Carrier screening for present disease prevalence and recessive genetic disorder in Taiwanese population.

Carrier screening is important to people have a higher prevalence of severe recessive or X-linked genetic conditions. This study is aimed that the frequency and uncertain nature of genetic variants was identified in Taiwanese population, providing individuals with information at risk of inherited diseases and their heritability to newborns. A total of 480 subjects receiving genetic counseling with no family history of inherited disorders were recruited into a cohort from 2018 to 2022. Next-generation sequencing (NGS) panel for autosomal dominant (AD), autosomal recessive (AR) and X-linked diseases was sequenced to assess disease prevalence and carrier frequency for the targeted diseases. Publicly available NGS datasets were analyzed following a tier-based system and ACMG recommendation. 5.3% of subjects showed the presence of variants for genetic disorder, and 2.3% of them were determined with AD. 14 of subjects with pathogenic variants were carriers for AR. The inherited genes were LDLR for AD disorders and AR disorders included GAA and ATP7B. 21.6% of subjects had highest carrier frequency of GJB2 gene. 0.5% of subjects had highest frequency of GJB6 for AR condition. In conclusions, the variants in LDLR, GAA and ATP7B genes were identified in Taiwanese population, indicating individuals had higher risk of Pompe disease, Wilson's disease and familial hypercholesterolemia. Taiwanese individuals carrying GJB2 and GJB6 had the considerable risk of hearing loss passing to their offspring.

Non-alcoholic fatty liver disease associated with greater herpes zoster risk than alcoholic fatty liver disease.

BACKGROUND: Disease-related stress can trigger the occurrence of herpes zoster (HZ). Fatty liver disease (FLD) can have adverse effects on the human body and may induce stress in affected individuals. In this study, we investigated whether FLD is associated with an elevated risk of HZ. METHODS: For this study, we utilized data from the National Health Insurance Research Database, patients with FLD from 2000 to 2017 were observed (follow-up until 2018). Patients were considered to have FLD if they had at least two outpatient visits or at least one admission record with a diagnostic code of FLD. Patients with FLD were matched 1:1 by age, sex, comorbidities, and index year with control patients. Additionally, the FLD was further categorized into non-alcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (AFLD) groups. Multivariable Cox proportional hazards model was used to calculate the incidence rate and adjusted hazard ratio (aHR) of HZ for FLD and AFLD and for various age groups, sex and comorbidities. Cumulative incidence curve for HZ was plotted through the Kaplan-Meier method, and p-value was calculated using the log-rank test. RESULTS: After 1:1 propensity-score matching, each cohort comprised 62,418 patients. The FLD cohort was further divided into NAFLD and AFLD groups, which respectively comprised 55,709 and 6709 patients. The FLD cohort had a risk of HZ significantly higher than that of the control cohort (aHR = 1.06; p < 0.001). Additionally, the NAFLD group exhibited a significantly higher risk of HZ than did the AFLD group (aHR = 1.22; p < 0.001). Among patients without any comorbidities, those with FLD had a higher risk of HZ than did those without FLD (aHR = 1.14; p < 0.001). CONCLUSION: Patients with FLD are at an increased risk of HZ development. Additionally, NAFLD is associated with a higher risk of HZ than AFLD. Therefore, patients with NAFLD should be informed of their increased risk of HZ.

Impact of maternal body mass index on outcomes of singleton pregnancies after assisted reproductive technology: a 14-year analysis of the US Nationwide Inpatient Sample.

