The CXCR4 chemokine receptor is a G protein-coupled receptor that plays a role in many physiological processes and diseases, such as cancer metastasis, HIV infection, and immune response. Because of this, it may be possible to target it therapeutically. In addition, the active ingredient of Phaseolus vulgaris L (PVL) has been reported to have anti-inflammatory, antioxidant, and anticancer properties. Novel CXCR4 antagonists from natural resources can be a promising drug development product using a computational approach. This study aims to explore the active compound in PVL that has the responsibility to inhibit CXCR4 using molecular docking and dynamics simulation. Pharmacokinetic analysis were performed using the pkCSM, OSIRIS for toxicity risk analysis, and the PerMM for membrane permeability assessment. Molecular docking was performed using PyRx software to determine the interaction between the CXCR4 target protein from the PDB database and the active component of PVL from the PubChem database. A molecular dynamics (MD) simulation was performed to determine the stability of the interaction using the WEBGRO Macromolecular Simulations online server. The analysis were performed by comparing the results with plerixafor as a control ligand. The pharmacokinetic analysis of quercetin, kaempferol, myricetin, catechin, 3,4-dihydroxybenzoic acid, and daidzin in PVL showed that they met the drug-like criteria. These chemicals were expected to have medium-risk effects on mutagenesis and tumorigenesis, with the exception of catechin, which has no risk of toxicity, and daidzin, which has high-risk effects on mutagenesis and reproduction. Molecular docking identified that quercetin (− 6.6 kcal/mol), myricetin (− 6.6 kcal/mol), catechin (− 6.5 kcal/mol), and 3,4-dihydroxybenzoic acid (− 5.4 kcal/mol) bind to CXCR4 with the highest affinity compared to plerixafor (− 5.0 kcal/mol) and can bind to the same binding pocket with key residues Asp187, Asp97, and Glu288. The MD simulation analysis showed that quercetin has a similar stability interaction compared to the control. Considering the pharmacokinetic analysis, molecular docking, and MD simulations, quercetin, myricetin, and 3,4-dihydroxybenzoic acid have the potential to become CXCR4 agonists with their good oral bioavailability and safety properties for the novel drug candidates. Future studies are needed to consider the molecular docking result.
{"title":"Exploring the potential of phytoconstituents from Phaseolus vulgaris L against C-X-C motif chemokine receptor 4 (CXCR4): a bioinformatic and molecular dynamic simulations approach","authors":"Cesarius Singgih Wahono, Mokhamad Fahmi Rizki Syaban, Mirza Zaka Pratama, Perdana Aditya Rahman, Nabila Erina Erwan","doi":"10.1186/s43042-024-00510-9","DOIUrl":"https://doi.org/10.1186/s43042-024-00510-9","url":null,"abstract":"The CXCR4 chemokine receptor is a G protein-coupled receptor that plays a role in many physiological processes and diseases, such as cancer metastasis, HIV infection, and immune response. Because of this, it may be possible to target it therapeutically. In addition, the active ingredient of Phaseolus vulgaris L (PVL) has been reported to have anti-inflammatory, antioxidant, and anticancer properties. Novel CXCR4 antagonists from natural resources can be a promising drug development product using a computational approach. This study aims to explore the active compound in PVL that has the responsibility to inhibit CXCR4 using molecular docking and dynamics simulation. Pharmacokinetic analysis were performed using the pkCSM, OSIRIS for toxicity risk analysis, and the PerMM for membrane permeability assessment. Molecular docking was performed using PyRx software to determine the interaction between the CXCR4 target protein from the PDB database and the active component of PVL from the PubChem database. A molecular dynamics (MD) simulation was performed to determine the stability of the interaction using the WEBGRO Macromolecular Simulations online server. The analysis were performed by comparing the results with plerixafor as a control ligand. The pharmacokinetic analysis of quercetin, kaempferol, myricetin, catechin, 3,4-dihydroxybenzoic acid, and daidzin in PVL showed that they met the drug-like criteria. These chemicals were expected to have medium-risk effects on mutagenesis and tumorigenesis, with the exception of catechin, which has no risk of toxicity, and daidzin, which has high-risk effects on mutagenesis and reproduction. Molecular docking identified that quercetin (− 6.6 kcal/mol), myricetin (− 6.6 kcal/mol), catechin (− 6.5 kcal/mol), and 3,4-dihydroxybenzoic acid (− 5.4 kcal/mol) bind to CXCR4 with the highest affinity compared to plerixafor (− 5.0 kcal/mol) and can bind to the same binding pocket with key residues Asp187, Asp97, and Glu288. The MD simulation analysis showed that quercetin has a similar stability interaction compared to the control. Considering the pharmacokinetic analysis, molecular docking, and MD simulations, quercetin, myricetin, and 3,4-dihydroxybenzoic acid have the potential to become CXCR4 agonists with their good oral bioavailability and safety properties for the novel drug candidates. Future studies are needed to consider the molecular docking result.","PeriodicalId":39112,"journal":{"name":"Egyptian Journal of Medical Human Genetics","volume":"100 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140594114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-09DOI: 10.1186/s43042-024-00525-2
Tuğba Semerci Sevimli, Murat Sevimli, Ayşe Esra Manguoğlu, Güven Lüleci
It is known that BRCA1 and BRCA2 genes’ mutation carriers are predisposed to breast and ovarian cancers and other organ cancers such as prostate, colon and cervix. In the previous study performed at X University, all coding exons of both genes were screened by denaturing gradient gel electrophoresis (DGGE). In addition to various nonsense, missense mutations, polymorphisms and intronic region changes, seven novel missense mutations, including H513L, H816P and S1517Y in BRCA1 and S326R, G258P, E2903K and N2742S in BRCA2, had been identified. To determine whether these unclassified variants are pathogenic, DNA samples of 150 healthy individuals without a known cancer history in the family were screened in this study for these seven novel missense mutations. These DNA samples were recruited from archives of previous polymorphism studies. PCR performed DNA amplifications, and denaturing high-performance liquid chromatography (DHPLC) techniques did mutation screenings. Peak patterns suggestive of a change in DNA fragments were considered for sequencing analyses. Analyses revealed that none of the 150 DNA samples had any change in the seven screened fragments. As a result, it is assumed that these seven mutations might be novel pathogenic mutations described in the Turkish population. In conclusion, these carriers must be informed about the mutation and given appropriate genetic counseling by their physicians. In addition, genetic testing must be offered to high-risk individuals (men/women) in the family so that it would be possible for other family members to have genetic counseling and contribute to disease prevention. On the other hand, these findings would contribute to current literature with novel results and shed light on future research.
