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Background De novo variations are a primary cause of Rett syndrome and Tubulinopathy, accounting for over 90% of cases. Some studies have identified and documented parental inheritance by mosaicism in these two disorders, albeit with limited data. Methods Clinical characteristics and diagnosis, including genetic tests of members of two families, were obtained from medical reports. Results The first family with Rett syndrome (RTT) presented with two offspring carrying FOXG1 c.460dup. Both affected RTT pregnancies did not show anomalies within the first trimester, preventing prenatal recognition at an early stage. The second family had two of three offspring confirmed with TUBA1A c.172G>A related to Tubulinopathy. Both young couples from the two families harbored none of the variants correlating to their children's conditions. Diagnosis of parental mosaics with higher rates of recurrence was reasonably determined, and genetic counseling played a major role in guiding and managing their subsequent pregnancies. Conclusion In genetic disorders with a high penetration of de novo variants, the risk of having a recurrent baby is an important topic to discuss with affected families. By examining variants that siblings share, clinical diagnosis can offer valuable information about the presence of mosaic inheritance. To effectively manage in the long term, adequate genetic counseling and strategic planning for future pregnancies should be emphasized to mitigate the risk of recurrent offspring.

This study aimed to measure the associations between different inflammatory factors, namely interleukin (IL)-17A, tumor necrosis factor (TNF)-α, and high-sensitivity C-reactive protein (hs-CRP), and atherosclerosis in patients with psoriasis vulgaris. A cross-sectional study was conducted at two hospitals in Hanoi, Vietnam. A total of 125 patients with psoriasis vulgaris and 50 healthy controls were recruited. Clinical characteristics and atherosclerosis were assessed. IL-17A, TNF-α, and hs-CRP levels were measured. Psoriasis vulgaris patients with atherosclerosis had higher levels of hs-CRP (median = 1.22; interquartile range-IQR = 0.34-12.11) and IL-17A (median = 1.30; IQR = 0.43-4.28), but a lower level of TNF-α (median = 0.54; IQR = 0.13-3.41) compared to those without atherosclerosis (  < 0.05). Only LogIL-17A was positively related to atherosclerosis in psoriasis patients (Odds Ratio-OR = 2.16, 95% CI = 1.06-4.38,  < 0.05). After excluding systemically treated patients, LogIL-17A and Log TNF-α were associated with the likelihood of atherosclerosis (  < 0.05). This study suggests a link between elevated levels of IL-17A and TNF-α and subclinical atherosclerosis. Further investigation on a larger scale is required to establish the causality of this relationship.

Abstract Purpose 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 under-represented in existing genetic studies. Here we reported the first comprehensive study of recessive diseases in the Vietnamese population. Methods Clinical exome sequencing (CES) data of 4,503 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. Results Eighty-five recessive diseases were identified in the Vietnamese population, among which seventeen diseases had carrier frequencies of at least 1% (1 in 100 individuals). Three diseases were especially prevalent in the Vietnamese population with carrier frequencies of 2-12 times higher than in other East Asia or the world populations, including Beta-thalassemia (1 in 25), citrin deficiency (1 in 33) and phenylketonuria (1 in 40). Seven novel pathogenic and three likely pathogenic variants associated with nine recessive diseases were also discovered. Conclusions The comprehensive profile of recessive diseases identified in this study shall enable the design of cost-effective carrier screening programs specific to the Vietnamese population. The newly discovered pathogenic variants may also exist in other populations at extremely low frequencies, thus representing a valuable resource for future research. Our study has demonstrated the advantage of population-specific genetic studies to advance the knowledge and practice of medical genetics. Competing Interest Statement This study was funded by Gene Solutions, Vietnam. The funder did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. NHT, HST, HTN, LPD, NMP, KHTN, HDLN, MTTQ, TPTN, VUT, PTCN, HG and MDP are current employees of Gene Solutions, Vietnam. The other authors declare no competing interests. Footnotes * The corresponding author has been changed to Ngoc Hieu Tran (the first author). Supplementary Tables S1-S5 have been added.

