Madison Strain, Melanie E. Garrett, Max Bucklan, Joan M. Jasien, Gordon Worley, Joseph G. Gleeson, Allison E. Ashley-Koch
Background
Spina bifida (SB), a common neural tube defects (NTDs), has a complex genetic architecture that remains incompletely understood. Although prior studies have identified rare, deleterious single nucleotide variants (SNVs) in SB, broader contributions to risk remain unclear. Here, we investigated shared genetic risk among 256 SB probands compared with 395 ancestry-matched controls using an unbiased sequencing approach.
Methods
We performed an exome-wide association study (ExWAS) of 46,887 SNVs with minor allele frequencies (MAF) > 0.001 to identify single-variant associations, followed by gene-based burden tests to assess the cumulative effect of SNVs within genes, using all variants and then restricting to rare variants (MAF < 0.05). Both burden tests were repeated in 510 unaffected parents to evaluate excess mutational burden relative to controls.
Results
Across all analyses, 16 genes were associated with SB: SRCIN1, PDE4DIP, XCL2, CTAGE10P, GLB1L3, PMS2P4, HSPA4, GLB1L2, FAM90A1, PLA1A, HLA-A, SPIRE2, TVP23B, CHD5, FOXA2, and PIF1. ExWAS identified 11 significant SNVs, nine of which were common (MAF > 0.05). The unrestricted burden test identified seven genes; four remained significant when restricted to rare variants, and two additional genes emerged only in that subset. Five burden-associated genes were not detected in the ExWAS, suggesting cumulative variant effects. Four burden-associated genes also showed enrichment in parents, supporting inherited risk. Three of these showed suggestive transmission disequilibrium (p values ≤ 0.10) and one was attributed to multiple SNVs.
Conclusion
These results provide new insight into the multifactorial genetic landscape of SB and highlight the importance of unbiased approaches in constructing genetic models of NTD.
{"title":"Sequencing Analysis Demonstrates That a Complex Genetic Architecture Contributes to Risk for Spina Bifida","authors":"Madison Strain, Melanie E. Garrett, Max Bucklan, Joan M. Jasien, Gordon Worley, Joseph G. Gleeson, Allison E. Ashley-Koch","doi":"10.1002/bdr2.2533","DOIUrl":"https://doi.org/10.1002/bdr2.2533","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Spina bifida (SB), a common neural tube defects (NTDs), has a complex genetic architecture that remains incompletely understood. Although prior studies have identified rare, deleterious single nucleotide variants (SNVs) in SB, broader contributions to risk remain unclear. Here, we investigated shared genetic risk among 256 SB probands compared with 395 ancestry-matched controls using an unbiased sequencing approach.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We performed an exome-wide association study (ExWAS) of 46,887 SNVs with minor allele frequencies (MAF) > 0.001 to identify single-variant associations, followed by gene-based burden tests to assess the cumulative effect of SNVs within genes, using all variants and then restricting to rare variants (MAF < 0.05). Both burden tests were repeated in 510 unaffected parents to evaluate excess mutational burden relative to controls.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Across all analyses, 16 genes were associated with SB: <i>SRCIN1</i>, <i>PDE4DIP</i>, <i>XCL2</i>, <i>CTAGE10P</i>, <i>GLB1L3</i>, <i>PMS2P4</i>, <i>HSPA4</i>, <i>GLB1L2</i>, <i>FAM90A1</i>, <i>PLA1A</i>, <i>HLA-A</i>, <i>SPIRE2</i>, <i>TVP23B</i>, <i>CHD5</i>, <i>FOXA2</i>, and <i>PIF1</i>. ExWAS identified 11 significant SNVs, nine of which were common (MAF > 0.05). The unrestricted burden test identified seven genes; four remained significant when restricted to rare variants, and two additional genes emerged only in that subset. Five burden-associated genes were not detected in the ExWAS, suggesting cumulative variant effects. Four burden-associated genes also showed enrichment in parents, supporting inherited risk. Three of these showed suggestive transmission disequilibrium (<i>p</i> values ≤ 0.10) and one was attributed to multiple SNVs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These results provide new insight into the multifactorial genetic landscape of SB and highlight the importance of unbiased approaches in constructing genetic models of NTD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"117 10","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145172042","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}
James E. Black III, Thomas O. Raymond, Amanda J. G. Dickinson
Introduction
Congenital heart defects (CHDs) are a leading cause of perinatal mortality, and maternal cigarette smoking is a well-established risk factor. In recent years, electronic cigarette (e-cigarette) use has surged, yet its safety during pregnancy remains poorly defined. Human epidemiologic studies have yielded inconsistent results, underscoring the need for complementary approaches. Developmental vertebrate models provide a cost-effective first-line strategy to identify potential risks. Here, we used the Xenopus laevis model to investigate the effects of e-cigarette aerosol extracts on cardiovascular development during embryogenesis.
