Southeast Asian Populations Research Articles

Complex chromosomal rearrangements in female carriers experiencing recurrent pregnancy loss or poor obstetric history and literature review.

Complex chromosomal rearrangements (CCRs) often remain unidentified as they are rarely observed in the general population. Females with CCRs are generally recognized on the identification of an affected child with multiple congenital anomalies (MCA) or having a history of repeated pregnancy loss/bad obstetric history (RPL/BOH). In contrast, males with CCRs are diagnosed primarily due to infertility. This study aimed to carry out a systematic epidemiological analysis of CCRs in one of the largest series from the Indian population. In addition, a review of the literature on female CCR carriers experiencing RPL/BOH has been compiled in an attempt to identify the genomic landscape of breakpoints, commonly involved chromosomes, and the breakpoint regions. A total of 8560 healthy individuals with normal physical and mental well-being and had no history of any obvious genetic disorder at the time of presentation were referred for chromosome analysis in view of RPL/BOH between 1994 and 2024. Of them, 8158 had a normal chromosome complement whereas, 402 (4.7%) showed chromosomal aberrations. CCRs were detected in seven individuals, i.e., one partner in each of seven couples with structural rearrangements, all of whom were females. Comprehensive characterization of CCR was carried out using various molecular cytogenetic techniques. Seven CCR carriers had a total of 25 pregnancies: 20 leading to miscarriages (80%), one leading to the birth of an abnormal child (4%), two medically terminated pregnancies (8%) due to abnormal antenatal findings, and the remaining two were healthy (8%). A total of 13 different chromosomes with 24 non-recurring breakpoints were identified in these cases. Chromosome (#) 2 showed four breaks (16.7%), followed by #1, #4, #6, and #13 with three breaks each (12.5% each), while one break each (4.2% each) was seen on the remaining eight chromosomes (#3, #5, #8, #11, #14, #15, #17, and #21). Type I and type IV CCRs were observed in five (71.4%) and one case (14.3%), respectively, along with a "not a true" CCR (14.3%) in the present study group. Overall, the prevalence of CCRs in couples with RPL/BOH was 0.16%. To the best of our knowledge, this is the first study on the epidemiology of CCRs in couples with RPL/BOH of Indian origin. The incidence of CCRs in couples experiencing RPL/BOH in the present cohort was found to be 0.16% with type I CCR being the most predominant of all types, which is congruent with observations from non-Hispanic white and South East Asian populations. The uniqueness and rarity of each CCR pose a challenge in genetic and reproductive counseling.

Sex estimation by discriminant function analysis of long bones in prehistoric Southeast Asian populations

AbstractBiological sex estimation is an integral part of reconstructing the biological profile of an individual in forensic anthropological and bioarchaeological contexts. Formulating population specific discriminant function equations for metric variables is vital for reconstructing biological sex of fragmentary skeletal remains. This study aimed to develop multivariable and univariable sectioning point sex estimation equations from long bones of prehistoric Thailand and Cambodia people dated from 4700 to 1450 BP. A total of 481 individuals (236 females and 245 males) with 997 long bone measurements were analyzed. Discriminant function analysis was used to analyze sexually dimorphic measurements from long bones of humeri (177 females and 183 males), femora (169 females and 178 males), and tibiae (139 females and 151 males). Stepwise and direct multivariable functions offered the highest accuracies of 97.3% for humeri, 97% for femora, and 96.7% for tibiae. Univariable functions indicated that the recommended measurements for use in sex estimations with high cross‐validation accuracies are the humeral epicondylar breadth (89.1%), femoral maximum head diameter (87.1%), and tibial midshaft circumference (88.3%). These equations are applicable for use in sex estimation for the specific prehistoric Southeast Asian populations to improve our understanding of the prehistoric demography. Further evaluation and validation of the equations are required to test whether these equations can also be applied to estimate biological sex of contemporary Southeast Asian populations.

