1.Habitat model based on lung CT for predicting brain metastasis of lung adenocarcinoma with epidermal growth factor receptor mutation
Lijuan LIN ; Ying LIN ; Yanqing WU ; Xiang LIN ; Wei GUO ; Yang SONG ; Dehua CHEN
Chinese Journal of Interventional Imaging and Therapy 2024;21(7):408-413
		                        		
		                        			
		                        			Objective To observe the value of habitat model based on lung CT for predicting brain metastasis(BM)of lung adenocarcinoma with epidermal growth factor receptor(EGFR)mutation.Methods Data of plain lung CT of 198 lung adenocarcinoma patients with EGFR-mutant were retrospectively analyzed.The patients were divided into training set(n=138)and test set(n=60)at the ratio of 7∶3,and further divided into BM subgroup and non-BM subgroup in each set.Then a logistic regression(LR)clinical model was constructed using variables being statistically different between subgroups in training set.For features extracted from tumor and subregion of tumor,radiomics models and habitat models were constructed based on random forest,Gaussian process(GP)and support vector machine(SVM)algorithms,and the best radiomics and habitat models with generalization ability were screened.LR combined model was constructed based on the predicted values of the best radiomics and habitat models with generalization ability,as well as the clinical model.Then receiver operating characteristic curves were drawn,and the area under the curves(AUC)were calculated to evaluate the efficacy of each model for predicting BM of lung adenocarcinoma with EGFR-mutant.Spearman correlation analysis was performed to observe the correlations between Ki-67 and habitat features of lung adenocarcinoma with EGFR-mutant.Results AUC of LR clinical model,GP radiomics model,SVM habitat model and LR combined model for predicting BM of lung adenocarcinoma with EGFR-mutant was 0.700,0.726,0.801 and 0.834 in training set,0.754,0.600,0.715 and 0.848 in test set,respectively.AUC of LR combined model was higher than that of LR clinical model in training set(P<0.001),also higher than that of GP radiomics model in test set(P=0.010).Compared with GP radiomics model and SVM habitat model,the performance of LR combined model was significantly and positively improved in training set(integrated discrimination improvement index[IDI]=8.60%,8.55%,both P<0.001).Ki-67 level of EGFR-mutant lung adenocarcinoma was lowly and positively correlated with habitatmap_original_glszm_lalgle extracted from habitat map(│rs│=0.201,P=0.004).Conclusion The habitat model based on lung CT could be used to predict BM of lung adenocarcinoma with EGFR-mutant effectively.
		                        		
		                        		
		                        		
		                        	
2.Study on the Innovative Development of Digital Health
Lejia XIONG ; Yi GUO ; Xusheng WU ; Dehua HU ; Xiaofeng HE
Journal of Medical Informatics 2024;45(6):19-23,29
		                        		
		                        			
		                        			Purpose/Significance To analyze the current situation and problems of the development of digital health in China,and to explore how to promote the innovative development of digital health.Method/Process The current situation and main problems of digital health are studied and analyzed by the method of literature research and network survey,and the paths of the innovative development of digital health are devised based on case analysis.Result/Conclusion Digital technology has become the key to breaking down multiple barriers to digital health development.The paper puts forward the specific path of"sharing and cooperative governance platform-indus-trial security system-intelligent supervision mechanism"and the digital technology-based countermeasures to promote innovative devel-opment of the industry.
		                        		
		                        		
		                        		
		                        	
3.Visualization Analysis of Clinical Decision Support Research Based on Electronic Medical Records
Jicheng HUANG ; Dehua HU ; Yi ZHENG ; Xusheng WU ; Yongheng DUAN ; Jianwei LIU
Journal of Medical Informatics 2024;45(6):44-49
		                        		
		                        			
		                        			Purpose/Significance To explore the research status,research hotspots and frontiers in the field of clinical decision sup-port based on electronic medical records(EMR).Method/Process The bibliometric method and CiteSpace 6.2.R2 software are used to draw scientific knowledge graph of country/region distribution,author cooperation,institutional cooperation,keyword co-occurrence and clustering for visualized comparative analysis.Python is used for clustering hotspot mining and analysis.Result/Conclusion The field of clinical decision support based on EMR data shows a rapid development trend,with the United States and China as the main research countries and strong cooperation between domestic and foreign institutions.The keywords mainly involve EMR,artificial intelligence(AI),etc.
		                        		