众所周知，BRCA1 和 BRCA2 基因突变携带者易患乳腺癌、卵巢癌和其他器官癌症，如前列腺癌、结肠癌和宫颈癌。在 X 大学之前进行的研究中，通过变性梯度凝胶电泳（DGGE）筛选了这两个基因的所有编码外显子。除了各种无义突变、错义突变、多态性和内含子区变化外，还发现了七种新型错义突变，包括 BRCA1 中的 H513L、H816P 和 S1517Y，以及 BRCA2 中的 S326R、G258P、E2903K 和 N2742S。为了确定这些未分类的变异是否具有致病性，本研究对 150 个没有已知家族癌症病史的健康人的 DNA 样本进行了筛查，以检测这 7 个新型错义突变。这些 DNA 样本是从以前的多态性研究档案中收集的。聚合酶链式反应（PCR）进行 DNA 扩增，变性高效液相色谱（DHPLC）技术进行突变筛选。对提示 DNA 片段发生变化的峰值模式进行测序分析。分析表明，在 150 份 DNA 样本中，7 个筛选出的片段均未发生任何变化。因此，推测这七种突变可能是土耳其人群中出现的新型致病突变。总之，医生必须告知这些基因突变携带者，并为他们提供适当的遗传咨询。此外，还必须为家族中的高危个体（男性/女性）提供基因检测，以便其他家庭成员也能接受基因咨询，为疾病预防做出贡献。另一方面，这些研究结果将为目前的文献提供新的成果，并为未来的研究提供启示。
{"title":"Turkish population-based screening for first identified changes of BRCA1 and BRCA2 genes in breast and/or ovarian cancer patients","authors":"Tuğba Semerci Sevimli, Murat Sevimli, Ayşe Esra Manguoğlu, Güven Lüleci","doi":"10.1186/s43042-024-00525-2","DOIUrl":"https://doi.org/10.1186/s43042-024-00525-2","url":null,"abstract":"It is known that BRCA1 and BRCA2 genes’ mutation carriers are predisposed to breast and ovarian cancers and other organ cancers such as prostate, colon and cervix. In the previous study performed at X University, all coding exons of both genes were screened by denaturing gradient gel electrophoresis (DGGE). In addition to various nonsense, missense mutations, polymorphisms and intronic region changes, seven novel missense mutations, including H513L, H816P and S1517Y in BRCA1 and S326R, G258P, E2903K and N2742S in BRCA2, had been identified. To determine whether these unclassified variants are pathogenic, DNA samples of 150 healthy individuals without a known cancer history in the family were screened in this study for these seven novel missense mutations. These DNA samples were recruited from archives of previous polymorphism studies. PCR performed DNA amplifications, and denaturing high-performance liquid chromatography (DHPLC) techniques did mutation screenings. Peak patterns suggestive of a change in DNA fragments were considered for sequencing analyses. Analyses revealed that none of the 150 DNA samples had any change in the seven screened fragments. As a result, it is assumed that these seven mutations might be novel pathogenic mutations described in the Turkish population. In conclusion, these carriers must be informed about the mutation and given appropriate genetic counseling by their physicians. In addition, genetic testing must be offered to high-risk individuals (men/women) in the family so that it would be possible for other family members to have genetic counseling and contribute to disease prevention. On the other hand, these findings would contribute to current literature with novel results and shed light on future research.","PeriodicalId":39112,"journal":{"name":"Egyptian Journal of Medical Human Genetics","volume":"298 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140594063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-09DOI: 10.1186/s43042-024-00522-5
S. P. Angelin Claret, Jose Prakash Dharmian, A. Muthu Manokar
Artificial intelligence (AI) has shown great promise in the field of healthcare as a means of improving the diagnosis of skin cancer. The objective of this research is to enhance the precision and effectiveness of skin cancer identification by the incorporation of convolutional neural networks (CNNs) and discrete wavelet transformation (DWT). Making use of AI-driven techniques has the potential to completely transform the diagnosis process by providing quicker and more accurate evaluations of skin lesions. In an effort to improve dermatology and give physicians reliable resources for early and precise skin cancer diagnosis, this work explores the combination of CNNs with DWT. The accurate and timely classification of skin cancer lesions plays a crucial role in early diagnosis and effective treatment. In this, we propose a novel approach for skin cancer classification using discrete wavelet transformation (DWT). The DWT is employed to extract relevant features from skin lesion images, which are then used to train a classification model. The effectiveness of the suggested approach is assessed through the examination of a dataset of skin lesion images with known classes (malignant or benign). The outcomes of the experiment demonstrate that the suggested model successfully attained a classification result of sensitivity as 94% and specificity as 91% when compared with artificial neural network (ANN) and multilayer perceptron methods. The HAM 10000 dataset is employed to explore and evaluate the effectiveness of the proposed model, leading to improved accuracy compared to the existing machine learning algorithms in utilization. The results demonstrate the effectiveness of the DWT-based approach in accurately classifying skin cancer lesions, thus aiding in early detection and diagnosis.