Regional variation of age-related blood pressure trajectories and their association with blood pressure control rates, disability-adjusted life years and death

Abstract Background/Introduction While the relationship between blood pressure (BP) changes and increasing age is well described, age-related BP trajectories may vary substantially across different populations and associated with differential CV risk and outcomes. Purpose The dataset of the May Measurement Month (MMM) international campaigns enables a unique investigation of regional, socio-economic and sex differences in age-BP trajectories and their association with major public-health outcomes. Method Global BP data from more than 4,5 million adult (≥18 years) screenees obtained during the cross-sectional MMM campaigns in 2017, 2018, 2019, and 2021 were used for analysis. Average BP and slopes of BP changes across age groups were calculated within regional, socio-economic and sex strata. BP slopes of individuals between 30 and 70 years of age were derived from adjusted linear regression models, along with baseline BP estimates at young age. These BP slopes were correlated in regression models adjusted for baseline BP at young age with country-specific all-cause rates of DALYs (Disability-Adjusted Life Years), death (both from Global Burden of Disease Study 2019), life expectancy (World Bank data SP.DYN.LE00.IN 2019) and BP control rates (NCD Risk Factor Collaboration). Results Age-related BP changes differed distinctly across global geographic regions, income levels, and between sexes. The steepest increase in BP with age was observed in populations from Africa and Europe, whereas a more gradual rise in BP with increasing age was seen in South-East Asian populations. Women had lower BP levels than men at younger ages (twenties and thirties), but subsequently experienced a more pronounced age-related BP increase resulting in diminishing sex differences across older age groups. Geographically divergent age-related BP trajectories were significantly associated with major national public health indicators. Globally, the steeper the age-related BP slope, the stronger the association with poor BP control (β = -0.46 [95% CI: -0.74; -0.19], p=0.001), increased DALY’s (β = 66155.68 [95% CI: 44847.0; 87464.36], p<0.001) and death rates. (β = 1017.3 [95% CI: 351.72; 1682.89], p=0.003). Conclusion Age-related BP trajectories vary considerably across global populations and contribute considerably to the variability in BP-related risks and adverse outcomes across regions. Effective public health strategies may require region-specific targeting of lifestyle and other factors contributing to adverse BP trajectories to improve health outcomes.Average blood pressure by ageAssiciations with public health metrics

The Effectiveness of E>Eye Intense Regulated Pulse Light Therapy in Treating Evaporative Dry Eye Disease among Southeast Asian Patients

Objective: Since the effectiveness of E>Eye Intense Regulated Pulsed Light (IRPL) therapy in treating evaporative dry eye condition caused by meibomian gland dysfunction (MGD) has not been reported among the Southeast Asian population, this study aimed to retrospectively report the effectiveness of this treatment in addressing evaporative dry eye due to MGD among this population using Tear Check analyzer after three consecutive treatments.Material and Methods: This is a retrospective study involving 71 male and 107 female patients, aged between 28 and 83 with complaints of dry eye symptoms accompanied by clinical signs of MGD who have been treated with E>Eye IRPL. All patients were treated with IRPL in three consecutive treatments where five overlapping flashes of light were administered on the lower lid and temporal part of each eye on day 1, 15, and 45. Improvement in lower meibomian gland loss, Tear Film Stability Evaluation (TFSE), and non-invasive breakup time (NIBUT) were assessed using the Tear Check analyzer at baseline and after the third treatment session.Results: Repeated-measure ANOVA showed that the percentage of lower meibomian gland loss and TFSE score significantly improved post-treatment, indicating recovery of the meibomian gland and improved tear stability. McNemar Change Test also showed that the percentage of patients having NIBUT of lower than 6 seconds has significantly reduced post-treatment.Conclusion: E>Eye IRPL treatment is effective in evaporative dry eye disease caused by MGD among Southeast Asian patients after three consecutive treatments by restoring meibomian gland and tear stability post-treatment.