		                        		
		                        		
		                        	
4.Prevalence and associated factors of diabetic retinopathy among diabetic residents in Longyan of Fujian Province
Shaoqing MA ; Jianning WU ; Dehua CAO ; Yan CHEN ; Pinsheng QIU
Chinese Journal of Ocular Fundus Diseases 2024;40(8):598-607
		                        		
		                        			
		                        			Objective:To investigate the prevalence and associated factors of diabetic retinopathy (DR) among diabetic residents in Longyan of Fujian Province.Methods:A investigative research. From January 2022 to December 2023, a total of 10 061 diabetic patients enrolled in the chronic disease follow-up management system from 112 towns and sub-districts in 7 counties and districts of Longyan of Fujian Province were selected as the target population. A questionnaire survey, routine physical examination, vision test, and non-mydriatic fundus photography were conducted. A total of 762 cases with missing height, weight, blood pressure, fasting plasma glucose (FPG), and diabetes duration, and 507 cases with unclear fundus photography were excluded, resulting in 8 792 cases included in the final statistical analysis. DR diagnosis and classification were based on the 2019 International Clinical Classification of DR. The prevalence of DR was calculated for single-eye or double-eye DR cases as 1 case; the more severe eye was used for DR grading in double-eye DR cases. Statistical analysis was performed by grouping based on the presence or absence of DR and dividing into age groups ≤67 years and >67 years. χ2 test was used to analyze factors associated with prevalence; binary multivariate logistic regression analysis was employed to identify influencing factors of DR. Results:Among the 8 792 cases, 888 (10.1%, 888/8 792) were diagnosed with DR (DR group), and 7 904 (89.9%, 7 904/8 792) had no DR (non-DR group). Compared to the non-DR group, the DR group showed significant increases in FPG ( Z=-12.448), diabetes duration ( Z=-18.936), systolic blood pressure ( Z=-4.237), diastolic blood pressure ( Z=-2.881), and body mass index (BMI) ≥24 kg/m 2 ( P<0.001). Significant differences were also found between the two groups in hypertension ( χ2=11.450), hyperlipidemia ( χ2=5.100), kidney disease ( χ2=7.039), family history of diabetes ( χ2=5.025), and regular medication use ( χ2=66.034) ( P<0.05). There were 4 688 cases in the ≤67 years group and 4 104 in the >67 years group. In the ≤67 years group, significant differences in DR prevalence were found for FPG levels ( χ2=111.754), diabetes duration ( χ2=231.658), BMI ( χ2=12.404), systolic blood pressure ( χ2=17.912), regular medication use ( χ2=40.727), hyperlipidemia ( χ2=6.816), and hypertension history ( χ2=6.775) ( P<0.05). In the >67 years group, significant differences in DR prevalence were found for FPG levels ( χ2=59.916), diabetes duration ( χ2=128.362), systolic blood pressure ( χ2=5.183), regular medication use ( χ2=22.097), kidney disease ( χ2=6.251), and family history of diabetes duration ( χ2=4.967) ( P<0.05). No significant differences in DR prevalence were found based on sex, education level, smoking history, alcohol consumption, exercise habits, heart disease history, or other family disease history ( P>0.05). Logistics regression analysis results show that patients aged >67 years, FPG [odds ratio (OR)=1.074, 95%confidence interval ( CI) 1.046-1.102], diabetes duration ( OR=1.088, 95% CI 1.071-1.106), systolic blood pressure ( OR=1.007, 95% CI 1.001-1.013), and kidney disease ( OR=3.617, 95% CI 1.268-10.320) were identified as risk factors for DR ( P<0.05). In patients aged ≤67 years, FPG ( OR=1.088, 95% CI 1.067-1.110), diabetes duration ( OR=1.108, 95% CI 1.091-1.125), and systolic blood pressure ( OR=1.008, 95% CI 1.003-1.013) were identified as independent risk factors for DR ( P<0.05), while BMI ≥24 kg/m 2 ( OR=0.934, 95% CI 0.908-0.965) was a protective factor for DR ( P<0.05). Age, regular medication use, hypertension, and hyperlipidemia were identified as potential confounding factors for DR occurrence. Conclusions:The prevalence of DR among diabetes patients in Longyan of Fujian Province, is 10.1%. FPG, diabete duration, and systolic blood pressure are independent risk factors for DR, while age, regular medication use, hypertension, and hyperlipidemia are potential confounding factors for DR occurrence.
		                        		
