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BackgroundOver the recent decades, Vietnam has attained remarkable achievements in all areas of health care. However, shortcomings including health disparities persist particularly with a rapidly aging population. This has resulted in a shift in the disease burden from communicable to noncommunicable diseases such as dementia, cancer, and diabetes. These medical conditions require long-term care, which causes an accelerating crisis for the health sector and society. The current health care system in Vietnam is unlikely to cope with these challenges. ObjectiveThe aim of this paper was to explore the opportunities, challenges, and necessary conditions for Vietnam in transforming toward a patient-centered care model to produce better health for people and reduce health care costs. MethodsWe examine the applicability of a personalized and integrated Bespoke Health Care System (BHS) for Vietnam using a strength, weakness, opportunity, and threat analysis and examining the successes or failures of digital health care innovations in Vietnam. We then make suggestions for successful adoption of the BHS model in Vietnam. ResultsThe BHS model of patient-centered care empowers patients to become active participants in their own health care. Vietnam’s current policy, social, technological, and economic environment favors the transition of its health care system toward the BHS model. Nevertheless, the country is in an early stage of health care digitalization. The legal and regulatory system to protect patient privacy and information security is still lacking. The readiness to implement electronic medical records, a core element of the BHS, varies across health providers and clinical practices. The scarcity of empirical evidence and evaluation regarding the effectiveness and sustainability of digital health initiatives is an obstacle to the Vietnamese government in policymaking, development, and implementation of health care digitalization. ConclusionsImplementing a personalized and integrated health care system may help Vietnam to address health care needs, reduce pressure on the health care system and society, improve health care delivery, and promote health equity. However, in order to adopt the patient-centered care system and digitalized health care, a whole-system approach in transformation and operation with a co-design in the whole span of a digital health initiative developing process are necessary.

Congenital heart disease (CHD) affecting the conotruncal region of the heart, occurs in 40-50% of patients with 22q11.2 deletion syndrome (22q11.2DS). This syndrome is a rare disorder with relative genetic homogeneity that can facilitate identification of genetic modifiers. Haploinsufficiency of TBX1, encoding a T-box transcription factor, is one of the main genes responsible for the etiology of the syndrome. We suggest that genetic modifiers of conotruncal defects in patients with 22q11.2DS may be in the TBX1 gene network. To identify genetic modifiers, we analyzed rare, predicted damaging variants in whole genome sequence of 456 cases with conotruncal defects and 537 controls, with 22q11.2DS. We then performed gene set approaches and identified chromatin regulatory genes as modifiers. Chromatin genes with recurrent damaging variants include EP400, KAT6A, KMT2C, KMT2D, NSD1, CHD7 and PHF21A. In total, we identified 37 chromatin regulatory genes, that may increase risk for conotruncal heart defects in 8.5% of 22q11.2DS cases. Many of these genes were identified as risk factors for sporadic CHD in the general population. These genes are co-expressed in cardiac progenitor cells with TBX1, suggesting that they may be in the same genetic network. The genes KAT6A, KMT2C, CHD7 and EZH2, have been previously shown to genetically interact with TBX1 in mouse models. Our findings indicate that disturbance of chromatin regulatory genes impact the TBX1 gene network serving as genetic modifiers of 22q11.2DS and sporadic CHD, suggesting that there are some shared mechanisms involving the TBX1 gene network in the etiology of CHD.

Schizophrenia occurs in about one in four individuals with 22q11.2 deletion syndrome (22q11.2DS). The aim of this International Brain and Behavior 22q11.2DS Consortium (IBBC) study was to identify genetic factors that contribute to schizophrenia, in addition to the ~20-fold increased risk conveyed by the 22q11.2 deletion. Using whole-genome sequencing data from 519 unrelated individuals with 22q11.2DS, we conducted genome-wide comparisons of common and rare variants between those with schizophrenia and those with no psychotic disorder at age ≥25 years. Available microarray data enabled direct comparison of polygenic risk for schizophrenia between 22q11.2DS and independent population samples with no 22q11.2 deletion, with and without schizophrenia (total n = 35,182). Polygenic risk for schizophrenia within 22q11.2DS was significantly greater for those with schizophrenia (padj = 6.73 × 10-6). Novel reciprocal case-control comparisons between the 22q11.2DS and population-based cohorts showed that polygenic risk score was significantly greater in individuals with psychotic illness, regardless of the presence of the 22q11.2 deletion. Within the 22q11.2DS cohort, results of gene-set analyses showed some support for rare variants affecting synaptic genes. No common or rare variants within the 22q11.2 deletion region were significantly associated with schizophrenia. These findings suggest that in addition to the deletion conferring a greatly increased risk to schizophrenia, the risk is higher when the 22q11.2 deletion and common polygenic risk factors that contribute to schizophrenia in the general population are both present.

The 22q11.2 deletion syndrome (22q11.2DS) results from non-allelic homologous recombination between low-copy repeats termed LCR22. About 60%-70% of individuals with the typical 3 megabase (Mb) deletion from LCR22A-D have congenital heart disease, mostly of the conotruncal type (CTD), whereas others have normal cardiac anatomy. In this study, we tested whether variants in the hemizygous LCR22A-D region are associated with risk for CTDs on the basis of the sequence of the 22q11.2 region from 1,053 22q11.2DS individuals. We found a significant association (FDR p < 0.05) of the CTD subset with 62 common variants in a single linkage disequilibrium (LD) block in a 350 kb interval harboring CRKL. A total of 45 of the 62 variants were associated with increased risk for CTDs (odds ratio [OR) ranges: 1.64-4.75). Associations of four variants were replicated in a meta-analysis of three genome-wide association studies of CTDs in affected individuals without 22q11.2DS. One of the replicated variants, rs178252, is located in an open chromatin region and resides in the double-elite enhancer, GH22J020947, that is predicted to regulate CRKL (CRK-like proto-oncogene, cytoplasmic adaptor) expression. Approximately 23% of patients with nested LCR22C-D deletions have CTDs, and inactivation of Crkl in mice causes CTDs, thus implicating this gene as a modifier. Rs178252 and rs6004160 are expression quantitative trait loci (eQTLs) of CRKL. Furthermore, set-based tests identified an enhancer that is predicted to target CRKL and is significantly associated with CTD risk (GH22J020946, sequence kernal association test (SKAT) p = 7.21 × 10-5) in the 22q11.2DS cohort. These findings suggest that variance in CTD penetrance in the 22q11.2DS population can be explained in part by variants affecting CRKL expression.