Methods
Xenopus embryos were exposed during critical stages (20–40) to an aerosolized extract of a vanillin flavored e-liquid (e-cigAM-F), nicotine only, or vanillin. Transgenic lines (gata1:GFP for blood, flk1:GFP for vessels) and O-dianisidine staining assessed blood and vascular development. Cardiac structure was evaluated by microscopy and immunofluorescence (troponin T); ventricular area and heart rate were quantified. RT-qPCR and reanalysis of existing RNA-Seq data assessed expression changes in cardiac and hematopoietic genes.
Results
Embryos exposed to e-cigAM-F had decreased levels of hemoglobin subunits, gata1, and heme biosynthetic genes in craniofacial tissues after exposure. Blood delivery to the head was reduced, though blood remained near the heart. Vascular labeling indicated altered vessel organization but not gross loss of vasculature. Tadpoles exposed to e-cigAM-F had smaller ventricles and modestly reduced heart rate. Early cardiogenic transcripts were also suppressed. Vanillin, but not nicotine, exposure phenocopied the e-cigAM-F effects with respect to heart morphology.
Conclusions
Exposure to an aerosolized e-liquid (particularly its vanillin component) perturbs cardiovascular development in Xenopus, manifesting as reduced cranial blood flow, vascular abnormalities, smaller ventricles, and slower heart rate. These results implicate flavoring chemicals (rather than nicotine alone) in developmental cardiotoxicity, underscoring the need for mechanistic and mammalian model studies of inhaled e-liquid constituents.
{"title":"E-Cigarette and Vanillin Exposure Disrupts Cardiovascular Development in Xenopus laevis","authors":"James E. Black III, Thomas O. Raymond, Amanda J. G. Dickinson","doi":"10.1002/bdr2.2535","DOIUrl":"https://doi.org/10.1002/bdr2.2535","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Congenital heart defects (CHDs) are a leading cause of perinatal mortality, and maternal cigarette smoking is a well-established risk factor. In recent years, electronic cigarette (e-cigarette) use has surged, yet its safety during pregnancy remains poorly defined. Human epidemiologic studies have yielded inconsistent results, underscoring the need for complementary approaches. Developmental vertebrate models provide a cost-effective first-line strategy to identify potential risks. Here, we used the <i>Xenopus laevis</i> model to investigate the effects of e-cigarette aerosol extracts on cardiovascular development during embryogenesis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p><i>Xenopus</i> embryos were exposed during critical stages (20–40) to an aerosolized extract of a vanillin flavored e-liquid (e-cigAM-F), nicotine only, or vanillin. Transgenic lines (gata1:GFP for blood, flk1:GFP for vessels) and O-dianisidine staining assessed blood and vascular development. Cardiac structure was evaluated by microscopy and immunofluorescence (troponin T); ventricular area and heart rate were quantified. RT-qPCR and reanalysis of existing RNA-Seq data assessed expression changes in cardiac and hematopoietic genes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Embryos exposed to e-cigAM-F had decreased levels of hemoglobin subunits, <i>gata1</i>, and heme biosynthetic genes in craniofacial tissues after exposure. Blood delivery to the head was reduced, though blood remained near the heart. Vascular labeling indicated altered vessel organization but not gross loss of vasculature. Tadpoles exposed to e-cigAM-F had smaller ventricles and modestly reduced heart rate. Early cardiogenic transcripts were also suppressed. Vanillin, but not nicotine, exposure phenocopied the e-cigAM-F effects with respect to heart morphology.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Exposure to an aerosolized e-liquid (particularly its vanillin component) perturbs cardiovascular development in <i>Xenopus</i>, manifesting as reduced cranial blood flow, vascular abnormalities, smaller ventricles, and slower heart rate. These results implicate flavoring chemicals (rather than nicotine alone) in developmental cardiotoxicity, underscoring the need for mechanistic and mammalian model studies of inhaled e-liquid constituents.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"117 10","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145172045","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}
Graziele Alícia Batista Caixeta, Diego dos Santos Reis, Kássya Inácio Soares, Isabella de Brito Ramos, Giovanna Helen Lopes Mendes, Pabline Silva Gasparoti, Monatha Nayara Guimarães Teófilo, Jamira Dias Rocha, Luiz Fernando Fróes Fleury, Elisa Flávia Luiz Cardoso Bailão, Clayson Moura Gomes, Wilson de Melo Cruvinel, Joelma Abadia Marciano de Paula, Vanessa Cristiane Santana Amaral
Background
Corn (Zea mays L., Poaceae) stigmas, popularly known as corn silk, have been traditionally used for their diuretic properties and to treat urinary tract disorders and hypertension. Although several studies have reported beneficial effects, such as anti-inflammatory and antioxidant activities, data on their safety during pregnancy remain limited. This study aimed to evaluate the effects of prenatal treatment with a standardized dry corn silk extract on maternal and fetal toxicity parameters in Wistar rats.