		                        		
		                        		
		                        	
5.A single-center, retrospective analysis of relapse and progression patterns of primary central nervous system lymphoma: can whole brain radiotherapy be replaced?.
Yue QIN ; Rongping LIU ; Xiaonan ZHANG ; Wan ZHANG ; Chen REN ; Dehua WU
Journal of Southern Medical University 2023;43(4):499-506
		                        		
		                        			OBJECTIVE:
		                        			To analyze recurrence and progression patterns of primary central nervous system lymphoma (PCNSL) in patients without whole brain radiotherapy (WBRT) and assess the value of WBRT in PCNSL treatment.
		                        		
		                        			METHODS:
		                        			This retrospective single-center study included 27 patients with PCNSL, who experienced recurrence/progression after achieving complete remission (CR), partial remission, or stable disease following initial treatments with chemotherapy but without WBRT. The patients were followed up regularly after the treatment for treatment efficacy assessment. By comparing the anatomical location of the lesions on magnetic resonance images (MRI) at the initial diagnosis and at recurrence/progression, we analyzed the patterns of relapse/progression in patients with different treatment responses and different initial status of the lesions.
		                        		
		                        			RESULTS:
		                        			MRI data showed that in 16 (59.26%) of the 27 patients, recurrence/progression occurred in out-field area (outside the simulated clinical target volume [CTV]) but within the simulated WBRT target area in 16 (59.26%) patients, and within the CTV (in-field) in 11 (40.74%) patients. None of the patients had extracranial recurrence of the tumor. Of the 11 patients who achieved CR after the initial treatments, 9 (81.82%) had PCNSL recurrences in the out-field area but within WBRT target area; of the 13 patients with a single lesion at the initial treatment, 11 (84.62%) experienced PCNSL recurrence in the out-field area but within WBRT target area.
		                        		
		                        			CONCLUSIONS
		                        			Systemic therapy combined with WBRT still remains the standard treatment for PCNSL patients, especially those who achieve CR after treatment or have a single initial lesion. Future prospective studies with larger sample sizes are needed to further explore the role of low-dose WBRT in PCNSL treatment.
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Lymphoma/radiotherapy*
		                        			;
		                        		
		                        			Central Nervous System Neoplasms/pathology*
		                        			;
		                        		
		                        			Retrospective Studies
		                        			;
		                        		
		                        			Prospective Studies
		                        			;
		                        		
		                        			Neoplasm Recurrence, Local/drug therapy*
		                        			;
		                        		
		                        			Combined Modality Therapy
		                        			;
		                        		
		                        			Brain/pathology*
		                        			;
		                        		
		                        			Antineoplastic Combined Chemotherapy Protocols/therapeutic use*
		                        			;
		                        		
		                        			Methotrexate
		                        			
		                        		
		                        	
6.FARSB stratifies prognosis and cold tumor microenvironment across different cancer types: an integrated single cell and bulk RNA sequencing analysis.
Ziran ZHANG ; Jiale TAN ; Zihang YU ; Chengdong LIU ; Jian WANG ; Dehua WU ; Xue BAI
Journal of Southern Medical University 2023;43(5):667-679
		                        		
		                        			OBJECTIVE:
		                        			Immunotherapy has brought significant clinical benefits to a subset of patients, but has thus far been disappointing in the treatment of immunologically "cold" tumors. Existing biomarkers that can precisely identify these populations are insufficient. In this context, a potential cold tumor microenvironment (TME) marker FARSB was investigated to reveal its impact on TME and patients' response to immunotherapy across pan-cancer.
		                        		
