Genetics causal analysis of oral microbiome on type 2 diabetes in East Asian populations: a bidirectional two-sample Mendelian randomized study.

Introduction: The dysbiosis of the oral microbiome is associated with the progression of various systemic diseases, including diabetes. However, the precise causal relationships remain elusive. This study aims to investigate the potential causal associations between oral microbiome and type 2 diabetes (T2D) using Mendelian randomization (MR) analyses. Methods: We conducted bidirectional two-sample MR analyses to investigate the impact of oral microbiome from saliva and the tongue T2D. This analysis was based on metagenome-genome-wide association studies (mgGWAS) summary statistics of the oral microbiome and a large meta-analysis of GWAS of T2D in East Asian populations. Additionally, we utilized the T2D GWAS summary statistics from the Biobank Japan (BBJ) project for replication. The MR methods employed included Wald ratio, inverse variance weighting (IVW), weighted median, MR-Egger, contamination mixture (ConMix), and robust adjusted profile score (RAPS). Results: Our MR analyses revealed genetic associations between specific bacterial species in the oral microbiome of saliva and tongue with T2D in East Asian populations. The MR results indicated that nine genera were shared by both saliva and tongue. Among these, the genera Aggregatibacter, Pauljensenia, and Prevotella were identified as risk factors for T2D. Conversely, the genera Granulicatella and Haemophilus D were found to be protective elements against T2D. However, different species within the genera Catonella, Lachnoanaerobaculum, Streptococcus, and Saccharimonadaceae TM7x exhibited multifaceted influences; some species were positively correlated with the risk of developing T2D, while others were negatively correlated. Discussion: This study utilized genetic variation tools to confirm the causal effect of specific oral microbiomes on T2D in East Asian populations. These findings provide valuable insights for the treatment and early screening of T2D, potentially informing more targeted and effective therapeutic strategies.

Carbon footprints and health security: A comparative assessment of the Sustainable Development Goals 3 and 13 in East Asian countries.

In East Asia, where several countries are among the top emitters of carbon dioxide globally, the need to address the dual challenges of reducing carbon footprints and ensuring health security is paramount. Against this backdrop, this study used a descriptive analysis to provide a comparative assessment of the carbon footprints and the level of health security in East Asia using secondary data, sourced from the World Development Indicators. The findings from the study show that it is only North Korea that its average carbon footprint of every person is less than 2.3 tons. However, China, Japan, Mongolia and South Korea are currently lagging behind in meeting the SDG 13 target. Meanwhile, North Korea recorded the highest incidence of tuberculosis in the region. Despite the fact that South Korea and Japan were the highest emitter of CO2, the duo had the lowest under five mortality, infant mortality, incidence of TB alongside the highest life expectancies which surpassed the regional performance. In view of the above, the policymakers in Asia and the rest of the countries with health insecurity should emulate the policymakers in Japan and South Korea by making adequate investment in health, education, and standard of living of their citizens.

En Asie de l'Est, où plusieurs pays comptent parmi les plus grands émetteurs de dioxyde de carbone au monde, la nécessité de relever le double défi de réduire l'empreinte carbone et d'assurer la sécurité sanitaire est primordiale. Dans ce contexte, cette étude a utilisé une analyse descriptive pour fournir une évaluation comparative des empreintes carbone et du niveau de sécurité sanitaire en Asie de l'Est à l'aide de données secondaires provenant des indicateurs de développement mondial. Les résultats de l'étude montrent que seule la Corée du Nord a une empreinte carbone moyenne par personne inférieure à 2,3 tonnes. Cependant, la Chine, le Japon, la Mongolie et la Corée du Sud sont actuellement à la traîne dans la réalisation de l'ODD 13. Pendant ce temps, la Corée du Nord a enregistré la plus forte incidence de tuberculose dans la région. Bien que la Corée du Sud et le Japon soient les plus grands émetteurs de CO2, ces deux pays ont les taux de mortalité des moins de cinq ans, de mortalité infantile et d'incidence de tuberculose les plus faibles, ainsi que les espérances de vie les plus élevées, dépassant les performances régionales. Compte tenu de ce qui précède, les décideurs politiques d'Asie et du reste des pays souffrant d'insécurité sanitaire devraient imiter les décideurs politiques du Japon et de la Corée du Sud en investissant de manière adéquate dans la santé, l'éducation et le niveau de vie de leurs citoyens.