{"title":"Artificial intelligence-driven enhanced skin cancer diagnosis: leveraging convolutional neural networks with discrete wavelet transformation","authors":"S. P. Angelin Claret, Jose Prakash Dharmian, A. Muthu Manokar","doi":"10.1186/s43042-024-00522-5","DOIUrl":"https://doi.org/10.1186/s43042-024-00522-5","url":null,"abstract":"Artificial intelligence (AI) has shown great promise in the field of healthcare as a means of improving the diagnosis of skin cancer. The objective of this research is to enhance the precision and effectiveness of skin cancer identification by the incorporation of convolutional neural networks (CNNs) and discrete wavelet transformation (DWT). Making use of AI-driven techniques has the potential to completely transform the diagnosis process by providing quicker and more accurate evaluations of skin lesions. In an effort to improve dermatology and give physicians reliable resources for early and precise skin cancer diagnosis, this work explores the combination of CNNs with DWT. The accurate and timely classification of skin cancer lesions plays a crucial role in early diagnosis and effective treatment. In this, we propose a novel approach for skin cancer classification using discrete wavelet transformation (DWT). The DWT is employed to extract relevant features from skin lesion images, which are then used to train a classification model. The effectiveness of the suggested approach is assessed through the examination of a dataset of skin lesion images with known classes (malignant or benign). The outcomes of the experiment demonstrate that the suggested model successfully attained a classification result of sensitivity as 94% and specificity as 91% when compared with artificial neural network (ANN) and multilayer perceptron methods. The HAM 10000 dataset is employed to explore and evaluate the effectiveness of the proposed model, leading to improved accuracy compared to the existing machine learning algorithms in utilization. The results demonstrate the effectiveness of the DWT-based approach in accurately classifying skin cancer lesions, thus aiding in early detection and diagnosis.","PeriodicalId":39112,"journal":{"name":"Egyptian Journal of Medical Human Genetics","volume":"10 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140594086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-08DOI: 10.1186/s43042-024-00520-7
Lili Yang, Yueming Ding
The link between anxiety and tinnitus severity has garnered significant scholarly interest, with numerous studies identifying a positive correlation. Despite this, the genetic basis of this relationship remains underexplored. Leveraging publicly accessible GWAS data, this study employs Mendelian randomization to elucidate the genetic causality between anxiety and tinnitus severity. This research analyzed single nucleotide polymorphisms (SNPs) related to anxiety and tinnitus severity from the UK Biobank, utilizing aggregated data from genome-wide association studies (GWAS). Instrumental variables linked to anxiety were meticulously selected. The study implemented several Mendelian randomization techniques, including “mr_ivw,” “mr_egger_regression,” “mr_weighted_median,” “mr_simple_mode,” and “mr_weighted_mode,” to assess the causal impact of anxiety on tinnitus risk through odds ratios (ORs). Sensitivity analyses, including MR-Egger and the leave-one-out method, were conducted to ensure result stability. The F-value was also calculated to ascertain the strength of the instrumental variables. Analysis identified five SNPs as instrumental variables. The calculated ORs and 95% confidence intervals from MR-Egger regression, weighted median, and inverse variance weighting showed no statistically significant causal relationship between anxiety and severe tinnitus, with all P-values exceeding 0.05. This lack of statistical significance, consistent across various methods, indicates no genetic causality between anxiety and tinnitus severity. Furthermore, no evidence of heterogeneity (P = 0.80) or horizontal pleiotropy (P = 0.31) was found, reinforcing the robustness of the instrumental variables (F > 10). Our Mendelian randomization analysis reveals no genetic causality between anxiety and tinnitus severity, suggesting the need for further research into the multifaceted etiology of tinnitus.
焦虑与耳鸣严重程度之间的关系引起了学者们的极大兴趣，许多研究都发现两者之间存在正相关关系。尽管如此，这种关系的遗传基础仍未得到充分探索。本研究利用公开的 GWAS 数据，采用孟德尔随机法来阐明焦虑与耳鸣严重程度之间的遗传因果关系。本研究利用全基因组关联研究（GWAS）的汇总数据，分析了英国生物库中与焦虑和耳鸣严重程度相关的单核苷酸多态性（SNPs）。与焦虑相关的工具变量均经过精心筛选。研究采用了多种孟德尔随机化技术，包括 "mr_ivw"、"mr_egger_regression"、"mr_weighted_median"、"mr_simple_mode "和 "mr_weighted_mode"，通过几率比（ORs）评估焦虑对耳鸣风险的因果影响。为确保结果的稳定性，还进行了敏感性分析，包括 MR-Egger 分析和撇除法分析。还计算了 F 值，以确定工具变量的强度。分析确定了五个 SNP 为工具变量。通过MR-Egger回归、加权中位数和反方差加权计算得出的ORs和95%置信区间显示，焦虑与严重耳鸣之间没有统计学意义上的因果关系，所有P值均超过0.05。在各种方法中均无统计学意义，这表明焦虑与耳鸣严重程度之间不存在遗传因果关系。此外，没有发现异质性（P = 0.80）或水平多效性（P = 0.31）的证据，这加强了工具变量（F > 10）的稳健性。我们的孟德尔随机分析表明，焦虑与耳鸣严重程度之间没有遗传因果关系，这表明有必要进一步研究耳鸣的多方面病因。