Genetic relationships of populations of the Black Kite Milvus migrans (Accipitriformes: Accipitridae) in the east of its range in Asia and Australia

While the Black Kite Milvus migrans is one of the most widespread birds of prey, occurring over Eurasia, Africa and Australia, it remains poorly understood outside of Europe, with southeast Asian populations particularly mysterious as their taxonomy is based on outdated morphological data. The subspecies M. m. formosanus, described in 1920, is thought to inhabit Taiwan and Hainan; however, populations in these areas have experienced dramatic changes over the past fifty years. Furthermore, M. m. formosanus is the only officially recognised subspecies for which almost no genetic data is yet available. Based on two mitochondrial genes, we compared Taiwanese Black Kites with northeast Asian and Japanese M. m. lineatus, Indian M. m. govinda and Australian M. m. affinis to reconstruct details of their population history. While Indian and Australian Black Kites are descendants of the same population, they do not share common haplotypes, probably having diverged by the end of the last glaciation. The Japanese population is distinctive in showing genetic uniformity, and it may be isolated from the mainland population. Nesting Taiwanese kites carry two previously known M. m. lineatus haplogroups and a new haplogroup possibly inherited from M. m. formosanus previously occurring in the area. A recent decline in the local population, along with expansion of M. m. lineatus, most likely led to Taiwan now being inhabited by descendants of both subspecies, which form two genetically isolated populations in southern and northern Taiwan.

7560 Using a Single Pre-test Cortisol Level To Reduce The Need For Dynamic Testing For Adrenal Insufficiency In A Southeast Asian Population

Abstract Disclosure: V. Ramadoss: None. L. Tan: None. A.E. Teo: None. K. Lazarus: None. K. Meeran: None. D. Deepak: None. L. Ong: None. C. Khoo: None. P. Eng: None. Introduction: The Short Synacthen Test (SST) is widely used in clinical practice to assess Adrenal Insufficiency (AI). Despite its relative ease of administration, Synacthen use is limited by its availability and its administration demands supervision by experienced staff, resulting in increased testing cost. A single measurement of serum cortisol has been shown to predict AI, but the suggested threshold varies according to the patient cohort studied, assay variation and the prevalence of the condition relative to the size of population tested. This study aims to (a) identify a threshold cortisol level to screen for AI in a South-East Asian population and (b) to determine the utility of a stimulated 60-minute cortisol level in the diagnosis of AI. Methods: This is a retrospective analysis of SSTs (250 micrograms) performed in our institution between 28th February 2022 to 28th February 2023. Serum cortisol in our institution was measured by Abbott Alinity analysers. We defined a normal response as a stimulated cortisol value of ≥ 420nmol/L at either 30-minutes, 60-minutes, or at both time points. Logistic regression analysis was performed to predict normal responses based on baseline cortisol level. Results: Median cortisol level at baseline, 30-minutes, and 60-minutes after Synacthen stimulation were 254 (IQR 191-320) nmol/L, 499 (IQR 415 -585) nmol/L, 574 (IQR 476 -662) nmol/L respectively. A total of 785 SSTs were performed, out of which 83.1% were normal and 16.9% were abnormal. Of the 785 SSTs, 55 (7.0%) would have failed if only the 30-minute cortisol was assessed without the 60-minute value, whereas 10 (1.4%) would have failed if only the 60-minute cortisol was assessed without the 30-minutes value. An early morning basal cortisol (0800am to 1200pm) cut-off of <300nmol/L identified subnormal cortisol with 95.0% sensitivity and an afternoon cortisol (1200pm to 1700) of < 312nmol/L achieved 95.2% sensitivity. A basal cortisol level of < 100nmol/L will confirm AI with 97.3% specificity. Using a basal cortisol level of ≥ 300nmol/L, 94.8% of individuals go on to pass the SST. Use of this basal cortisol value would avoid 252 (32.1%) SSTs. Conclusion: A single measurement of basal cortisol of ≥ 300nmol/L has the potential to exclude AI with 95% sensitivity on Abbott Alinity platform in our cohort of patients. Using a threshold cortisol level of 300nmol/L, at least 32% of the SSTs could be avoided. This would have improved patients experience with cost savings implications. Furthermore, a stimulated 60-minute cortisol level identifies 55 (7%) of individuals who would otherwise be misclassified as AI, thereby avoiding unnecessary long-term glucocorticoid replacement. Presentation: 6/1/2024

A genotype imputation reference panel specific for native Southeast Asian populations.

