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Abstract Background Lipoteichoic acid (LTA), a gram-positive bacterial outer membrane component, can cause septic shock. Our previous studies showed that the gram-negative endotoxin, lipopolysaccharide (LPS), could induce surfactant protein-A (SP-A) production in human alveolar epithelial (A549) cells. Objectives In this study, we further evaluated the effect of LTA on SP-A biosynthesis and its possible signal-transducing mechanisms. Methods A549 cells were exposed to LTA. Levels of SP-A, nuclear factor (NF)-κB, extracellular signal-regulated kinase 1/2 (ERK1/2), and mitogen-activated/extracellular signal-regulated kinase kinase (MEK)1 were determined. Results Exposure of A549 cells to 10, 30, and 50 μg/ml LTA for 24 h did not affect cell viability. Meanwhile, when exposed to 30 μg/ml LTA for 1, 6, and 24 h, the biosynthesis of SP-A mRNA and protein in A549 cells significantly increased. As to the mechanism, LTA enhanced cytosolic and nuclear NF-κB levels in time-dependent manners. Pretreatment with BAY 11–7082, an inhibitor of NF-κB activation, significantly inhibited LTA-induced SP-A mRNA expression. Sequentially, LTA time-dependently augmented phosphorylation of ERK1/2. In addition, levels of phosphorylated MEK1 were augmented following treatment with LTA. Conclusions Therefore, this study showed that LTA can increase SP-A synthesis in human alveolar type II epithelial cells through sequentially activating the MEK1-ERK1/2-NF-κB-dependent pathway.

Abstract Background Although methadone has been used for the maintenance treatment of opioid dependence for decades, it was not introduced in China or Taiwan until 2000s. Methadone-drug interactions (MDIs) have been shown to cause many adverse effects. However, such effects have not been scrutinized in the ethnic Chinese community. Methods The study was performed in two major hospitals in southern Taiwan. A total of 178 non-HIV patients aged ≥ 20 years who had participated in the Methadone Maintenance Treatment Program (MMTP) ≥ 1 month were recruited. An MDI is defined as concurrent use of drug(s) with methadone that may result in an increase or decrease of effectiveness and/or adverse effect of methadone. To determine the prevalence and clinical characteristics of MDIs, credible data sources, including the National Health Insurance (NHI) database, face-to-face interviews, medical records, and methadone computer databases, were linked for analysis. Socio-demographic and clinical factors associated with MDIs and co-medications were also examined. Results 128 (72%) MMTP patients took at least one medication. Clinically significant MDIs included withdrawal symptoms, which were found among MMTP patients co-administered with buprenorphine or tramadol; severe QTc prolongation effect, which might be associated with use of haloperidol or droperidol; and additive CNS and respiratory depression, which could result from use of methadone in combination with chlorpromazine or thioridazine. Past amphetamine use, co-infection with hepatitis C, and a longer retention in the MMTP were associated with increased odds of co-medication. Among patients with co-medication use, significant correlates of MDIs included the male gender and length of co-medication in the MMTP. Conclusions The results demonstrate clinical evidence of significant MDIs among MMTP patients. Clinicians should check the past medical history of MMTP clients carefully before prescribing medicines. Because combinations of methadone with other psychotropic or opioid medications can affect treatment outcomes or precipitate withdrawal symptoms, clinicians should be cautious when prescribing these medications to MMTP patients and monitor the therapeutic effects and adverse drug reactions. Although it is difficult to interconnect medical data from different sources for the sake of privacy protection, the incumbent agency should develop pharmacovigilant measures to prevent the MDIs from occurring. Physicians are also advised to check more carefully on the medication history of their MMTP patients.

Abstract Background Cochlear outer hair cells change their length in response to variations in membrane potential. This capability, called electromotility, is believed to enable the sensitivity and frequency selectivity of the mammalian cochlea. Prestin is a transmembrane protein required for electromotility. Homozygous prestin knockout mice are profoundly hearing impaired. In humans, a single nucleotide change in SLC26A5, encoding prestin, has been reported in association with hearing loss. This DNA sequence variation, IVS2-2A>G, occurs in the exon 3 splice acceptor site and is expected to abolish splicing of exon 3. Methods To further explore the relationship between hearing loss and the IVS2-2A>G transition, and assess allele frequency, genomic DNA from hearing impaired and control subjects was analyzed by DNA sequencing. SLC26A5 genomic DNA sequences from human, chimp, rat, mouse, zebrafish and fruit fly were aligned and compared for evolutionary conservation of the exon 3 splice acceptor site. Alternative splice acceptor sites within intron 2 of human SLC26A5 were sought using a splice site prediction program from the Berkeley Drosophila Genome Project. Results The IVS2-2A>G variant was found in a heterozygous state in 4 of 74 hearing impaired subjects of Hispanic, Caucasian or uncertain ethnicity and 4 of 150 Hispanic or Caucasian controls (p = 0.45). The IVS2-2A>G variant was not found in 106 subjects of Asian or African American descent. No homozygous subjects were identified (n = 330). Sequence alignment of SLC26A5 orthologs demonstrated that the A nucleotide at position IVS2-2 is invariant among several eukaryotic species. Sequence analysis also revealed five potential alternative splice acceptor sites in intron 2 of human SLC26A5. Conclusion These data suggest that the IVS2-2A>G variant may not occur more frequently in hearing impaired subjects than in controls. The identification of five potential alternative splice acceptor sites in intron 2 of human SLC26A5 suggests a potential mechanism by which expression of prestin might be maintained in cells carrying the SLC26A5 IVS2-2A>G DNA sequence variation. Additional studies are needed to evaluate the effect of the IVS2-2A>G transition on splicing of SLC26A5 transcripts and characterize the hearing status of individuals homozygous for the IVS2-2A>G variant.

Background: Family health history (FHH) is central to human genomic profiling construction; however, there is no protocol for documenting FHH in a pedigree format in Vietnam. Aim: A "Gia Su Suc Khoe" (GSSK) tool was developed to create a user-friendly interface for collecting FHH and offering diseases' risk assessment. Results: A tool was described (https://giasusuckhoe.vn/) with good feedback from genetic counselors and family-medicine doctors. Among 20 surveys, 100% of respondents noted that the report accurately reflected their FHH and were satisfied with the tool's display. About 74% of familial conditions were covered. Overall, all constructive feedback has been adapted into the updated version. Conclusion: Gia Su Suc Khoe has the potential to significantly improve healthcare delivery and outcomes in Vietnam.

A new naphthalene diimides extended-pillar[6]arene 1 with a large cavity and rich host-guest complexation properties was synthesized in high yield. It can not only form 1:2 complexes with large size polycyclic aromatic hydrocarbons but also form 1:1:1 ternary complex with perylene and 2,7-diazapyrenium. Moreover, the supramolecular exchange reaction from a 1:2 host-guest complex 1•(G3)2 formed by 1 and perylene to a 1:1:1 ternary complex 1•G3•G5 formed by 1 with perylene and 2,7-diazapyrenium salt was also investigated by 1H NMR experiments as well as theoretically calculations., (© 2024 Wiley‐VCH GmbH.)

Competing Interests: M.Y.N. has received funding from Circle CVI, Arterys, TeraRecon, Lode, GE, and Bayer. The remaining authors declare no conflict of interest.

The emergence of multicancer early detection (MCED) tests holds promise for improving early cancer detection and public health outcomes. However, positive MCED test results require confirmation through recommended cancer diagnostic imaging modalities. To address these challenges, we have developed a consultation and work-up protocol for definitive diagnostic results post MCED testing, named SPOT-MAS. Developed through circulating tumor DNA (ctDNA) analysis and in line with professional guidelines and advisory board consensus, this protocol standardizes information to aid general practitioners in accessing, interpreting and managing SPOT-MAS results. Clinical effectiveness is demonstrated through a series of identified cancer cases. Our research indicates that the protocol could empower healthcare professionals to confidently interpret circulating tumor DNA test results for 5 common types of cancer, thereby facilitating the clinical integration of MCED tests.

