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OBJECTIVE To examine whether serum procalcitonin (PCT) is useful for differentiating acute pyelonephritis (APN) from asymptomatic bacteriuria and acute cystitis during pregnancy. METHODS A multicenter prospective observational study was conducted to compare serum white blood cell (WBC) counts, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, and PCT level among pregnant women with asymptomatic bacteriuria, acute cystitis, and APN and healthy pregnant women (controls). Utility of WBC count, ESR, CRP, and PCT biomarkers for the prediction of APN during pregnancy were measured. RESULTS Area under the curve (AUC) values of PCT, CRP, ESR, and WBC count for predicting asymptomatic bacteriuria were 0.576, 0.628, 0.542, and 0.532, respectively; those for predicting acute cystitis were 0.766, 0.735, 0.681, and 0.597, respectively; and those for predicting acute pyelonephritis 0.859, 0.763, 0.711, and 0.732, respectively. Compared with the other inflammatory markers used to predict APN, PCT exhibited the highest AUC (0.859 [95% confidence interval (CI) 0.711-0.935]). A cutoff value of >0.25 ng/ml had a sensitivity of 87% and a specificity of 79%. CONCLUSION Serum PCT can be a valuable addition to existing methods of differentiating asymptomatic bacteriuria, acute cystitis, and APN during pregnancy and can facilitate the early identification of APN during pregnancy.

Objective: To examine whether serum procalcitonin (PCT) is useful for differentiating acute pyelonephritis (APN) from asymptomatic bacteriuria and acute cystitis during pregnancy Design: A multicentre prospective observational study Setting: Eleven maternity hospitals in Taiwan Population: Two hundred and seventy pregnant women with asymptomatic bacteriuria, 243 pregnant women with acute cystitis, 186 pregnant women with APN, and 270 healthy pregnant controls Method: To compare serum white blood cell (WBC) counts, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, and PCT level among pregnant women with asymptomatic bacteriuria, acute cystitis, and APN and healthy pregnant women (controls) Main outcome measures: Utility of WBC count, ESR, CRP, and PCT biomarkers for the prediction of APN during pregnancy Results: Area under the curve (AUC) values of PCT, CRP, ESR, and WBC count for predicting asymptomatic bacteriuria were 0.576, 0.628, 0.542, and 0.532, respectively; those for predicting acute cystitis were 0.766, 0.735, 0.681, and 0.597, respectively; and those for predicting acute pyelonephritis 0.859, 0.763, 0.711, and 0.732, respectively. Compared with the other inflammatory markers used to predict APN, PCT exhibited the highest AUC (0.859 [95% confidence interval (CI) 0.711–0.935]). A cutoff value of >0.25 ng/mL had a sensitivity of 87% and a specificity of 79%. Conclusion: Serum PCT can be a valuable addition to existing methods of differentiating asymptomatic bacteriuria, acute cystitis, and APN during pregnancy and can facilitate the early identification of APN during pregnancy.

Background: To assess the value of chromosomal microarray analysis (CMA) during the prenatal diagnosis of high-risk pregnancies. Methods: Between January 2016 and November 2021, we included 178 chorionic villi and 859 amniocentesis samples from consecutive cases at a multiple tertiary hospital. Each of these high-risk singleton pregnancies had at least one of the following indications: (1) advanced maternal age (AMA; ≥35 years; 546, 52.7%); (2) fetal structural abnormality on ultrasound (197, 19.0%); (3) high-risk first- or second-trimester Down syndrome screen (189, 18.2%), including increased nuchal translucency (≥3.5 mm; 90, 8.7%); or (4) previous pregnancy, child, or family history (105, 10.1%) affected by chromosomal abnormality or genetic disorder. Both G-banding karyotype analysis and CMA were performed. DNA was extracted directly and examined with oligonucleotide array-based comparative genomic hybridization. Results: Aneuploidies were detected by both G-banding karyotyping and CMA in 42/1037 (4.05%) cases. Among the 979 cases with normal karyotypes, 110 (10.6%) cases had copy number variants (CNVs) in CMA, including 30 (2.9%) cases with reported pathogenic and likely pathogenic CNVs ≥ 400 kb, 37 (3.6%) with nonreported VOUS, benign, or likely benign CNVs ≥ 400 kb, and 43 (4.1%) with nonreported CNVs < 400 kb. Of the 58 (5.6%) cases with aneuploidy rearrangements, 42 (4.1%) were diagnosed by both G-banding karyotyping and CMA; four inversions, six balanced translocations, and six low mosaic rates were not detected with CMA. Conclusions: CMA is an effective first step for the prenatal diagnosis of high-risk pregnancies with fetal structural anomalies found in ultrasonography or upon positive findings.