Methods
Corn silk was extracted with 41% (v/v) ethanol, concentrated, and spray-dried. The total flavonoid content was determined by spectrophotometry, and phenolic compounds, including maysin, were analyzed using HPLC-DAD and HPLC-ESI-MS/MS. Pregnant Wistar rats (n = 10/group) received the vehicle or extract doses of 300, 600, or 1200 mg/kg from gestational Day (GD) 0–20. Clinical signs of toxicity, body weight gain, and food and water intake were monitored. On GD 21, blood samples were collected for biochemical analysis. Reproductive performance and genotoxicity were assessed, along with histopathological examinations of selected organs.
Results
The extract contained 1.698% flavonoids, including maysin as the predominant one. No clinical signs of toxicity, changes in body weight gain, water and food intake, genotoxicity, histopathological alterations, or biochemical disturbances were observed. However, the 1200 mg/kg dose increased pre-implantation losses. No external, skeletal, or visceral malformations were detected in fetuses.
Conclusions
Under these experimental conditions, the extract did not induce maternal or fetal toxicity. Nevertheless, the 1200 mg/kg dose may interfere with early pregnancy in Wistar rats.
{"title":"Toxicological Assessment of a Standardized Dry Extract of Zea mays L. (Poaceae) Stigmas During Gestation: Effects on Maternal Parameters and Fetal Outcomes in Wistar Rats","authors":"Graziele Alícia Batista Caixeta, Diego dos Santos Reis, Kássya Inácio Soares, Isabella de Brito Ramos, Giovanna Helen Lopes Mendes, Pabline Silva Gasparoti, Monatha Nayara Guimarães Teófilo, Jamira Dias Rocha, Luiz Fernando Fróes Fleury, Elisa Flávia Luiz Cardoso Bailão, Clayson Moura Gomes, Wilson de Melo Cruvinel, Joelma Abadia Marciano de Paula, Vanessa Cristiane Santana Amaral","doi":"10.1002/bdr2.2526","DOIUrl":"10.1002/bdr2.2526","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Corn (<i>Zea mays</i> L., Poaceae) stigmas, popularly known as corn silk, have been traditionally used for their diuretic properties and to treat urinary tract disorders and hypertension. Although several studies have reported beneficial effects, such as anti-inflammatory and antioxidant activities, data on their safety during pregnancy remain limited. This study aimed to evaluate the effects of prenatal treatment with a standardized dry corn silk extract on maternal and fetal toxicity parameters in Wistar rats.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Corn silk was extracted with 41% (v/v) ethanol, concentrated, and spray-dried. The total flavonoid content was determined by spectrophotometry, and phenolic compounds, including maysin, were analyzed using HPLC-DAD and HPLC-ESI-MS/MS. Pregnant Wistar rats (<i>n</i> = 10/group) received the vehicle or extract doses of 300, 600, or 1200 mg/kg from gestational Day (GD) 0–20. Clinical signs of toxicity, body weight gain, and food and water intake were monitored. On GD 21, blood samples were collected for biochemical analysis. Reproductive performance and genotoxicity were assessed, along with histopathological examinations of selected organs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The extract contained 1.698% flavonoids, including maysin as the predominant one. No clinical signs of toxicity, changes in body weight gain, water and food intake, genotoxicity, histopathological alterations, or biochemical disturbances were observed. However, the 1200 mg/kg dose increased pre-implantation losses. No external, skeletal, or visceral malformations were detected in fetuses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Under these experimental conditions, the extract did not induce maternal or fetal toxicity. Nevertheless, the 1200 mg/kg dose may interfere with early pregnancy in Wistar rats.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"117 9","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145123969","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}
M. Bluett-Duncan, J. Adams, M. Berkovitch, M. Berlin, A. Cahoon, J. Clayton-Smith, C. Jackson, S. Khanom, D. Mølgaard-Nielsen, J. L. Richardson, V. Simms, M. Stellfeld, U. Winterfeld, L. M. Yates, R. L. Bromley
Certain medications, when used during pregnancy, are known to impact human prenatal development. Historically, little attention has been given to the impact of in utero exposure on the developing brain, despite the significance of known teratogen-induced neurodevelopmental difficulties. This scoping review systematically identified and extracted neurodevelopmental outcome data for medications with established physical teratogenic effects and synthesized the key study characteristics. Medications with evidence of physical teratogenicity (n = 24) were defined by a panel of experts. Eligible studies reporting any neurodevelopmental outcomes following pregnancy exposure to the defined list of human structural teratogens were identified through electronic searches of MEDLINE and EMBASE. We identified 207 studies (254 publications) for inclusion, comprising 81 empirical cohorts and 126 case series. Concerningly, only 13 of 24 (54%) confirmed structural teratogens have been subject to any empirical investigation of neurodevelopmental outcomes. The mean time between authorization of known structural teratogens and the first empirical study investigating neurodevelopmental outcomes using a comparison group and formal data analysis is 33 years (Range: 11–64 years). When neurodevelopmental outcomes are investigated for medication exposures with physical teratogenic signatures, there are high levels of neurodevelopmental alterations (77%). These findings do not speak to a pharmacovigilance system that is functioning efficiently to identify and ameliorate neurodevelopmental risk, even for the medications with identified structural teratogenic risk. Given the high proportion of known physical teratogens exhibiting additional altered neurodevelopmental outcomes and the substantial lifetime burden of such alterations, to the individual and society, the timelines remain too long.