A causal relationship between bone mineral density and breast cancer risk: a mendelian randomization study based on east Asian population.

BACKGROUND: Breast cancer (BC) poses significant burdens on women globally. While past research suggests a potential link between bone mineral density (BMD) and BC risk, findings remain inconsistent. Our study aims to elucidate the causal relationship between BMD and BC in East Asians using bidirectional Mendelian randomization (MR). METHODS: Genetic association data for bone mineral density T-scores (BMD-T) and Z-scores (BMD-Z) (Sample size = 92,615) and BC from two different sources (Sample size1 = 98,283; Sample size2 = 79,550) were collected from publicly available genome-wide association studies (GWAS). Single-nucleotide polymorphisms (SNPs) associated with BMD-T and BMD-Z as phenotype-related instrumental variables (IVs) were used, with BC as the outcome. As the primary means of causal inference, the inverse variance weighted (IVW) approach was employed. Heterogeneity analysis was conducted using Cochran's Q test, while MR-Egger regression analysis was implemented to assess the pleiotropic effects of the IVs. Sensitivity analyses were performed using methods such as MR-Egger, weighted median, and weighted mode to analyze the robustness and reliability of the results. The MR-PRESSO method and the RadialMR were used to detect and remove outliers. The PhenoScanner V2 website was utilized to exclude confounding factors shared between BMD and BC. Besides, the Bonferroni correction was also used to adjust the significance threshold. Then, the meta-analysis method was applied to combine the MR analysis results from the two BC sources. Finally, a reverse MR analysis was conducted. RESULTS: The results of the IVW method were consolidated through meta-analysis, revealing a positive correlation between genetically predicted BMD-T ([Formula: see text], [Formula: see text], [Formula: see text]) and BMD-Z ([Formula: see text],[Formula: see text], [Formula: see text]) with increased BC risk. The Cochran's [Formula: see text] test and MR-Egger regression suggested that neither of these causal relationships was affected by heterogeneity or horizontal pleiotropy. The sensitivity analyses supported the IVW results, indicating the robustness of the findings. Reverse MR analysis showed no causal relationship between BC and BMD. CONCLUSION: Our MR study results provide evidence for the causal relationship between BMD and BC risk in East Asian populations, suggesting that BMD screening is of great significance in detecting and preventing BC.

Comparative phylogenomic study of East Asian endemic genus, Corchoropsis Siebold & Zucc. (Malvaceae s.l.), based on complete plastome sequences.

BACKGROUND: Endemic plants are key to understanding the evolutionary history and enhancing biodiversity within their unique regions, while also offering significant economic potential. The East Asian endemic genus Corchoropsis Siebold & Zucc., classified within the subfamily Dombeyoideae of Malvaceae s.l., comprises three species. RESULTS: This study characterizes the complete plastid genomes (plastomes) of C. crenata var. crenata Siebold & Zucc. and C. crenata var. hupehensis Pamp., which range from 160,093 to 160,724 bp. These genomes contain 78 plastid protein-coding genes, 30 tRNA, and four rRNA, except for one pseudogene, infA. A total of 316 molecular diagnostic characters (MDCs) specific to Corchoropsis were identified. In addition, 91 to 92 simple sequence repeats (SSRs) in C. crenata var. crenata and 75 in C. crenata var. hupehensis were found. Moreover, 49 long repeats were identified in both the Chinese C. crenata var. crenata and C. crenata var. hupehensis, while 52 were found in the South Korean C. crenata var. crenata. Our phylogenetic analyses, based on 78 plastid protein-coding genes, reveal nine subfamilies within the Malvaceae s.l. with high support values and confirm Corchoropsis as a member of Dombeyoideae. Molecular dating suggests that Corchoropsis originated in the Oligocene, and diverged during the Miocene, influenced by the climate shift at the Eocene-Oligocene boundary. CONCLUSIONS: The research explores the evolutionary relationships between nine subfamilies within the Malvaceae s.l. family, specifically identifying the position of the Corchoropsis in the Dombeyoideae. Utilizing plastome sequences and fossil data, the study establishes that Corchoropsis first appeared during the Eocene and experienced further evolutionary divergence during the Miocene, paralleling the evolutionary patterns observed in other East Asian endemic species.