In this article, we investigate the task of normalizing transcribed texts in Vietnamese Automatic Speech Recognition (ASR) systems in order to improve user readability and the performance of downstream tasks. This task usually consists of two main sub-tasks: predicting and inserting punctuation (i.e., period, comma); and detecting and standardizing named entities (i.e., numbers, person names) from spoken forms to their appropriate written forms. To achieve these goals, we introduce a complete corpus including of 87,700 sentences and investigate conditional joint learning approaches which globally optimize two sub-tasks simultaneously. The experimental results are quite promising. Overall, the proposed architecture outperformed the conventional architecture which trains individual models on the two sub-tasks separately. The joint models are furthered improved when integrated with the surrounding contexts (SCs). Specifically, we obtained 81.13% for the first sub-task and 94.41% for the second sub-task in the F1 scores using the best model. [ABSTRACT FROM AUTHOR]

Background: Vietnam is experiencing an increasing prevalence of hypertension in its adult population. In addition to medical therapy, modifying adverse lifestyle practices is important for effective blood pressure control. There are limited data on unhealthy lifestyle practices in patients with chronic diseases, however, particularly among hypertensive patients living in rural Vietnam. Our study objectives were to examine the prevalence of unhealthy lifestyle practices and associated factors among rural Vietnamese adults with uncontrolled hypertension. Methods: Data from the baseline survey of a cluster randomized trial among hypertensive Vietnamese adults (2017–2022) were utilized. Information on unhealthy lifestyle practices including smoking, excessive alcohol consumption, physical inactivity, and inadequate fruit and vegetable intake was collected from study participants. The primary study outcome was having ≥2 unhealthy lifestyle practices. A multivariable logistic regression model was used to examine factors associated with the primary study outcome. Results: The mean age of the 671 patients was 67 years and 45.0% were men. Nearly three out of every four participants had one or fewer unhealthy practices, 24.0% had two, and 3.3% had three or all four unhealthy lifestyle practices. Men, individuals who did unpaid work or were unemployed, and individuals with hypertension level III were more likely to have ≥2 unhealthy lifestyle practices, whereas individuals with higher education were less likely to have ≥2 unhealthy lifestyle practices compared with respective comparison groups. Conclusions: We observed a high prevalence of unhealthy lifestyle practices among rural Vietnamese patients with uncontrolled hypertension. Several demographic factors were associated with a greater number of unhealthy lifestyle practices. Newer interventions and educational programs encouraging lifestyle modification practices are needed to control hypertension among adults living in rural settings of Vietnam. [ABSTRACT FROM AUTHOR]

Background: In Vietnam, trastuzumab is included in social health insurance's benefits package with a reimbursement rate of 60%, but policymakers have been concerned about its cost-effectiveness. The research aims to evaluate the cost-effectiveness of one-year adjuvant trastuzumab therapy for early-stage breast cancer patients with human epidermal growth receptor 2 (HER2+) from a societal perspective. Method: A Markov model was developed and validated to estimate the lifetime cost and effectiveness (using life year and quality-adjusted life year) of one-year adjuvant trastuzumab therapy compared to chemotherapy (using paclitaxel) alone. Treatment efficacy and transition probabilities were estimated based on published trials (i.e., N9831, NSABP B-31, HERA, and BCIRG 006). Local cost and utility data were employed to capture the Vietnam context. One-way sensitivity analysis, probabilistic sensitivity analysis, threshold, and scenario analysis were also performed. Results: One-year adjuvant trastuzumab therapy combined with chemotherapy compared to chemotherapy alone yielded an additional cost of 888,453,971VND (39,062 US$) with an additional 3.09 LYs and 1.61 QALYs, resulting in an ICER of 287,390,682 VND (12,635 US$) per LY gained, or 519,616,972 VND (22,845 US$) per QALY gained. The ICER exceeds the cost-effective threshold of 1- and 3-time GDP per capita by 6.3 and 2.1 times. The probabilistic sensitivity analysis shows similar results. According to one-way sensitivity analysis, ICERs were driven mainly by transition probabilities and trastuzumab price. One-year adjuvant trastuzumab therapy would be cost-effective at the 3-time GDP per capita threshold if the cost of Herceptin 150mg and 450mg vials were reduced by 56% and 54%, correspondingly. Conclusion: In Vietnam, one-year adjuvant trastuzumab therapy for early-stage breast cancer with HER2+ is not cost-effective. The research provided reliable and updated evidence to support policymakers in revising the health insurance benefit package. The policymakers should consider the options to reduce the cost of trastuzumab (e.g., regarding the use of trastuzumab biosimilars, price negotiation options, and options of optimizing the use of Herceptin vials among concurrent hospitalized breast cancer patients). [ABSTRACT FROM AUTHOR]

Platelets assume a pivotal role in the cardiovascular diseases (CVDs). Thus, targeting platelet activation is imperative for mitigating CVDs. Ginkgetin (GK), from Ginkgo biloba L, renowned for its anticancer and neuroprotective properties, remains unexplored concerning its impact on platelet activation, particularly in humans. In this investigation, we delved into the intricate mechanisms through which GK influences human platelets. At low concentrations (0.5–1 μM), GK exhibited robust inhibition of collagen and arachidonic acid (AA)‐induced platelet aggregation. Intriguingly, thrombin and U46619 remained impervious to GK's influence. GK's modulatory effect extended to ATP release, P‐selectin expression, intracellular calcium ([Ca2+]i) levels and thromboxane A2 formation. It significantly curtailed the activation of various signaling cascades, encompassing phospholipase Cγ2 (PLCγ2)/protein kinase C (PKC), phosphoinositide 3‐kinase/Akt/glycogen synthase kinase‐3β and mitogen‐activated protein kinases. GK's antiplatelet effect was not reversed by SQ22536 (an adenylate cyclase inhibitor) or ODQ (a guanylate cyclase inhibitor), and GK had no effect on the phosphorylation of vasodilator‐stimulated phosphoproteinSer157 or Ser239. Moreover, neither cyclic AMP nor cyclic GMP levels were significantly increased after GK treatment. In mouse studies, GK notably extended occlusion time in mesenteric vessels, while sparing bleeding time. In conclusion, GK's profound impact on platelet activation, achieved through inhibiting PLCγ2–PKC cascade, culminates in the suppression of downstream signaling and, ultimately, the inhibition of platelet aggregation. These findings underscore the promising therapeutic potential of GK in the CVDs. [ABSTRACT FROM AUTHOR]

