Fragile X syndrome (FXS) is the most frequent genetic cause of intellectual disability (ID). It was previously believed that the FXS prevalence was low in Chinese population, and the cost-efficiency ...of FXS carrier screening was questioned. This retrospective observational study was conducted between September 2014 and May 2017 to determine the prevalence of FXS carriers in a large Chinese cohort of pregnant women. The FMR1 CGG repeat status was determined in 20,188 pregnant Taiwanese women and we identified 26 women with premutation (PM). The PM allele was transmitted to the fetus in 17 pregnancies (56.6%), and six of 17 expanded to full mutation (FM). One asymptomatic woman had a FM allele with 280 CGG repeats. Prenatal genetic diagnosis of her first fetus revealed a male carrying a FMR1 gene deletion of 5' UTR and exon 1. Her second fetus was a female carrying a FM allele as well. This is so far the largest study of the FXS carrier screening in Chinese women. The prevalence of premutation allele for FXS in normal asymptomatic Taiwanese women was found to be as high as 0.13% (1 in 777) in this study. The empirical evidence suggests that reproductive FXS carrier screening in Taiwan might be cost-effective.
Mitochondria are the organelles that generate energy for the cells. Many studies have suggested that mitochondrial dysfunction or impairment may be related to cancer and other neurodegenerative ...disorders such as Alzheimer’s and Parkinson’s diseases. Therefore, morphologically detailed alterations in mitochondria and 3D reconstruction of mitochondria are highly demanded research problems in the performance of clinical diagnosis. Nevertheless, manual mitochondria segmentation over 3D electron microscopy volumes is not a trivial task. This study proposes a two-stage cascaded CNN architecture to achieve automated 3D mitochondria segmentation, combining the merits of top-down and bottom-up approaches. For top-down approaches, the segmentation is conducted on objects’ localization so that the delineations of objects’ contours can be more precise. However, the combinations of 2D segmentation from the top-down approaches are inadequate to perform proper 3D segmentation without the information on connectivity among frames. On the other hand, the bottom-up approach finds coherent groups of pixels and takes the information of 3D connectivity into account in segmentation to avoid the drawbacks of the 2D top-down approach. However, many small areas that share similar pixel properties with mitochondria become false positives due to insufficient information on objects’ localization. In the proposed method, the detection of mitochondria is carried out with multi-slice fusion in the first stage, forming the segmentation cues. Subsequently, the second stage is to perform 3D CNN segmentation that learns the pixel properties and the information of 3D connectivity under the supervision of cues from the detection stage. Experimental results show that the proposed structure alleviates the problems in both the top-down and bottom-up approaches, which significantly accomplishes better performance in segmentation and expedites clinical analysis.
In many applications of two-component mixture models for discrete data such as zero-inflated models, it is often of interest to conduct inferences for the mixing weights. Score tests derived from the ...marginal model that allows for negative mixing weights have been particularly useful for this purpose. But the existing testing procedures often rely on restrictive assumptions such as the constancy of the mixing weights and typically ignore the structural constraints of the marginal model. In this article, we develop a score test of homogeneity that overcomes the limitations of existing procedures. The technique is based on a decomposition of the mixing weights into terms that have an obvious statistical interpretation. We exploit this decomposition to lay the foundation of the test. Simulation results show that the proposed covariate-adjusted test statistic can greatly improve the efficiency over test statistics based on constant mixing weights. A real-life example in dental caries research is used to illustrate the methodology.
To evaluate the effectiveness of adding carbetocin to regular uterotonic agents for prevention of postpartum hemorrhage (PPH) after cesarean section for twin pregnancies.
This is a retrospective ...uncontrolled before-after study done in a tertiary center in Taiwan, 2010–2017. Women with twin pregnancies that underwent cesarean section were enrolled. The control group (n = 114) received oxytocin infusion and direct uterine injection. In addition to these, the study group (n = 127) received 100ug of intravenous carbetocin. Primary endpoint was the change in hemoglobin. Secondary endpoints included risk of PPH and undiagnosed PPH (Hb dropped more than 2 g/dL), blood loss, the need for additional uterotonic maneuvers, and blood transfusion. Hemodynamic changes were also investigated.