Synergistic effects of Pleistocene geological and climatic events on complex phylogeographic history of widespread sympatric species of Megaloptera in East Asia.

Unraveling the phylogeographic histories of species remains a key endeavor for comprehending the evolutionary processes contributing to the rich biodiversity and high endemism found in East Asia. In this study, we explored the phylogeographic patterns and demographic histories of three endemic fishfly and dobsonfly species ( Neochauliodes formosanus, Protohermes costalis, and Neoneuromus orientalis) belonging to the holometabolan order Megaloptera. These species, which share a broad and largely overlapping distribution, were analyzed using comprehensive mitogenomic data. Our findings revealed a consistent influence of vicariance on the population isolation of Neoc. formosanus and P. costalis between Hainan, Taiwan, and the East Asian mainland during the early Pleistocene, potentially hindering subsequent colonization of the later diverged Neon. orientalis to these islands. Additionally, we unveiled the dual function of the major mountain ranges in East Asia, serving both as barriers and conduits, in shaping the population structure of all three species. Notably, we demonstrated that these co-distributed species originated from Southwest, Southern, and eastern Central China, respectively, then subsequently migrated along multi-directional routes, leading to their sympatric distribution on the East Asian mainland. Furthermore, our results highlighted the significance of Pleistocene land bridges along the eastern coast of East Asia in facilitating the dispersal of mountain-dwelling insects with low dispersal ability. Overall, this study provides novel insight into the synergistic impact of Pleistocene geological and climatic events in shaping the diversity and distribution of aquatic insects in East Asia.

The disease burden of bladder cancer and its attributable risk factors in five Eastern Asian countries, 1990-2019: a population-based comparative study.

BACKGROUNDS: The study aimed to estimate bladder cancer burden and its attributable risk factors in China, Japan, South Korea, North Korea and Mongolia from 1990 to 2019, to discuss the potential causes of the disparities. METHODS: Data were obtained from the Global Burden of Disease Study 2019. The annual percent change (APC) and average annual percent change (AAPC) were calculated by Joinpoint analysis, and the independent age, period and cohort effects were estimated by age-period-cohort analysis. RESULTS: In 2019, the highest incidence (7.70 per 100,000) and prevalence (51.09 per 100,000) rates of bladder cancer were in Japan, while the highest mortality (2.31 per 100,000) and DALY rates (41.88 per 100,000) were in South Korea and China, respectively. From 1990 to 2019, the age-standardized incidence and prevalence rates increased in China, Japan and South Korea (AAPC > 0) and decreased in Mongolia (AAPC < 0), while mortality and DALY rates decreased in all five countries (AAPC < 0). Age effects showed increasing trends for incidence, mortality and DALY rates, while the prevalence rates increased first and then decreased in older groups. The cohort effects showed downward trends from 1914-1918 to 2004-2008. Smoking was the greatest contributor and males had the higher burden than females. CONCLUSION: Bladder cancer was still a major public health problem in East Asia. Male and older population suffered from higher risk, and smoking played an important role. It is recommended that more efficient preventions and interventions should be operated among high-risk populations, thereby reduce bladder cancer burden in East Asia.

Height and cancer risk in East Asians: Evidence from a prospective cohort study and Mendelian randomization analyses.