This study examines the income effect on health spending and health behaviors in Vietnam. We measure income shock by lottery prizes, controlling for spending on the lottery. Lottery prizes have no significant effect on the healthcare utilization of individuals. However, we find that lottery winnings result in a significant increase in spending on healthcare. A 1% increase in lottery winnings results in a 0.08% increase in expenditure on medicine and a 0.09% increase in the total amount individuals spend on healthcare. The effect on expenditure on healthcare tends to be larger for older people. A concern with increased income is the unexpected effect on risky health behaviors, such as smoking and drinking. In this study, we do not find that lottery prizes lead to greater spending on tobacco and alcohol. [ABSTRACT FROM AUTHOR]

Implementing violence prevention programs has become a priority for schools; however, most programs used for this purpose are limited in the skills they teach. In this study, two different resiliency building/violence prevention models were evaluated to assess their effectiveness at preventing violent and maladaptive behaviors in youth. Data from the California Healthy Kids Survey (CHKS) was used to compare a narrow versus a comprehensive/ecological approach for resiliency building. Structural equation modeling was employed to test the preventive impact of both resiliency building approaches. The results showed that the comprehensive/ecological approach is much stronger than the traditional narrow approach for preventing violent and maladaptive behaviors. Implications for program development and implementation are discussed.

Accounting has been faced with a severe shortage in the supply of qualified doctoral faculty. Drawing upon the international mobility of foreign scholars and the spirit of the international medical graduate program, this article suggests a model to fill the demand in accounting doctoral faculty. The underlying assumption of the suggested model is that there is enough qualified international accounting doctoral scholars who are willing to work in the United States because of natural and artificial benefits, such as the existence of national innovation, knowledge-intensive clusters system, favorable working conditions, and career and earning prospects. A 10-week International Accounting Post-Doctoral Program (IAPDP) is designed to prepare academically competent international accounting faculty to be qualified to work in the United States at AACSB International-accredited institutions. A survey was employed to examine the viability of the proposed model. Our results indicate that qualified international accounting doctoral scholars are interested in the suggested model and the nondoctoral U.S. accounting programs will represent the major job market for these IAPDP graduates. This article should be of interest to accounting educators, business schools, the American Institute of Certified Public Accountants (AICPA), the Association to Advance Collegiate Schools of Business (AACSB) International, and the American Accounting Association (AAA).

A survey study was conducted to examine teachers' knowledge, perceptions, and practices regarding social and emotional learning (SEL) in the classroom. Teachers from two states (N = 263) provided a range of responses regarding how to promote SEL in their classrooms, increase the effectiveness of SEL, and reduce barriers to implementation. Results indicated that many teachers believe that SEL is important, schools should take an active role, receiving training/support from a variety of professionals would be helpful, and current academic demands decrease the opportunity for SEL. In addition to broadening the very limited research in this area, this study provides important new information regarding teachers' knowledge and practices of SEL in classrooms. This information is useful to school psychologists, other specialists, and administrators in helping set the stage for establishing social-emotional learning practices in schools. (Contains 6 tables.)

This article describes the results of three pilot studies that were conducted to evaluate the recently developed "Strong Kids" and "Strong Teens" social-emotional learning programs in increasing students' knowledge of healthy social-emotional behavior and decreasing their symptoms of negative affect and emotional distress. The first study included 120 middle school students (in grade 5) from a general education student population. The second study included 65 general education students in grades 7-8. The third study included 14 high school students (grades 9-12) from a regional special education high school, who were identified as having emotional disturbance. The three groups participated in either the "Strong Kids" (groups 1 and 2) or "Strong Teens" (group 3) programs, receiving one-hour lessons and associated assignments once a week for 12 weeks. Social-emotional knowledge and negative emotional symptoms of participants were assessed using brief self-report measures, in pretest-posttest intervention designs. All three studies showed that, following participation in the respective programs, students evidenced statistically significant and clinically meaningful changes in desired directions on the target variables. Implications for future research are discussed, as is the importance of social and emotional learning as a prevention and intervention strategy to promote mental health among students in schools. (Contains 1 table.)

There is limited research on the relationship between adolescent smoking and related social and psychological factors, but it is known that adolescent tobacco users are at higher risk for behavioral disorders and substance abuse. Of great interest to those who work in youth tobacco prevention is expanding knowledge about those factors that lead to tobacco use as well as about those that may buffer against its use. This study examined protective factors and personal strengths in 386 adolescents as part of a high school Tobacco Use Prevention Education (TUPE) program funded by the California Department of Education. Multivariate analysis indicated a significant relationship between gender, smoking status, and personal strengths with smokers having lower levels of personal strengths. It is suggested that cessation programs consider smoking within the context of youths' personal assets and their social support networks. School support services professionals can contribute to youth tobacco prevention efforts by attending to smoking behavior and its correlates when they are involved in assessments, consultation, or direct counseling with students. (Contains 3 tables.)