BACKGROUND. MRI-based prognostic evaluation in patients with dilated cardiomyopathy (DCM) has historically used markers of late gadolinium enhancement (LGE) and feature tracking (FT)-derived left ventricular global longitudinal strain (LVGLS). Early data indicate that FT-derived left atrial strain (LAS) parameters, including reservoir, conduit, and booster, may also have prognostic roles in such patients. OBJECTIVE. The purpose of our study was to evaluate the prognostic utility of LAS parameters, derived from MRI FT, in patients with ischemic or nonischemic DCM, including in comparison with the traditional parameters of LGE and LVGLS. METHODS. This retrospective study included 811 patients with ischemic or nonischemic DCM (median age, 60 years; 640 men, 171 women) who underwent cardiac MRI at any of five centers. FT-derived LAS parameters and LVGLS were measured using two- and four-chamber cine images. LGE percentage was quantified. Patients were assessed for a composite outcome of all-cause mortality or heart failure hospitalization. Multivariable Cox regression analyses including demographic characteristics, cardiovascular risk factors, medications used, and a wide range of cardiac MRI parameters were performed. Kaplan-Meier analyses with log-rank tests were also performed. RESULTS. A total of 419 patients experienced the composite outcome. Patients who did, versus those who did not, experience the composite outcome had larger LVGLS (-6.7% vs -8.3%, respectively; p < .001) as well as a smaller LAS reservoir (13.3% vs 19.3%, p < .001), LAS conduit (4.7% vs 8.0%, p < .001), and LAS booster (8.1% vs 10.3%, p < .001) but no significant difference in LGE (10.1% vs 11.3%, p = .51). In multivariable Cox regression analyses, significant independent predictors of the composite outcome included LAS reservoir (HR = 0.96, p < .001) and LAS conduit (HR = 0.91, p < .001). LAS booster and LGE were not significant independent predictors in the models. LVGLS was a significant independent predictor only in a model that initially included LAS booster but not the other LAS parameters. In Kaplan-Meier analysis, all three LAS parameters were significantly associated with the composite outcome ( p < .001). CONCLUSION. In this multicenter study, LAS reservoir and LAS conduit were significant independent prognostic markers in patients with ischemic or nonischemic DCM, showing greater prognostic utility than the currently applied markers of LVGLS and LGE. CLINICAL IMPACT. FT-derived LAS analysis provides incremental prognostic information in patients with DCM.

Background: Copy number variation sequencing (CNV-seq) is a powerful tool to discover structural genomic variation, but limitations associated with its retrospective study design and inadequate diversity of participants can be impractical for clinical application. Aim: This study aims to use CNV-seq to assess chromosomal aberrations in pregnant Vietnamese women. Materials & methods: A large-scale study was conducted on 3776 pregnant Vietnamese women with abnormal ultrasound findings. Results: Chromosomal aberrations were found in 448 (11.86%) women. Of these, 274 (7.26%) had chromosomal aneuploidies and 174 (4.61%) carried pathogenic/likely pathogenic CNVs. Correlations were established between chromosomal aberrations and various phenotypic markers. Conclusion: This comprehensive clinical study illuminates the pivotal role of CNV-seq in prenatal diagnosis for pregnancies featuring fetal ultrasound anomalies.

Objective: To evaluate the efficacy and safety of cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of pseudomyxoma peritonei (PMP). Methods: In this descriptive case series study, we retrospective analyzed the records of PMP patients treated with CRS and HIPEC between January 2013 and June 2023 at Affiliated Cancer Hospital and Institute of Guangzhou Medical University. The inclusion criteria were as follows: (1) Aged 18 to 75 years and nonpregnant women. (2) Histologically confirmed diagnosis of pseudomyxoma peritonei. (3) Karnofsky Performance Scale (KPS)>70. (4) The functions of major organs such as the heart, liver, lungs, and kidneys can tolerate major surgery for long periods of time. (5) No evidence of extra-abdominal metastasis. Patients with extensive intra-abdominal adhesions or severe infectious diseases were excluded. The main outcomes were overall survival (OS) and postoperative major complications. The postoperative major complications were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 5.0). We used the peritoneal cancer index (PCI) score to quantitatively assess the peritoneal metastases and the completeness of cytoreduction (CCR) score at the end of surgery (CCR-0 and CCR-1 considered to be complete CRS). Results: A total of the 186 PMP patients with a median age of 56 (interquartile range extremes (IQRE), 48-64) years were included, 65 (34.9%) males and 121 (65.1%) females. The median peritoneal cancer index (PCI) score was 28 (20-34). Appendiceal origin accounted for 91.4%. Histological types were low grade in 99 patients (53.2%), high grade in 57 patients (30.6%), and 55 patients (29.6%) received complete cytoreduction (CCR-0/1). The median operative duration was 300 (211-430) minutes for all patients. Treatment-related 30-day mortality was 2.7%; 90-day mortality 4.3%; reoperation 1.6%; and severe morbidity 43.0%. Within the entire series, anemia(27.4%), electrolyte disturbance(11.6%), and hypoalbuminemia(7.5%) were the most frequent major complications (grade 3-4). The incidences of gastrointestinal anastomotic leakage, abdominal bleeding, and abdominal infection were 2.2%, 2.2%, and 4.3%, respectively. After a median follow-up of 38.1 (95%CI:31.2-45.1) months, the 5-year OS was 50.3% (95%CI: 40.7%-59.9%) with a median survival time of 66.1 (95%CI: 43.1-89.1) months. The survival analysis showed that patients with pathological low grade, low PCI, and low CCR score had better survival with statistically significant differences (all P <0.05). Further stratified into complete and incomplete CRS subgroups, the 5-year OS of the CCR-0 and CCR-1 subgroups was 88.9% (95%CI: 68.3%-100.0%) and 77.6% (95%CI: 62.7%-92.5%), respectively; and 42.0% (95%CI: 29.5%-54.5%) in the CCR-2/3 subgroup. Conclusions: CRS and HIPEC may result in a long-term survival benefit for PMP patients with acceptable perioperative morbidity and mortality. This strategy, when complete CRS is possible, could significantly prolong survival for strictly selected patients at experienced centers.

Objective: Anti-synthetase syndrome (ASyS) patients have heterogeneous clinical manifestations with different initial presentations, complications, and outcomes. This study aimed to assess the clinical characteristics and complications in patients with ASyS, and to identify factors that were associated with the survival of ASyS patients., Methods: This was a retrospective multicentre longitudinal study. Patients fulfilling either the Connor's criteria or Solomon's criteria for ASyS were recruited. Electronic health records were reviewed until October 2022. Multivariate Cox-regression analysis was used to determine the independent prognostic factors. Auto-antibodies were checked by commercial immunoassays., Results: A total of 205 patients (anti-Jo-1 49.3%, anti-PL-7 19.0%, anti-EJ 11.2%, anti-PL-12 10.2% and anti-OJ 3.4%) were included. The median follow-up time was 4 years. The time from symptoms onset to diagnosis was significantly longer for non-anti-Jo1 patients (median 5 vs 3 months). Common initial presentations included myositis (56.1%), arthritis (54.6%), and interstitial lung disease (ILD) (54.1%). Patients with anti-Jo-1 had significantly higher muscle enzyme levels and more arthritis. All patients with anti-EJ would develop ILD on follow-up and malignancy was noted in 28.6% of the anti-OJ positive patients. 15.6% of the patients died and pulmonary diseases (ILD or pneumonia) were the major causes. Age at diagnosis, malignancy and rapidly progressive-ILD were independently associated with mortality, while joint manifestation was a protective factor., Conclusion: In view of the heterogeneity of clinical presentation of ASyS, high index of suspicion and early checking of specific autoantibodies might help prompt diagnosis of ASyS and detection of related complications., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: To demonstrate the prevalence of maternal mosaic monosomy X (MMXO) in a cohort of pregnant women in Vietnam., Methods: All 105,594 singleton pregnant women undergoing noninvasive prenatal screening (NIPS) between January 2019 and February 2021 in Vietnam were analyzed by measuring discordance between size- and count-based z-scores for chromosome X (ChrX) to identify suspected cases of MMXO and validated by fluorescence in situ hybridization (FISH) on maternal blood., Results: We identified 295 (0.279%) suspected MMXO cases. After FISH analysis, MMXO was confirmed in 125 cases (42.37%), revealing the MMXO prevalence of 0.118% (95% CI: 0.097-0.139%) in this cohort., Conclusion: We found a relatively high prevalence of MMXO in Vietnamese pregnant women and demonstrated a strong influence of MMXO on the ChrX z-score using a count-based method, resulting in false positives. The size-based method is not sensitive to MMXO and therefore achieves higher PPV.