BACKGROUND: Height is associated with increased cancer risk, but most studies focus on Western populations. We aimed to evaluate this relationship in East Asians. METHOD: Observational analyses were performed utilizing data from China Kadoorie Biobank (CKB) prospective cohort. Adjusted hazard ratios (HRs) and corresponding 95 % confidence intervals (CIs) were estimated using Cox proportional hazards models. Two-sample Mendelian randomization (MR) analyses explored causal effects between height and cancer using data from Korean Genome and Epidemiology Study (KoGES), Biobank Japan (BBJ), and CKB. RESULTS: Over a median 10.1-years follow-up, 22,731 incident cancers occurred. In observational analyses, after Bonferroni correction, each 10 cm increase in height was significantly associated with higher risk of overall cancer (HR 1.16, 95 % CI 1.14-1.19, P < 0.001), lung cancer (1.18, 95 % CI 1.12-1.24, P < 0.001), esophageal cancer (1.21, 95 % CI 1.12-1.30, P < 0.001), breast cancer (1.41, 95 % CI 1.31-1.53, P < 0.001), and cervix uteri cancer (1.29, 95 % CI 1.15-1.45, P < 0.001). Each 10 cm increase in height was suggestively associated with increased risk for lymphoma (1.18, 95 % CI 1.04-1.34, P = 0.010), colorectal cancer (1.09, 95 % CI 1.02-1.16, P = 0.010), and stomach cancer (1.07, 95 % CI 1.00-1.14, P = 0.044). In MR analyses, genetically predicted height (per 1 standard deviation increase, 8.07 cm) was suggestively associated with higher risk of lung cancer (odds ratio [OR] 1.17, 95 % confidence interval [CI] 1.02-1.35, P = 0.0244) and gastric cancer (OR 1.14, 95 % CI 1.02-1.29, P = 0.0233). CONCLUSIONS: Taller height was significantly related to a higher risk for overall cancer, lung cancer, esophageal cancer, breast cancer, and cervix uteri cancer. Our findings suggest that height may be a potential causal risk factor for lung and gastric cancers among East Asians.

Rosacea in East Asian populations: Clinical manifestations and pathophysiological perspectives for accurate diagnosis.

Rosacea is a chronic inflammatory disorder primarily affecting the facial skin, prominently involving the cheeks, nose, chin, forehead, and periorbital area. Cutaneous manifestations encompass persistent facial erythema, phymas, papules, pustules, telangiectasia, and flushing. The pathogenesis of rosacea is associated with various exacerbating or triggering factors, including microbial infestation, temperature fluctuations, sunlight exposure, physical exertion, emotional stress, consumption of hot beverages and spicy foods, and exposure to airborne pollen. These environmental factors interact with genetic predispositions in the development of rosacea. The roles of the lipophilic microbiome, ultraviolet radiation, nociceptive responses, and vascular alterations have been proposed as significant factors in the pathogenesis. These insights contribute to understanding the anatomical specificity of facial involvement and the progressive nature of rosacea. East Asian skin, predominantly classified as Fitzpatrick skin phototypes III to IV, is characterized by relatively diminished skin barrier function and increased sensitivity to irritants. Airborne pollen exposure may particularly act as a trigger in East Asian individuals, possibly mediated through toll-like receptors. The lack of specificity in objective clinical and histopathological findings leads to diagnostic challenges for individuals with colored skin, including East Asians, particularly when erythema is the sole objective manifestation. An alternative diagnostic scheme may thus be necessary. A diagnostic approach emphasizing vascular manifestations and nociceptive symptoms potentially holds promise for individuals with darker skin tones. More research focusing on potential variations in skin physiology across different racial groups is essential to establish more effective diagnostic schemes applicable to both dark and light skin colors.

Association between inflammatory bowel disease and osteoporosis in European and East Asian populations: exploring causality, mediation by nutritional status, and shared genetic architecture.

Background: While previous research has established an association between inflammatory bowel disease (IBD) and osteoporosis (OP), the nature of this association in different populations remains unclear. Objective: Our study used linkage disequilibrium scores(LDSC) regression analysis and Mendelian randomization(MR) to assess the genetic correlation and causal relationship between IBD and OP in European and East Asian populations. Methods: We performed separate genetic correlation and causal analyses for IBD and OP in European and East Asian populations, used the product of coefficients method to estimate the mediating effect of nutritional status on the causal relationship, and used multi-trait analysis to explore the biological mechanisms underlying the IBD-nutrition-OP causal pathway. Results: Our analysis revealed a significant genetic correlation and causal relationship between IBD and OP in the European population. Conversely, no such correlation or causal relationship was observed in the East Asian population. Mediation analysis revealed a significant mediating effect of nutritional status on the causal pathway between IBD and OP in the European population. Multi-trait analysis of the IBD-nutrition-OP causal pathway identified MFAP2, ATP13A2, SERPINA1, FTO and VCAN as deleterious variants. Conclusion: Our findings establish a genetic correlation and causal relationship between IBD and OP in the European population, with nutritional status playing a crucial mediating role.