{"title":"The causal relationship between anxiety and tinnitus severity: a Mendelian randomization study","authors":"Lili Yang, Yueming Ding","doi":"10.1186/s43042-024-00520-7","DOIUrl":"https://doi.org/10.1186/s43042-024-00520-7","url":null,"abstract":"The link between anxiety and tinnitus severity has garnered significant scholarly interest, with numerous studies identifying a positive correlation. Despite this, the genetic basis of this relationship remains underexplored. Leveraging publicly accessible GWAS data, this study employs Mendelian randomization to elucidate the genetic causality between anxiety and tinnitus severity. This research analyzed single nucleotide polymorphisms (SNPs) related to anxiety and tinnitus severity from the UK Biobank, utilizing aggregated data from genome-wide association studies (GWAS). Instrumental variables linked to anxiety were meticulously selected. The study implemented several Mendelian randomization techniques, including “mr_ivw,” “mr_egger_regression,” “mr_weighted_median,” “mr_simple_mode,” and “mr_weighted_mode,” to assess the causal impact of anxiety on tinnitus risk through odds ratios (ORs). Sensitivity analyses, including MR-Egger and the leave-one-out method, were conducted to ensure result stability. The F-value was also calculated to ascertain the strength of the instrumental variables. Analysis identified five SNPs as instrumental variables. The calculated ORs and 95% confidence intervals from MR-Egger regression, weighted median, and inverse variance weighting showed no statistically significant causal relationship between anxiety and severe tinnitus, with all P-values exceeding 0.05. This lack of statistical significance, consistent across various methods, indicates no genetic causality between anxiety and tinnitus severity. Furthermore, no evidence of heterogeneity (P = 0.80) or horizontal pleiotropy (P = 0.31) was found, reinforcing the robustness of the instrumental variables (F > 10). Our Mendelian randomization analysis reveals no genetic causality between anxiety and tinnitus severity, suggesting the need for further research into the multifaceted etiology of tinnitus. ","PeriodicalId":39112,"journal":{"name":"Egyptian Journal of Medical Human Genetics","volume":"2019 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140594052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-08DOI: 10.1186/s43042-024-00524-3
Sara A. Nusair, Gehan Galal, Sara M. Radwan
Hepatocellular carcinoma (HCC) is a severe threat and a main reason for cancer-related deaths around the world. Drug resistance to sorafenib (Sorf), the effective HCC first-line therapy, is very common. A number of natural compounds, notably bee venom (BV), have been claimed to show a great impact against cancer when administered on its own or in conjunction with chemotherapy. Thus, this study aimed to investigate the anticancer effect of BV alone and/or combined with Sorf on HepG2 liver cancer cell lines. Both mRNA and protein expressions of Bax, Bcl-2 and Beclin-1 were investigated by quantitative real-time PCR (qPCR) and western blot respectively, to examine the apoptotic and autophagic regulatory effects of BV and Sorf single treatments plus BV/Sorf combination on HepG2 cell lines. Our findings showed that BV and Sorf had considerable dose-dependent anti-proliferative effects on HepG2 cells whether administered alone or in combination, with the greatest impact for the combined therapies. Single BV and Sorf treatments showed IC50 of 93.21 and 7.28 μg/ml respectively, while combined treatment showed IC50 of 6.73 μg/ml BV + 6.73 μg/ml Sorf. Moreover, both the pro-apoptotic gene Bax and the autophagy-related gene Beclin-1 showed significant up-regulation in their mRNA expression, while the anti-apoptotic Bcl-2 mRNA gene expression showed significant down-regulation after BV/Sorf treatment as compared to either BV or Sorf single treatment. These qPCR results were further confirmed by western blot. These findings indicate that BV synergistically potentiates the anticancer effect of Sorf on HepG2 cells through induction of apoptotic and autophagic machineries.
{"title":"The potential anticancer effect of bee venom in combination with sorafenib against HepG2 cell lines via induction of apoptosis and autophagy candidate genes","authors":"Sara A. Nusair, Gehan Galal, Sara M. Radwan","doi":"10.1186/s43042-024-00524-3","DOIUrl":"https://doi.org/10.1186/s43042-024-00524-3","url":null,"abstract":"Hepatocellular carcinoma (HCC) is a severe threat and a main reason for cancer-related deaths around the world. Drug resistance to sorafenib (Sorf), the effective HCC first-line therapy, is very common. A number of natural compounds, notably bee venom (BV), have been claimed to show a great impact against cancer when administered on its own or in conjunction with chemotherapy. Thus, this study aimed to investigate the anticancer effect of BV alone and/or combined with Sorf on HepG2 liver cancer cell lines. Both mRNA and protein expressions of Bax, Bcl-2 and Beclin-1 were investigated by quantitative real-time PCR (qPCR) and western blot respectively, to examine the apoptotic and autophagic regulatory effects of BV and Sorf single treatments plus BV/Sorf combination on HepG2 cell lines. Our findings showed that BV and Sorf had considerable dose-dependent anti-proliferative effects on HepG2 cells whether administered alone or in combination, with the greatest impact for the combined therapies. Single BV and Sorf treatments showed IC50 of 93.21 and 7.28 μg/ml respectively, while combined treatment showed IC50 of 6.73 μg/ml BV + 6.73 μg/ml Sorf. Moreover, both the pro-apoptotic gene Bax and the autophagy-related gene Beclin-1 showed significant up-regulation in their mRNA expression, while the anti-apoptotic Bcl-2 mRNA gene expression showed significant down-regulation after BV/Sorf treatment as compared to either BV or Sorf single treatment. These qPCR results were further confirmed by western blot. These findings indicate that BV synergistically potentiates the anticancer effect of Sorf on HepG2 cells through induction of apoptotic and autophagic machineries.","PeriodicalId":39112,"journal":{"name":"Egyptian Journal of Medical Human Genetics","volume":"9 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140593920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-05DOI: 10.1186/s43042-024-00521-6
Zahraa Isam Jameel