Studies of successive vaccination suggest that immunological memory against past influenza viruses may limit responses to vaccines containing current strains. The impact of memory induced by prior infection is rarely considered and is difficult to ascertain, because infections are often subclinical. This study investigated influenza vaccination among adults from the Ha Nam cohort (Vietnam), who were purposefully selected to include 72 with and 28 without documented influenza A(H3N2) infection during the preceding 9 years (Australian New Zealand Clinical Trials Registry 12621000110886). The primary outcome was the effect of prior influenza A(H3N2) infection on hemagglutinin-inhibiting antibody responses induced by a locally available influenza vaccine administered in November 2016. Baseline and postvaccination sera were titrated against 40 influenza A(H3N2) strains spanning 1968–2018. At each time point (baseline, day 14 and day 280), geometric mean antibody titers against 2008–2018 strains were higher among participants with recent infection (34 (29–40), 187 (154–227) and 86 (72–103)) than among participants without recent infection (19 (17–22), 91 (64–130) and 38 (30–49)). On days 14 and 280, mean titer rises against 2014–2018 strains were 6.1-fold (5.0- to 7.4-fold) and 2.6-fold (2.2- to 3.1-fold) for participants with recent infection versus 4.8-fold (3.5- to 6.7-fold) and 1.9-fold (1.5- to 2.3-fold) for those without. One of 72 vaccinees with recent infection versus 4 of 28 without developed symptomatic A(H3N2) infection in the season after vaccination ( P  = 0.021). The range of A(H3N2) viruses recognized by vaccine-induced antibodies was associated with the prior infection strain. These results suggest that recall of immunological memory induced by prior infection enhances antibody responses to inactivated influenza vaccine and is important to attain protective antibody titers. Recent prior influenza A infection is associated with elevated hemagglutinin-inhibiting antibody responses and greater breadth of reactivity to influenza strains following vaccination, suggesting that infection history boosts vaccine responses.

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.

Background Late detection of hepatocellular carcinoma (HCC) results in an overall 5-year survival rate of less than 16%. Liquid biopsy (LB) assays based on detecting circulating tumor DNA (ctDNA) might provide an opportunity to detect HCC early noninvasively. Increasing evidence indicates that ctDNA detection using mutation-based assays is significantly challenged by the abundance of white blood cell-derived mutations, non-tumor tissue-derived somatic mutations in plasma, and the mutational tumor heterogeneity. Methods Here, we employed concurrent analysis of cancer-related mutations, and their fragment length profiles to differentiate mutations from different sources. To distinguish persons with HCC (PwHCC) from healthy participants, we built a classification model using three fragmentomic features of ctDNA through deep sequencing of thirteen genes associated with HCC. Results Our model achieved an area under the curve (AUC) of 0.88, a sensitivity of 89%, and a specificity of 82% in the discovery cohort consisting of 55 PwHCC and 55 healthy participants. In an independent validation cohort of 54 PwHCC and 53 healthy participants, the established model achieved comparable classification performance with an AUC of 0.86 and yielded a sensitivity and specificity of 81%. Conclusions Our study provides a rationale for subsequent clinical evaluation of our assay performance in a large-scale prospective study.