Clinical Efficacy and Safety of Anti-Obesity Medications Among Adult East Asian People with Obesity: A Systematic Literature Review and Indirect Treatment Comparison.

INTRODUCTION: The prevalence of obesity has increased worldwide over the past decades. Regional variations exist in the relationship between body mass index (BMI), body fat, and health risks: Asians typically have a lower BMI than people of European descent, but a higher risk of obesity-related comorbidities. However, there is a paucity of evidence for anti-obesity medications (AOMs) in East Asian populations. In this study, we aimed to systematically review evidence regarding the safety and efficacy of AOMs among adults with obesity disease in East Asia, and to assess the feasibility of conducting an indirect treatment comparison (ITC) between the semaglutide and mazindol trials. METHODS: The Embase, MEDLINE, and ICHUSHI databases were searched via the Ovid SP platform for randomized controlled trials, in English or Japanese, reporting data on semaglutide or mazindol therapy with placebo or diet and exercise as comparators. The potential risks of bias in conducting a population-adjusted ITC were determined based on the heterogeneity of potential effect modifiers and variations in study design. RESULTS: Of 21 publications, 2 were included in this study based on the eligibility criteria. The STEP 6 study established the clinical efficacy of subcutaneous semaglutide compared with placebo in the reduction of body weight and cardiometabolic risk factors [glycated hemoglobin (HbA1c), total cholesterol, and systolic blood pressure] among Japanese and South Korean people with obesity disease. Mazindol also proved beneficial in reducing body weight and total cholesterol compared with placebo in Japan. Both semaglutide and mazindol were associated with higher rates of adverse events and treatment discontinuation than placebo. An ITC between the two studies was not deemed feasible based on the potential risks of bias. CONCLUSIONS: Semaglutide and mazindol are associated with significant body weight reduction among people with obesity in East Asia. Further research based on label indications and up-to-date real-world data among East Asian people with obesity would help determine additional clinical benefits.

Delineation of the phenotypes and genotypes of PIK3CA-related overgrowth spectrum in East asians.

PIK3CA-related overgrowth spectrum (PROS) is an umbrella term to describe a diverse range of developmental disorders. Research to date has predominantly emerged from Europe and North America, resulting in a notable scarcity of studies focusing on East Asian populations. Currently, the prevalence and distribution of PIK3CA variants across various genetic loci and their correlation with distinct phenotypes in East Asian populations remain unclear. This study aims to elucidate the phenotype-genotype correlations of PROS in East Asian populations. We presented the phenotypes and genotypes of 82 Chinese patients. Among our cohort, 67 individuals carried PIK3CA variants, including missense, frameshift, and splice variants. Six patients presented with both PIK3CA and an additional variant. Seven PIK3CA-negative patients exhibited overlapping PROS manifestations with variants in GNAQ, AKT1, PTEN, MAP3K3, GNA11, or KRAS. An integrative review of the literature pertaining to East Asian populations revealed that specific variants are uniquely associated with certain PROS phenotypes. Some rare variants were exclusively identified in cases of megalencephaly and diffuse capillary malformation with overgrowth. Non-hotspot variants with undefined oncogenicity were more common in CNS phenotypes. Diseases with vascular malformation were more likely to have variants in the helical domain, whereas phenotypes involving adipose/muscle overgrowth without vascular abnormalities predominantly presented variants in the C2 domain. Our findings underscore the unique phenotype-genotype patterns within the East Asian PROS population, highlighting the necessity for an expanded cohort to further elucidate these correlations. Such endeavors would significantly facilitate the development of PI3Kα selective inhibitors tailored for the East Asian population in the future.

Exploring the causal association between uric acid and lung cancer in east Asian and European populations: a mendelian randomization study.