BACKGROUND: Obesity is increasing globally, which affects multiple human functions, including reproductive health. Many women with overweight and obesity of child-bearing years are treated with assisted reproductive technology (ART). However, the clinical impact of body mass index (BMI) on pregnancy outcomes after ART remains to be determined. Therefore, this population-based retrospective cohort study aimed to assess whether and how higher BMI affects singleton pregnancy outcomes. METHODS: This study used the large nationally representative database of the US National Inpatient Sample (NIS), extracting data of women with singleton pregnancies who had received ART from 2005 to 2018. Diagnostic codes of the International Classification of Diseases, Ninth and Tenth edition (ICD-9 and ICD-10) were used to identify females admitted to US hospitals with delivery-related discharge diagnoses or procedures and secondary diagnostic codes for ART, including in vitro fertilization. The included women were further categorized into three groups based on BMI values < 30, 30-39, and ≥ 40 kg/m2. Univariate and multivariable regression analysis were conducted to assess the associations between study variables and maternal and fetal outcomes. RESULTS: Data of totally 17,048 women were included in the analysis, which represented a population of 84,851 women in the US. Number of women in the three BMI groups were 15, 878 (BMI < 30 kg/m2), 653 (BMI 30-39 kg/m2), and 517 (BMI ≥ 40 kg/m2), respectively. The multivariable regression analysis revealed that, compared to BMI < 30 kg/m2, BMI 30-39 kg/m2 was significantly associated with increased odds for pre-eclampsia and eclampsia (adjusted OR = 1.76, 95% CI = 1.35, 2.29), gestational diabetes (adjusted OR = 2.25, 95% CI = 1.70, 2.98), and Cesarean delivery (adjusted OR = 1.36, 95% CI = 1.15, 1.60). Further, BMI ≥ 40 kg/m2 was associated with greater odds for pre-eclampsia and eclampsia (adjusted OR = 2.25, 95% CI = 1.73, 2.94), gestational diabetes (adjusted OR = 3.64, 95% CI = 2.80, 4.72), disseminated intravascular coagulation (DIC) (adjusted OR = 3.79, 95% CI = 1.47, 9.78), Cesarean delivery (adjusted OR = 1.85, 95% CI = 1.54, 2.23), and hospital stay ≥ 6 days (adjusted OR = 1.60, 95% CI = 1.19, 2.14). However, higher BMI was not significantly associated with greater risk of the fetal outcomes assessed. CONCLUSIONS: Among US pregnant women who received ART, having a higher BMI level independently increases the risk for adverse maternal outcomes such as pre-eclampsia and eclampsia, gestational diabetes, DIC, longer hospital stays, and higher rates of Cesarean delivery, while risk is not increased for fetal outcomes.

Comparing the effects of two different progesterone vaginal gels, Progeson™ and Crinone™, from pharmacokinetics study to clinical applications in patients undergone fresh embryo transfer and frozen-thawed embryo transfer via natural cycle endometrial preparation protocol.

OBJECTIVE: The pharmacokinetics performance and clinical pregnancy rate of two vaginal progesterone gel, Progeson™ and Crinone™, were compared in this study. MATERIALS AND METHODS: In the pharmacokinetics performance, Progeson showed similar long-term dissolution rate as Crinone. In the clinical study, 141 subjects undergone in vitro fertilization (IVF) treatments were included to compare serum progesterone level and clinical pregnancy rates. RESULTS: Among the subjects, 78 subjects received fresh embryo transfer and 63 subjects received frozen embryo transfer via natural cycle endometrial preparation protocol. In each group, subjects were given either Crinone™ or Progeson™ for luteal phase support without combination with other progesterone products. The study showed that Crinone™ group led to higher estrogen level at mid-luteal phase in the fresh embryo transfer group, and Progeson™ group led to higher progesterone level at mid-luteal phase and pregnancy test day in the frozen-thawed embryo transfer group. CONCLUSION: Subjects received Crinone™ or Progeson™ had similar rate of pregnancy, live birth, and stillbirth in both fresh embryo transfer and frozen-thawed embryo transfer group. Thus, Progeson™ might be a suitable substitute for Crinone™ in assisted reproductive therapy.

Predicting glioblastoma molecular subtypes and prognosis with a multimodal model integrating convolutional neural network, radiomics, and semantics.