		                        			METHODS:
		                        			The expression levels and mutational landscape of FARSB in pan-cancer were investigated. Kaplan-Meier and univariate Cox regression analyses were applied to analyze the prognostic significance of FARSB. Pathways affected by FARSB were investigated by gene set enrichment and variation analysis. The relationship between FARSB expression and immune infiltration was examined using the TIMER2 and R packages. Single-cell RNA sequencing (scRNA-seq) data of several cancer types from GSE72056, GSE131907, GSE132465, GSE125449 and PMID32561858 were analyzed to validate the impact of FARSB on the TME. The predictive effect of FARSB on immunotherapy efficacy was explored in 3 immune checkpoint inhibitors (ICIs)- treated cohorts (PMID32472114, GSE176307, and Riaz2017).
		                        		
		                        			RESULTS:
		                        			FARSB expression was significantly higher in 25 tumor tissues than in normal tissues and was associated with poor prognosis in almost all tumor types. FARSB expression exhibited a strong association with several DNA damage repair pathways and was significantly associated with TP53 mutation in lung adenocarcinoma (P < 0.0001, OR=2.25). FARSB characterized a typical immune desert TME and correlated with impaired expression of chemokines and chemokines receptors. Large-scale scRNA-seq analysis confirmed the immunosuppressive role of FARSB and revealed that FARSB potentially shapes the cold TME by impeding intercellular interactions. In 3 ICI-treated cohorts, FARSB demonstrated predictive value for immunotherapy.
		                        		
		                        			CONCLUSION
		                        			This study provides a pan-cancer landscape of the FARSB gene by integrated single-cell and bulk DNA sequencing analysis and elucidates its biological function to promote DNA damage repair and construct the immune desert TME, suggesting the potential value of FARSB as a novel marker for stratifying patients with poor immunotherapeutic benefits and "cold" TME.
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Tumor Microenvironment
		                        			;
		                        		
		                        			Prognosis
		                        			;
		                        		
		                        			Adenocarcinoma of Lung/genetics*
		                        			;
		                        		
		                        			Lung Neoplasms/genetics*
		                        			;
		                        		
		                        			Sequence Analysis, RNA
		                        			
		                        		
		                        	
7.Mechanism of Buyang Huanwutang Combined with Bone Marrow Mesenchymal Stem Cell Transplantation in Treatment of Spinal Cord Injury Based on PI3K/Akt Signaling Pathway
Yang XU ; Chenglin WU ; Dehua GUO ; Yinzhen YU ; Guofu ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(4):9-17
		                        		
		                        			
		                        			ObjectiveTo explore the mechanism of Buyang Huanwutang combined with bone marrow mesenchymal stem cell (BMSC) transplantation in the treatment of spinal cord injury (SCI). MethodDifferent concentrations (12.5, 25, 50 g·kg-1) of Buyang Huanwutang were administrated to rats by gavage. The spinal cord function of rats was measured by modified Tarlov score, and the most suitable concentration of Buyang Huanwutang was screened out. SD rats were then divided into 6 groups, namely, the sham operation group (gavage of equal amount of normal saline), the model group (gavage of equal amount of normal saline), the Buyang Huanwutang group (gavage of 25 g·kg-1 Buyang Huanwutang), the BMSC transplantation group (tail vein injection of BMSCs 1 mL), the Buyang Huanwutang+BMSC group (gavage of 25 g·kg-1 Buyang Huanwutang and tail vein injection of BMSCs 1 mL), the Buyang Huanwutang+BMSC+LY294002 group (gavage of 25 g·kg-1 Buyang Huanwutang and tail vein injection of BMSCs 1 mL and 40 mg·kg-1 LY294002), with 10 rats in each group. The spinal cord function was measured by the modified Tarlov score, inclined plate test, and latency of cortical somatosensory evoked potential. Immunohistochemistry was used to detect the number of 5-bromo-2-deoxyuracil nucleoside (Brdu)-labeled positive cells in the spinal cord tissue. The protein expression levels of phosphorylated protein kinase B (p-Akt), glycoprotein 130 (gp130), and interleukin-6 (IL-6) in spinal cord were detected by Western blot. ResultAs compared with the sham operation group, the Tarlov score and the critical angle of tilt plane in the model group were significantly decreased (P<0.05), and the latency of cortical somatosensory evoked potential wave and the protein expression levels of p-Akt, gp130, and IL-6 were significantly increased (P<0.05). As compared with the model group, the Tarlov score and the critical angle of tilt plane in the sham operation group and each treatment group were significantly increased (P<0.05), and the latency of cortical somatosensory evoked potential wave and the protein expression levels of p-Akt, gp130, and IL-6 were significantly decreased (P<0.05). As compared with the BMSC group, the Tarlov score and the critical angle of inclined plane in the Buyang Huanwutang+BMSC group increased (P<0.05), the latency of cortical somatosensory evoked potential wave and the protein expression levels of p-Akt, gp130, and IL-6 decreased (P<0.05), and the number of Brdu-labeled positive cells increased 5 weeks after transplantation (P<0.05). As compared with the Buyang Huanwutang+BMSC group, the Tarlov score and the critical angle of the inclined plane in the Buyang Huanwutang+BMSC+LY294002 group increased (P<0.05), and the latency of cortical somatosensory evoked potential wave and the protein expression levels of p-Akt, gp130, and IL-6 decreased significantly (P<0.05). Five weeks after transplantation, the number of Brdu-labeled positive cells increased significantly in the Buyang Huanwutang+BMSC+LY294002 group (P<0.05). ConclusionBuyang Huanwutang can promote BMSCs migration and restore spinal cord function by inhibiting phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signal. 
		                        		