Summary Protein kinases are a family of signaling proteins, crucial for maintaining cellular homeostasis. When dysregulated, kinases drive the pathogenesis of several diseases, and are thus one of the largest target categories for drug discovery. Kinase activity is tightly controlled by switching through several active and inactive conformations in their catalytic domain. Kinase inhibitors have been designed to engage kinases in specific conformational states, where each conformation presents a unique physico-chemical environment for therapeutic intervention. Thus, modeling kinases across conformations can enable the design of novel and optimally selective kinase drugs. Due to the recent success of AlphaFold2 in accurately predicting the 3D structure of proteins based on sequence, we investigated the conformational landscape of protein kinases as modeled by AlphaFold2. We observed that AlphaFold2 is able to model several kinase conformations across the kinome, however, certain conformations are only observed in specific kinase families. Furthermore, we show that the per residue predicted local distance difference test can capture information describing structural flexibility of kinases. Finally, we evaluated the docking performance of AlphaFold2 kinase structures for enriching known ligands. Taken together, we see an opportunity to leverage AlphaFold2 models for structure-based drug discovery against kinases across several pharmacologically relevant conformational states. Availability and implementation All code used in the analysis is freely available at https://github.com/Harmonic-Discovery/AF2-kinase-conformational-landscape. [ABSTRACT FROM AUTHOR]

22q11.2 deletion syndrome (22q11.2DS) is the most common genomic disorder with an extremely broad phenotypic spectrum. The aim of our study was to investigate how often the additional variants in the genome can affect clinical variation among patients with the recurrent deletion. To examine the presence of additional variants affecting the phenotype, we performed microarray in 82 prenatal and 77 postnatal cases and performed exome sequencing in 86 postnatal patients with 22q11.2DS. Within those 159 patients where array was performed, 5 pathogenic and 5 likely pathogenic CNVs were identified outside of the 22q11.2 region. This indicates that in 6.3% cases, additional CNVs most likely contribute to the clinical presentation. Additionally, exome sequencing in 86 patients revealed 3 pathogenic (3.49%) and 5 likely pathogenic (5.81%) SNVs and small CNV. These results show that the extension of diagnostics with genome-wide methods can reveal other clinically relevant changes in patients with 22q11 deletion syndrome. [ABSTRACT FROM AUTHOR]

Ca2+/calmodulin (Ca2+/CaM) interaction with connexins (Cx) is well-established; however, the mechanistic basis of regulation of gap junction function by Ca2+/CaM is not fully understood. Ca2+/CaM is predicted to bind to a domain in the C-terminal portion of the intracellular loop (CL2) in the vast majority of Cx isoforms and for a number of Cx-s this prediction has proved correct. In this study, we investigate and characterise both Ca2+/CaM and apo-CaM binding to selected representatives of each of the α, β and γ connexin family to develop a better mechanistic understanding of CaM effects on gap junction function. The affinity and kinetics Ca2+/CaM and apo-CaM interactions of CL2 peptides of β-Cx32, γ-Cx35, α-Cx43, α-Cx45 and α-Cx57 were investigated. All five Cx CL2 peptides were found to have high affinity for Ca2+/CaM with dissociation constants (Kd(+Ca)) from 20 to 150 nM. The limiting rate of binding and the rates of dissociation covered a broad range. In addition, we obtained evidence for high affinity Ca2+-independent interaction of all five peptides with CaM, consistent with CaM remaining anchored to gap junctions in resting cells. However, for the α-Cx45 and α-Cx57 CL2 peptides, Ca2+-dependent association at resting [Ca2+] of 50–100 nM is indicated in these complexes as one of the CaM Ca2+ binding sites displays high affinity with Kd of 70 and 30 nM for Ca2+, respectively. Furthermore, complex conformational changes were observed in peptide-apo-CaM complexes with the structure of CaM compacted or stretched by the peptide in a concentration dependent manner suggesting that the CL2 domain may undergo helix-to-coil transition and/or forms bundles, which may be relevant in the hexameric gap junction. We demonstrate inhibition of gap junction permeability by Ca2+/CaM in a dose dependent manner, further cementing Ca2+/CaM as a regulator of gap junction function. The motion of a stretched CaM–CL2 complex compacting upon Ca2+ binding may bring about the Ca2+/CaM block of the gap junction pore by a push and pull action on the CL2 C-terminal hydrophobic residues of transmembrane domain 3 (TM3) in and out of the membrane. [ABSTRACT FROM AUTHOR]

Detecting intents and extracting necessary contextual information (aka named entities) in input utterances are two fundamental tasks in understanding what the users say in chatbot systems. While most work in this field has been dedicated to high-resource languages in popular domains like business and home automation, little research has been done for low-resource languages, especially in a less popular domain like education. To narrow this gap, this paper presents the first study on learning to detect student intents and to recognize named entities in the education domain targeted to the Vietnamese language. Specifically, we first introduce a complete corpus consisting of 3690 utterances of students. It was manually annotated with both named entities and intent information at two levels of granularity: the fine-grained and the coarse-grained levels. We then systematically investigate different approaches to deal with the two tasks using not only independent but also joint learning architectures. The experimental results show that the joint architectures based on pre-trained language models are superior in boosting the performance of both tasks. They outperformed the conventional independent learning architectures which looked at the two tasks separately. Moreover, to further enhance the final performance, this paper proposes a technique to enrich the models with more useful linguistic features. Compared to the standard approaches, we achieve considerably better results for two tasks in both architectures. Overall, for the named entity recognition task, the best model yielded an F1 score of 88.61%. For the intent detection task, it yielded F1 scores of 94.36% and 91.62% at the coarse-grained and fine-grained levels, respectively. [ABSTRACT FROM AUTHOR]

Learning and intellectual disabilities are hallmark features of 22q11.2 deletion syndrome. Data are limited, however, regarding influences on full-scale IQ (FSIQ). Here, we investigated possible 22q11.2 deletion parent-of-origin effects. In 535 individuals, we compared FSIQ (≥50), 481 with de novo and 54 with inherited 22q11.2 deletions. In the subsets with data available, we examined parent-of-origin effects on FSIQ. We used linear regression models to account for covariates. Median FSIQ was significantly higher in de novo vs. inherited deletions (77; range 50–116 vs. 67; range 50–96, p < 0.0001). Results remained significant using a regression model accounting for age at IQ testing, sex and cohort site. No significant parent-of-origin differences in FSIQ were observed for de novo deletions (n = 81, 63.0% maternal; p = 0.6882). However, median FSIQ was significantly lower in maternally than in paternally inherited familial deletions (65, range 50–86 vs. 71.5, range 58–96, respectively, p = 0.0350), with the regression model indicating an ~8 point decrement in FSIQ for this variable (p = 0.0061). FSIQ is higher on average in de novo than in inherited 22q11.2 deletions, regardless of parental origin. However, parent-of-origin appears relevant in inherited deletions. The results have potential clinical implications with further research needed to delineate possible actionable mechanisms. [ABSTRACT FROM AUTHOR]