OBJECTIVE: The aim of this study was to build a convolutional neural network (CNN)-based prediction model of glioblastoma (GBM) molecular subtype diagnosis and prognosis with multimodal features. METHODS: In total, 222 GBM patients were included in the training set from Sun Yat-sen University Cancer Center (SYSUCC) and 107 GBM patients were included in the validation set from SYSUCC, Xuanwu Hospital Capital Medical University, and the First Hospital of Jilin University. The multimodal model was trained with MR images (pre- and postcontrast T1-weighted images and T2-weighted images), corresponding MRI impression, and clinical patient information. First, the original images were segmented using the Multimodal Brain Tumor Image Segmentation Benchmark toolkit. Convolutional features were extracted using 3D residual deep neural network (ResNet50) and convolutional 3D (C3D). Radiomic features were extracted using pyradiomics. Report texts were converted to word embedding using word2vec. These three types of features were then integrated to train neural networks. Accuracy, precision, recall, and F1-score were used to evaluate the model performance. RESULTS: The C3D-based model yielded the highest accuracy of 91.11% in the prediction of IDH1 mutation status. Importantly, the addition of semantics improved precision by 11.21% and recall in MGMT promoter methylation status prediction by 14.28%. The areas under the receiver operating characteristic curves of the C3D-based model in the IDH1, ATRX, MGMT, and 1-year prognosis groups were 0.976, 0.953, 0.955, and 0.976, respectively. In external validation, the C3D-based model showed significant improvement in accuracy in the IDH1, ATRX, MGMT, and 1-year prognosis groups, which were 88.30%, 76.67%, 85.71%, and 85.71%, respectively (compared with 3D ResNet50: 83.51%, 66.67%, 82.14%, and 70.79%, respectively). CONCLUSIONS: The authors propose a novel multimodal model integrating C3D, radiomics, and semantics, which had a great performance in predicting IDH1, ATRX, and MGMT molecular subtypes and the 1-year prognosis of GBM.

Survival Benefit from Surgical Resection in Lung Cancer Patients with Brain Metastases: a Single-Center, Propensity-Matched Analysis Cohort Study.

BACKGROUND: Brain metastases (BMs) are the most serious complication of lung cancer, affecting the prognosis of lung cancer patients, and pose distinct clinical challenges. This study was designed to explore the prognostic factors related to lung cancer BM and the value of surgical resection in BMs from lung cancer. METHODS: A retrospective analysis was performed on 714 patients with lung cancer BMs screened between January 2010 and January 2018 at the Sun Yat-sen University Cancer Center. A 1:1 propensity score matching analysis was performed to reduce the potential bias between the surgery and the nonsurgery group. In both the raw and the propensity-score matched dataset, univariate and multivariate Cox proportional hazards regression analyses were used to evaluate risk factors for survival. RESULTS: After matching, 258 patients (129 surgery, 129 no surgery) were analyzed. Multivariate analyses after propensity score matching demonstrated that surgical resection was an independent protective factor for overall survival (OS), and older age, lower Karnofsky Performance Scale (KPS) score, and extracranial metastases were independent risk factors for worse OS. Patients without extracranial metastases, without synchronous BM and with a single BM had a better prognosis. CONCLUSIONS: The findings showed that surgical resection, age, KPS score, and extracranial metastases are independent prognostic factors for predicting the OS of patients with lung cancer BMs, and surgical resection for brain metastatic lesions could significantly improve the OS. However, only certain groups of patients with BMs can benefit from intracranial lesion resection, such as no extracranial metastases and metachronous metastases.

Comparison of short-term and long-term outcomes between thoracoscopic pneumonectomy and open pneumonectomy for non-small cell lung cancer: a study based on propensity score matching / 中华外科杂志

To compare the short-term and long-term results of thoracoscopic and open pneumonectomy for non-small cell lung cancer. The clinical data of patients with non-small cell lung cancer who underwent pneumonectomy in the Department of Thoracic Surgery, Qingdao University Hospital from January 2008 to December 2016 were collected. Totally 142 patients (55 in the thoracoscopic group and 87 in the open group) were included in the study. A total of 29 pairs of patients were successfully matched by propensity score matching (PSM). Perioperative outcomes and overall survival were compared between the two groups using test, χ(2) test, Kaplan-Meier curve and Log-rank test, respectively. Camparion with open group, the thoracoscopic group had longer operative time ((209.7±70.2) minutes . (171.3±43.5) minutes, 2.50, 0.02), more mediastinal lymph node dissection ((): 17(9) . 11(10), =388, 0.02) and shorter postoperative hospital stay (7.0(3.5) . 9.0(3.0), =285, 0.03). There was no significant difference in estimated blood loss, postoperative drainage time, dissected lymph node number, dissected lymph node station and perioperative complications. After PSM, there were no signifificant differences found in 3-year survival (71.4% . 48.1%, 0.10) and 3-year disease-free survival (67.4% . 47.2%, 0.13) between the two groups. Thoracoscopic pneumonectomy is safe and feasible for the treatment of non-small cell lung cancer with more mediastinal lymph node dissection and accelerating recovery, and equivalent long-term prognosis when compared with open approach.