		                        		
		                        		
		                        	
8.Prenatal diagnosis and genetic analysis of a special case with complex structural rearrangements of chromosome 8.
Yan ZENG ; Tingting LUO ; Feiyan QIAN ; Dehua CHENG ; Caiping CHEN ; Jiaming FAN ; Lifang ZHANG ; Tao ZHANG ; Hongmei LI ; Zhiqiang WU
Chinese Journal of Medical Genetics 2023;40(9):1181-1184
		                        		
		                        			OBJECTIVE:
		                        			To present on a prenatally diagnosed case with complex structural rearrangements of chromosome 8.
		                        		
		                        			METHODS:
		                        			Chromosome karyotyping, chromosomal microarray analysis (CMA) and fluorescence in situ hybridization (FISH) were carried out for a fetus with increased nuchal thickness.
		                        		
		                        			RESULTS:
		                        			The karyotype of the amniotic fluid sample showed extra materials on 8p. FISH revealed a centromeric signal at the terminal of 8p with absence of telomeric signal. CMA revealed partial deletion of 8p23.3 [(208049_2256732)×1], partial duplication of 8p23.3p23.2 [(2259519_3016818)×3], and partial duplication of 8q [8q11.1q12.2(45951900_60989083)×3].
		                        		
		                        			CONCLUSION
		                        			The complex structural rearrangements of chromosome 8 in this case has differed from the commonly seen inv dup del(8p).
		                        		
		                        		
		                        		
		                        			Female
		                        			;
		                        		
		                        			Pregnancy
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Chromosomes, Human, Pair 8/genetics*
		                        			;
		                        		
		                        			In Situ Hybridization, Fluorescence
		                        			;
		                        		
		                        			Gene Rearrangement
		                        			;
		                        		
		                        			Prenatal Diagnosis
		                        			;
		                        		
		                        			Centromere
		                        			
		                        		
		                        	
9.A multi-center study on evaluation of leukocyte differential performance by an artificial intelligence-based Digital Cell Morphology Analyzer
Haoqin JIANG ; Wei CHEN ; Jun HE ; Hong JIANG ; Dandan LIU ; Min LIU ; Mianyang LI ; Zhigang MAO ; Yuling PAN ; Chenxue QU ; Linlin QU ; Dehua SUN ; Ziyong SUN ; Jianbiao WANG ; Wenjing WU ; Xuefeng WANG ; Wei XU ; Ying XING ; Chi ZHANG ; Lei ZHENG ; Shihong ZHANG ; Ming GUAN
Chinese Journal of Laboratory Medicine 2023;46(3):265-273
		                        		