BACKGROUND: Lung cancer still ranks first in the mortality rate of cancer. Uric acid is a product of purine metabolism in humans. Its presence in the serum is controversial; some say that its high levels have a protective effect against tumors, others say the opposite, that is, high levels increase the risk of cancer. Therefore, the aim of this study was to investigate the potential causal association between serum uric acid levels and lung cancer. METHODS: Mendelian randomization was used to achieve our aim. Sensitivity analyses was performed to validate the reliability of the results, followed by reverse Mendelian analyses to determine a potential reverse causal association. RESULTS: A significant causal association was found between serum uric acid levels and lung cancer in East Asian and European populations. Further sublayer analysis revealed a significant causal association between uric acid and small cell lung cancer, while no potential association was observed between uric acid and non-small cell lung cancer, squamous lung cancer, and lung adenocarcinoma. The sensitivity analyses confirmed the reliability of the results. Reverse Mendelian analysis showed no reverse causal association between uric acid and lung cancer. CONCLUSIONS: The results of this study suggested that serum uric acid levels were negatively associated with lung cancer, with uric acid being a potential protective factor for lung cancer. In addition, uric acid level monitoring was simple and inexpensive. Therefore, it might be used as a biomarker for lung cancer, promoting its wide use clinical practice.

Genetic characterization of cucumber genetic resources in the NARO Genebank indicates their multiple dispersal trajectories to the East.

KEY MESSAGE: Genotyping-by-sequencing of 723 worldwide cucumber genetic resources revealed that cucumbers were dispersed eastward via at least three distinct routes, one to Southeast Asia and two from different directions to East Asia. The cucumber (Cucumis sativus) is an economically important vegetable crop cultivated and consumed worldwide. Despite its popularity, the manner in which cucumbers were dispersed from their origin in South Asia to the rest of the world, particularly to the east, remains a mystery due to the lack of written records. In this study, we performed genotyping-by-sequencing (GBS) on 723 worldwide cucumber accessions, mainly deposited in the Japanese National Agriculture and Food Research Organization (NARO) Genebank, to characterize their genetic diversity, relationships, and population structure. Analyses based on over 60,000 genome-wide single-nucleotide polymorphisms identified by GBS revealed clear genetic differentiation between Southeast and East Asian populations, suggesting that they reached their respective region independently, not progressively. A deeper investigation of the East Asian population identified two subpopulations with different fruit characteristics, supporting the traditional classification of East Asian cucumbers into two types thought to have been introduced by independent routes. Finally, we developed a core collection of 100 accessions representing at least 93.2% of the genetic diversity present in the entire collection. The genetic relationships and population structure, their associations with geographic distribution and phenotypic traits, and the core collection presented in this study are valuable resources for elucidating the dispersal history and promoting the efficient use and management of genetic resources for research and breeding in cucumber.

Challenges, experiences, and potential supports for East and Southeast Asian mothers in the workforce: a systematic review.

OBJECTIVE: To examine the challenges faced by Asian working mothers with a focus on re-entry to the workplace. In addition, we highlight potential supports that retain women in the workforce. DESIGN: A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations and registered with PROSPERO database (CRD42022341130). METHODS: Three independent reviewers were involved in the study selection to screen the search results sequentially by title, abstract, and full text using predefined inclusion and exclusion criteria. The methodological quality of each article was assessed via the Critical Appraisal Skills Programme (CASP) tool. RESULTS: We analysed a total of 36 studies conducted across different regions: 30 from the East and 6 from Southeast Asia. Among these studies, 20 were quantitative in nature, 15 were qualitative, and one intervention. The 36 studies cover five themes: 1) policies, 2) external support sources, 3) external pressure, 4) breastfeeding and 5) health status. Within each theme the same factor can have a positive or negative impact on the mother depending on her having a pro-career or pro-family mindset. Companies can take various initiatives to support working mothers, such as providing facilities for expressing breast milk at the workplace, educating staff to promote breastfeeding and accommodate childcare needs, and extending maternity leaves. However, there is a lack of literature that directly addresses the barriers and concrete support available to working mothers in Asia, beyond the scope of breastfeeding. CONCLUSIONS: Our findings underscore several obstacles that can impede a woman's seamless return to work. Pro-family and pro-career mothers have differing needs that cannot be addressed at the same time. There is a lack of comprehensive understanding regarding effective strategies or interventions that can support a positive reintegration into the workforce.