The automatic detection of atrial fibrillation (AF) is crucial for its association with the risk of embolic stroke. Most of the existing AF detection methods usually convert 1D time-series electrocardiogram (ECG) signal into 2D spectrogram to train a complex AF detection system, which results in heavy training computation and high implementation cost. This paper proposes an AF detection method based on an end-to-end 1D convolutional neural network (CNN) architecture to raise the detection accuracy and reduce network complexity. By investigating the impact of major components of a convolutional block on detection accuracy and using grid search to obtain optimal hyperparameters of the CNN, we develop a simple, yet effective 1D CNN. Since the dataset provided by PhysioNet Challenge 2017 contains ECG recordings with different lengths, we also propose a length normalization algorithm to generate equal-length records to meet the requirement of CNN. Experimental results and analysis indicate that our method of 1D CNN achieves an average F1 score of 78.2%, which has better detection accuracy with lower network complexity, as compared with the existing deep learning-based methods.

Objective: This study investigates the performance of first- and second-trimester screening tests for detecting fetal trisomy 21 in a Taiwanese population. Materials and methods: This multicenter study 29,137 cases enrolled the chromosomal abnormality screening between 2013 and 2014 two years period from Taipei city. There were 23,990 was done the first trimester screening using a combination of fetal nuchal translucency, maternal serum β-human chorionic gonadotropin, and pregnancy-associated plasma protein-A between 11+0 and 13+6 weeks of gestation age. Second-trimester screening was done for 5149 cases using a double test (β-human chorionic gonadotropin and serum alpha fetoprotein) between 15 and 20 weeks of gestation. The cut-off risk for both is 1:270 or higher. Results: This multicenter study 29,137 cases that completed first- and second-trimester screening, and the outcome was available in 28,726 cases. The mean maternal age of the screen-positive group was 34.6 ± 4.2 years. The first-trimester had 891 cases screening positive with a detection rate of 97.5% for fetal trisomy 21, and false positive rate of 3.5%. In the second-trimester had 334 cases screening positive, the detection rate and false positive rate were 33.3% and 6.4% for trisomy 21, respectively. Conclusion: The first-trimester screening had higher performance with a lower false positive rate than the second-trimester screening. First-trimester screening could reduce the rate of unnecessary invasive testing for all pregnant women. Keywords: Down syndrome, First-trimester screening, Second-trimester screening

Background Prenatal genetic testing (PGT) for Autism Spectrum Disorders (ASD) raises more complex ethical, legal, and social implications in Taiwan than in Western countries due to policy-related, practical, cultural, and familial reasons. This first qualitative study examines attitudes towards PGT for ASD among Taiwanese parents of children with ASD – an elevated risk group for having another affected child, and one that is mostly likely to be impacted by PGT for ASD. Methods We conducted in-depth, face-to-face, individual, semi-structured interviews with 39 parents of children with ASD from various ASD organizations in Taiwan. Results Most parents favored PGT for ASD mainly for terminating the affected pregnancy and receiving early intervention and treatment. Less than one-third of participants was against PGT for ASD due to perceived no value for this testing, contradiction with religion and/or personal beliefs, doubt of the test’s accuracy, or concerns about the negative consequences of the testing. Conclusion The majority of Taiwanese parents of children with ASD in this study supported PGT for ASD. Guidelines and regulations should be developed to regulate the provision and quality of this testing. Genetic counseling should also be recommended to parents of children with ASD in Taiwan.