Influence of medical nutrition therapy on borderline glucose intolerance in pregnant Taiwanese women.

OBJECTIVE: To investigate the influence of medical nutrition therapy (MNT) on borderline glucose intolerance (BGI) in pregnant Taiwanese women. METHODS: A total of 5194 singleton pregnant women were enrolled in this prospective, non-randomized study. The participants were subjected to the 50 g 1-h glucose challenge test (GCT) and 100 g 3-h oral glucose tolerance test (OGTT) to screening gestational diabetes mellitus (GDM). BGI was defined as a positive GCT and normal OGTT results. GDM was defined as a positive GCT and abnormal OGTT results. The women were categorized into the following groups: (1) GCT-negative, n = 3881; (2) BGI with MNT, n = 273; (3) BGI without MNT, n = 712; and (4) GDM, n = 328. Multiple logistic analyses were used to estimate the risks of pregnancy outcomes. RESULTS: The odds ratios (95% confidence interval) for total cesareans, third- or fourth-degree perineal lacerations, gestational hypertension or preeclampsia and macrosomia were 1.24 (1.04-1.49), 1.55 (1.06-1.28), 1.78 (1.21-2.61) and 2.50 (1.28-4.91) in the BGI without MNT group compared to the GCT-negative group. There was no difference between BGI with MNT and GCT-negative groups. CONCLUSIONS: Women with BGI who did not receive MNT had increased risks of adverse pregnancy outcomes, whereas who received MNT had no different risk with GCT-negative women.

The Evaluation of Antioxidant Interactions among 4 Common Vegetables using Isobolographic Analysis.

Isobolographic analysis was used to assess the antioxidant interactions (synergism, addition, and antagonism) of 4 common vegetables (tomato [T], carrot [C], eggplant [E], and purple potato [P]). The lipophilic (L) extracts of T and C (main carotenoids), the hydrophilic (H) extracts of E and P (main phenolics) were mixed by the certain ratios (1:9, 3:7, 1:1, 7:3, 9:1, w/w) and their antioxidant activities were investigated by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-Azinobis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS) radical scavenging assays, respectively. Most of the binary mixtures (LC-HE, LC-HP, HE-HP, LT-HE, and LT-HP combinations) showed the synergistic antioxidant effects. In DPPH assay, the greatest antioxidant activity of vegetable combinations was 1:9 LT-HP (EC50 : 2.45 ± 0.13 mg/mL), followed by 9:1 HE-HP (EC50 : 3.62 ± 0.12 mg/mL) and 1:9 LC-HE (EC50 : 3.74 ± 0.47 mg/mL). In ABTS assay, the greatest antioxidant activity of vegetable combinations was 9:1 HE-HP (EC50 : 4.20 ± 0.10 mg/mL), followed by 7:3 HE-HP (EC50 : 4.41 ± 0.63 mg/mL) and 1:1 HE-HP (EC50 : 5.35 ± 0.85 mg/mL). Among these combinations, 1:1 LC-HE combination showed the highest synergistic antioxidant effects in DPPH assay (synergistic rate: 87.4%), and 7:3 LC-HE combination showed the highest synergistic antioxidant effects in ABTS assay (synergistic rate: 87.0%). The mixtures of phenolics and carotenoids with suitable ratios in vegetables effectively enhanced the synergistic antioxidant effects.

Influence of the time of day and fasting duration on glucose level following a 1-hour, 50-gram glucose challenge test in pregnant women.