The most prevalent microdeletion in the human population occurs at 22q11.2, a region rich in chromosome-specific low copy repeats (LCR22s). The structure of this region has eluded characterization due to a combination of size, regional complexity, and haplotype diversity. To further complicate matters, it is not well represented in the human reference genome. Most individuals with 22q11.2 deletion syndrome (22q11.2DS) carry a de novo, hemizygous deletion approximately 3 Mbp in size occurring by non-allelic homologous recombination (NAHR) mediated by the LCR22s. The ability to fully delineate an individual's 22q11.2 regional structure will likely be important for studies designed to assess an unaffected individual's risk for generating rearrangements in germ cells, potentially leading to offspring with 22q11.2DS. Towards understanding these risk factors, optical mapping has been previously employed to successfully elucidate the structure and variation of LCR22s across 30 families affected by 22q11.2DS. The father in one of these families carries a t(11;22)(q23;q11) translocation. Surprisingly, it was determined that he is the parent-of-deletion-origin. NAHR, which occurred between his der(22) and intact chromosome 22, led to a 22q11.2 deletion in his affected child. The unaffected sibling of the proband with 22q11.2DS inherited the father's normal chromosome 22, which did not aberrantly recombine. This unexpected observation definitively shows that haplotypes that engage in NAHR can also be inherited intact. This study is the first to identify all structures involving a rearranged chromosome 22 that also participates in NAHR leading to a 22q11.2 deletion. [ABSTRACT FROM AUTHOR]

Using the panel data vector autoregression (PVAR) model, this study examines the correlation between the stock market, gold price and USD exchange rate in the context of the COVID-19 pandemic in 55 Asian and 32 European countries from 11 March 2021 to 29 October 2021. The results of Granger causality test show that in Asian countries, there is a bidirectional causality between stock market and gold price. In addition, there is a unidirectional relationship between the stock market and the USD exchange rate, while the gold price and the USD exchange rate are completely independent of each other. Meanwhile, in European countries, stock market, gold price and USD exchange rate have a causal relationship at 1% significant level. The results of the impulse-response function analysis show that, in Asia, the stock market has a negative impact on the gold price and a positive effect on the USD exchange rate. In Europe, the stock market has a negative impact on the other two markets in the short term. The variance decomposition results suggest that, in Europe, the stock market return explains 2.5% for the gold price shock and 6.2% for the USD exchange rate shock from the tenth period. Meanwhile, these figures in the Asian countries are 1.6% and 3.2%, respectively. [ABSTRACT FROM AUTHOR]

Using panel data regression of 48 countries during 2000–2019, the research aims to examine the role of budget balance on economic growth in Asia. Also, with the application of Panel Threshold Regression (PTR), the author tests the nonlinear relationship and to identify an optimal budget balance threshold to achieve the most effective economic growth. The study shows that the lower national budget deficit level is remained, the greater economic growth in Asia is driven. Additionally, it is revealed that an effective economic growth is best promoted with budget balance ranging from 22.6935% GDP to 25.1950% GDP. However, only a few of nations in the sample have achieved the optimal threshold of budget balance above during the period of research. Meanwhile, several countries in Asia have been suffering from the budget deficit for many years. Therefore, in order to stabilize the economic development, most of the Asian countries should adjust the national budget revenue and expenditure process to keep the balance properly. [ABSTRACT FROM AUTHOR]

The growing number of next-generation sequencing (NGS) data presents a unique opportunity to study the combined impact of mitochondrial and nuclear-encoded genetic variation in complex disease. Mitochondrial DNA variants and in particular, heteroplasmic variants, are critical for determining human disease severity. While there are approaches for obtaining mitochondrial DNA variants from NGS data, these software do not account for the unique characteristics of mitochondrial genetics and can be inaccurate even for homoplasmic variants. We introduce MitoScape, a novel, big-data, software for extracting mitochondrial DNA sequences from NGS. MitoScape adopts a novel departure from other algorithms by using machine learning to model the unique characteristics of mitochondrial genetics. We also employ a novel approach of using rho-zero (mitochondrial DNA-depleted) data to model nuclear-encoded mitochondrial sequences. We showed that MitoScape produces accurate heteroplasmy estimates using gold-standard mitochondrial DNA data. We provide a comprehensive comparison of the most common tools for obtaining mtDNA variants from NGS and showed that MitoScape had superior performance to compared tools in every statistically category we compared, including false positives and false negatives. By applying MitoScape to common disease examples, we illustrate how MitoScape facilitates important heteroplasmy-disease association discoveries by expanding upon a reported association between hypertrophic cardiomyopathy and mitochondrial haplogroup T in men (adjusted p-value = 0.003). The improved accuracy of mitochondrial DNA variants produced by MitoScape will be instrumental in diagnosing disease in the context of personalized medicine and clinical diagnostics. Author summary: Recent studies have highlighted the importance of mitochondrial DNA variation in both primary mitochondrial disease and complex, human pathology including COVID-19, and space-flight stress. The vast amount of existing, next-generation sequencing (NGS) data can be leveraged to interrogate both nuclear and mitochondrial DNA (mtDNA) sequence simultaneously, allowing for analysis of the interplay between mitochondrial and nuclear encoded genes in mitochondrial function. Identifying mtDNA sequence accurately is complicated by the presence of nuclear encoded mitochondrial sequences (NUMTs), which are homologous to mtDNA. Current software for analyzing mtDNA from NGS do not accurately model the unique characteristics of mitochondrial genetics. We introduce MitoScape, a novel, big-data, software which models mitochondrial genetics through machine learning to accurately identify mtDNA sequence from NGS data. MitoScape takes advantage of rho-zero cell data to model the characteristics of NUMTs. We show that MitoScape produces more accurate heteroplasmy estimates compared to published software. We provide an example of applying MitoScape in replicating an association between hypertrophic cardiomyopathy and mitochondrial haplogroup T in men. MitoScape is an important contribution to mitochondrial genomics allowing for accurate mtDNA variants, and the ability to tailor mtDNA analysis in different population and disease contexts, which is not available in other software. [ABSTRACT FROM AUTHOR]