We report three cases of fetalis hydrops associated with nondeletional α-thalassemia. Two cases were caused by hemoglobin (Hb) H-Quong Sz disease, and one caused by homozygous Hb Constant Spring. Fetal hydrops occurred in the late second trimester in all three cases. Our study indicates that for pregnancies at risk for fetal nondeletional Hb H disease, strict ultrasound follow-up is particularly important. Even without techniques of intrauterine transfusion treatment, early prenatal diagnosis can enable parents to make timely decisions.

Background: Noninvasive prenatal tests for monogenic diseases (NIPT-SGG) have recently been reported as helpful in early-stage antenatal screening. Our study describes the clinical and genetic features of cases identified by NIPT-SGG. Materials & methods: In a cohort pregnancy with abnormal sonograms, affected cases were confirmed by invasive diagnostic tests concurrently, with NIPT-SGG targeting 25 common dominant single-gene diseases. Results: A total of 13 single-gene fetuses were confirmed, including Noonan and Costello syndromes, thanatophoric dysplasia, achondroplasia, osteogenesis imperfecta and Apert syndrome. Two novel variants seen were tuberous sclerosis complex ( TSC2 c.4154G>A) and Alagille syndrome ( JAG1 c.3452del). Conclusion: NIPT-SGG and standard tests agree on the results for 13 fetuses with monogenic disorders. This panel method of screening can benefit high-risk Vietnamese pregnancies, but further research is encouraged to expand on the causative gene panel.

Despite their promise, circulating tumor DNA (ctDNA)-based assays for multi-cancer early detection face challenges in test performance, due mostly to the limited abundance of ctDNA and its inherent variability. To address these challenges, published assays to date demanded a very high-depth sequencing, resulting in an elevated price of test. Herein, we developed a multimodal assay called SPOT-MAS (screening for the presence of tumor by methylation and size) to simultaneously profile methylomics, fragmentomics, copy number, and end motifs in a single workflow using targeted and shallow genome-wide sequencing (~0.55×) of cell-free DNA. We applied SPOT-MAS to 738 non-metastatic patients with breast, colorectal, gastric, lung, and liver cancer, and 1550 healthy controls. We then employed machine learning to extract multiple cancer and tissue-specific signatures for detecting and locating cancer. SPOT-MAS successfully detected the five cancer types with a sensitivity of 72.4% at 97.0% specificity. The sensitivities for detecting early-stage cancers were 73.9% and 62.3% for stages I and II, respectively, increasing to 88.3% for non-metastatic stage IIIA. For tumor-of-origin, our assay achieved an accuracy of 0.7. Our study demonstrates comparable performance to other ctDNA-based assays while requiring significantly lower sequencing depth, making it economically feasible for population-wide screening., Competing Interests: VN VTCN is affiliated with Gene Solutions. The author has no other competing interests to declare, TN HTN is affiliated with Gene Solutions. The author has no other competing interests to declare, ND NNTD is affiliated with Gene Solutions. The author has no other competing interests to declare, TP TMQP is affiliated with Gene Solutions. The author has no other competing interests to declare, GN GTHN is affiliated with Gene Solutions. The author has no other competing interests to declare, TN TDN is affiliated with Gene Solutions. The author has no other competing interests to declare, TT TTTT is affiliated with Gene Solutions. The author has no other competing interests to declare, DV, TP, TJ, VN, HN, TN, QD, TD, AT, VN, VN, LH, QT, TP, TH, BN, TN, TN, DP, BP, TV, TN, TT, MT, NT, TL, TT, MD, HB, VK, TP, DT, TL, TP, ML, VC, TD No competing interests declared, TN THHN is affiliated with Gene Solutions. The author has no other competing interests to declare, LH LAKH is affiliated with Gene Solutions. The author has no other competing interests to declare, TT THT is affiliated with Gene Solutions. The author has no other competing interests to declare, DV DHV is affiliated with Gene Solutions. The author has no other competing interests to declare, TT TMTT is affiliated with Gene Solutions. The author has no other competing interests to declare, MN MNN is affiliated with Gene Solutions. The author has no other competing interests to declare, TV TTVV is affiliated with Gene Solutions. The author has no other competing interests to declare, AN ANN is affiliated with Gene Solutions. The author has no other competing interests to declare, TT TTT is affiliated with Gene Solutions. The author has no other competing interests to declare, VT VUT is affiliated with Gene Solutions. The author has no other competing interests to declare, ML MPL is affiliated with Gene Solutions. The author has no other competing interests to declare, TD TTD is affiliated with Gene Solutions. The author has no other competing interests to declare, TP TVP is affiliated with Gene Solutions. The author has no other competing interests to declare, HN HDN is affiliated with Gene Solutions. The author has no other competing interests to declare, DN DSN holds equity in Gene Solutions.DSN is affiliated with Gene Solutions. The author has no other competing interests to declare, DT DKT is affiliated with Gene Solutions. The author has no other competing interests to declare, HT HST is affiliated with Gene Solutions. The author has no other competing interests to declare, HG HG holds equity in Gene Solutions. The funder Gene Solutions provided support in the form of salaries for HG who is inventor on the patent application (USPTO 17930705).HG is affiliated with Gene Solutions. The author has no other competing interests to declare, HN HNN holds equity in Gene Solutions. The funder Gene Solutions provided support in the form of salaries for HNN who is inventor on the patent application (USPTO 17930705).HNN is affiliated with Gene Solutions. The author has no other competing interests to declare, MP MDP holds equity in Gene Solutions. The funder Gene Solutions provided support in the form of salaries for MDP who is inventor on the patent application (USPTO 17930705).MDP is affiliated with Gene Solutions. The author has no other competing interests to declare, LT LST holds equity in Gene Solutions. The funder Gene Solutions provided support in the form of salaries for LST who is inventor on the patent application (USPTO 17930705).LST is affiliated with Gene Solutions. The author has no other competing interests to declare, (© 2023, Nguyen, Nguyen et al.)

