M. DeSesso","doi":"10.1016/j.reprotox.2024.108687","DOIUrl":"10.1016/j.reprotox.2024.108687","url":null,"abstract":"<div><p>Food-grade titanium dioxide E171 was administered in feed to Sprague Dawley rats in an extended one-generation reproductive toxicity (EOGRT) study (OECD Test 443). The dosed diet (0, 100, 300, or 1000 mg/kg body weight/day) started 10 weeks before mating and continued throughout the study. After weaning, pups were allocated to Cohorts 1 A/1B (to assess reproductive toxicity), 2 A/2B (to assess developmental neurotoxicity), and 3 (to assess developmental immunotoxicity); in addition, Cohort 1B was mated to produce an F₂ generation and satellite F₀ animals were evaluated for colonic aberrant crypt foci (ACF). In F₀ animals, there were no systemic toxicity or reproductive effects, no treatment-related histopathological changes, and no ACF in the colon. Serum estradiol or testosterone concentrations were not changed in F₀ or F₁ animals. No pre-/postnatal developmental changes related to treatment were noted in F₁ animals, and the reproductive performance of F₁ Cohort 1B animals was unaffected. F₂ pups showed no abnormalities in pre- or postnatal development (postnatal days 4–8). No treatment-related developmental neurotoxicity was observed in Cohorts 2 A/2B. Although no treatment-related immunotoxicity was observed in Cohort 3, the positive control did not induce the expected response; this segment of the study will be repeated. Analyses of blood and urine showed negligible systemic absorption of E171 from the gastrointestinal tract upon dietary ingestion. The no observed adverse effect level (NOAEL) for parental systemic toxicity, reproductive toxicity, offspring toxicity, and developmental neurotoxicity was considered 1000 mg/kg body weight/day. For developmental immunotoxicity, a NOAEL was not determined owing to insufficient T-cell-dependent antibody response in the positive control. Our study provides robust data on the reproductive toxicity and preneoplastic potential of E171.</p></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"130 ","pages":"Article 108687"},"PeriodicalIF":3.3,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0890623824001540/pdfft?md5=982d8363f8cb73a287d87f8e794be996&pid=1-s2.0-S0890623824001540-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142036837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Maternal coffee consumption and biomarkers of reproductive health in young, adult sons: a cohort study","authors":"Mette Jørgensen Langergaard ,&nbsp;Andreas Ernst ,&nbsp;Bodil Hammer Bech ,&nbsp;Sandra Søgaard Tøttenborg ,&nbsp;Nis Brix ,&nbsp;Gunnar Toft ,&nbsp;Anne Gaml-Sørensen ,&nbsp;Karin Sørig Hougaard ,&nbsp;Linn Håkonsen Arendt ,&nbsp;Jens Peter Ellekilde Bonde ,&nbsp;Cecilia Høst Ramlau-Hansen","doi":"10.1016/j.reprotox.2024.108689","DOIUrl":"10.1016/j.reprotox.2024.108689","url":null,"abstract":"<div><p>It has been proposed that poor semen quality may have its origins from fetal programming due to environmental factors. We investigated whether maternal coffee consumption during early pregnancy was associated with biomarkers of reproductive health in adult sons in the Fetal Programming of Semen Quality (FEPOS) cohort. In 2017–2019, 1058 young men provided a semen and blood sample and self-measured their testis volume. Daily maternal coffee consumption was reported by the mothers around gestational week 17. We estimated relative percentage differences with 95 % confidence intervals (CI) for semen quality measures, testis volume, and reproductive hormone levels according to maternal coffee consumption during pregnancy. Maternal coffee consumption (yes/no (reference)) was associated with lower semen volume (-7.0 % (95 % CI:-12.9;-0.7)), lower proportion of morphologically normal spermatozoa (-8.3 % (95 % CI:-16.5;0.8)), higher proportion of non-progressive and immotile spermatozoa (4.3 % (95 % CI:-1.5;10.3)), and lower testis volume (-4.8 % (95 % CI:-9.0;-0.4)). No indication of a dose-response association or threshold effects was observed in the categorized and continuous analyses. No associations with reproductive hormone levels were observed in any of the analyses. Overall, the study does not provide obvious indications that maternal coffee consumption in early pregnancy deteriorates male offspring fecundity. While some minor changes were observed, most estimates were small with confidence intervals overlapping the null. Future studies, preferably with greater exposure contrast, are warranted before a conclusion can be drawn as to whether maternal coffee consumption during pregnancy constitutes a risk for reproductive health in adult sons.</p></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"130 ","pages":"Article 108689"},"PeriodicalIF":3.3,"publicationDate":"2024-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0890623824001564/pdfft?md5=7ab244d8ec89d4a5a2ea4ff84695b0bb&pid=1-s2.0-S0890623824001564-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142005134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}