{"title":"A Scoping Review of Human Teratogens and Their Impact on the Developing Brain: A Contribution From the ConcePTION Project","authors":"M. Bluett-Duncan, J. Adams, M. Berkovitch, M. Berlin, A. Cahoon, J. Clayton-Smith, C. Jackson, S. Khanom, D. Mølgaard-Nielsen, J. L. Richardson, V. Simms, M. Stellfeld, U. Winterfeld, L. M. Yates, R. L. Bromley","doi":"10.1002/bdr2.2497","DOIUrl":"10.1002/bdr2.2497","url":null,"abstract":"<p>Certain medications, when used during pregnancy, are known to impact human prenatal development. Historically, little attention has been given to the impact of in utero exposure on the developing brain, despite the significance of known teratogen-induced neurodevelopmental difficulties. This scoping review systematically identified and extracted neurodevelopmental outcome data for medications with established physical teratogenic effects and synthesized the key study characteristics. Medications with evidence of physical teratogenicity (<i>n</i> = 24) were defined by a panel of experts. Eligible studies reporting any neurodevelopmental outcomes following pregnancy exposure to the defined list of human structural teratogens were identified through electronic searches of MEDLINE and EMBASE. We identified 207 studies (254 publications) for inclusion, comprising 81 empirical cohorts and 126 case series. Concerningly, only 13 of 24 (54%) confirmed structural teratogens have been subject to any empirical investigation of neurodevelopmental outcomes. The mean time between authorization of known structural teratogens and the first empirical study investigating neurodevelopmental outcomes using a comparison group and formal data analysis is 33 years (Range: 11–64 years). When neurodevelopmental outcomes are investigated for medication exposures with physical teratogenic signatures, there are high levels of neurodevelopmental alterations (77%). These findings do not speak to a pharmacovigilance system that is functioning efficiently to identify and ameliorate neurodevelopmental risk, even for the medications with identified structural teratogenic risk. Given the high proportion of known physical teratogens exhibiting additional altered neurodevelopmental outcomes and the substantial lifetime burden of such alterations, to the individual and society, the timelines remain too long.</p>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"117 9","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12442749/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145074461","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}
Sarah LaPointe, Xiaping Zheng, Vijaya Kancherla, Howard H. Chang, Audrey J. Gaskins
Introduction
Epidemiologic evidence on extreme ambient temperature exposures and gastroschisis is limited and conflicting.
Methods
This case–control study included records for liveborn infants in the state of Georgia, USA from 2008 to 2017. Cases included any live births with isolated gastroschisis matched 1:4 to controls free of birth defects based on county of residence and maternal age. Exposure to extreme ambient heat was defined using the 95th percentile of the county-level climatological temperature averages during periconception. Multivariable conditional logistic regression models estimated the adjusted odds ratios (aORs) and 95% confidence intervals (95% CI) for the associations between extreme ambient heat exposure during periconception and isolated gastroschisis.
Results
There were 191 cases of isolated gastroschisis and 764 controls in our study. Compared to no days of extreme heat exposure in the periconception period, exposure to 1–3, 4–7, and ≥ 8 days of extreme apparent temperatures was associated with 19% (aOR = 1.19; 95% CI 1.03, 1.38), 42% (aOR = 1.42; 95% CI 1.06, 1.91), and 70% (aOR = 1.70; 95% CI 1.09, 2.63) higher odds of isolated gastroschisis, respectively. Exposure to two or more and three or more consecutive days of extreme apparent temperature was associated with 58% (aOR = 1.58; 95% CI 1.08, 2.30) and 66% (aOR = 1.66; 95% CI 1.14, 2.41) higher odds of isolated gastroschisis, respectively.
Conclusions
We observed a positive association between exposure to extreme ambient heat and the odds of isolated gastroschisis. These findings highlight the need for more research on these associations and potential interventions to protect mothers and babies.