Colorectal cancer (CRC) is a major cause to global cancer-related mortality. The development of colorectal cancer is linked to hereditary variables that exhibit variability. The objective of this investigation was to assess the potential correlation between microRNA gene polymorphisms and colorectal cancer (CRC) throughout the Iraqi population. DNA samples were obtained from a cohort of 100 individuals diagnosed with the (CRC) disease, as well as 100 samples as control group. Four primers were designed to amplify four specific high-frequency variants found within microRNA molecules. These variants include Mir146a GC, Mir423 AC, Mir196a2, and Mir370. The genotyping of the PCR fragments was performed using the single-strand conformation polymorphism (SSCP) method, followed by direct sequencing of each genotype. Genotyping experiments confirmed the variability of four targeted variants, namely Mir146a GC, Mir 423 AC, Mir196a2, and Mir370 tend to exhibit a significant association with (CRC). Individuals with Mir146a: GC and Mir 423 AC genotype showed a possible association with the increased risk of (CRC), respectively (P = 0.001; OD 0.50; CI 95% 0.33–0.76; P = 0.002; OD 0.53; CI 95% 0.36–0.80). Individuals with Mir196a2: TT and Mir370 GG genotype exhibited a potential association with (CRC) (P = 0.017; OD 0.44; CI 95% 0.22–0.86; P ≤ 0.001; OD 0.24; CI 95% 0.11–0.50). The study reveals that single nucleotide polymorphisms (SNPs) in microRNA have a notable and distinct correlation with the heightened susceptibility to colorectal cancer (CRC).
结直肠癌（CRC）是全球癌症相关死亡率的主要原因。结直肠癌的发生与遗传变量有关，而遗传变量又具有变异性。这项调查的目的是评估伊拉克人口中 microRNA 基因多态性与结直肠癌（CRC）之间的潜在相关性。研究人员从 100 名被诊断患有（CRC）疾病的患者以及 100 名对照组样本中获取了 DNA 样本。设计了四种引物来扩增 microRNA 分子中的四种特定高频变异。这些变异包括 Mir146a GC, Mir423 AC, Mir196a2 和 Mir370。利用单链构象多态性（SSCP）方法对 PCR 片段进行基因分型，然后对每个基因型进行直接测序。基因分型实验证实了 Mir146a GC 、Mir 423 AC 、Mir196a2 和 Mir370 这四个目标变异体的变异性往往与癌症（CRC）有显著的关联。Mir146a：GC和Mir 423 AC 基因型分别显示与（CRC）风险增加可能有关（P = 0.001; OD 0.50; CI 95% 0.33-0.76；P = 0.002; OD 0.53; CI 95% 0.36-0.80）。具有 Mir196a2: TT 和 Mir370 GG 基因型的个体与（CRC）有潜在关联（P = 0.017; OD 0.44; CI 95% 0.22-0.86; P ≤ 0.001; OD 0.24; CI 95% 0.11-0.50）。该研究揭示了微RNA的单核苷酸多态性（SNPs）与结直肠癌（CRC）易感性的升高有着显著而明显的相关性。
{"title":"Four microRNA gene polymorphisms are associated with Iraqi patients with colorectal cancer","authors":"Zahraa Isam Jameel","doi":"10.1186/s43042-024-00521-6","DOIUrl":"https://doi.org/10.1186/s43042-024-00521-6","url":null,"abstract":"Colorectal cancer (CRC) is a major cause to global cancer-related mortality. The development of colorectal cancer is linked to hereditary variables that exhibit variability. The objective of this investigation was to assess the potential correlation between microRNA gene polymorphisms and colorectal cancer (CRC) throughout the Iraqi population. DNA samples were obtained from a cohort of 100 individuals diagnosed with the (CRC) disease, as well as 100 samples as control group. Four primers were designed to amplify four specific high-frequency variants found within microRNA molecules. These variants include Mir146a GC, Mir423 AC, Mir196a2, and Mir370. The genotyping of the PCR fragments was performed using the single-strand conformation polymorphism (SSCP) method, followed by direct sequencing of each genotype. Genotyping experiments confirmed the variability of four targeted variants, namely Mir146a GC, Mir 423 AC, Mir196a2, and Mir370 tend to exhibit a significant association with (CRC). Individuals with Mir146a: GC and Mir 423 AC genotype showed a possible association with the increased risk of (CRC), respectively (P = 0.001; OD 0.50; CI 95% 0.33–0.76; P = 0.002; OD 0.53; CI 95% 0.36–0.80). Individuals with Mir196a2: TT and Mir370 GG genotype exhibited a potential association with (CRC) (P = 0.017; OD 0.44; CI 95% 0.22–0.86; P ≤ 0.001; OD 0.24; CI 95% 0.11–0.50). The study reveals that single nucleotide polymorphisms (SNPs) in microRNA have a notable and distinct correlation with the heightened susceptibility to colorectal cancer (CRC).","PeriodicalId":39112,"journal":{"name":"Egyptian Journal of Medical Human Genetics","volume":"17 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140593933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-03DOI: 10.1186/s43042-024-00511-8
Nur Ain Azman, Zefarina Zulkafli, Nur Salwani Bakar, Mat Ghani Siti Nor Assyuhada, Siti Nur Nabeela A’ifah Mohammad
Iron deficiency contributes for over half of all anaemia cases, especially among women and children. Iron deficiency anaemia remains a serious public health concern worldwide. The aim of this study is to determine the association between the single nucleotide polymorphism rs235756 in the bone morphogenetic protein 2 (BMP2) gene and iron deficiency status. 104 total anaemic samples were selected from Hospital Universiti Sains Malaysia. ARMS-PCR was performed to genotype the rs235756 SNP in the 104 samples. The genotype distribution of BMP2 rs235756 showed that AG genotypes had the highest frequency 51(86.4%) followed by GG 6(10.2%) and AA 2(3.4%) in IDA group, whereas AG 42(93.3%), AA 2(4.4%) and GG 1(2.2%) were found in the other anaemia group. The minor allele frequency in BMP 2 rs235756 from this study (0.514) was not similar to the East Asian (EAS) population (0.135); however, the allelic frequency showed significant association between these two. The mean of total iron binding capacity level differed significantly between homozygous-dominant AA and AG + GG genotypes (P < 0.05) but no significant difference for the mean of haematological parameter, ferritin and serum iron. In future clinical settings, this finding can potentially be as a guide in the early prediction for IDA patients through the genetic testing.