In Vietnam, colorectal cancer is one of the top diagnosed cancers, with 5-10% originating from inherited mutations. This study aims to define the mutation spectrum associated with hereditary colorectal cancer syndromes (HCCS) in Vietnam, evaluate the influence of genetic testing on carriers' awareness, and also investigate the barriers in familial testing. Genetic test reports were collected to identify HCCS cases, then cases underwent a survey investigating self-risk and familial-risk awareness, proactive cancer screening, and familial testing barriers. Participant characteristics, mutation prevalence, and results from the survey were descriptively analyzed and reported. Of all genetic test results, 3% (49/1632) were identified with mutations related to HCCS. Over 77% of them belonged to Lynch syndrome. PMS2 appeared to be the gene with the highest mutation frequency, while MLH1 was the lowest. 44% of cases further undertook cancer screening tests, and 48% of cases' families had uptake genetic testing. The biggest barrier of familial members for not taking genetic test was psychological reasons (fear, not being interested, or not feeling necessary). This study provided new evidence for HCCS mutation spectrum in Vietnamese population and the success in promoting cascade test in high-risk family members through financial and technical support. Also, study has suggested the needs of an innovative genetic testing process focusing on the quality of pre-and post-test consultancy, an increase in follow-ups, and the change in policy for permission of contacting relatives directly to improve the rate of cascade testing and proactive cancer screening., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Diagnosing heart failure with preserved ejection fraction (HFpEF) remains challenging. Intraventricular four-dimensional flow (4D flow) phase-contrast cardiovascular magnetic resonance (CMR) can assess different components of left ventricular (LV) flow including direct flow, delayed ejection, retained inflow and residual volume. This could be utilised to identify HFpEF. This study investigated if intraventricular 4D flow CMR could differentiate HFpEF patients from non-HFpEF and asymptomatic controls. Suspected HFpEF patients and asymptomatic controls were recruited prospectively. HFpEF patients were confirmed using European Society of Cardiology (ESC) 2021 expert recommendations. Non-HFpEF patients were diagnosed if suspected HFpEF patients did not fulfil ESC 2021 criteria. LV direct flow, delayed ejection, retained inflow and residual volume were obtained from 4D flow CMR images. Receiver operating characteristic (ROC) curves were plotted. 63 subjects (25 HFpEF patients, 22 non-HFpEF patients and 16 asymptomatic controls) were included in this study. 46% were male, mean age 69.8 ± 9.1 years. CMR 4D flow derived LV direct flow and residual volume could differentiate HFpEF vs combined group of non-HFpEF and asymptomatic controls (p < 0.001 for both) as well as HFpEF vs non-HFpEF patients (p = 0.021 and p = 0.005, respectively). Among the 4 parameters, direct flow had the largest area under curve (AUC) of 0.781 when comparing HFpEF vs combined group of non-HFpEF and asymptomatic controls, while residual volume had the largest AUC of 0.740 when comparing HFpEF and non-HFpEF patients. CMR 4D flow derived LV direct flow and residual volume show promise in differentiating HFpEF patients from non-HFpEF patients., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Over 60% of single-gene diseases in newborns are autosomal dominant variants. Noninvasive prenatal testing for monogenic conditions (NIPT-SGG) is cost-effective and timesaving, but not widely applied. This study introduces and validates NIPT-SGG in detecting 25 monogenic conditions. Methods: NIPT-SGG with a 30-gene panel applied next-generation sequencing and trio assays to confirm de novo variants. Diagnostic tests confirmed NIPT-detected cases. Results: Among 93 pregnancies with ultrasound findings, 11 (11.8%) fetuses were screened and diagnosed with monogenic diseases, mostly with Noonan syndrome. NIPT-SGG determined >99.99% of actual positive and negative cases, confirmed by diagnostic tests. No false-negatives or false-positives were reported. Conclusion: NIPT-SGG effectively identifies the fetuses affected with monogenic diseases, which is a promisingly safe and timely antenatal screening option for high-risk pregnancies.

Some metabolic enzymes normally occur in the nucleus and cytoplasm. These compartments differ in molecular composition. Since post-translational modification and interaction with allosteric effectors can tune enzyme activity, it follows that the behavior of an enzyme as a catalyst may differ between the cytoplasm and nucleus. We explored this possibility for the glycolytic enzyme glyceraldehyde 3-phosphate dehydrogenase (GAPDH). Homogenates of pristine nuclei and cytoplasms isolated from Xenopus laevis oocytes were used for whole compartment activity profiling in a near-physiological buffer. Titrations of NAD+ revealed similar whole compartment activity profiles for GAPDH in nuclear and cytoplasmic homogenates. Surprisingly however GAPDH in these compartments did not have the same behavior in assays of the dependence of initial velocity (v0) on G3P concentration. First, the peak v0 for nuclear GAPDH was up to 2.5-fold higher than the peak for cytoplasmic GAPDH. Second, while Michaelis Menten-like behavior was observed in all assays of cytoplasm, the v0 versus [G3P] plots for nuclear GAPDH typically exhibited a non-Michaelis Menten (sigmoidal) profile. Apparent Km and Vmax (G3P) values for nuclear GAPDH activity were highly variable, even between replicates of the same sample. Possible sources of this variability include in vitro processing of a metabolite that allosterically regulates GAPDH, turnover of a post-translational modification of the enzyme, and fluctuation of the state of interaction of GAPDH with other proteins. Collectively these findings are consistent with the hypothesis that the environment of the nucleus is distinct from the environment of the cytoplasm with regard to GAPDH activity and its modulation. This finding warrants further comparison of the regulation of nuclear and cytoplasmic GAPDH, as well as whole compartment activity profiling of other enzymes of metabolism with cytosolic and nuclear pools., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Tang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Although the adiponectin signalling exerts exercise-mimicking effects, whether this pathway contributes to the anti-ageing benefits of physical exercise has not been established yet., Methods: Swim exercise training and wheel running were used to measure lifespan in the nematode Caenorhabditis elegans and skeletal muscle quality in mice, respectively. Muscle weight, muscle fibre cross-sectional area (CSA) and myonuclei number were used to evaluate muscle mass. RNA sequencing (RNA-Seq) analysis of skeletal muscle in exercised mice was used to study the underlying mechanisms. Western blot and immunofluorescence were performed to explore autophagy- and senescence-related markers., Results: The C. elegans adiponectin receptor PAQR-1/AdipoR1, but not PAQR-2/AdipoR2, was activated (3.55-fold and 3.48-fold increases in p-AMPK on Days 1 and 6, respectively, P < 0.001), which was involved in lifespan extension in exercised worms. Exercise training increased skeletal muscle mass index (1.29-fold, P < 0.01), muscle weight (1.75-fold, P < 0.001), myonuclei number (1.33-fold, P < 0.05), muscle fibre CSA (1.39-fold, P < 0.05) and capillary abundance (2.19-fold, P < 0.001 for capillary density; 1.58-fold, P < 0.01 for capillary number) in aged mice. Physical exercise reduced protein (2.94-fold, P < 0.001) and mRNA levels (1.70-fold, P < 0.001) of p16 INK4a , a marker for cellular senescence, in skeletal muscle of aged mice. These beneficial effects of exercise on skeletal muscle of mice were dependent on AdipoR1. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis for differentially expressed genes in skeletal muscle between exercised mice with and without AdipoR1 knockdown by RNA-Seq analysis revealed that several KEGG pathways, such as 'AMPK signalling pathway' (P < 0.001), 'FOXO signalling pathway' (P < 0.001) and 'autophagy' (P < 0.001) were overrepresented. Knockdown of FoxO3a inhibited exercise-mediated beneficial effects on skeletal muscle quality of mice by inhibiting autophagy/mitophagy (3.81-fold reduction in LC3-II protein, P < 0.001; 1.53-fold reduction in BNIP3 protein, P < 0.05). Knockdown of daf-16, the FoxO homologue in C. elegans, reduced autophagy (2.77-fold and 2.06-fold reduction in GFP::LGG-1 puncta in seam cells and the intestine, respectively, P < 0.05) and blocked lifespan extension by exercise in worms., Conclusions: Our findings provide insights into how the AdipoR1 pathway has an impact on the anti-ageing benefits of exercise and implicate that activation of the AdipoR1 signalling may represent a potential therapeutic strategy for reducing age-related loss of skeletal muscle., (© 2023 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