Adaptive Evolution of Two Distinct Adaptive Haplotypes of Neanderthal Origin at the Immunoglobulin Heavy-chain Locus in East Asian and European Populations.

Immunoglobulins (Igs) have a crucial role in humoral immunity. Two recent studies have reported a high-frequency Neanderthal-introgressed haplotype throughout Eurasia and a high-frequency Neanderthal-introgressed haplotype specific to southern East Asia at the immunoglobulin heavy-chain (IGH) gene locus on chromosome 14q32.33. Surprisingly, we found the previously reported high-frequency Neanderthal-introgressed haplotype does not exist throughout Eurasia. Instead, our study identified two distinct high-frequency haplotypes of putative Neanderthal origin in East Asia and Europe, although they shared introgressed alleles. Notably, the alleles of putative Neanderthal origin reduced the expression of IGHG1 and increased the expression of IGHG2 and IGHG3 in various tissues. These putatively introgressed alleles also affected the production of IgG1 upon antigen stimulation and increased the risk of systemic lupus erythematosus. Additionally, the greatest genetic differentiation across the whole genome between southern and northern East Asians was observed for the East Asian haplotype of putative Neanderthal origin. The frequency decreased from southern to northern East Asia and correlated positively with the genome-wide proportion of southern East Asian ancestry, indicating that this putative positive selection likely occurred in the common ancestor of southern East Asian populations before the admixture with northern East Asian populations.

Understanding the factors related to how East and Southeast Asian immigrant youth and families access mental health and substance use services: A scoping review.

The objective of the review is to identify factors related to how East and Southeast Asian immigrant youth aged 12-24 and their families access mental health and substance use (MHSU) services. To address how East and Southeast Asian youth and their families access mental health and substance use services, a scoping review was conducted to identify studies in these databases: PubMed, MEDLINE (Ovid), EMBASE (Ovid), PsychINFO, CINAHL, and Sociology Collection. Qualitative content analysis was used to deductively identify themes and was guided by Bronfenbrenner's Ecological Systems Theory, the process-person-context-time (PPCT) model, and the five dimensions of care accessibility (approachability, acceptability, availability and accommodation, appropriateness, affordability). Seventy-three studies met the inclusion criteria. The dimensions of healthcare accessibility shaped the following themes: 1) Acceptability; 2) Appropriateness; 3) Approachability; 4) Availability and Accommodation. Bronfenbrenner's Ecological Systems Theory and the PPCT model informed the development of the following themes: 1) Immediate Environment/Proximal Processes (Familial Factors, Relationships with Peers; 2) Context (School-Based Services/Community Resources, Discrimination, Prevention, Virtual Care); 3) Person (Engagement in Services/Treatment/Research, Self-management); 4) Time (Immigration Status). The study suggests that there is a growing body of research (21 studies) focused on identifying acceptability factors, including Asian cultural values and the model minority stereotype impacting how East and Southeast Asian immigrant youth access MHSU services. This review also highlighted familial factors (16 studies), including family conflict, lack of MHSU literacy, reliance on family as support, and family-based interventions, as factors affecting how East and Southeast Asian immigrant youth access MHSU care. However, the study also highlighted a dearth of research examining how East and Southeast Asian youth with diverse identities access MHSU services. This review emphasizes the factors related to the access to MHSU services by East and Southeast Asian immigrant youth and families while providing insights that will improve cultural safety.

Bemarituzumab plus mFOLFOX6 as first-line treatment in East Asian patients with FGFR2b-overexpressing locally advanced or metastatic gastric/gastroesophageal junction cancer: subgroup of FIGHT final analysis.