We report the development of a "Southeast Asian Specific (SEA-specific) Reference Panel" through a "Cross-panel Imputation" approach, consisting of 2550 samples derived from the GA100K, SG10K, and the Peninsular Malaysia Orang Asli (OA) datasets, covering 113,851,450 variants. The SEA-specific panel produced more high confidence variants than 1000 Genomes Project (1KGP) when imputing the OA (8.9 million SEA-specific vs 8.1 million 1KGP) and the Singapore Genome Variation Project (SGVP) (12.5 million SEA-specific vs 11.8 million 1KGP) genotyping datasets. Further, the SEA-specific panel imputed SNPs with better estimated quality scores (INFO, DR2 and R2) on the OA genotyping dataset when comparing with TOPMED and the Human Genome Diversity Project, but performed similarly on SGVP dataset. This panel also exhibited higher recall and non-reference disconcordance rates, indicating the influence of ancestry closeness of the reference panel. However, we note that the imputation accuracy may be compromised by the size of the reference panel.

Inflammatory Factor Interleukin-6 and its Correlation with Rheumatoid Arthritis: A Meta-analysis

Introduction: at present, there are inconsistent research findings regarding the precise relationship between IL-6 gene polymorphisms (GPMs) and rheumatoid arthritis (RA). This work employed meta-analysis (MA) methodology to systematically evaluate the correlation between IL-6 GPMs and susceptibility to RA. Material and Methods: this study comprehensively searched multiple databases from inception to March 31, 2024. The search utilized keywords including “IL-6,” “Interleukin-6,” “Cytokines,” “Autoimmune diseases,” “Arthritis,” “rheumatoid arthritis,” “Inflammation,” “genetic polymorphism,” and “genetic variation.” Included studies focused on patients diagnosed with rheumatoid arthritis (RA), with healthy individuals or those without RA-related diseases as controls. The study designs encompassed cohort studies and case-control studies. Genetic frequency distributions of IL-6 gene rs1800795 (G-174C), rs1800796 (G-572C), and rs1800797 (G-597A) polymorphic sites were statistically analyzed. Quality of included studies was assessed. The preliminary assessment of literature heterogeneity was conducted. Quantitative assessment of heterogeneity results was performed using the I2 statistic in RevMan5.3. Publication bias (PB) assessment was conducted. Result: the study included a total of 21 articles, comprising 9,772 participants, with 4,679 cases diagnosed with RA and 5,093 individuals in the control (CT) group. The IL-6 gene allelic model (G vs C) exhibited a notable association with RA [OR=0.66, 95%CI: 0.51∼0.87, Z=3.02, P=0.003]. In Southeast Asian populations, IL-6 gene rs1800795 (G-174C) genotype (CC) demonstrated a considerable correlation with RA [OR=15.23, 95%CI: 3.53∼65.67, P=0.00003]. IL-6 gene rs1800795 (G-174C) genotype (CG) was associated with RA [OR=1.54, 95%CI: 1.10∼2.17, Z=2.48, P=0.01], with only the Asian population showing an observable correlation [OR=6.55, 95%CI: 1.28∼33.45, P=0.02]. Additionally, IL-6 rs1800795 (G-174C) genotype (GG) was associated with RA [OR=0.66, 95%CI: 0.49∼0.91, Z=2.55, P=0.01], with notable associations observed in the Asian [OR=0.17, 95%CI: 0.03∼0.83, P=0.03] and mixed populations [OR=1.29, 95%CI: 1.011.65, P=0.04]. No correlation was found between rs1800796 (G-572C) and rs1800797 (G-597A) GPMs and RA (P>0.05). ConclusionIL-6 gene rs1800795 (G-174C) allelic model and genotypes (CC, CG, GG) were all associated with susceptibility to RA, with the G allele model being susceptible in Southeast Asian populations, and genotypes (CG and GG) being susceptible in Asian populations. However, there was neglectable correlation between rs1800796 (G-572C) and rs1800797 (G-597A) GPMs and susceptibility to RA.