在所有贫血症病例中，缺铁症占一半以上，尤其是在妇女和儿童中。缺铁性贫血仍是全球严重的公共卫生问题。本研究旨在确定骨形态发生蛋白 2（BMP2）基因中的单核苷酸多态性 rs235756 与缺铁状况之间的关联。研究人员从马来西亚理科大学医院选取了104个贫血样本。对 104 个样本中的 rs235756 SNP 进行了 ARMS-PCR 基因分型。BMP2 rs235756的基因型分布显示，在IDA组中，AG基因型的频率最高，为51（86.4%），其次是GG 6（10.2%）和AA 2（3.4%）；而在其他贫血组中，AG 42（93.3%）、AA 2（4.4%）和GG 1（2.2%）。本研究中 BMP 2 rs235756 的小等位基因频率（0.514）与东亚（EAS）人群（0.135）并不相似，但二者的等位基因频率有显著关联。同卵显性 AA 基因型和 AG + GG 基因型的总铁结合能力平均值有显著差异（P < 0.05），但血液学参数、铁蛋白和血清铁的平均值无显著差异。在未来的临床环境中，这一发现有可能成为通过基因检测早期预测 IDA 患者的指南。
{"title":"Association of single nucleotide polymorphism at BMP2 gene with iron deficiency status among anaemic patients in Hospital Universiti Sains Malaysia","authors":"Nur Ain Azman, Zefarina Zulkafli, Nur Salwani Bakar, Mat Ghani Siti Nor Assyuhada, Siti Nur Nabeela A’ifah Mohammad","doi":"10.1186/s43042-024-00511-8","DOIUrl":"https://doi.org/10.1186/s43042-024-00511-8","url":null,"abstract":"Iron deficiency contributes for over half of all anaemia cases, especially among women and children. Iron deficiency anaemia remains a serious public health concern worldwide. The aim of this study is to determine the association between the single nucleotide polymorphism rs235756 in the bone morphogenetic protein 2 (BMP2) gene and iron deficiency status. 104 total anaemic samples were selected from Hospital Universiti Sains Malaysia. ARMS-PCR was performed to genotype the rs235756 SNP in the 104 samples. The genotype distribution of BMP2 rs235756 showed that AG genotypes had the highest frequency 51(86.4%) followed by GG 6(10.2%) and AA 2(3.4%) in IDA group, whereas AG 42(93.3%), AA 2(4.4%) and GG 1(2.2%) were found in the other anaemia group. The minor allele frequency in BMP 2 rs235756 from this study (0.514) was not similar to the East Asian (EAS) population (0.135); however, the allelic frequency showed significant association between these two. The mean of total iron binding capacity level differed significantly between homozygous-dominant AA and AG + GG genotypes (P < 0.05) but no significant difference for the mean of haematological parameter, ferritin and serum iron. In future clinical settings, this finding can potentially be as a guide in the early prediction for IDA patients through the genetic testing.","PeriodicalId":39112,"journal":{"name":"Egyptian Journal of Medical Human Genetics","volume":"35 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140593941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-02DOI: 10.1186/s43042-024-00487-5
Iraj Zareban, Zahra Oudi-Akbari, Mohammad Saeed Jadgal, Hossein Ansari, Jamshid Hosseinzehi Zamani
Thalassemia is one of the most common chronic diseases, which cause many problems for the patients, families, and health system. The aim of this study was to evaluate the effectiveness of the application of an educational program based on the Theory of Planned Behavior in adopting preventive behaviors from thalassemia. This randomized controlled trial study was associated with the participation of 160 mothers of children suffering from thalassemia major, who were divided into two groups including intervention and control. Demographic information, knowledge, and data related to the constructs of the Theory of Planned Behavior were collected. Data were analyzed using SPSS16 software and descriptive and analytical tests. The mean scores of perceived behavioral control, behavioral intention, and behavior in the intervention group in the pre-intervention phase were 9.83 ± 1.45, 9.1 ± 21.32, and 2.1 ± 18.42, respectively. The stage after the intervention was increased to 12.00 ± 0.00, 11.51 ± 0.59, and 5 ± 0.37.95, respectively, and the difference of the means in the two stages was significant (P value < 0.0001). But no significant change was observed in the control group (P value > 0.05). The results of the study showed the effect of the training intervention based on the Theory of Planned Behavior on the promotion of preventive behaviors in mothers of children suffering from thalassemia major.