Purpose: Postoperative adjuvant trans-catheter arterial chemoembolization (TACE) is regarded as a common strategy for hepatocellular carcinoma (HCC) patients at a high risk of recurrence. However, there are currently no clinically available biomarkers to predict adjuvant TACE response. Vessels that encapsulate tumor clusters (VETC) can be used as an independent predictor of HCC prognosis. In this study, we aimed to explore whether the VETC pattern could predict adjuvant TACE benefit., Methods: Vascular pattern and HIF-1α expression were detected in immunohistochemistry. The survival benefit of adjuvant TACE therapy for patients with or without VETC pattern (VETC+ /VETC-) was evaluated., Results: The adjuvant TACE therapy obviously improved the TTR and OS in VETC+ patients, while adjuvant TACE therapy could not benefit from VETC- patients. Univariate and multivariate analysis revealed that adjuvant TACE therapy significantly improved the TTR and OS in VETC+ patients, but not in VETC- patients. In addition, the VETC+ , but not VETC- , patients could benefit from adjuvant TACE therapy in patients with high-risk factors of vascular invasion, larger tumor or multiple tumor. The mechanistic investigations revealed that the favorable efficacy of adjuvant TACE on VETC+ patients, but not VETC- ones, may be not due to the activation of HIF-1α pathway., Conclusion: The VETC pattern may represent a novel and reliable factor for selecting HCC patients who may benefit from adjuvant TACE therapy, and the combination of VETC pattern and tumor characteristics may help stratify patients' outcomes and responses to adjuvant TACE therapy., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Citrin deficiency (CD), a disorder caused by mutations in the SLC25A13 gene, may result in neonatal intrahepatic cholestasis. This study was purposely to explore the mutation spectrum of SLC25A13 gene in Vietnamese CD patients., Methods: The 292 unrelated CD patients were first screened for four high-frequency mutations by PCR/PCR-RFLP. Then, Sanger sequencing was performed directly for heterozygous or undetected patients. Novel mutations identified would need to be confirmed by their parents., Results: 12 pathogenic SLC25A13 mutations were identified in all probands, including three deletions c.851&#95;854del (p.R284Rfs*3), c.70-63&#95;133del (p.Y24&#95;72Ifs*10), and c.[1956C>A;1962del] (p.[N652K;F654Lfs*45]), two splice-site mutations (IVS6+5G>A and IVS11+1G>A), one nonsense mutations c.1399C>T (p.R467*), one duplication mutation c.1638&#95;1660dup (p.A554fs*570), one insertion IVSl6ins3kb (p.A584fs*585), and four missense mutation c.2T>C (p.M1T), c.1231G>A (p.V411M), c.1763G>A (p.R588Q), and c.135G>C (p.L45F). Among them, c.851&#95;854del (mut I) was the most identified mutant allele (91.78%) with a total of 247 homozygous and 42 heterozygous genotypes of carriers. Interestingly, two novel mutations were identified: c.70-63&#95;133del (p.Y24&#95;72Ifs*10) and c.[1956C>A;1962del] (p.[N652K;F654Lfs*45])., Conclusion: The SLC25A13 mutation spectrum related to intrahepatic cholestasis infants in Vietnam revealed a quite similar pattern to Asian countries' reports. This finding supports the use of targeted SLC25A13 mutation for CD screening in Vietnam and contributed to the SLC25A13 mutation spectra worldwide. It also helps emphasize the role of DNA analysis in treatment, genetic counseling, and prenatal diagnosis., (© 2022. The Author(s), under exclusive licence to The Japan Society of Human Genetics.)

BACKGROUND. Prior small single-center studies have yielded conflicting results regarding the prognostic significance of myocardial strain parameters derived from feature tracking (FT) on cardiac MRI in patients with dilated cardiomyopathy (DCM). OBJECTIVE. The purpose of this study was to evaluate the prognostic utility of FT parameters on cardiac MRI in patients with ischemic and nonischemic DCM and to determine the optimal strain parameter for outcome prediction. METHODS. This retrospective study included 471 patients (median age, 61 years; 365 men, 106 women) with ischemic ( n = 233) or nonischemic ( n = 238) DCM and left ventricular (LV) ejection fraction (EF) less than 50% who underwent cardiac MRI at any of four centers from January 2011 to December 2019. Cardiac MRI parameters were determined by manual contouring. In addition, software-based FT was used to calculate six myocardial strain parameters (LV and right ventricular [RV] global radial strain, global circumferential strain, and global longitudinal strain [GLS]). Late gadolinium enhancement (LGE) was also evaluated. Patients were assessed for a composite outcome of all-cause mortality and/or heart-failure hospitalization. Cox regression models were used to determine associations between strain parameters and the composite outcome. RESULTS. Mean LV EF was 27.5% and mean LV GLS was -6.9%. The median follow-up period was 1328 days. The composite outcome occurred in 220 patients (125 deaths, 95 heart-failure hospitalizations). All six myocardial strain parameters were significant independent predictors of the composite outcome (hazard ratio [HR] = 0.92-1.16; all p < .05). In multivariable models that included age, corrected LV and RV end-diastolic volume, LV and RV EF, and presence of LGE, the only strain parameter that was a significant independent predictor of the composite outcome was LV GLS (HR = 1.13, p = .006); LV EF and presence of LGE were not independent predictors of the composite outcome in the models ( p > .05). A LV GLS threshold of -6.8% had sensitivity of 62.6% and specificity of 62.6% in predicting the composite outcome rate at 4.0 years. CONCLUSION. LV GLS, derived from FT on cardiac MRI, is a significant independent predictor of adverse outcomes in patients with DCM. CLINICAL IMPACT. This study strengthens the body of evidence supporting the clinical implementation of FT when performing cardiac MRI in patients with DCM.

Aims: Heart failure with preserved ejection fraction (HFpEF) continues to be a diagnostic challenge. Cardiac magnetic resonance atrial measurement, feature tracking (CMR-FT), tagging has long been suggested to diagnose HFpEF and potentially complement echocardiography especially when echocardiography is indeterminate. Data supporting the use of CMR atrial measurements, CMR-FT or tagging, are absent. Our aim is to conduct a prospective case-control study assessing the diagnostic accuracy of CMR atrial volume/area, CMR-FT, and tagging to diagnose HFpEF amongst patients suspected of having HFpEF., Methods and Results: One hundred and twenty-one suspected HFpEF patients were prospectively recruited from four centres. Patients underwent echocardiography, CMR, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) measurements within 24 h to diagnose HFpEF. Patients without HFpEF diagnosis underwent catheter pressure measurements or stress echocardiography to confirm HFpEF or non-HFpEF. Area under the curve (AUC) was determined by comparing HFpEF with non-HFpEF patients. Fifty-three HFpEF (median age 78 years, interquartile range 74-82 years) and thirty-eight non-HFpEF (median age 70 years, interquartile range 64-76 years) were recruited. Cardiac magnetic resonance left atrial (LA) reservoir strain (ResS), LA area index (LAAi), and LA volume index (LAVi) had the highest diagnostic accuracy (AUCs 0.803, 0.815, and 0.776, respectively). Left atrial ResS, LAAi, and LAVi had significantly better diagnostic accuracy than CMR-FT left ventricle (LV)/right ventricle (RV) parameters and tagging ( P < 0.01). Tagging circumferential and radial strain had poor diagnostic accuracy (AUC 0.644 and 0.541, respectively)., Conclusion: Cardiac magnetic resonance LA ResS, LAAi, and LAVi have the highest diagnostic accuracy to identify HFpEF patients from non-HFpEF patients amongst clinically suspected HFpEF patients. Cardiac magnetic resonance feature tracking LV/RV parameters and tagging had low diagnostic accuracy to diagnose HFpEF., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

The SPOT-MAS assay "Screening for the Presence Of Tumor by Methylation And Size" detects the five most common cancers in Vietnam by evaluating circulating tumor DNA in the blood. Here, we validated its performance in a prospective multi-center clinical trial, K-DETEK. Our analysis of 2795 participants from 14 sites across Vietnam demonstrates its ability to detect cancers in asymptomatic individuals with a positive predictive value of 60%, with 83.3% accuracy in detecting tumor location. We present a case report to support further using SPOT-MAS as a complementary method to achieve early cancer detection and provide the opportunity for early treatment.

α-Thalassemia is a common inherited blood disorder manifested mainly by the deletions of α-globin genes. In geographical areas with high carrier frequencies, screening of α-thalassemia carrier state is therefore of vital importance. This study presents a novel method for identifying female carriers of common α-thalassemia deletions using samples routinely taken for non-invasive prenatal tests for screening of fetal chromosomal aneuploidies. A total of 68,885 Vietnamese pregnant women were recruited and α-thalassemia statuses were determined by gap-PCR, revealing 5344 women (7.76%) carried deletions including αα/-- SEA (4.066%), αα/-α 3.7 (2.934%), αα/-α 4.2 (0.656%), and rare genotypes (0.102%). A two-stage model was built to predict these α-thalassemia deletions from targeted sequencing of the HBA gene cluster on maternal cfDNA. Our method achieved F1-scores of 97.14-99.55% for detecting the three common genotypes and 94.74% for detecting rare genotypes (-α 3.7 /-α 4.2 , αα/-- THAI , -α 3.7 /-- SEA , -α 4.2 /-- SEA ). Additionally, the positive predictive values were 100.00% for αα/αα, 99.29% for αα/-- SEA , 94.87% for αα/-α 3.7 , and 96.51% for αα/-α 4.2 ; and the negative predictive values were 97.63%, 99.99%, 99.99%, and 100.00%, respectively. As NIPT is increasingly adopted for pregnant women, utilizing cfDNA from NIPT to detect maternal carriers of common α-thalassemia deletions will be cost-effective and expand the benefits of NIPT., (© 2022. The Author(s).)