Importance: Discovery of mechanisms that underlie variable penetrance for neuropsychiatric illness in the context of genetic variants that carry elevated risk can advance novel treatment approaches for these disorders.Objective: To test the hypothesis that mitochondrial compensation is associated with the variable penetrance of schizophrenia in the 22q11.2 deletion syndrome (22q11DS).Design, Setting, and Participants: This case-control study compared measures of mitochondrial function and the expression of related genes in 14 induced pluripotent stem cell-derived neurons from typically developing control individuals (6 lines) and from adults with 22q11DS (8 lines). The individuals with 22q11DS included 2 groups, those carrying a diagnosis of schizophrenia and those without this diagnosis (4 lines each). Similar measures were made of lymphoblastic cells lines (LCLs) from a separate group of adults with 22q11DS with (10 lines) or without (8 lines) schizophrenia. The study included samples derived from a clinical setting. The induced pluripotent stem cell lines were derived from individuals with 22q11DS with or without a diagnosis of schizophrenia at Stanford University. The LCLs were from adults within the 22q and You Center at the Children's Hospital of Philadelphia. Data were analyzed between July 1, 2019, and January 24, 2021.Main Outcomes and Measures: Total adenosine triphosphate (ATP), oxidative phosphorylation (OXPHOS) complex activity, and messenger RNA expression via reverse transcription-polymerase chain reaction of selected genes encoding for mitochondrial proteins.Results: Study participants included men and women aged 18 to 37 years. Of 32 participants, the mean (SD) age of men was 27 (1.9) years and of women was 29 (1.2) years. Replicating a previous study, neurons from the 22q11DS and schizophrenia (22q+Sz) group had reduced ATP levels (mean [SD], 15.6 [1.5] vs 21.9 [1.4]; P = .02) and reduced OXPHOS activity (ie, complex I; 1.51 [0.1] vs 1.89 [0.1]; P = .01). These deficits were not present in neurons from individuals with 22q11DS without schizophrenia (22q[-]Sz). In this group, the expression of multiple genes encoding OXPHOS subunits was significantly upregulated. For example, compared with control individuals, NDUFV2 expression was increased by 50% in the 22q(-)Sz group (P < .001) but not significantly changed in the 22q+Sz group. Expression of genes driving mitochondrial biogenesis, including PGC1α, showed a similar pattern of upregulation in the 22q(-)Sz group compared with the control and the 22q+Sz groups. Stimulation of mitochondrial biogenesis normalizes the ATP deficit seen in 22q+Sz neurons. Finally, using LCLs from a separate group of adults with 22q11DS, evidence for enhanced mitochondrial biogenesis was again found in the 22q(-)Sz group.Conclusions and Relevance: In this study, an increase in mitochondrial biogenesis and function was associated with the absence of schizophrenia in neurons and LCLs from individuals with 22q11DS, but the deficit in the 22q+Sz group was reversible by agents that enhance mitochondrial biogenesis. Enhancement of mitochondrial biogenesis may provide a targetable opportunity for treatment or prevention of this disorder in individuals with 22q11DS. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic has had a profound worldwide impact. Vietnam, a lower middle-income country with limited resources, has successfully slowed this pandemic. The objectives of this report are to explore the impact of the COVID-19 pandemic on the research activities of an ongoing hypertension trial using a storytelling intervention in Vietnam. Methods: Data were collected in a mixed-methods study among 86 patients and 10 health care workers participating in a clinical trial designed to improve hypertension control. Several questions related to the impact of COVID-19 on patient's daily activities and adherence to the study interventions were included in the follow-up visits. A focus group discussion was conducted among health care workers to discuss the impact of COVID-19 on research related activities. Results: Fewer patients in the intervention group reported that they faced difficulties in adhering to prescribed study interventions, wanted to receive a call from a dedicated hotline, or have a visit from a community health worker as compared with those in the comparison group. Most study patients are willing to participate in future health research studies. When asked about the potential use of mobile phones in health research studies, fewer patients in the intervention group felt comfortable using a mobile phone for the delivery of intervention and interviews compared with those in the comparison condition. Community health workers shared that they visited patient's homes more often than previously due to the pandemic and health care workers had to perform more virus containment activities without a corresponding increase in ancillary staff. Conclusions: Both patients and health care workers in Vietnam faced difficulties in adhering to recommended trial interventions and procedures. Multiple approaches for intervention delivery and data collection are needed to overcome these difficulties during future health crises and enhance the implementation of future research studies. Trial registration: ClinicalTrials.gov. Registration number: https://clinicaltrials.gov/ct2/show/NCT03590691 (registration date July 17, 2018). [ABSTRACT FROM AUTHOR]

This paper presents the task of normalizing Vietnamese transcribed texts in Speech-to-Text (STT) systems. The main purpose is to develop a text normalizer that automatically converts proper nouns and other context-specific formatting of the transcription such as dates, time, and numbers into their appropriate expressions. To this end, we propose a solution that exploits deep neural networks with rich features followed by manually designed rules to recognize and then convert these text sequences. We also introduce a new corpus of 13 K spoken sentences to facilitate the process of the text normalization. The experimental results on this corpus are quite promising. The proposed method yields 90.67% in the F1 score in recognizing sequences of texts that need converting. We hope that this initial work will inspire other follow-up research on this important but unexplored problem. [ABSTRACT FROM AUTHOR]