		                        			
		                        			Objective:To evaluate the performance of an artificial intelligent (AI)-based automated digital cell morphology analyzer (hereinafter referred as AI morphology analyzer) in detecting peripheral white blood cells (WBCs).Methods:A multi-center study. 1. A total of 3010 venous blood samples were collected from 11 tertiary hospitals nationwide, and 14 types of WBCs were analyzed with the AI morphology analyzers. The pre-classification results were compared with the post-classification results reviewed by senior morphological experts in evaluate the accuracy, sensitivity, specificity, and agreement of the AI morphology analyzers on the WBC pre-classification. 2. 400 blood samples (no less than 50% of the samples with abnormal WBCs after pre-classification and manual review) were selected from 3 010 samples, and the morphologists conducted manual microscopic examinations to differentiate different types of WBCs. The correlation between the post-classification and the manual microscopic examination results was analyzed. 3. Blood samples of patients diagnosed with lymphoma, acute lymphoblastic leukemia, acute myeloid leukemia, myelodysplastic syndrome, or myeloproliferative neoplasms were selected from the 3 010 blood samples. The performance of the AI morphology analyzers in these five hematological malignancies was evaluated by comparing the pre-classification and post-classification results. Cohen′s kappa test was used to analyze the consistency of WBC pre-classification and expert audit results, and Passing-Bablock regression analysis was used for comparison test, and accuracy, sensitivity, specificity, and agreement were calculated according to the formula.Results:1. AI morphology analyzers can pre-classify 14 types of WBCs and nucleated red blood cells. Compared with the post-classification results reviewed by senior morphological experts, the pre-classification accuracy of total WBCs reached 97.97%, of which the pre-classification accuracies of normal WBCs and abnormal WBCs were more than 96% and 87%, respectively. 2. The post-classification results reviewed by senior morphological experts correlated well with the manual differential results for all types of WBCs and nucleated red blood cells (neutrophils, lymphocytes, monocytes, eosinophils, basophils, immature granulocytes, blast cells, nucleated erythrocytes and malignant cells r>0.90 respectively, reactive lymphocytes r=0.85). With reference, the positive smear of abnormal cell types defined by The International Consensus Group for Hematology, the AI morphology analyzer has the similar screening ability for abnormal WBC samples as the manual microscopic examination. 3. For the blood samples with malignant hematologic diseases, the AI morphology analyzers showed accuracies higher than 84% on blast cells pre-classification, and the sensitivities were higher than 94%. In acute myeloid leukemia, the sensitivity of abnormal promyelocytes pre-classification exceeded 95%. Conclusion:The AI morphology analyzer showed high pre-classification accuracies and sensitivities on all types of leukocytes in peripheral blood when comparing with the post-classification results reviewed by experts. The post-classification results also showed a good correlation with the manual differential results. The AI morphology analyzer provides an efficient adjunctive white blood cell detection method for screening malignant hematological diseases.
		                        		
		                        		
		                        		
		                        	
10.Abnormal chromosome karyotype characteristics of common external genital malformations in male children
Hengyou WANG ; Daxing TANG ; Dehua WU ; Chang TAO ; Guangjie CHEN ; Jia WEI ; Hongjuan TIAN
Chinese Journal of Urology 2023;44(12):930-934
		                        		
		                        			
		                        			Objective:To explore the characteristics of abnormal chromosome karyotype of common external genital malformations in male children.Methods:A retrospective analysis of the clinical data of 2 408 children was made in outpatient or inpatient from January 2012 to December 2017. The mean age was (38±7) months. There were 1115 cases of hypospadias, 189 cases of cryptorchidism, 304 cases of micropenis, 681 cases of concealed penis and 119 cases of disorders of sex development. All children were tested for chromosome 550 band in peripheral blood, and the results of chromosome karyotype were analyzed.Results:A total of 131 cases of abnormal chromosome karyotypes were detected, with a detection rate of 5.4%, including 46 cases of chromosome number abnormalities, 85 cases of structural abnormalities, 64 cases of sex chromosome abnormalities and 67 cases of autosomal abnormalities. The karyotype of chromosome was 46, XY, inv (9) (p12q13) in 28 cases accounting for 21.4%. It was followed by 47, XXY, with 16 cases, accounting for 12.2%. The detection rate of chromosomal abnormalities in children with disorders of sex development was 12.6%(15 cases), hypospadias was 5.5%(61 cases), cryptorchidism was 5.3%(10 cases), micropenis was 4.9%(15 cases), and concealed penis was 4.4%(30 cases).Conclusions:Chromosomal abnormalities are not uncommon in male children with external genital malformations. Chromosome structural abnormalities are more common than quantitative abnormalities, and sex chromosome abnormalities account for a comparable proportion to autosomal abnormalities.
		                        		
		                        		
		                        		
		                        	
            
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