关于极端环境温度暴露和胃裂的流行病学证据有限且相互矛盾。方法：本病例对照研究纳入了2008年至2017年美国佐治亚州活产婴儿的记录。病例包括根据居住县和产妇年龄与无出生缺陷的对照组匹配1:4的孤立性腹裂活产婴儿。暴露于极端环境高温的定义是使用围孕期县级气候温度平均值的第95个百分位数。多变量条件logistic回归模型估计了围孕期极端环境热暴露与孤立性胃裂之间的校正优势比（aORs）和95%置信区间（95% CI）。结果：本组分离性腹裂191例，对照组764例。与感觉期无极端高温暴露天数相比，暴露于极端表面温度1-3、4-7和≥8天的患儿发生孤立性胃裂的几率分别增加19% （aOR = 1.19; 95% CI 1.03, 1.38）、42% （aOR = 1.42; 95% CI 1.06, 1.91）和70% （aOR = 1.70; 95% CI 1.09, 2.63）。暴露于连续两天或更长时间的极端表面温度和连续三天或更长时间的极端表面温度分别与58% （aOR = 1.58; 95% CI 1.08, 2.30）和66% （aOR = 1.66; 95% CI 1.14, 2.41）孤立性胃裂的几率增加相关。结论：我们观察到暴露于极端环境高温与孤立性胃裂的几率呈正相关。这些发现强调需要对这些关联和潜在的干预措施进行更多的研究，以保护母亲和婴儿。
{"title":"Associations Between Exposure to Extreme Ambient Heat During Periconception and Gastroschisis in Georgia, USA: A Population-Based, Matched Case–Control Study","authors":"Sarah LaPointe, Xiaping Zheng, Vijaya Kancherla, Howard H. Chang, Audrey J. Gaskins","doi":"10.1002/bdr2.2531","DOIUrl":"10.1002/bdr2.2531","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Epidemiologic evidence on extreme ambient temperature exposures and gastroschisis is limited and conflicting.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This case–control study included records for liveborn infants in the state of Georgia, USA from 2008 to 2017. Cases included any live births with isolated gastroschisis matched 1:4 to controls free of birth defects based on county of residence and maternal age. Exposure to extreme ambient heat was defined using the 95th percentile of the county-level climatological temperature averages during periconception. Multivariable conditional logistic regression models estimated the adjusted odds ratios (aORs) and 95% confidence intervals (95% CI) for the associations between extreme ambient heat exposure during periconception and isolated gastroschisis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>There were 191 cases of isolated gastroschisis and 764 controls in our study. Compared to no days of extreme heat exposure in the periconception period, exposure to 1–3, 4–7, and ≥ 8 days of extreme apparent temperatures was associated with 19% (aOR = 1.19; 95% CI 1.03, 1.38), 42% (aOR = 1.42; 95% CI 1.06, 1.91), and 70% (aOR = 1.70; 95% CI 1.09, 2.63) higher odds of isolated gastroschisis, respectively. Exposure to two or more and three or more consecutive days of extreme apparent temperature was associated with 58% (aOR = 1.58; 95% CI 1.08, 2.30) and 66% (aOR = 1.66; 95% CI 1.14, 2.41) higher odds of isolated gastroschisis, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>We observed a positive association between exposure to extreme ambient heat and the odds of isolated gastroschisis. These findings highlight the need for more research on these associations and potential interventions to protect mothers and babies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"117 9","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145074414","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}
This study aimed to examine the preconception care awareness and knowledge of couples preparing for marriage.
Methods
The sample of this cross-sectional study consisted of 240 engaged couples who applied for marriage to the marriage directorate of a central district municipality in the Mediterranean Region of Türkiye. The researchers collected the data through face-to-face interviews using the “Personal Information Form” and “Preconception Care Awareness and Information Form.”
Results
While 71.7% of women and 45.4% of men are 25 years old and below, 76.3% of women and 64.6% of men have a high school education or above. It was reported that 54.2% of women and 56.3% of men planned to have children immediately or 1 year after marriage. It was found that 8.8% of women and 4.2% of men had heard of the concept of preconception care, and there was a significant difference between women and men in terms of hearing the concept of preconception care (p < 0.05). The mean preconception care knowledge score of the participants was 59.26 ± 31.85 (possible scores are between 0 and 100). In this study, gender, educational status, occupation, presence of a disease that may affect health during pregnancy, presence of a genetic disease in the family, and planned time to have a child after marriage were determined as factors affecting knowledge of preconception care.
Conclusion
In this study, the rate of hearing the concept of preconception care among couples preparing for marriage is quite low, while their knowledge regarding its content and benefits is at an intermediate level. It is important to increase the awareness of preconception care in couples preparing for marriage and to eliminate the information gap.