Base excision repair, which is initiated by the DNA N -glycosylase proteins, is the frontline for repairing potentially mutagenic DNA base damage. Several base excision repair genes are deregulated in cancer and affect cellular outcomes to chemotherapy and carcinogenesis. Endonuclease VIII-like 3 (NEIL3) is a DNA glycosylase protein that is involved in oxidative and interstrand crosslink DNA damage repair. Our previous work has showed that NEIL3 is required to maintain replication fork integrity. It is unknown whether NEIL3 overexpression could contribute to cancer phenotypes, and its prognostic value and use as potential drug target remain unexplored. Our analysis of cancer genomics data sets reveals that NEIL3 frequently undergoes overexpression in several cancers. Furthermore, patients who exhibited NEIL3 overexpression with pancreatic adenocarcinoma, lung adenocarcinoma, lower grade glioma, kidney renal clear cell carcinoma, and kidney papillary cell carcinoma had worse overall survival. Importantly, NEIL3 overexpressed tumors accumulate mutation and chromosomal variations. Furthermore, NEIL3 overexpressed tumors exhibit simultaneous overexpression of homologous recombination genes (BRCA1/2) and mismatch repair genes (MSH2/MSH6). However, NEIL3 overexpression is negatively correlated with tumor overexpressing nucleotide excision repair genes (XPA, XPC, ERCC1 / 2). Our results suggest that NEIL3 might be a potential prognosis marker for high-risk patients, and/or an attractive therapeutic target for selected cancers. [ABSTRACT FROM AUTHOR]

Purpose – The purpose of this paper is to develop and illustrate a theoretically grounded framework capable of strategic guidance in making sourcing decisions. Design/methodology/approach – Based on literature review and secondary data from the US operation of 7-Eleven, a large international retailer, this study develops and supports a framework for understanding and undertaking business process sourcing decisions. The framework considers internal core competencies, as well as the role of external actors in value creation, in analyzing sourcing decisions for business processes. Findings – Case analysis reveals that a firm's successful sourcing decisions can be explained by resource based view (RBV) and value co-creation theories. RBV is shown to provide an internal view of the firm considering its core competencies, while value co-creation illuminates the external perspective considering the role of customers when making sourcing decisions. Further, these theories can be decomposed and simplified, thereby providing scholars with new theoretical insights for this phenomenon and practitioners with a decision-making tool for undertaking sourcing decisions. Originality/value – This paper explains in granular detail how effective outsourcing decisions can be made. It employs a rarely considered perspective by combining nascent literature from the value co-creation stream with established beliefs about RBV core competencies to make three contributions. First, it shows how sourcing decisions can be explained not only by the RBV perspective but also by the value co-creation view. Second, in considering the role of value co-creation with the customer, it introduces the perspective of the customer as a decision-making consideration for sourcing. Third, it provides practitioners with a sourcing decision-making tool. [ABSTRACT FROM AUTHOR]

This article provides an overview of the literature on relational aggression of school-aged children and adolescents, with the specific aim of making this information relevant to school settings and education professionals. Relational aggression is discussed in terms of definitions, terms, and the importance of the school context. The literature on gender and familial influences as they relate to relational aggression is overviewed. Assessment methods for detecting relational aggression in children and adolescents are described, with an emphasis on measurement techniques most viable for capturing this sometimes-elusive construct. We conclude with a discussion of proposed best practices in school settings for effectively preventing and responding to incidents of relational aggression within the context of social and emotional learning interventions and positive behavioral interventions and supports. © 2006 Wiley Periodicals, Inc. Psychol Schs 43: 345–360, 2006. [ABSTRACT FROM AUTHOR]

The role of activated platelets in acute and chronic cardiovascular diseases (CVDs) is well established. Therefore, antiplatelet drugs significantly reduce the risk of severe CVDs. Evodia rutaecarpa (Wu-Chu-Yu) is a well-known Chinese medicine, and rutaecarpine (Rut) is a main bioactive component with substantial beneficial properties including vasodilation. To address a research gap, we investigated the inhibitory mechanisms of Rut in washed human platelets and experimental mice. At low concentrations (1–5 μM), Rut strongly inhibited collagen-induced platelet aggregation, whereas it exerted only a slight or no effect on platelets stimulated with other agonists (e.g., thrombin). Rut markedly inhibited P-selectin expression; adenosine triphosphate release; [Ca2+]i mobilization; hydroxyl radical formation; and phospholipase C (PLC)γ2/protein kinase C (PKC), mitogen-activated protein kinase, and phosphoinositide 3-kinase (PI3K)/Akt/glycogen synthase kinase-3β (GSK3β) phosphorylation stimulated by collagen. SQ22536 (an adenylate cyclase inhibitor) or ODQ (a guanylate cyclase inhibitor) did not reverse Rut-mediated antiplatelet aggregation. Rut was not directly responding to vasodilator-stimulated phosphoprotein phosphorylation. Rut significantly increased the occlusion time of fluorescence irradiated thrombotic platelet plug formation. The findings demonstrated that Rut exerts a strong effect against platelet activation through the PLCγ2/PKC and PI3K/Akt/GSK3β pathways. Thus, Rut can be a potential therapeutic agent for thromboembolic disorders. [ABSTRACT FROM AUTHOR]

Sindbis virus (SINV) infection of neurons in the brain and spinal cord in mice provides a model system for investigating recovery from encephalomyelitis and antibody-mediated clearance of virus from the central nervous system (CNS). To determine the roles of IgM and IgG in recovery, we compared the responses of immunoglobulin-deficient activation-induced adenosine deaminase-deficient (AID-/-), secretory IgM-deficient (sIgM-/-), and AID-/- sIgM-/- double-knockout (DKO) mice with those of wild-type (WT) C57BL/6 mice for disease, clearance of infectious virus and viral RNA from brain and spinal cord, antibody responses, and B cell infiltration into the CNS. Because AID is essential for immunoglobulin class switch recombination and somatic hypermutation, AID-/- mice produce only germ line IgM, while sIgM-/- mice secrete IgG but no IgM and DKO mice produce no secreted immunoglobulin. After intracerebral infection with the TE strain of SINV, most mice recovered. Development of neurologic disease occurred slightly later in sIgM-/- mice, but disease severity, weight loss, and survival were similar between the groups. AID-/- mice produced high levels of SINV-specific IgM, while sIgM-/- mice produced no IgM and high levels of IgG2a compared to WT mice. All mice cleared infectious virus from the spinal cord, but DKO mice failed to clear infectious virus from brain and had higher levels of viral RNA in the CNS late after infection. The numbers of infected cells and the amount of cell death in brain were comparable. We conclude that antibody is required and that either germ line IgM or IgG is sufficient for clearance of virus from the CNS. IMPORTANCE Mosquito-borne alphaviruses that infect neurons can cause fatal encephalomyelitis. Recovery requires a mechanism for the immune system to clear virus from infected neurons without harming the infected cells. Antiviral antibody has previously been shown to be a noncytolytic means for alphavirus clearance. Antibody-secreting cells enter the nervous system after infection and produce antiviral IgM before IgG. Clinical studies of human viral encephalomyelitis suggest that prompt production of IgM is associated with recovery, but it was not known whether IgM is effective for clearance. Our studies used mice deficient in production of IgM, IgG, or both to characterize the antibody necessary for alphavirus clearance. All mice developed similar signs of neurologic disease and recovered from infection. Antibody was necessary for virus clearance from the brain, and either early germ line IgM or IgG was sufficient. These studies support the clinical observation that prompt production of antiviral antibody is a determinant of outcome. [ABSTRACT FROM AUTHOR]