Community acquired K. pneumoniae pneumonia is still common in Asia and is reportedly associated with alcohol use. Oropharyngeal carriage of K. pneumoniae could potentially play a role in the pathogenesis of K. pneumoniae pneumonia. However, little is known regarding K. pneumoniae oropharyngeal carriage rates and risk factors. This population-based cross-sectional study explores the association of a variety of demographic and socioeconomic factors, as well as alcohol consumption with oropharyngeal carriage of K. pneumoniae in Vietnam. 1029 subjects were selected randomly from age, sex, and urban and rural strata. An additional 613 adult men from a rural environment were recruited and analyzed separately to determine the effects of alcohol consumption. Demographic, socioeconomic, and oropharyngeal carriage data was acquired for each subject. The overall carriage rate of K. pneumoniae was 14.1% (145/1029, 95% CI 12.0%-16.2%). By stepwise logistic regression, K. pneumoniae carriage was found to be independently associated with age (OR 1.03, 95% CI 1.02-1.04), smoking (OR 1.9, 95% CI 1.3-2.9), rural living location (OR 1.6, 95% CI 1.1-2.4), and level of weekly alcohol consumption (OR 1.7, 95% CI 1.04-2.8). Moderate to heavy weekly alcohol consumption, old age, smoking, and living in a rural location are all found to be associated with an increased risk of K. pneumoniae carriage in Vietnamese communities. Whether K. pneumoniae carriage is a risk factor for pneumonia needs to be elucidated.

Drug-related problems (DRPs) are common in clinical practice and occur at all stages of the medication process. The major factor contributing to DRPs is prescription, although patients' poor adherence to treatment is also a significant factor. This study evaluated type 2 diabetes outpatients in a hospital in Vietnam for drug-related problems (DRPs) and related variables. A cross-sectional descriptive study was conducted on 495 outpatients who met the criteria and 157 people agreed to participate in the interview. Medication order review and medication adherence review were used to identify DRPs. The types of DRP were based on the Pharmaceutical Care Network Europe (PCNE) categories version 9.0. The identification and assessment DRPs were carried out by clinical pharmacists and get agreed upon by physicians who had not directly prescribed patients who participated in the study. A total of 762 DRPs were identified via prescribing review process, the average number of DRP on each prescription was 1.54±1.07, while 412 DRPs were determined through patient interviewing. The most frequent DRPs were \"ADR (Adverse Drug Reaction) occurring\" (68.8%). The main causes were \"patient is unable to understand instructions properly\" or \"patient is not properly instructed\", \"patient stores insulin inappropriately\", \"patient decides to use unnecessary drugs\" and \"patient intentionally uses/takes less drug than prescribed or does not take the drug at all for whatever reason\" which accounted for 65.0%, 41.4%, 38.2%, and 28.7%, respectively. From the prescribing review, the most observed DRPs were \"Inappropriate drug according to guidelines/formulary\" and \"No or incomplete drug treatment in spite of existing indication\", accounting for 45.0% and 42.9%, respectively. There was a significant association between age (OR 3.38, 95% CI: 1.01-11.30), duration of diabetes (OR 3.61, 95%CI: 1.11-11.74), presence of comorbidity (OR 5.31, 95%CI: 1.97-14.30), polypharmacy (OR: 2.95, 95%CI: 1.01-8.72) and DRPs. In patients, poor knowledge of antidiabetic agents was the main reason to lack adherence and occurring ADR (OR 2.73, 95%CI: 1.32-5.66, p = 0.007 and OR 2.49, 95%CI: 1.54-4.03, p = 0.001 respectively). DRPs occurred in the prescribing stage and relating to patient's behavior of drug administration was high. Clear identification of DRPs and the associated factors are essential for building the intervention process to improve effectiveness and safety in the treatment of type 2 diabetes mellitus patients.

Background Breast cancer (BC) remains the second leading cause of cancer-related mortality among women worldwide. Liquid biopsy based on circulating tumor DNA (ctDNA) offers a promising noninvasive approach for early detection; however, differentiating malignant tumors from benign abnormalities remains a significant challenge. Results Here, we developed a multimodal approach to analyze cfDNA methylation and fragmentomic patterns in 273 BC patients, 108 individuals with benign breast conditions, and 134 healthy controls. Genome-wide analyses revealed distinct cfDNA copy number alterations and cytosine-enriched cleavage sites in BC patients. Targeted sequencing further revealed unique methylation patterns, including hypermethylation in GPR126 , KLF3 , and TLR10 and hypomethylation in TOP1 and MAFB . Our machine-learning model achieved an AUC of 0.90, with 93.6% specificity and 62.1–66.3% sensitivity for stage I–II cancers. In symptomatic populations, sensitivities were 50.0%, 68.2%, and 64.7% for BI-RADS categories 3, 4, and 5, respectively, with 96.1% specificity. Conclusions These findings underscore the potential of cfDNA biomarkers to enhance BC detection and reduce the rate of unnecessary biopsies.