After adjusting for confounding factors, the change in Hb (0.35 g/dL, 95% CI: −0.03∼0.74) and incidence of PPH (OR 0.30, 95% CI: 0.03∼3.28) were comparable in both groups. However, women with undiagnosed PPH decreased (OR 0.43, 95% CI:0.22∼0.85). Total blood loss in 24 h after delivery also decreased (−40.33 mL, 95%CI: −80.32∼ −0.34). The use of extra uterotonic medications and the need for blood transfusion did not differ. The systolic blood pressure 4 h after childbirth was higher in the carbetocin group (6.71, 95% CI: 2.27∼11.15).
The use of carbetocin in addition to regular uterotonic agents decreased total blood loss and undiagnosed PPH. Also, systolic blood pressure 4 h after childbirth is higher in the carbetocin group. There was no significant difference in hemoglobin change and risk of PPH.
Earlier studies focused on training ResNet50 deep learning models on a dataset of fundus images from the National Taiwan University Hospital HsinChu Branch. The study aimed to identify class-specific ...discriminative areas related to various conditions of ganglion cell complex (GCC) thickness, center focus areas, cropped patches from the fundus, and dataset partitions. The study utilized two visualization methods to evaluate and explain the areas of interest of the network model and determine if they aligned with clinical diagnostic knowledge. The results of the experiments demonstrated that incorporating GCC thickness information improved the accuracy of glaucoma determination. The deep learning models primarily focused on the optic nerve head (ONH) for glaucoma diagnosis, which was consistent with clinical rules. Nonetheless, the models achieved high prediction accuracy in detecting glaucomatous cases using only cropped images of macular areas. Moreover, the model’s focus on regions with GCC impairment in some cases indicates that deep learning models can identify morphologically detailed alterations in fundus photographs that may be beyond the scope of visual diagnosis by experts. This highlights the significant contribution of deep learning models in the diagnosis of glaucoma.
During the last 20 years, the epidemiology of Japanese encephalitis virus (JEV) has changed significantly in its endemic regions due to the gradual displacement of the previously dominant genotype ...III (GIII) with clade b of GI (GI-b). Whilst there is only limited genetic difference distinguishing the two GI clades (GI-a and GI-b), GI-b has shown a significantly wider and more rapid dispersal pattern in several regions in Asia than the GI-a clade, which remains restricted in its geographic distribution since its emergence. Although previously published molecular epidemiological evidence has shown distinct phylodynamic patterns, characterization of the two GI clades has only been limited to in vitro studies. In this study, Culex quinquefasciatus, a known competent JEV mosquito vector species, was orally challenged with three JEV strains each representing GI-a, GI-b, and GIII, respectively. Infection and dissemination were determined based on the detection of infectious viruses in homogenized mosquitoes. Detection of JEV RNA in mosquito saliva at 14 days post infection indicated that Cx. quinquefasciatus can be a competent vector species for both GI and GIII strains. Significantly higher infection rates in mosquitoes exposed to the GI-b and GIII strains than the GI-a strain suggest infectivity in arthropod vectors may lead to the selective advantage of previously and currently dominant genotypes. It could thus play a role in enzootic transmission cycles for the maintenance of JEV if this virus were ever to be introduced into North America.