Objective: To examine the factors affecting pregnant women's decisions to accept or decline the prenatal pertussis (Tdap) vaccination in Taiwan. Materials and methods: We conducted a cross-sectional survey, recruiting pregnant women who had received prenatal care from eight maternity hospitals between January and December 2018. We examined the participants’ demographic characteristics, perceptions of pertussis disease risk and vaccination effectiveness, beliefs regarding vaccine information, physician recommendation, and other potential factors affecting decision-making regarding prenatal vaccination. Results: The complete survey response rate among eligible women was 78%. Among the participants, 74% accepted and 26% declined prenatal Tdap vaccination. Most women accepted Tdap during pregnancy because of perceived severity of pertussis in their infants, perceived effectiveness of the prenatal Tdap in preventing neonatal pertussis, and perceived safety of the prenatal Tdap vaccine for the fetus, as well as a provider's recommendation, which was the factor strongly associated with actual Tdap reception. Most of the participants who accepted Tdap vaccination during pregnancy and who believed that the Tdap vaccine could protect their infants from pertussis reported the receiving sufficient information to make an informed decision and trust in the information. By contrast, a large proportion of the participants who declined Tdap and who did not want to experience possible fetal side effects of Tdap reported not getting sufficient information to make an informed decision and a lack of trust in the information. Conclusion: Developing a comprehensive strategy involving government policy, the health care system, public media, health professionals, and pregnant women to launch a successful campaign may improve the nationwide acceptance of the prenatal pertussis vaccination. Keywords: Pertussis, Vaccine, Prenatal

Vertebral compression fractures (VCFs) are common in elderly and are treated with immobilization. Moreover, immobilization and old age may increase venous thromboembolism (VTE) risk. However, the incidence of VCFs-related VTE is unknown in elderly. The purposes of this study were to determine the incidence of VTE among VCF patients, to explore whether percutaneous vertebroplasty (PV) intervention may reduce VTE risk in VCFs patients.We conducted a population-based case-control study by using the National Health Insurance Research Database. We identified 1407 patients aged ≥65 with VCF who received PV and 1407 VCFs patients who did not receive PV after developing a 1:1 propensity score-matched study cohort and were followed up for 5 years. Using PV intervention as the exposure factor, a cause-specific Cox's proportional hazards model was used to examine the association between PV and VTE.After propensity score matching, the mean age of the study participants was 78 years and ∼23% of the analyzed participants were men, incidence of VTE in the PV and control cohorts was 5.77 and 4.19 per 1000 person-years, respectively. Both groups were nonsignificant difference after examination with different adjustment models. Patients with VCF and a history of heart failure, coronary artery disease, receiving antihypertension medication were at a significantly increased VTE risk.Elderly patients with VCF who received PV had a neutral impact on risk of VTE. VCF patients with heart failure, coronary artery disease, and receiving antihypertension medication were prone to developing VTE should be monitored cautiously.

Prenatal examination plays an important role in present medical diagnosis. It provides information on fetal health status as well as the diagnosis of fetal treatment feasibility. The diagnosis can provide peace of mind for the perspective mother. Timely pregnancy termination diagnosis can also be determined if required. Amniocentesis and chorionic villus sampling are two widely used invasive prenatal diagnostic procedures. To obtain complete fetal genetic information and avoid endangering the fetus, noninvasive prenatal diagnosis has become the vital goal of prenatal diagnosis. However, the development of a high-efficiency separation technology is required to obtain the scarce fetal cells from maternal circulation. In recent years, the rapid development of microfluidic systems has provided an effective method for fetal cell separation. Advantages such as rapid analysis of small samples, low cost, and various designs, greatly enhance the efficiency and convenience of using microfluidic systems for cell separation. In addition, microfluidic disks can be fully automated for high throughput of rare cell selection from blood samples. Therefore, the development of microfluidic applications in noninvasive prenatal diagnosis is unlimited.