{"title":"Effectiveness of the application of an educational program based on the Theory of Planned Behavior (TPB) in adopting preventive behaviors among mothers who have thalassemia children in Iran: a randomized controlled trial","authors":"Iraj Zareban, Zahra Oudi-Akbari, Mohammad Saeed Jadgal, Hossein Ansari, Jamshid Hosseinzehi Zamani","doi":"10.1186/s43042-024-00487-5","DOIUrl":"https://doi.org/10.1186/s43042-024-00487-5","url":null,"abstract":"Thalassemia is one of the most common chronic diseases, which cause many problems for the patients, families, and health system. The aim of this study was to evaluate the effectiveness of the application of an educational program based on the Theory of Planned Behavior in adopting preventive behaviors from thalassemia. This randomized controlled trial study was associated with the participation of 160 mothers of children suffering from thalassemia major, who were divided into two groups including intervention and control. Demographic information, knowledge, and data related to the constructs of the Theory of Planned Behavior were collected. Data were analyzed using SPSS16 software and descriptive and analytical tests. The mean scores of perceived behavioral control, behavioral intention, and behavior in the intervention group in the pre-intervention phase were 9.83 ± 1.45, 9.1 ± 21.32, and 2.1 ± 18.42, respectively. The stage after the intervention was increased to 12.00 ± 0.00, 11.51 ± 0.59, and 5 ± 0.37.95, respectively, and the difference of the means in the two stages was significant (P value < 0.0001). But no significant change was observed in the control group (P value > 0.05). The results of the study showed the effect of the training intervention based on the Theory of Planned Behavior on the promotion of preventive behaviors in mothers of children suffering from thalassemia major.","PeriodicalId":39112,"journal":{"name":"Egyptian Journal of Medical Human Genetics","volume":"17 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140593928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cognitive impairment and depression are two common mental health conditions affecting millions worldwide. CI and depression both have complex etiology and multiple genetic and environmental factors are thought to play a role in their onset and progression. Further, CI and depression often occur as comorbidities, indicating an overlap in their etiologies. The likelihood of developing major depressive illness and CI, the prognosis in response to treatments, and the possibility of adverse reactions to antidepressant medicines are all significantly influenced by genetics. Looking at the limited literature on the role of ACE I/D polymorphism in CI and depression among Indian populations, the present population-based pilot study was conducted with the aim to understand the association of ACE I/D polymorphism with CI and depression among North Indian adults. The present study was conducted among 195 individuals aged 30 years and above. The results of the present study show that the distributions of some of the studied sociodemographic variables, viz., gender, educational status, and employment status, were significantly different between those with and without CI, where a higher percentage of females, nonliterate and unemployed participants were in CI group than in the without CI group (p value < 0.05). For cognitive impairment, none of the models showed a statistically significant association with ACE I/D genotypes or alleles. For depression, two of the models showed a statistically significant association with ACE I/D genotypes or alleles. The ID + DD (D allele) and DD genotypes of ACE I/D polymorphism, with II as a reference, were found to pose a significantly reduced risk for depression (p value < 0.05). In conclusion, the findings of this study suggest that the D allele of ACE I/D gene polymorphism poses a potentially reduced risk of depression among North Indian adults. In the case of cognitive impairment, the findings suggest that gender, educational status, and employment status may be important factors to consider when assessing the risk of cognitive impairment. However, more research is needed to better understand the complex interplay between sociodemographic and genetic factors and cognitive impairment and depression.
认知障碍和抑郁症是两种常见的精神疾病，影响着全球数百万人。认知障碍和抑郁症的病因都很复杂，多种遗传和环境因素被认为在其发病和发展过程中起了作用。此外，CI 和抑郁症经常出现合并症，这表明它们的病因存在重叠。患重度抑郁症和 CI 的可能性、对治疗反应的预后以及对抗抑郁药物产生不良反应的可能性都受到遗传学的重大影响。鉴于有关 ACE I/D 多态性在印度人群中对 CI 和抑郁症的作用的文献有限，本研究以人群为基础，旨在了解北印度成年人中 ACE I/D 多态性与 CI 和抑郁症的关系。本研究在 195 名 30 岁及以上的人群中进行。研究结果表明，一些研究的社会人口学变量，即性别、教育状况和就业状况的分布在有 CI 和无 CI 的人群中存在显著差异，其中女性、文盲和失业者在有 CI 组中的比例高于无 CI 组（P 值小于 0.05）。在认知障碍方面，没有一个模型显示与 ACE I/D 基因型或等位基因有统计学意义的关联。在抑郁症方面，有两个模型显示与 ACE I/D 基因型或等位基因有统计学意义的关联。发现 ACE I/D 多态性的 ID + DD（D 等位基因）和 DD 基因型（以 II 为参照）可显著降低患抑郁症的风险（P 值 < 0.05）。总之，本研究结果表明，ACE I/D 基因多态性的 D 等位基因可能会降低北印度成年人患抑郁症的风险。在认知障碍方面，研究结果表明，性别、教育状况和就业状况可能是评估认知障碍风险时需要考虑的重要因素。然而，要更好地理解社会人口和遗传因素与认知障碍和抑郁之间复杂的相互作用，还需要进行更多的研究。
{"title":"ACE I/D polymorphism in cognitive impairment and depression among North Indian adults: a pilot study","authors":"Apoorva Sharma, Vineet Chaudhary, Mamta Kumari Thakur, Naorem Kiranmala Devi, Kallur Nava Saraswathy","doi":"10.1186/s43042-024-00515-4","DOIUrl":"https://doi.org/10.1186/s43042-024-00515-4","url":null,"abstract":"Cognitive impairment and depression are two common mental health conditions affecting millions worldwide. CI and depression both have complex etiology and multiple genetic and environmental factors are thought to play a role in their onset and progression. Further, CI and depression often occur as comorbidities, indicating an overlap in their etiologies. The likelihood of developing major depressive illness and CI, the prognosis in response to treatments, and the possibility of adverse reactions to antidepressant medicines are all significantly influenced by genetics. Looking at the limited literature on the role of ACE I/D polymorphism in CI and depression among Indian populations, the present population-based pilot study was conducted with the aim to understand the association of ACE I/D polymorphism with CI and depression among