Investigating the Clinical Appropriateness of Short Synacthen Testing and Utility of Pretest Cortisol to Predict Short Synacthen Testing Outcomes: A Tertiary Center Experience in Southeast Asia

ObjectiveNo studies have investigated the predictors of an adequate cortisol response to the short synacthen test (SST) and the appropriateness of patient selection for SST in the Southeast Asian population. The aim of our study is to investigate the predictors and indications of SSTs and concondance of SSTs conducted with outcomes. MethodsThis is a retrospective study investigating all SSTs performed over a year in a tertiary center. Clinical data of patients with SSTs between February 2022 and February 2023 were extracted. We determined the appropriateness of SST testing. Binary logistic regression was used to assess the parameters that predict adequate cortisol response on SST. The proportion of individuals with biochemical “pass” or “fail” on SST was compared with the Χ2 test. Baseline cortisol levels that predicted SST pass were determined using area under receiving operating characteristics curves. ResultsOf the 781 SSTs, 83.9% of SSTs showed an adequate cortisol response. Postural hypotension (26.9%) and exogenous glucocorticoid administration (14.2%) were common indications for SST. In our cohort, 50.2% of the SSTs were inappropriately indicated. Pretest serum cortisol and albumin predict biochemical pass on SST. A pretest cortisol level of 300 nmol/L predicted SST response with 93% sensitivity and a cortisol level of <100 nmol/L confirmed adrenal insufficiency (AI) with 97.3% specificity. Using these cortisol thresholds could avoid 302 (38.5%) of SSTs. ConclusionOur analysis showed that clinical features of AI do not reliably predict SST outcomes. We advocate careful assessment of the pretest probability of AI in patients referred for SST. A pretest cortisol level can reduce the number of SSTs, with cost savings implications.

Population data for 12 X-STRs loci in Malaysian Malay and Chinese populations

The utilization of X-chromosome short tandem repeats (X-STRs) for human identification particularly in resolving complex kinship cases has been advocated. Since, forensic statistical parameters vary among different populations, and because the X-STRs population data representing the diverse population of Peninsular Malaysia remain unavailable, the specific attempt reported here for the Malays (n = 224) and Chinese (n = 201) populations appears forensically relevant to support the evidential value of the 12 X-STRs markers for human identification in Malaysia. Results derived from the Qiagen Investigator® Argus X-12 kit revealed that DXS10135 as the most polymorphic locus with high genetic diversity, polymorphic information content, heterozygosity as well as power of exclusion. Based on allele frequencies, the combined power of discrimination as well as the mean exclusion chance (MECKrüger, MECKishida, MECDesmarais and MECDesmaraisDuo) values for the Malays and Chinese were individually ≥0.999995532964908. As for the combined power of discrimination as well as the mean exclusion chance (MECKrüger, MECKishida, MECDesmarais and MECDesmaraisDuo) calculated based on haplotype frequencies, the values were ≥0.9999986410567 for the Malays and Chinese populations. In addition, results from the genetic distance, neighbor-joining phylogenetic tree and principal component analysis revealed close biogeographical distributions of the studied populations with other South East Asian populations. Hence, the utilization of the X-STRs data for identifying individuals among the Malays and Chinese populations in Peninsular Malaysia for forensic application appears as highly supported.