Objective: To examine the performance of first-trimester screening test combining several fetal sonographic and maternal biochemical markers for major aneuploidy in a Chinese population. Methods: This was a prospective study performed over 5 years between January 2005 and December 2010 in Taiwan, with 20,586 cases that had a combination of a variety of sonographic markers and maternal serological β-human chorionic gonadotropin and pregnancy-associated plasma protein-A levels assessed at first trimester screening between 11+0 and 13+6 weeks of gestation. The risk of aneuploidy was calculated using algorithm software developed by Fetal Medicine Foundation, London. Fetal karyotyping was performed when the prenatal screening showed a risk of 1/300 or higher. All cases were followed for fetal outcome. Results: The study population was divided into four groups according to the screening strategy performed. The combination of maternal serological biochemistry and nuchal translucency measurement had a 66.7% detection rate of trisomy 21. Addition of nasal bone status increased the detection rate of trisomy 21 to 88.2%. Inclusion of tricuspid regurgitation flow showed an 87.5% detection rate of trisomy 21. Further inclusion of ductus venosus flow increased the detection rate of trisomy 21 to 100%. Incorporating more markers greatly increased the detection rate and decreased the false-positive rate (FPR). Conclusion: Extension of first-trimester screening to include more sonographic markers greatly increased the sensitivity and decreased FPR for detection of chromosomal abnormalities. Such screening strategy is effective in clinical practice for the Chinese ethnic population.

Objective The aim of this research was to compare the fetal frontomaxillary facial (FMF) angle between normal and trisomy 21 fetuses at 11+0–13+6 weeks gestation in a Chinese population. Methods A prospective observational study was performed that included 640 euploid and 45 trisomy 21 singleton pregnancies undergoing first trimester ultrasound screening between 11 and 13+6 weeks of gestation. The FMF angle was measured in the midsagittal plane using the standard technique. Results The fetal mean FMF angle decreased with the increasing crown-rump length (CRL) from 88.6°at a CRL of 45 mm to 78.5° at a CRL of 84 mm (FMF angle = 100.212 − 0.258 × CRL, R2 = 0.222, p

Objective: The posterior fossa of normal fetuses was evaluated and compared with those having chromosomal abnormalities at 11-13+6 weeks' gestation in Chinese population. Methods: In 518 normal fetuses referred to first trimester screening, fetal brain stem (BS) and brain stem to occipital bone distance (BSOB) were measured prospectively. The BS and BSOB were also measured on stored images in fetuses with confirmed trisomy 21 (n = 38), Trisomy 18 (n = 26), Trisomy 13 (n = 8), and monosomy X (n = 8). Results: The BS diameter and BSOB distance correlated linearly with fetal crown-rump length (CRL) by regression analysis. The BS to BSOB ratio was below the 5th percentile in 2 (5.26%), 11 (44%), 4 (50%) and 4 (50%) fetuses with trisomy 21, trisomy 18, trisomy 13 and monosomy X, respectively. Thus, both BS and BS/BSOB ratio were significantly lower in trisomy 18, trisomy 13 and monosomy X fetuses when compared to the reference range but not in fetuses with Trisomy 21. Conclusion: In ultrasound scans performed at the 11-13+6 gestation weeks, fetuses with trisomy 18, 13, and monosomy X had lower BS/BSOB ratios. But trisomy 21 fetuses did not show significant differences in posterior fossa compared to the normal population.