North Indian adults. The present study was conducted among 195 individuals aged 30 years and above. The results of the present study show that the distributions of some of the studied sociodemographic variables, viz., gender, educational status, and employment status, were significantly different between those with and without CI, where a higher percentage of females, nonliterate and unemployed participants were in CI group than in the without CI group (p value < 0.05). For cognitive impairment, none of the models showed a statistically significant association with ACE I/D genotypes or alleles. For depression, two of the models showed a statistically significant association with ACE I/D genotypes or alleles. The ID + DD (D allele) and DD genotypes of ACE I/D polymorphism, with II as a reference, were found to pose a significantly reduced risk for depression (p value < 0.05). In conclusion, the findings of this study suggest that the D allele of ACE I/D gene polymorphism poses a potentially reduced risk of depression among North Indian adults. In the case of cognitive impairment, the findings suggest that gender, educational status, and employment status may be important factors to consider when assessing the risk of cognitive impairment. However, more research is needed to better understand the complex interplay between sociodemographic and genetic factors and cognitive impairment and depression.","PeriodicalId":39112,"journal":{"name":"Egyptian Journal of Medical Human Genetics","volume":"178 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140593935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-28DOI: 10.1186/s43042-024-00516-3
Magda Sayed Mahmoud, Mohamed K. Khalifa, Amira M. Nageeb, Lobna R. Ezz El-Arab, Manal El-Mahdy, Amal Ramadan, Maha Hashim, Noha M. Bakr, Menha Swellam
Impact of Isocitrate dehydrogenase1 (IDH1) and O6-methylguanine-DNA methyltransferase (MGMT) in glioblastoma (GBM) have been of great interest due to their implications in prediction of prognosis of several types of cancer. It was aimed to investigate the clinical role of IDH1 mutation and MGMT methylation pattern among GBM patients versus non-neuro-oncological diseases (NND) patients and their impact on survival criteria. Formalin-fixed paraffin-embedded (FFPE) tissue sections of 58 GBM and 20 non-neuro-oncological diseases patients were recruited and IDH1 mutation and MGMT methylation was detected using Cast-PCR technology and Methyl II quantitative PCR approach, respectively. Results were assessed with other clinicopathological criteria and survival patterns. IDH1 mutation was detected among 15 GBM cases (15/58) and it was not reported among NND (P = 0.011). Receiver operating characteristic (ROC) curve was plotted to discriminate between MGMT methylation among studied groups. Patients with MGMT methylation ≥ 66% were reported as high methylation, which was recorded significantly in 51.7% and 100% of GBM cases and NND, respectively. Both showed significant difference with performance status, while MGMT methylation was significantly related with tumor size and tumor location. IDH1 mutation and MGMT methylation reported significant increase with GB patients revealed complete response to treatment. Survival pattern was better for IDH1 mutation and MGMT high methylation as compared to IDH1 wild type or MGMT low–moderate methylation, respectively, and favorable survival was detected when both were combined than using either of them alone. Detection of IDH1 mutation and MGMT methylation among GB patients could aid in prediction of their response to treatment and their survival patterns, and their combination is better than using any of them alone.
{"title":"Clinical impact of IDH1 mutations and MGMT methylation in adult glioblastoma","authors":"Magda Sayed Mahmoud, Mohamed K. Khalifa, Amira M. Nageeb, Lobna R. Ezz El-Arab, Manal El-Mahdy, Amal Ramadan, Maha Hashim, Noha M. Bakr, Menha Swellam","doi":"10.1186/s43042-024-00516-3","DOIUrl":"https://doi.org/10.1186/s43042-024-00516-3","url":null,"abstract":"Impact of Isocitrate dehydrogenase1 (IDH1) and O6-methylguanine-DNA methyltransferase (MGMT) in glioblastoma (GBM) have been of great interest due to their implications in prediction of prognosis of several types of cancer. It was aimed to investigate the clinical role of IDH1 mutation and MGMT methylation pattern among GBM patients versus non-neuro-oncological diseases (NND) patients and their impact on survival criteria. Formalin-fixed paraffin-embedded (FFPE) tissue sections of 58 GBM and 20 non-neuro-oncological diseases patients were recruited and IDH1 mutation and MGMT methylation was detected using Cast-PCR technology and Methyl II quantitative PCR approach, respectively. Results were assessed with other clinicopathological criteria and survival patterns. IDH1 mutation was detected among 15 GBM cases (15/58) and it was not reported among NND (P = 0.011). Receiver operating characteristic (ROC) curve was plotted to discriminate between MGMT methylation among studied groups. Patients with MGMT methylation ≥ 66% were reported as high methylation, which was recorded significantly in 51.7% and 100% of GBM cases and NND, respectively. Both showed significant difference with performance status, while MGMT methylation was significantly related with tumor size and tumor location. IDH1 mutation and MGMT methylation reported significant increase with GB patients revealed complete response to treatment. Survival pattern was better for IDH1 mutation and MGMT high methylation as compared to IDH1 wild type or MGMT low–moderate methylation, respectively, and favorable survival was detected when both were combined than using either of them alone. Detection of IDH1 mutation and MGMT methylation among GB patients could aid in prediction of their response to treatment and their survival patterns, and their combination is better than using any of them alone.","PeriodicalId":39112,"journal":{"name":"Egyptian Journal of Medical Human Genetics","volume":"2 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140322109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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