Background: Several inherited metabolic diseases are underreported in Vietnam, namely glucose-6-phosphate dehydrogenase deficiency (G6PDd), phenylketonuria (PKU) and galactosemia (GAL). Whilst massively parallel sequencing (MPS) allows researchers to screen several loci simultaneously for pathogenic variants, no screening programme uses MPS to uncover the variant spectra of these diseases in the Vietnamese population., Methods: Pregnant women (mean age of 32) from across Vietnam attending routine prenatal health checks agreed to participate and had their blood drawn. MPS was used to detect variants in their G6PD, PAH and GALT genes., Results: Of 3259 women screened across Vietnam, 450 (13.8%) carried disease-associated variants for G6PD, PAH and GALT. The prevalence of carriers was 8.9% (291 of 3259) in G6PD and 4.6% (152 of 3259) in PKU, whilst GAL was low at 0.2% (7 of 3259). Two GALT variants, c.593 T > C and c.1034C > A, have rarely been reported., Conclusion: This study highlights the need for routine carrier screening, where women give blood whilst receiving routine prenatal care, in Vietnam. The use of MPS is suitable for screening multiple variants, allowing for identifying rare pathogenic variants. The data from our study will inform policymakers in constructing cost-effective genetic metabolic carrier screening programmes., (© 2022 Gene Solutions. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

Vietnam has a high thalassemia burden. We collected blood samples from 5880 pregnant Vietnamese women during prenatal health checks to assess thalassemia carrier frequency using combined gap-polymerase chain reaction (gap-PCR) and targeted next-generation sequencing (NGS). Thalassemia carriers were identified with prevalence of 13.13% (772), including 7.82% (460) carriers of α-thalassemia (α-thal), 5.31% (312) carriers of β-thalassemia (β-thal), and 0.63% (37) concurrent α-/β-thal carriers. Deletional mutations (368) accounted for 80.0% of α-thal carriers, of which, -- SEA (Southeast Asian) ( n  = 254; 55.0%) was most prevalent, followed by the -α 3.7 (rightward) ( n  = 66; 14.0%) and -α 4.2 (leftward) ( n  = 45; 9.8%) deletions. Hb Westmead ( HBA2 : c.369C>G) ( n  = 53) and Hb Constant Spring (Hb CS or HBA2 : c.427T>C) (in 28) are the two most common nondeletional α-globin variants, accounting for 11.5 and 6.0% of α-thal carriers. We detected 11 different β-thal genotypes. Hb E ( HBB : c.79G>A) (in 211) accounted for 67.6% of β-thal carriers. The most common β-thal genotypes were associated with mutations at codon 17 (A>T) ( HBB : c.52A>T), codons 41/42 (-TTCT) ( HBB : c.126&#95;129delCTTT), and codon 71/72 (+A) ( HBB : c.217&#95;218insA) (prevalence 0.70%, 0.68%, and 0.2%, respectively). Based on mutation frequencies calculated in this study, estimates of 5021 babies in Vietnam are affected with clinically severe thalassemia annually. Our data suggest a higher thalassemia carrier frequency in Vietnam than previously reported. We established that combining NGS with gap-PCR creates an effective large-scale thalassemia screening method that can detect a broad range of mutations.

Rationale: Congenital bile acid synthesis defect (BASD) is a rare disease caused by mutations in the aldo-keto reductase 1D1 gene, which encodes the primary Δ4-3-oxosteroid 5β-reductase enzyme. Early disease diagnosis is critical for early treatment with bile acid replacement therapy, with an excellent chance for recovery. In contrast, protracted diagnosis and treatment may lead to poor outcomes, including decompensated hepatic cirrhosis, liver transplant, and even death., Patient Concerns: Three clinical congenital bile acid synthesis defect cases in the Vietnamese population are herein reported. These pediatric patients presented with symptoms of prolonged postpartum jaundice and abnormal loose stool (mucus, lipids, and white). The clinical examinations showed hepatosplenomegaly. Urinalysis showed a very low fraction of primary bile acids and atypical 3-oxo-Δ4- bile acids in all three patients., Diagnoses: The patients were diagnosed with primary Δ4-3-oxosteroid 5β-reductase deficiency. Next-generation gene sequencing revealed two homozygous mutations in the aldo-keto reductase family 1 member D1 gene. The first is a documented variant, c.797G>A (p.Arg266Gln), and the second is a novel mutation at c.155T>C (p.Ile52Thr)., Interventions: Immediately after diagnosis, patients were treated with oral chenodeoxycholate 5 mg/kg/d., Outcomes: The patients' symptoms, signs, and primary bile acids levels improved significantly., Lessons: Clinicians should consider genetic disorders related to cholestasis for effective and life-saving treatment. A prompt genetic analysis by next-generation gene sequencing enables patients to access bile acid replacement therapy earlier, significantly improving short- and long-term outcomes., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Hereditary cancer syndromes (HCS) are responsible for 5-10% of cancer cases. Genetic testing to identify pathogenic variants associated with cancer predisposition has not been routinely available in Vietnam. Consequently, the prevalence and genetic landscape of HCS remain unknown., Methods: 1165 Vietnamese individuals enrolled in genetic testing at our laboratory in 2020. We performed analysis of germline mutations in 17 high- and moderate- penetrance genes associated with HCS by next generation sequencing., Results: A total of 41 pathogenic variants in 11 genes were detected in 3.2% individuals. The carrier frequency was 4.2% in people with family or personal history of cancer and 2.6% in those without history. The percentage of mutation carriers for hereditary colorectal cancer syndromes was 1.3% and for hereditary breast and ovarian cancer syndrome was 1.6%. BRCA1 and BRCA2 mutations were the most prevalent with the positive rate of 1.3% in the general cohort and 5.1% in breast or ovarian cancer patients. Most of BRCA1 mutations located at the BRCA C-terminus domains and the top recurrent mutation was NM&#95;007294.3:c.5251C>T (p.Arg1751Ter). One novel variant NM&#95;000038.6(APC):c.6665C>A (p.Pro2222His) was found in a breast cancer patient with a strong family history of cancer. A case study of hereditary cancer syndrome was illustrated to highlight the importance of genetic testing., Conclusion: This is the first largest analysis of carrier frequency and mutation spectrum of HCS in Vietnam. The findings demonstrate the clinical significance of multigene panel testing to identify carriers and their at-risk relatives for better cancer surveillance and management strategies., Competing Interests: H-DN, NN, DD, VUT, HHN, ML, YN, HT, M-DP, HG, and LT are current employees of Gene Solutions, Vietnam. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Tran, Nguyen, Pham, Phan, Nguyen, Nguyen, Nguyen, Doan, Le, Nguyen, Jasmine, Nguyen, Nguyen, Nguyen, Do, Tran, Nguyen, Le, Nguyen, Do, Truong, Tang, Phan, Nguyen, Giang and Tu.)

To explore the effects of phenolic binding on the structure and activity of lotus root polysaccharides (LRPs), five LRP-phenol complexes containing catechin (61.22 mg/g), gallic acid (9.37 mg/g), ferulic acid (29.28 mg/g), chlorogenic acid (83.80 mg/g) or caffeic acid (14.80 mg/g) were prepared via noncovalent intermolecular interaction, respectively. The interaction was confirmed by the differences among LRPs, phenols and their complexes in ultraviolet-visible and Fourier-transform infrared spectra. The phenolic binding caused significant changes in the molecular weight (MW) distribution and aggregation behavior of LRPs, particularly their average MW (34.49 kDa) increased by 3.73-8.30 times. Compared to LRPs, the complexes all showed stronger antioxidant activities. Notably, the binding of catechin improved the macrophage-stimulating effect of LRPs, specifically promoting the NO production at normal condition and inhibiting the NO overproduction induced by lipopolysaccharide. The noncovalent interaction with phenolic compounds is a promising method for the structural and functional improvement of LRPs., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Accurate profiling of population-specific recessive diseases is essential for the design of cost-effective carrier screening programs. However, minority populations and ethnic groups, including Vietnamese, are still underrepresented in existing genetic studies. Here, we reported the first comprehensive study of recessive diseases in the Vietnamese population. Clinical exome sequencing data of 4503 disease-associated genes obtained from a cohort of 985 Vietnamese individuals was analyzed to identify pathogenic variants, associated diseases and their carrier frequencies in the population. A total of 118 recessive diseases associated with 164 pathogenic or likely pathogenic variants were identified, among which 28 diseases had carrier frequencies of at least 1% (1 in 100 individuals). Three diseases were prevalent in the Vietnamese population with carrier frequencies of 2-12 times higher than in the world populations, including beta-thalassemia (1 in 23), citrin deficiency (1 in 31), and phenylketonuria (1 in 40). Seven novel pathogenic and two likely pathogenic variants associated with nine recessive diseases were discovered. The comprehensive profile of recessive diseases identified in this study enables the design of cost-effective carrier screening programs specific to the Vietnamese population., (© 2021 Wiley Periodicals LLC.)