Primary ovarian leiomyoma of the ovary is an extremely rare tumor; only approximately 70 cases have been reported worldwide [1]. The lesions are usually found incidentally, with the majority being discovered in perimenopausal and postmenopausal women (85%) [2,3]. They are difficult to diagnose preoperatively based on ultrasonographic results, because they are usually small in size (< 3 cm in diameter) and rarely induce serious clinical symptoms [1,3]. We present a case of asymptomatic primary leiomyoma of the left ovary of a pregnant woman. A 41-year-old woman, gravida 3, para 1, ectopic 1, had a history of a right tubal ectopic pregnancy, and a left ovarian echogenic mass measuring about 3.5 × 2.4 × 2.5 cm was observed using ultrasonography 1 year prior to this presentation. She received medical treatment with two doses of methotrexate, and the ectopic pregnancy had terminated at the 6-week follow-up examination (tested by β-hCG). Follow-up laboratory test results showed that CA-125 was within the reference range limits. Intrauterine pregnancy was noted 1 year after the ectopic pregnancy. The patient underwent an uneventful routine prenatal examination. On acute severe variable fetal distress during labor, the patient received emergency cesarean section and was delivered of a female infant weighing 2,930 g. During this procedure, the opportunity was taken to review the left ovary, and a fasciculated grey-white left ovarian tumor that was firm and solid measuring 4.5 × 4.4 × 3.2 cm, suggesting fibroma/thecoma or leiomyoma, was discovered, and a left oophorectomy was performed. No ascites fluid was noted in the abdomen. Following meticulous examination of the uterus, three small intramural leiomyomas of approximately 1 cm in diameter, were further discovered. The patient was discharged 5 days after surgery, and her recovery period was uneventful. The final histopathologic examination revealed ovarian leiomyoma. The mass consisted mostly of interacting

Objective: To evaluate the performance of noninvasive prenatal testing for all fetal chromosomal aneuploidies in an extremely high-risk group undergoing first trimester combined Down syndrome screening. Method: A multicenter cohort prospective study in Taiwan was performed between June and December 2012. Maternal plasma was collected and shotgun massive parallel sequencing was performed on each fetal chromosome. 201 Taiwanese pregnant women at >12 weeks' gestation from 11 medical centers were enrolled in this trial. The extremely high-risk group was defined as a Down syndrome risk cutoff >1:30 or nuchal translucency >3.0 mm (n = 100), while the low-risk group was defined as a Down syndrome cutoff Results: There were 11 cases of trisomy 21, 8 cases of trisomy 18, 3 cases of trisomy 13, 1 case of trisomy 16, 3 cases of 45,X, and 1 case of 47,XYY detected prenatally in 100 extremely high-risk gravidas [n = 27/100 (27%)]. The overall autosomal or sex chromosome aneuploidy detection rate was 96% (27/28) because of an insufficient amount maternal plasma for one fetus with Turner syndrome. In the low-risk group, no chromosomal abnormalities were detected (specificity = 100%). There were no false-positive cases in this study. Conclusions: This first trial in Taiwan shows that noninvasive prenatal testing for whole chromosome aneuploidies can be efficiently applied in extremely high- and low-risk populations.

The aim of this research was to compare the fetal frontomaxillary facial (FMF) angle between normal and trisomy 21 fetuses at 11(+0) -13(+6) weeks gestation in a Chinese population.A prospective observational study was performed that included 640 euploid and 45 trisomy 21 singleton pregnancies undergoing first trimester ultrasound screening between 11 and 13(+6) weeks of gestation. The FMF angle was measured in the midsagittal plane using the standard technique.The fetal mean FMF angle decreased with the increasing crown-rump length (CRL) from 88.6°at a CRL of 45 mm to 78.5° at a CRL of 84 mm (FMF angle = 100.212 - 0.258 × CRL, R(2) = 0.222, p 0.001). The overall mean FMF angle in the euploid population was 82.9° ± 4.1° and in trisomy 21 cases, 92.3° ± 5.2°.Fetal FMF angle is affected by gestational age in a Chinese population, although it remains a significant predictor of fetal trisomy 21.

In this paper, we determine the mutant W203F structure of TFsβ-glucanase, which contains aromatic residue Trp203 at the active site of the enzyme. Residue Trp203 is stacked with the glucose product of cellotriose. Further analysis reveals that two extra calcium ions and a Tris molecule bind to the mutant structure. A Tris molecule, bound to the catalytic residues of Glu56 and Glu60, was found at the position normally taken by substrate binding at the -1 subsite. In addition, a second Ca(2+) ion was found near the residues Phe152 and Glu154 on the protein's surface, and a third one near the active site residue Asp202. Kinetic experiments reveal that both Tris and imidazole are competitive inhibitors, while calcium is a noncompetitive inhibitor for TFsβ-glucanase. The two types of enzymatic inhibition are first-time descriptions for the glycosyl hydrolase family 16.