WHO recommends treating hepatitis C infection with one of three antiviral combinations for 8–12 weeks. No randomised trials have compared these regimens, and high cure rates might be achievable with shorter durations of therapy. We aimed to compare sofosbuvir–daclatasvir with sofosbuvir–velpatasvir, and to evaluate potential novel treatment strategies. We conducted a multi-arm, open-label, randomised controlled non-inferiority trial in two public hospitals in Viet Nam. Adults (aged ≥18 years) with chronic hepatitis C infection and mild-to-moderate liver fibrosis were eligible. Recruitment was stratified by centre and viral genotype (1–5 vs 6) with 1:1 random allocation to an oral fixed-dose combination of sofosbuvir 400 mg plus daclatasvir 60 mg (sofosbuvir–daclatasvir) or sofosbuvir 400 mg plus velpatasvir 100 mg (sofosbuvir–velpatasvir). Participants were simultaneously factorially randomly assigned to one of four treatment strategies: 12 weeks’ standard of care (SOC); 4 weeks’ therapy with four weekly PEGylated interferon alfa-2a subcutaneous injections; induction and maintenance therapy with 2 weeks’ standard therapy followed by 10 weeks’ therapy 5 days a week; and response-guided therapy (RGT) for 4, 8, or 12 weeks determined by viral load on day 7. The primary outcome was sustained virological response (SVR) 12 weeks after treatment completion, analysed in all evaluable participants regardless of actual treatment received. We chose a 5% non-inferiority margin for the drug comparison, and a 10% non-inferiority margin for the treatment strategy comparisons. Safety was assessed in all randomised participants. This trial is registered with ISRCTN, 61522291, and is completed. Between June 19, 2020, and May 10, 2023, 624 participants were randomised (470 [75%] were male and 154 [25%] were female). 296 (47%) had genotype 6 and 328 (53%) had genotypes 1–5. The primary outcome was assessable in 609 (98%) participants. SVR occurred in 294 (97%) of 302 participants in the sofosbuvir–daclatasvir group and 292 (95%) of 307 participants in the sofosbuvir–velpatasvir group (risk difference 2·2%, 90% credible interval [CrI] –0·2 to 4·8, within the 5% non-inferiority margin; 93% probability that sofosbuvir–daclatasvir is superior to sofosbuvir–velpatasvir). SVR occurred in 148 (99%) of 150 in the SOC group, 143 (94%) of 152 in the 4-week antiviral plus interferon group (–4·5%, 90% CrI –8·3 to –1·3), 151 (99%) of 152 in the induction–maintenance group (0·6%, –1·1 to 2·7), and 144 (93%) of 155 in the RGT group (–5·7%, –9·6 to –2·3); all risk differences were within the 10% non-inferiority margin. Serious adverse events were rare (11 [4%] of 313 participants in the sofosbuvir–velpatasvir group vs six [2%] of 311 in the sofosbuvir–daclatasvir group; risk difference –1·6% [95% CrI –4·2 to 0·8]) with no evidence of differences between regimens or strategies, but adverse reactions were very common in the 4-week antiviral plus interferon group compared with the other treatment strategies (risk difference vs SOC group, 66·8% [59·2 to 74·0]; p<0·0001). Sofosbuvir–daclatasvir was non-inferior to sofosbuvir–velpatasvir. High efficacy was seen with novel strategies, which might help to inform approaches to treatment for harder-to-reach populations. Wellcome Trust.