{"title":"Examination of Preconception Care Awareness and Knowledge of Couples Preparing for Marriage: A Cross-Sectional Study","authors":"Merve Ceren, Döndü Batkın Ertürk","doi":"10.1002/bdr2.2529","DOIUrl":"https://doi.org/10.1002/bdr2.2529","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study aimed to examine the preconception care awareness and knowledge of couples preparing for marriage.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The sample of this cross-sectional study consisted of 240 engaged couples who applied for marriage to the marriage directorate of a central district municipality in the Mediterranean Region of Türkiye. The researchers collected the data through face-to-face interviews using the “Personal Information Form” and “Preconception Care Awareness and Information Form.”</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>While 71.7% of women and 45.4% of men are 25 years old and below, 76.3% of women and 64.6% of men have a high school education or above. It was reported that 54.2% of women and 56.3% of men planned to have children immediately or 1 year after marriage. It was found that 8.8% of women and 4.2% of men had heard of the concept of preconception care, and there was a significant difference between women and men in terms of hearing the concept of preconception care (<i>p</i> < 0.05). The mean preconception care knowledge score of the participants was 59.26 ± 31.85 (possible scores are between 0 and 100). In this study, gender, educational status, occupation, presence of a disease that may affect health during pregnancy, presence of a genetic disease in the family, and planned time to have a child after marriage were determined as factors affecting knowledge of preconception care.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In this study, the rate of hearing the concept of preconception care among couples preparing for marriage is quite low, while their knowledge regarding its content and benefits is at an intermediate level. It is important to increase the awareness of preconception care in couples preparing for marriage and to eliminate the information gap.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"117 9","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145038390","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}
Jawad Laadraoui, Mehdi Ait Laaradia, Zineb El Gabbas, Bilal El Mansoury, Taoufik El Rasafi, Hamid Kabdy, Abdelfatah Ait Baba, El Yazouli Loubna, Abderrahman Chait
Introduction
The use of medicinal plants during pregnancy, including Nigella sativa (Ns), or black seed, has gained interest for its therapeutic properties such as antioxidant, anti-inflammatory, and neuroprotective effects. However, its safety and effects on pregnancy and offspring development remain unclear. This study aimed to assess the effects of maternal Ns consumption on fertility, morphological growth, and behavioral development of mouse offspring.
Methods
Pregnant Swiss mice were given 300 mg/kg of Ns methanolic extract daily by gavage throughout gestation. Reproductive outcomes (litter size, birth viability, gestation period), physical growth, and behavioral reflexes of offspring were evaluated.
Results
Ns consumption significantly reduced litter size while birth viability was not significantly affected, and extended the gestation period. Morphological assessments revealed increased body weight and length of Ns-exposed offspring but delayed hair growth. Behavioral tests, including surface righting, negative geotaxis, and swimming development, showed delayed neuromotor reflexes in Ns-treated pups.
Conclusion
Ns has both growth-promoting and neurodevelopmentally disruptive effects when consumed during pregnancy. While it enhances certain physical growth parameters, it negatively affects reproductive outcomes and delays neuromotor reflex development. These findings highlight the need for caution to ensure its safe and beneficial use during gestation.
{"title":"Effect of Nigella sativa Consumption During Pregnancy on Fertility, Morphological and Behaviors of Mice Offspring","authors":"Jawad Laadraoui, Mehdi Ait Laaradia, Zineb El Gabbas, Bilal El Mansoury, Taoufik El Rasafi, Hamid Kabdy, Abdelfatah Ait Baba, El Yazouli Loubna, Abderrahman Chait","doi":"10.1002/bdr2.2530","DOIUrl":"https://doi.org/10.1002/bdr2.2530","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>The use of medicinal plants during pregnancy, including <i>Nigella sativa</i> (<i>Ns</i>), or black seed, has gained interest for its therapeutic properties such as antioxidant, anti-inflammatory, and neuroprotective effects. However, its safety and effects on pregnancy and offspring development remain unclear. This study aimed to assess the effects of maternal <i>Ns</i> consumption on fertility, morphological growth, and behavioral development of mouse offspring.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Pregnant Swiss mice were given 300 mg/kg of <i>Ns</i> methanolic extract daily by gavage throughout gestation. Reproductive outcomes (litter size, birth viability, gestation period), physical growth, and behavioral reflexes of offspring were evaluated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p><i>Ns</i> consumption significantly reduced litter size while birth viability was not significantly affected, and extended the gestation period. Morphological assessments revealed increased body weight and length of <i>Ns</i>-exposed offspring but delayed hair growth. Behavioral tests, including surface righting, negative geotaxis, and swimming development, showed delayed neuromotor reflexes in <i>Ns</i>-treated pups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p><i>Ns</i> has both growth-promoting and neurodevelopmentally disruptive effects when consumed during pregnancy. While it enhances certain physical growth parameters, it negatively affects reproductive outcomes and delays neuromotor reflex development. These findings highlight the need for caution to ensure its safe and beneficial use during gestation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"117 9","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145038454","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}
Cesar Ghadbane, Elisia Maalouf, Tigresse Boutros, Elie Ghadban
Background
Orofacial clefts (OFCs) are among the most common craniofacial birth defects and have been investigated for possible associations with increased cancer risk in affected individuals and their families.
Method
This narrative review synthesizes current evidence from epidemiological, familial, and genetic studies.
Results
Population-based and registry analyses have reported elevated risks of breast, brain, lung, oral, colorectal, and hematologic cancers, while meta-analyses highlight inconsistent findings and frequent null associations. Familial clustering studies provide stronger support, with excess colorectal and gastric cancers observed in AXIN2- and CDH1-positive pedigrees and an increased prevalence of cancer among relatives of non-syndromic cleft lip and palate patients. At the genetic level, variants in AXIN2, CDH1, FOXE1, BRCA1/2, BRIP1, and E2F1 have been implicated in both craniofacial development and tumorigenesis. Evidence also points to the modifying role of environmental exposures, particularly maternal smoking, which may interact with susceptibility variants to amplify risk. Current research is limited by small sample sizes, subtype heterogeneity, and underrepresentation of late-onset cancers. Larger, subtype-specific studies integrating genomic and environmental data are needed to clarify risk pathways and guide the development of targeted screening strategies for individuals with OFCs and their families.