Femoral and tibial phenotypes of varus alignment in a Southeast Asian arthritic population: a descriptive study.

Knowledge of femoral and tibial morphology is important for patient-specific surgery in both joint reconstruction and preservation procedures. Studies evaluating morphological variance in femoral and tibial alignments in Asian populations are scarce. This is the first descriptive study evaluating the femoral and tibial phenotypes of varus alignment in a Southeast Asian population. Long-leg coronal standing radiographs of 2021 limbs were obtained, and the hip-knee-ankle angle, mechanical lateral distal femoral angle, medial proximal tibial angle and joint line convergence angle were measured. Joint line obliquity was calculated, and the knees were classified according to the Coronal Plane Alignment of Knee (CPAK) classification. Descriptive analyses on alignment parameters and demographic data (age, gender, ethnicity and body mass index [BMI]) were performed and entered into a linear regression model. The highest frequency of limb alignment in the population was found to be CPAK type I (52.71%, n = 1003). Tibial varus was the largest contributor of varus malignment. Of the varus knees (n = 1247), varus deformity was found solely in the tibia (68.60%), solely in the femur (2.07%) and was contributed by both the femur and the tibia (4.97%). In the linear regression model, BMI was found to be a strong determinant for femoral varus (P = 0.004) and joint line incongruence (P < 0.001). The findings of this study will be important to surgeons during planning for joint preservation procedures (such as corrective osteotomies) and joint arthroplasties to restore alignment.

Candidate SNPs associated with anxiety and depression in children and adolescents in the USH1C gene

Introduction: Anxiety and depression in children and adolescents are growing concerns globally, with significant rates of diagnosis across diverse populations. According to the Centers for Disease Control and Prevention (CDC), approximately 7.1% of children aged 3 to 17 years in the United States have been diagnosed with anxiety, and 3.2% with depression. The aim of this study is to analyze the correlation between SNPs in the USH1C gene and predisposition to anxiety and depression in children and adolescents from specific populations.Methods: Genotypes from the 1000 Genomes Project were used to evaluate SNPs in Southeast Asian and European populations. Linkage disequilibrium (LD) analysis was performed using VcfTools and the biological effects of the SNPs were assessed using the Variant Effect Predictor (VEP).Results: Two SNPs, rs4757538 and rs16934376, were identified, which showed strong LD with SNP rs79878474 in South Asian populations (r² &gt; 0.7), suggesting their possible association with anxiety and depression. Allele frequencies varied significantly between populations. Hardy-Weinberg equilibrium analysis showed significant imbalance at the global level, but not within individual populationsConclusions: The analyzed SNPs might be related to predisposition to anxiety and depression in specific populations. These findings underline the importance of considering genetic diversity in future studies and developing personalized interventions to address these disorders in children and adolescents

A Cross-Sectional Study Exploring the Relationship between Work-Related, Lifestyle Factors and Non-Specific Neck and Shoulder Pain in a Southeast Asian Population.

Non-specific neck and shoulder pain (NSNSP) is prevalent among working adults. The increased use of electronic devices and prevalence of remote working and study following the COVID-19 pandemic have raised concerns about the potential rise in such conditions. This study aims to investigate the associations between work-related, lifestyle factors and NSNSP in the adult Southeast Asian Singaporean population. An online survey was administered electronically to Singaporeans aged 21 and above. Demographic data, NSNSP prevalence, computer and smartphone usage durations, sleep patterns, and exercise frequency were captured after obtaining informed consent (SIT institutional review board approval #2023014). A total of 302 validated responses were recorded, including 212 suffering from NSNSP versus 90 in the comparison group. The NSNSP group showed significantly longer smartphone usage (5.37 ± 3.50 h/day) compared to the comparison group (4.46 ± 3.36 h/day, p = 0.04). Furthermore, the NSNSP group had lower exercise frequency (2.10 ± 1.74 days/week vs. 2.93 ± 2.21 days/week, p < 0.01) and shorter weekly exercise duration (2.69 ± 3.05 h/week vs. 4.11 ± 4.15 h/week, p < 0.01). The average NSNSP severity in this group was 34.9 ± 19.96 out of 100, correlating significantly with age (r = 0.201, p < 0.01) and BMI (r = 0.27, p < 0.01). This preliminary cross-sectional study examines characteristics of adult Southeast Asians with NSNSP post-COVID-19 pandemic. The findings indicate significantly longer smartphone use and less exercise in NSNSP respondents, with both age and body mass index (BMI) demonstrating significant correlations with NSNSP severity.