Introduction U.S. Military healthcare providers increasingly perform prolonged casualty care because of operations in settings with prolonged evacuation times. Varied training and experience mean that this care may fall to providers unfamiliar with providing critical care. Telemedicine tools with audiovisual capabilities, artificial intelligence (AI), and augmented reality (AR) can enhance inexperienced personnel's competence and confidence when providing prolonged casualty care. Furthermore, implementing offline functionality provides assistance options in communications-limited settings. The intent of the Trauma TeleHelper for Operational Medical Procedure Support and Offline Network (THOMPSON) is to develop (1) a voice-controlled mobile application with video references for procedural guidance, (2) audio narration of each video using procedure mentoring scripts, and (3) an AI-guided intervention system using AR overlay and voice command to create immersive video modeling. These capabilities will be available offline and in downloadable format. Materials and Methods The Trauma THOMPSON platform is in development. Focus groups of subject matter experts will identify appropriate procedures and best practices. Procedural video recordings will be collected to develop reference materials for the Trauma THOMPSON mobile application and to train a machine learning algorithm on action recognition and anticipation. Finally, an efficacy evaluation of the application will be conducted in a simulated environment. Results Preliminary video collection has been initiated for tube thoracostomy, needle decompression, cricothyrotomy, intraosseous access, and tourniquet application. Initial results from the machine learning algorithm show action recognition and anticipation accuracies of 20.1% and 11.4%, respectively, in unscripted datasets "in the wild," notably on a limited dataset. This system performs over 100 times better than a random prediction. Conclusions Developing a platform to provide real-time, offline support will deliver the benefits of synchronous expert advice within communications-limited and remote environments. Trauma THOMPSON has the potential to fill an important gap for clinical decision support tools in these settings. [ABSTRACT FROM AUTHOR]

The article examines the impact of FirstEnergy's EXPORT NOW program which is carried out by FirstEnergy Corp. on exports, employment or other related dimensions of corporate performance in the U.S. It is believed that exports can be a driver for job creation, thus economic development organizations have established export assistance programs to garner employment growth. It is stated that the EXPORT NOW program has assisted 180 companies with exporting products and services between 1995 and 2004. It is emphasized that the program reveals that small to medium sized manufacturers, which are open-minded about international trade and willing to explore opportunities, can find and create jobs in the process.

Between 2010 and 2011, stakeholders implemented a multi-faceted community-based intervention in response to the escalating issue of uncontrolled hypertension in Hung Yen province, Vietnam. This initiative integrated expanded community health worker services, home blood pressure self-monitoring, and a unique "storytelling intervention" into routine clinical care. From the limited societal perspective, our study evaluates the cost-effectiveness of this intervention using a Markov model with a one-year cycle over a lifetime horizon. The analysis, based on a cohort of 671 patients, reveals a lifetime incremental cost of approximately VND 90.37 million (USD 3,930) per quality-adjusted life year (QALY) gained. With a willingness to pay at three times GDP (VND 259.2 million per QALY), the intervention proves cost-effective 80% of the time. This research underscores the potential of the community-based approach to effectively control hypertension, offering valuable insights into its broader implications for public health., Competing Interests: Conflicts of Interest The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Introduction: Genetically encoded biosensors for monitoring intracellular calcium changes have advanced our understanding of cell signaling and neuronal activity patterns in health and disease. Successful application of GCaMP biosensors to a wide range of biological questions requires that sensor properties such as brightness and dynamic range, ligand affinity and response kinetics be tuned to the specific conditions or phenomena to be investigated. Random as well as rational targeted mutations of such sensor molecules have led to a number of important breakthroughs in this field, including the calcium sensors GCaMP6f and GCaMP6f u . jGCaMP8f of the most recently developed generation is promising a step-change in in vivo imaging with further increased fluorescence dynamic range. Here, we critically examine the biophysical properties of jGCaMP8f and report development by rational design of two novel variants of jGCaMP8f., Methods: We determined the in vitro biophysical properties of jGCaMP8f and selected variants by fluorescence spectroscopies and compared their performance monitoring intracellular Ca 2+ transients with previously developed fast and bright GCaMP sensors by live cell imaging., Results: We demonstrate that the physiologically highly relevant Mg 2+ not only majorly affects the kinetic responses of GCaMPs but also their brightness and fluorescence dynamic range. We developed novel variants jGCaMP8f L27A which has threefold faster off-kinetics and jGCaMP8f F366H which shows a ∼3-fold greater dynamic range than jGCaMP8f, in vitro as well as in HEK293T cells and endothelial cell line HUVEC in response to ATP stimulation., Discussion: We discuss the importance of optimization of biosensors for studying neurobiology in the context of the novel variants of jGCaMP8f. The jGCaMP8f F366H variant with a large dynamic range has the potential to improve in vivo imaging outcomes with increased signal-to-noise ratio. The L27A variant with faster kinetics than jGCaMP8f has larger cellular responses than previous fast GCaMP variants. The jGCaMP8f generation and novel improved variants presented here will further increase the application potential of GECIs in health and disease., Competing Interests: The 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 © 2023 Tran, Hughes, Carter and Török.)