Objective: To evaluate whether cell-free DNA (cfDNA) testing could replace an invasive procedure in pregnancies with isolated fetal omphalocele. Study design: This was a retrospective study of all pregnancies with sonographically detected fetal omphalocele at three tertiary referral centers between 2012 and 2016. Invasive diagnostic testing was performed for genetic investigations using conventional karyotyping or chromosomal microarray. cfDNA testing was assumed to be offered to patients with isolated fetal omphalocele for screening for common aneuploidies. Results: Invasive genetic testing was performed in a total of 107 pregnancies with a fetal omphalocele. Abnormal karyotype was found in 66% (31/47) of nonisolated omphalocele cases and in 1.7% (1/60) of isolated omphalocele cases. No pathogenic copy number variations (CNVs) were detected in 59 cases with isolated omphalocele and normal karyotype. If cfDNA screening was used in cases with isolated omphalocele, the affected fetus with trisomy 18 would be detected, and no rare chromosomal aberrations or submicroscopic pathogenic CNVs would be missed. Conclusions: cfDNA testing could be recommended for prenatal genetic evaluation in pregnancies with isolated fetal omphalocele after thorough pretest counseling. Key Message: A very low percentage of aneuploidies and rare chromosomal/subchromosomal abnormalities are found in prenatal cases of isolated omphalocele. It seems that for pregnancies with isolated omphalocele, cfDNA testing represents an alternative for patients who choose to continue the pregnancies and are reluctant to undertake invasive diagnostic testing.

Objective: The aim of this study was to evaluate the utility of chromosomal microarray (CMA) in patients who were solely referred for molecular diagnosis. Methods: During a 2-year period, CMA was the patients' choice, whether to opt for it or not, for those at risk for fetal hemoglobin Bart's disease or β-thalassemia major who were referred for invasive prenatal diagnosis and had a normal fetal genotype. CytoScan 750 K array (Affymetrix Inc., Santa Clara, CA) was used for CMA. The CMA testing results were collected. Results: There were 184 patients, who had a normal genotypic result, opting CMA testing without an obvious indication for fetal karyotyping. The median maternal age was 29 years (range, 17-34); the median gestational age was 13 weeks (range, 11-20). In two out of 184 (1.1%) cases unexpected de novo pathogenic microdeletions were found: a 3.2 Mb 22q11.21 microdeletion and a 0.8 Mb 16p11.2 microdeletion. Conclusions: Pregnancies at risk for thalassemia can also benefit from performing CMA. This information might be a part of the contents in comprehensive pretest counseling for those who are referred for diagnostic testing due to a molecular disorder.

A series of new fluoro-substituted benzimidazole derivatives were designed, synthesized and pharmacologically evaluated. All the target compounds were characterized by 1 HNMR, 13 CNMR, mass spectra and elemental analysis. The biological evaluation showed that most of the synthesized compounds displayed nanomolar affinity to the angiotensin II type 1 (AT 1 ) receptor and could decrease blood pressure efficiently in spontaneously hypertensive rats. The maximal response of mean blood pressure (MBP) lowered 74.5 ± 3.5 mmHg (1g) and 69.2 ± 0.9 mmHg (2a) at 10 g/kg after oral administration, and the antihypertensive effect lasted beyond 24 h, which performed better than both losartan and telmisartan. So, compounds 1g and 2a may be considered as potential antihypertension drug candidates., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: The study was performed to estimate the diagnostic blood loss (DBL) volume during hospitalization and investigate its relationship with the development of moderate to severe hospital acquired anemia (HAA) and increased number of red blood cell (RBC) transfusion following extensive burns., Materials and Methods: This was a retrospective study of adult burned patients with total body surface area (TBSA) burn larger than 40%, who were admitted to burn center of Changhai hospital between January 2005 and December 2017., Results: We included a final number of 157 patients in the present study. Moderate to severe HAA within the fourth week postburn was developed in 46 of 121 patients who stayed over 28-day hospitalization. Patients with moderate to severe HAA had both significantly higher total DBL volume [245 (IQR: 183.75, 325.25) mL vs 168 (119, 163) mL ; P = 0.001] and DBL volume per day [10.22 (IQR: 8.57, 12.38) mL vs 6.63 (5.22, 10.42) mL/day; P = 0.005]. Logistic regression analysis revealed that both DBL volume per day and TBSA burn were independent risk factors for the development of moderate to severe HAA., Conclusions: Severely burned patients appear to be prone to develop HAA during hospitalization. The DBL volume contribute to the occurrence of moderate to severe HAA, which might be a modifiable target for preventing HAA., (Copyright © 2019 Elsevier Ltd and ISBI. All rights reserved.)

Complying with overall requirements of the government and regulations on public health emergencies, as well as the clinical features of diagnosis and treatment of oral diseases, this article reviews previous guidelines and studies on the infection control in dental practices in China and foreign countries. The emergency management protocol for the prevention and control of COVID-19 has been implemented in Nanjing Stomatological Hospital, which mainly focuses on the implementation of the training programs for dental staff and the infection control project in the hospital environment. This article could be used as a reference for rapid response and emergency management for the prevention and control of COVID-19 in the departments of stomatology.

Background: Sheath blight (SB), caused by Rhizoctonia solani, is a common rice disease worldwide. Currently, rice cultivars with robust resistance to R. solani are still lacking. To provide theoretic basis for molecular breeding of R. solani-resistant rice cultivars, the changes of transcriptome profiles in response to R. solani infection were compared between a moderate resistant cultivar (Yanhui-888, YH) and a susceptible cultivar (Jingang-30, JG)., Results: In the present study, 3085 differentially express genes (DEGs) were detected between the infected leaves and the control in JG, with 2853 DEGs in YH. A total of 4091 unigenes were significantly upregulated in YH than in JG before infection, while 3192 were significantly upregulated after infection. Further analysis revealed that YH and JG showed similar molecular responses to R. solani infection, but the responses were earlier in JG than in YH. Expression levels of trans-cinnamate 4-monooxygenase (C4H), ethylene-insensitive protein 2 (EIN2), transcriptome factor WRKY33 and the KEGG pathway plant-pathogen interaction were significantly affected by R. solani infection. More importantly, these components were all over-represented in YH cultivar than in JG cultivar before and/or after infection., Conclusions: These genes possibly contribute to the higher resistance of YH to R. solani than JG and were potential target genes to molecularly breed R. solani-resistant rice cultivar.