{"title":"Cancer Risk and Genetic Associations in Individuals With Cleft Lip and Palate and Their Families: A Narrative Review","authors":"Cesar Ghadbane, Elisia Maalouf, Tigresse Boutros, Elie Ghadban","doi":"10.1002/bdr2.2528","DOIUrl":"https://doi.org/10.1002/bdr2.2528","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Orofacial clefts (OFCs) are among the most common craniofacial birth defects and have been investigated for possible associations with increased cancer risk in affected individuals and their families.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>This narrative review synthesizes current evidence from epidemiological, familial, and genetic studies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Population-based and registry analyses have reported elevated risks of breast, brain, lung, oral, colorectal, and hematologic cancers, while meta-analyses highlight inconsistent findings and frequent null associations. Familial clustering studies provide stronger support, with excess colorectal and gastric cancers observed in <i>AXIN2</i>- and <i>CDH1</i>-positive pedigrees and an increased prevalence of cancer among relatives of non-syndromic cleft lip and palate patients. At the genetic level, variants in <i>AXIN2</i>, <i>CDH1</i>, <i>FOXE1</i>, <i>BRCA1</i>/2, <i>BRIP1</i>, and <i>E2F1</i> have been implicated in both craniofacial development and tumorigenesis. Evidence also points to the modifying role of environmental exposures, particularly maternal smoking, which may interact with susceptibility variants to amplify risk. Current research is limited by small sample sizes, subtype heterogeneity, and underrepresentation of late-onset cancers. Larger, subtype-specific studies integrating genomic and environmental data are needed to clarify risk pathways and guide the development of targeted screening strategies for individuals with OFCs and their families.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"117 9","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145038419","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}
Wells, B. K., G. K. Garramone, A. Mahomed, and M. Ezin. 2025. “Teratogenic Effects of Serotonin Receptor 2B Disruption on the Migration and Cardiac Derivatives of the Cardiac Neural Crest.” Birth Defects Research 117, no. 7: e2506. https://doi.org/10.1002/bdr2.2506.
The Data Availability Statement for this article has been updated from the originally-published version:
Incorrect:
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Correct:
Data Availability Statement
The data that support the findings of this study are available in the Supporting Information of this article.
The data for this article are available on the publisher's website, and the online version of the article has been updated.
We apologize for this error.
Wells, b.k., g.k. Garramone， A. Mahomed和M. Ezin, 2025。5 -羟色胺受体2B干扰对心脏神经嵴迁移和心脏衍生物的致畸作用出生缺陷研究117，no。7: e2506。https://doi.org/10.1002/bdr2.2506.The本文的数据可用性声明已从原始发布的版本更新：错误：数据可用性声明支持本研究结果的数据可根据通讯作者的合理要求获得。正确：数据可用性声明支持本研究结果的数据可在本文的支持信息中找到。这篇文章的数据可以在出版商的网站上找到，文章的在线版本已经更新了。我们为这个错误道歉。
{"title":"Correction to Teratogenic Effects of Serotonin Receptor 2B Disruption on the Migration and Cardiac Derivatives of the Cardiac Neural Crest","authors":"","doi":"10.1002/bdr2.2519","DOIUrl":"https://doi.org/10.1002/bdr2.2519","url":null,"abstract":"<p>Wells, B. K., G. K. Garramone, A. Mahomed, and M. Ezin. 2025. “Teratogenic Effects of Serotonin Receptor 2B Disruption on the Migration and Cardiac Derivatives of the Cardiac Neural Crest.” <i>Birth Defects Research</i> 117, no. 7: e2506. https://doi.org/10.1002/bdr2.2506.</p><p>The Data Availability Statement for this article has been updated from the originally-published version:</p><p>Incorrect:</p><p>\u0000 <b>Data Availability Statement</b>\u0000 </p><p>The data that support the findings of this study are available from the corresponding author upon reasonable request.</p><p>Correct:</p><p>\u0000 <b>Data Availability Statement</b>\u0000 </p><p>The data that support the findings of this study are available in the Supporting Information of this article.</p><p>The data for this article are available on the publisher's website, and the online version of the article has been updated.</p><p>We apologize for this error.</p>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"117 9","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bdr2.2519","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145012189","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}
Traditional observational studies suggest that socioeconomic status (SES) may influence the risk of congenital anomalies; however, an association remains unclear due to residual confounding. This study used Mendelian randomization (MR) to explore the potential causal relationship between SES indicators and specific congenital anomalies.