The early detection of cancer can reduce cancer-related mortality. There is no clinically useful noninvasive biomarker for early detection of breast cancer. The aim of this study was to develop ...accurate and precise early detection biomarkers and a dynamic monitoring system following treatment. We analyzed a genome-wide methylation array in Taiwanese and The Cancer Genome Atlas (TCGA) breast cancer (BC) patients. Most breast cancer-specific circulating methylated
,
and
biomarkers were found in the plasma. An automatic analysis process of methylated ccfDNA was established. A combined analysis of
,
and
(CGIm) was performed in R using Recursive Partitioning and Regression Trees to establish a new prediction model. Combined analysis of
,
and
(CGIm) was found to have a sensitivity level of 97% and an area under the curve (AUC) of 0.955 in the training set, and a sensitivity level of 100% and an AUC of 0.961 in the test set. The circulating methylated
,
and
was also significantly decreased after surgery (all
< 0.001). The aberrant methylation patterns of the
,
and
genes means that they are potential biomarkers for the detection of early BC and can be combined with breast imaging data to achieve higher accuracy, sensitivity and specificity, facilitating breast cancer detection. They may also be applied to monitor the surgical treatment response.
To assess the complication rates following chorionic villus sampling (CVS) and midtrimester amniocentesis in Taiwan.
This is a national registry-based cohort study from Taiwan. We included all women ...with singleton pregnancies who received either CVS (n = 1409) or midtrimester amniocentesis (n = 250,566) during 2006–2012. We assessed preterm premature rupture of membranes (PPROM), intrauterine fetal demise (IUFD), infection and spontaneous abortion (SA) that occurred within fourteen days after the procedures. We also assessed the risks of preterm delivery and miscarriage before 24 gestational weeks after amniocentesis. These complications were collected from the Genetic Disease Database of the Ministry of Health and Welfare, Taiwan National Birth Certificate Registry, and the Taiwan National Health Insurance Database. Pearson χ2 tests were used to compare the distributions between groups.
For patients who underwent midtrimester amniocentesis, the rates of PPROM, IUFD, infection and SA within fourteen days were 0.24%, 0.11%, 0.05%, and 0.05%, respectively. Women with a normal fetal karyotype had a preterm birth rate (<37 gestational weeks) of 9.38%. The miscarriage rate (<24 gestational weeks) was 0.68%, which was 0.22% higher than those who did not receive the invasive procedures (p < 0.0001). After CVS, the IUFD rate was 1.68%, and the SA rate within fourteen days was 0.77%.
The use of our large cohort demonstrated that the procedure-related complication rates were comparable to recent review or meta-analysis. This dataset might facilitate counselling in women who consider invasive genetic diagnostic procedures.
Paternal uniparental disomy 14 (UDP(14)pat) is a rare imprinting disorder with a set of unique neonatal clinical features documented, including craniofacial abnormalities, thoracic and abdominal wall ...defects, and polyhydraminos. To date, no studies focus on prenatal diagnosis of uniparental disomy have been published. We report a case of a fetus with abnormal ultrasound features at 18 weeks of gestation and normal karyotype result. Subsequent Single nucleotide polymorphism (SNP)-based Affymetrix 750K Microarray analysis revealed the complete loss of heterozygosity for chromosome 14, identifying a case of uniparental disomy. Postmortem examination of the aborted fetus at 21 weeks, coupled with further Affymetrix 750K microarray analysis on the parents, confirmed the diagnosis of parental uniparental disomy for chromosome 14.
Supremum score test statistics are often used to evaluate hypotheses with unidentifiable nuisance parameters under the null hypothesis. Although these statistics provide an attractive framework to ...address non-identifiability under the null hypothesis, little attention has been paid to their distributional properties in small to moderate sample size settings. In situations where there are identifiable nuisance parameters under the null hypothesis, these statistics may behave erratically in realistic samples as a result of a non-negligible bias induced by substituting these nuisance parameters by their estimates under the null hypothesis. In this paper, we propose an adjustment to the supremum score statistics by subtracting the expected bias from the score processes and show that this adjustment does not alter the limiting null distribution of the supremum score statistics. Using a simple example from the class of zero-inflated regression models for count data, we show empirically and theoretically that the adjusted tests are superior in terms of size and power. The practical utility of this methodology is illustrated using count data in HIV research.
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