Objective: To investigate the value of texture analysis based on diffusion-weighted magnetic resonance imaging (DWI) in the differential diagnosis of atypically enhanced small hepatocellular carcinoma (sHCC) and dysplastic nodules (DNs) in liver cirrhosis. Methods: Data of 59 cases with atypical enhancement and solitary cirrhotic nodule (≤2 cm) confirmed by dynamic contrast enhanced MRI and surgical pathology specimen were analyzed retrospectively. Among them, 37 cases were of atypically enhanced sHCC and 22 cases of DNS. The DWI signal characteristics of the lesions were analyzed to measure the average apparent diffusion coefficient (ADC) value of the lesions, and the ADC ratio of the lesion to the liver parenchyma. MaZda software was used to manually draw the region of interest to extract the texture parameters of DWI lesions. The three sets (combination of Fisher coefficient, classification of error probability combined with average correlation coefficient and interactive information) were used to select the thirty optimal texture parameters. Raw data analysis (RDA), principal component analysis (PCA), linear discriminant analysis (LDA) and non-linear discriminant analysis (NDA) were performed for texture classification. The difference of ADC value and ADC ratio between sHCC and DNS group was compared by independent sample t-test, and χ2 test was used to compare the count data (or rate). ROC curve analysis was used to evaluate the diagnostic efficiency. Results: The sensitivity, specificity and accuracy of DWI high-signal in the identification of atypically enhanced sHCC and DNs were 94.6% (35/37), 68.2% (15/22), and 84.7% (50/59), respectively. The ADC ratio of atypically enhanced sHCC was significantly lower than DNs, and the difference was statistically significant ( t = 2.99, P = 0.002). The sensitivity, specificity, and accuracy for the diagnosis of atypically enhanced sHCC were 73.0% (27/37), 72.7% (16/22) and 72.9% (43/59), respectively. The sensitivity, specificity and accuracy of DWI texture analysis in diagnosing atypically enhanced sHCC were 94.6% (35/37), 95.5% (21/22) and 94.9% (56/59).The diagnostic efficiency of DWI texture analysis (AUC = 0.94) was significantly higher than DWI high-signal (AUC = 0.81) and ADC ratio (AUC = 0.72). Conclusion: The texture analysis based on DWI can identify atypically enhanced sHCC and dysplastic nodules under the background of cirrhosis, and its efficacy is better than qualitative and quantitative DWI.

Hyperthermic intraperitoneal chemotherapy (HIPEC) has a unique effect on the prevention and treatment of peritoneal metastasis from malignancies. Recently, the first prospective, multicenter, randomized controlled clinical trial of HIPEC to prevent the development of peritoneal metastasis after curative surgery for patients with locally advanced colon cancer was published in the " Lancet Gastroenterol Hepatol " (COLOPEC). Regrettably, no significant difference was observed in 18-month peritoneal metastasis-free survival between postoperative adjuvant HIPEC and standard systemic chemotherapy for patients with T4 stage or perforated colon cancer. However, we wonder whether we might achieve better outcomes by further optimizing the following issues: (1) We propose that the inclusion criteria for that trial may not be entirely reasonable, which included pT4N0-2M0 and perforation. Additionally, we found that 91% of patients underwent HIPEC 5-8 weeks after primary tumor resection. (2) The imbalance in starting time of postoperative systemic chemotherapy between the two groups may have a negative impact.(3) Nine patients with peritoneal metastasis preceding HIPEC might weaken the potential efficacy of HIPEC. (4) We wonder whether HIPEC using high-dese oxaliplatin (460 mg/m(2)) perfusing 30 minutes for one cycle is the optimal regimen. Therefore, we are planning to conduct a randomized controlled trial (HIPEC-06) in accordcance with the characteristics of Chinese patients, to explore the clinical efficacy of curative surgery combined with HIPEC in the treatment of cT4 colorectal cancer.

Bone marrow-derived mesenchymal stem cells differentiate into neurons under the induction of Schwann cells. However, key microRNAs and related pathways for differentiation remain unclear. This study screened and identified differentially expressed microRNAs in bone marrow-derived mesenchymal stem cells induced by Schwann cell-conditioned medium, and explored targets and related pathways involved in their differentiation into neuronal-like cells. Primary bone marrow-derived mesenchymal stem cells were isolated from femoral and tibial bones, while primary Schwann cells were isolated from bilateral saphenous nerves. Bone marrow-derived mesenchymal stem cells were cultured in unconditioned (control group) and Schwann cell-conditioned medium (bone marrow-derived mesenchymal stem cell + Schwann cell group). Neuronal differentiation of bone marrow-derived mesenchymal stem cells induced by Schwann cell-conditioned medium was observed by time-lapse imaging. Upon induction, the morphology of bone marrow-derived mesenchymal stem cells changed into a neural shape with neurites. Results of quantitative reverse transcription-polymerase chain reaction revealed that nestin mRNA expression was upregulated from 1 to 3 days and downregulated from 3 to 7 days in the bone marrow-derived mesenchymal stem cell + Schwann cell group. Compared with the control group, microtubule-associated protein 2 mRNA expression gradually increased from 1 to 7 days in the bone marrow-derived mesenchymal stem cell + Schwann cell group. After 7 days of induction, microRNA analysis identified 83 significantly differentially expressed microRNAs between the two groups. Gene Ontology analysis indicated enrichment of microRNA target genes for neuronal projection development, regulation of axonogenesis, and positive regulation of cell proliferation. Kyoto Encyclopedia of Genes and Genomes pathway analysis demonstrated that Hippo, Wnt, transforming growth factor-beta, and Hedgehog signaling pathways were potentially associated with neural differentiation of bone marrow-derived mesenchymal stem cells. This study, which carried out successful microRNA analysis of neuronal-like cells differentiated from bone marrow-derived mesenchymal stem cells by Schwann cell induction, revealed key microRNAs and pathways involved in neural differentiation of bone marrow-derived mesenchymal stem cells. All protocols were approved by the Animal Ethics Committee of Institute of Radiation Medicine, Chinese Academy of Medical Sciences on March 12, 2017 (approval number: DWLI-20170311)., Competing Interests: None

The aim of this study was to investigate pathway relationship of personality characteristics and alexithymic traits in OCD symptoms of obsession, and compulsive behavior of washing and checking. Two-hundred and seventy patients diagnosed with OCD were consecutively recruited from the psychiatric outpatient department of a teaching hospital. Structural equation modeling showed those more neurotic, less extraverted and with higher levels of alexithymia difficulty identifying feelings (DIF), difficulty describing feelings (DDF) and externally oriented thinking (EOT) were more likely to develop obsessive thoughts. Those less extraverted was more prone to develop washing compulsions, and those more neurotic were more likely to develop checking compulsions. EOT was the only alexithymic trait to have no gender difference within this group of patients with OCDs. The different personality and alexithymic trait pathways found between OCD obsession, washing and checking symptoms provide support that they may be different subtypes within the OCD diagnosis. Obsession was associated with washing, but not checking. Furthermore, no gender difference was found between the obsession and compulsive symptoms. Extraversion and neuroticism can be used to differentiate washing and checking, and alexithymia to differentiate washing and obsessions. This should be taken into consideration for intervention targeting patients with different OCD symptoms.

A Chinese family with δ-thalassemia (δ-thal) was found, in which the daughter is homozygous for δ-thal (HBD: c.-127T>C) with complete deficiency of Hb A 2 and the mother is a heterozygote with low level of Hb A 2 . The father, however, is a heterozygote with a normal Hb A 2 value due to coinheritance of a β-thalassemia (β-thal). Although no abnormal clinical or hematological findings were noted in the individuals with δ-thal, one should keep in mind that β-thal can be missed during routine preliminary screening when β-thal and δ-thal coexist in a subject.

The FOXO6 correlated with tumor progression in a wide range of carcinomas, yet little is known in gastric cancer. The expression of FOXO6 and matrix metallopeptidase 9 (MMP-9) was assessed by immunohistochemistry in 192 gastric carcinoma specimens. The correlation between FOXO6 expression with MMP-9, clinicopathological/prognostic value in gastric cancer was examined. FOXO6 overexpression was significantly associated with depth of invasion, lymph node metastasis and stage of disease. In univariate and multivariate analyses, FOXO6 was an independent prognostic factor for both overall survival (OS) and recurrence-free survival (RFS). Moreover, FOXO6 over-expression was correlated with poor prognosis in patients subgroups stratified by tumor size, depth of invasion and lymph node metastasis. FOXO6 expression was increased in both prominent serosal invasion group and lymph node metastasis group. In addition, FOXO6 expression was positively correlated with MMP-9 among 192 gastric cancer tissues. Patients with FOXO6 over-expression had poor OS and shorter RFS in low and high invasiveness groups. Furthermore, stratified analysis showed that the TNM stage I patients with high FOXO6 expression had poor prognosis than those with low FOXO6 expression. In conclusion, FOXO6 overexpression promotes tumor aggressiveness and prognosis, and could be a promising target for prognostic prediction in gastric cancer patients., Condensed Abstract: The aim of this study was to analyze the role of FOXO6 in patients with gastric carcinoma. FOXO6 may play an important role on tumor invasion, metastasis and prognosis. It may also serve as a novel target for prognostic prediction.