Methods
We performed two-sample MR analyses to explore whether three indicators of SES—educational attainment, household income, and the Townsend Deprivation Index—have a relationship with the risk of major congenital anomalies. Genetic variants associated with these SES indicators were obtained from the MRC Integrative Epidemiology Unit (IEU) OpenGWAS database, based on UK Biobank data. Genetic associations with nine categories of congenital anomalies were sourced from the FinnGen study. The primary MR method was inverse-variance weighted (IVW), with sensitivity analyses and Bonferroni correction applied to account for multiple testing.
Results
Prior to correction for multiple testing, higher educational attainment was associated with reduced risk of congenital heart defects (CHDs) (OR = 0.60, 95% CI: 0.41–0.88; p = 0.001), congenital respiratory system malformations (OR = 0.20, 95% CI: 0.06–0.62; p = 0.005), and musculoskeletal malformations (OR = 0.47, 95% CI: 0.29–0.76; p = 0.002). A lower Townsend Deprivation Index was unexpectedly associated with a higher risk of congenital digestive tract anomalies (OR = 4.53, 95% CI: 1.10–18.63; p = 0.036). However, after Bonferroni correction, only the association between educational attainment and CHDs remained significant (adjusted p = 0.02).
Conclusions
We found limited evidence on the association between SES and congenital anomalies. Only higher educational attainment was significantly associated with reduced risk of CHDs after multiple testing correction. Further research with refined methods is needed to clarify these associations.
传统的观察性研究表明，社会经济地位（SES）可能影响先天性异常的风险；然而，由于残留的混淆，其关联仍不清楚。本研究采用孟德尔随机化（MR）方法探讨SES指标与特定先天性异常之间的潜在因果关系。方法采用两样本磁共振分析，探讨ses的三个指标——受教育程度、家庭收入和汤森剥夺指数——是否与重大先天性异常的风险有关。与这些SES指标相关的遗传变异来自MRC综合流行病学单位（IEU） OpenGWAS数据库，基于UK Biobank数据。与九类先天性异常的遗传关联来源于FinnGen研究。主要MR方法是反方差加权（IVW），采用敏感性分析和Bonferroni校正来解释多重检验。结果在校正多重测试之前，较高的教育程度与先天性心脏缺陷（CHDs） （OR = 0.60, 95% CI: 0.41-0.88; p = 0.001）、先天性呼吸系统畸形（OR = 0.20, 95% CI: 0.06-0.62; p = 0.005）和肌肉骨骼畸形（OR = 0.47, 95% CI: 0.29-0.76; p = 0.002）的风险降低相关。汤森剥夺指数越低，先天性消化道异常的风险越高（OR = 4.53, 95% CI: 1.10-18.63; p = 0.036）。然而，经Bonferroni校正后，只有受教育程度与冠心病之间的关系仍然显著（调整p = 0.02）。结论：我们发现有限的证据表明SES与先天性异常之间存在关联。在多次测试校正后，只有较高的教育程度与降低冠心病风险显著相关。需要用更精确的方法进行进一步的研究来澄清这些关联。
{"title":"Association Between Socioeconomic Status and Major Congenital Anomalies: A Two-Sample Mendelian Randomization Study","authors":"Daniel Linares, Qun Miao, Beatriz Luna","doi":"10.1002/bdr2.2524","DOIUrl":"https://doi.org/10.1002/bdr2.2524","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Traditional observational studies suggest that socioeconomic status (SES) may influence the risk of congenital anomalies; however, an association remains unclear due to residual confounding. This study used Mendelian randomization (MR) to explore the potential causal relationship between SES indicators and specific congenital anomalies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We performed two-sample MR analyses to explore whether three indicators of SES—educational attainment, household income, and the Townsend Deprivation Index—have a relationship with the risk of major congenital anomalies. Genetic variants associated with these SES indicators were obtained from the MRC Integrative Epidemiology Unit (IEU) OpenGWAS database, based on UK Biobank data. Genetic associations with nine categories of congenital anomalies were sourced from the FinnGen study. The primary MR method was inverse-variance weighted (IVW), with sensitivity analyses and Bonferroni correction applied to account for multiple testing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Prior to correction for multiple testing, higher educational attainment was associated with reduced risk of congenital heart defects (CHDs) (OR = 0.60, 95% CI: 0.41–0.88; <i>p</i> = 0.001), congenital respiratory system malformations (OR = 0.20, 95% CI: 0.06–0.62; <i>p</i> = 0.005), and musculoskeletal malformations (OR = 0.47, 95% CI: 0.29–0.76; <i>p</i> = 0.002). A lower Townsend Deprivation Index was unexpectedly associated with a higher risk of congenital digestive tract anomalies (OR = 4.53, 95% CI: 1.10–18.63; <i>p</i> = 0.036). However, after Bonferroni correction, only the association between educational attainment and CHDs remained significant (adjusted <i>p</i> = 0.02).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>We found limited evidence on the association between SES and congenital anomalies. Only higher educational attainment was significantly associated with reduced risk of CHDs after multiple testing correction. Further research with refined methods is needed to clarify these associations.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"117 9","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144998684","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}
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