BACKGROUND: Previous studies have shown that the time of day (TD) of glucose measurement and the fasting duration (FD) influence the glucose levels in adults. Few studies have examined the effects of the TD and FD on the glucose level following a 1-hour, 50-gram glucose challenge test (GCT) in pregnant women in screening for or diagnosing gestational diabetes mellitus (GDM). The objective of this study was to investigate the influence of the TD (morning, afternoon, night) and the FD (the time of the last food ingestion as follows: ≤1 hour, 1-2 hours, and >2 hours) by examining their combined effects on the glucose levels following a 50-gram GCT in pregnant women. METHODS AND RESULTS: We analyzed the data of 1,454 non-diabetic pregnant Taiwanese women in a prospective study. Multiple linear regression and multiple logistic regression were used to estimate the relationships between the 9 TD-FD groups and the continuous and binary glucose levels (cut-off at 140 mg/dL) following a 50-gram GCT, after adjusting for maternal age, nulliparity, pre-pregnancy body mass index, and weight gain. Different TD and FD groups were associated with variable glucose responses to the 50-gram GCT, some of which were significant. The estimate coefficients (ß) of the TD-FD groups "night, ≤1 hr" and "night, 1-2 hr" revealed significantly lower glucose concentrations [ß (95% confidence interval [CI]): -6.46 (-12.53, -0.38) and -6.85 (-12.50, -1.20)] compared with the "morning, >2 hr" group. The TD-FD groups "afternoon, ≤1 hr" and "afternoon, 1-2 hr" showed significantly lower odds ratios (OR) of a positive GCT; the adjusted ORs (95% CI) were 0.54 (0.31-0.95) and 0.58 (0.35-0.96), respectively. CONCLUSIONS: Our findings demonstrate the importance of standardizing the TD and FD for the 1-hour, 50-gram GCT. In screening for and diagnosing GDM, the TD and FD are modifiable factors that should be considered in clinical practice and epidemiological studies.

Influence of food intake on the predictive value of the gestational diabetes mellitus screening test.

OBJECTIVE: To investigate the influence of prior food ingestion on the predictive value of a screening test for gestational diabetes mellitus. METHODS: This prospective, nonrandomized study enrolled 1,387 pregnant women who underwent the 50-g glucose challenge test. Gestational diabetes mellitus was diagnosed according to the National Diabetes Data Group criteria. A nutritional survey of dietary information before the glucose challenge test was conducted. The patients were stratified into three groups based on the time of last food ingestion (fasting interval): 1 hour or less, 1-2 hours, and more than 2 hours. The more than 2-hours fasting interval group was defined as the "fasting" group, and the combined 1 hour or less and 1-2 hours fasting interval groups were defined as the "fed" group. We calculated the positivity rate and the positive predictive value to detect the predictive value. RESULTS: Among women who fasted 1 hour or less, 1-2 hours, and more than 2 hours before a glucose challenge test, 2.5%, 3.1%, and 6.9% were diagnosed with gestational diabetes mellitus, respectively. The positive predictive value of the glucose challenge test was greater in the fasting group than in the fed group (27.1% compared with 13.7%, P=.003). A multinomial logistic analysis showed that gestational diabetes mellitus was more prevalent in the fasting group than in the fed group (adjusted odds ratio 2.86, 95% confidence interval 1.65-4.95). CONCLUSION: Our findings suggest that food intake influences the predictive value of the gestational diabetes screening test. LEVEL OF EVIDENCE: II.

A high capacity 3D steganography algorithm.

In this paper, we present a very high-capacity and low-distortion 3D steganography scheme. Our steganography approach is based on a novel multilayered embedding scheme to hide secret messages in the vertices of 3D polygon models. Experimental results show that the cover model distortion is very small as the number of hiding layers ranges from 7 to 13 layers. To the best of our knowledge, this novel approach can provide much higher hiding capacity than other state-of-the-art approaches, while obeying the low distortion and security basic requirements for steganography on 3D models.

Single lung transplantation with concomitant contralateral lung volume reduction for end- stage emphysema / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the effect of single lung transplantation with concomitant contralateral lung volume reduction surgery (LVRS) for the management of end-stage emphysema.</p><p><b>METHODS</b>A 46 year-old patient with end-stage emphysema received right lung transplantation and LVRS through the bilateral anterior-lateral intercostal incisions simultaneously.</p><p><b>RESULTS</b>Hyperinflation of the native lung or mediastinal shift did not occur after the operation, and the transplanted right lung dilated well without suppression. Acute rejection was not observed and the patient weaned from tracheal intubation 60 h after operation and from ventilator 108 h postoperatively. Persistent air leak occurred after LVRS but closed after instillation of hyperosmotic glucose. The patient was discharged 45 days after operation with significantly improved pulmonary function and normal life.</p><p><b>CONCLUSION</b>Single lung transplantation with concomitant contralateral lung volume reduction for emphysema eliminates such complications of single lung transplantation as native lung hyperinflation, mediastinal shift, excessive suppression of the transplanted lung and hemodynamics instability, and can improve the success rate of the operation.</p>