BACKGROUND: In the FIGHT study (NCT03694522) bemarituzumab, a humanized monoclonal antibody selective for fibroblast growth factor receptor 2b (FGFR2b), plus mFOLFOX6 showed clinically meaningful efficacy in patients with FGFR2b-positive (2+/3+ membranous staining by immunohistochemistry) locally advanced unresectable/metastatic gastric/gastroesophageal cancer (G/GEJC). A meaningful proportion of patients in FIGHT were enrolled in East Asia, reflecting global epidemiology of G/GEJC. METHODS: This subgroup analysis of the global, phase 2, double-blind FIGHT study included all patients enrolled in East Asian sites. Patients were randomized 1:1 to bemarituzumab-mFOLFOX6 (15 mg/kg and one 7.5 mg/kg dose on cycle 1, day 8) or matching placebo-mFOLFOX6. The primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate, and safety. Efficacy was evaluated after a minimum follow-up of 24 months. RESULTS: The East Asian subgroup comprised 89 patients (57% of overall study population); 45 were randomized to bemarituzumab-mFOLFOX6 and 44 to placebo-mFOLFOX6. Median PFS (95% confidence interval [CI]) was 12.9 months (8.8-17.9) with bemarituzumab-mFOLFOX6 and 8.2 months (5.6-10.3) with placebo-mFOLFOX6 (HR 0.50, 95% CI 0.29-0.87); median OS (95% CI) was 24.7 months (13.8-33.1) vs 12.9 months (9.3-21.4), respectively (HR 0.56, 95% CI 0.32-0.96). Treatment benefit was more pronounced in patients with FGFR2b-positive G/GEJC in ≥ 10% of tumor cells. No new safety signals were reported. CONCLUSION: In East Asian patients with FGFR2b-positive advanced/metastatic G/GEJC enrolled in the global FIGHT study, bemarituzumab-mFOLFOX6 showed clinically meaningful outcomes over placebo-mFOLFOX6.

Causal relationship between blood traits and severe influenza A(H1N1)pdm09 infection in East Asian: A Mendelian randomization study.

Although a range of blood traits have been reported to be associated with influenza A(H1N1)pdm09 (H1N1pdm09) disease severity, their underlying causal relationships and biological mechanisms have remained unclear. This study aimed to investigate the causal relationship between blood traits and H1N1pdm09 using a two-sample Mendelian randomization analysis. Based on the data from our in-house genome-wide association study (GWAS) on H1N1pdm09 disease severity (Ncase [severe] = 70, Ncontrol [mild] = 95) and GWAS summaries of 44 blood traits from Biobank Japan (N = 12 303-143 658), we identified the potential causal effect of blood traits on severe H1N1pdm09. The inverse variance weighted method analysis revealed significant causal effects of lower aspartate aminotransferase (AST, ß = -3.212, p = 0.019), low-density-lipoprotein cholesterol (LDL-C, ß = -1.372, p = 0.045), and basophil counts (Baso, ß = -1.638, p = 0.047) on severe H1N1pdm09 disease. Additionally, polygenic risk score analysis further confirmed genetic overlap between these blood traits and severe H1N1pdm09 disease. This study provided evidence linking the lower level of AST, LDL-C, and lower count of Baso with severe H1N1pdm09 disease, potentially identifying new therapeutic targets for patients with severe influenza.

Core health system measures response to COVID-19 among East Asian countries.

Objective: The purpose of this study is to summarize the health system response to COVID-19 in four East Asian countries, analyze the effectiveness of their health system response, and provide lessons for other countries to control the epidemic and optimize their health system response. Methods: This study investigated and summarized COVID-19 data and health system response in four East Asian countries, China, Japan, Mongolia, and South Korea from national governments and ministries of health, WHO country offices, and official websites of international organizations, to assess the effectiveness of health system measures. Result: As of June 30, 2022, all four countries are in a declining portion of COVID-19. China has two waves, and new cases increased slowly, with the total cases per million remaining within 4, indicating a low level. Japan has experienced six waves, with case growth at an all-time high, total cases per million of 250.994. Mongolia started the epidemic later, but also experienced four waves, with total cases per million of 632.658, the highest of the four countries. South Korea has seen an increasing number of new cases per wave, with a total case per million of 473.759. Conclusion: In containment strategies adopted by China and Mongolia, and mitigation strategies adopted by Japan and South Korea, health systems have played important roles in COVID-19 prevention and control. While promoting vaccination, countries should pay attention to non-pharmaceutical health system measures, as evidenced by: focusing on public information campaigns to lead public minds; strengthening detection capabilities for early detection and identification; using technical ways to participate in contact tracing, and promoting precise judging isolation.