1,3-1,4-beta-D-Glucanases (EC 3.2.1.73) specifically hydrolyze beta-1,4-glycosidic bonds located prior to beta-1,3-glycosidic linkages in lichenan or beta-D-glucans. It has been suggested that truncated Fibrobacter succinogenes 1,3-1,4-beta-D-glucanase (TFsbeta-glucanase) can accommodate five glucose rings in its active site upon enzyme-substrate interaction. In this study, 12 mutant enzymes were created by mutating the conserved residues Gln70, Asn72, Gln81 and Glu85 proposed to bind to substrate subsites +1 and +2 and the catalytic properties of these mutants were determined. The most significant change in catalytic activity was observed on mutation of Gln70, with a 299-fold and 498-fold lower k(cat)/K(m) for the mutants Q70A and Q70I, respectively, compared with the wild-type enzyme. Mutagenesis, kinetic and structural studies revealed that the conserved residues surrounding the active site of TFsbeta-glucanase at substrate subsites +1 and +2 play an important role in its catalytic function, with the following order of importance: Gln70Asn72Glu85Gln81. The crystal structure of mutant E85I was determined at 2.2 A resolution. Further analysis of the E85I mutant structure revealed that the loop located at the concave site moved approximately 2 A from its position in the native enzyme complex without changing the core structure.

SUMMARY Down syndrome (DS) is the most common human disease caused by a structural chromosome defect. The original screening test for DS was maternal age or a history of a previously affected infant. Maternal serum screening has been incorporated into routine prenatal checkup in Taiwan since 1994. We used free β-human chorionic gonadotropin and α-fetoprotein (double test) as the serum markers, and this was carried out between the 15 th to 20 th week of gestation. The overall detection rate was 56% and was compatible with studies of Caucasian populations. The impact of double tests in Taiwan has shown itself by a dramatic lowering of the rate of DS live birth from 0.63 before screening to 0.16 per 1,000 live births at present. However, because of its relatively low detection rate and poor cost-effectiveness, the double test is not justified as a routine screening tool currently. First-trimester combined test is now becoming more widely available and provides increased sensitivity when detecting DS; it has a detection rate of approximately 85% with a false-positive rate of 5%. Nuchal translucency measurement requires ongoing quality control and sufficient certificated obstetricians; therefore, first-trimester ultrasound is limited only in designated centers. The quadruple test, having comparable detection rate, should be considered for incorporation into second-trimester screening in Taiwan in the near future. Other screening approaches and combinations have also been utilized in the Western countries. In this review, we outline the various options with respect to DS screening and hope that this will provide practical information for physicians offering such screenings. [Taiwan J Obstet Gynecol 2008;47(2):157–162]

This paper highlights the cell current characterization of a low leakage 6T SRAM by adjusting the threshold voltages of the transistors in the memory array to reduce the standby power. Experiments using a 0.25 /spl mu/m 2.5V standard CMOS process with and without the additional threshold voltage adjustment implant on a 1Mb test chip demonstrate the effectiveness. A substantial standby power reduction by an order of magnitude is achievable. However, it incurs a wider cell current variation, which is pronounced only at a lower supply voltage. As the supply voltage decreases, the percent deviation from the average value increases. This can be modeled by a simple power-law relationship. The result has important implications in both design and manufacturing of the low leakage SRAM. Comparing with the generic cell current without the additional threshold voltage adjustment, the crossover point of their percent deviations at 2V signifies two separate circuit strategies: operating at 1.5V requires larger sensing margin and operating at 2.5V enjoys better manufacturability. Hence, for the applications requiring low voltage operations, it favors a boosted supply voltage applied to a selected cell during the read access.