Anthropometric indices in predicting 10-year cardiovascular risk among males and females aged 40–74 years in south and southeast Asia: analysis of 12 WHO STEPS survey data

The relevance of anthropometric indices in predicting cardiovascular disease (CVD) or CVD risk factors is established across different countries, particularly in the high-income countries. However, past studies severely lacked representation from the south and southeast Asian countries. The main aim of this study was to determine the performance of conventional and new anthropometric indices to best predict 10-year cardiovascular disease (CVD) risk in south Asian and southeast Asian populations. The present study examined data from 14,532 participants in three south Asian and 13,846 participants (all aged between 40 and 74 years) in six southeast Asian countries, drawn from twelve cross-sectional studies (WHO STEPwise approaches to NCD risk factor surveillance [STEPS] survey data from 2008 to 2019). A Predictive performance of ten anthropometric indices were examined for predicting 10-year CVD risk ≥ 10% (CVD-R ≥ 10%). The 10-year CVD-R ≥ 10% was calculated by utilising the WHO CVD risk non-laboratory-based charts. Receiver operating characteristic (ROC) curve analysis was used to identify the optimal anthropometric index. Among the ten anthropometric indices, a body shape index (ABSI), body adiposity index (BAI), body roundness index (BRI), hip index (HI), and waist-height ratio (WHtR) performed best in predicting 10-year CVD risk among south Asian males and females. Improved performances were found for ABSI, BRI, conicity index (CI), WHtR, and waist-hip ratio (WHR) for 10-year CVD-R ≥ 10% predictions among southeast Asian males. Contrastingly, among southeast Asian females, ABSI and CI demonstrated optimal performance in predicting 10-year CVD-R ≥ 10%. The performance of anthropometric indices in predicting CVD risk varies across countries. ABSI, BAI, BRI, HI, and WHtR showed better predictions in south Asians, whereas ABSI, BRI, CI, WHtR, and WHR displayed enhanced predictions in southeast Asians. None.

An IGHG1 variant exhibits polarized prevalence and confers enhanced IgG1 antibody responses against life-threatening organisms.

Evolutionary pressures sculpt population genetics, whereas immune adaptation fortifies humans against life-threatening organisms. How the evolution of selective genetic variation in adaptive immune receptors orchestrates the adaptation of human populations to contextual perturbations remains elusive. Here, we show that the G396R coding variant within the human immunoglobulin G1 (IgG1) heavy chain presents a concentrated prevalence in Southeast Asian populations. We uncovered a 190-kb genomic linkage disequilibrium block peaked in close proximity to this variant, suggestive of potential Darwinian selection. This variant confers heightened immune resilience against various pathogens and viper toxins in mice. Mechanistic studies involving severe acute respiratory syndrome coronavirus 2 infection and vaccinated individuals reveal that this variant enhances pathogen-specific IgG1+ memory B cell activation and antibody production. This G396R variant may have arisen on a Neanderthal haplotype background. These findings underscore the importance of an IGHG1 variant in reinforcing IgG1 antibody responses against life-threatening organisms, unraveling the intricate interplay between human evolution and immune adaptation.

Genomic analysis of Strongyloides stercoralis and Strongyloides fuelleborni in Bangladesh.

About 600 million people are estimated to be infected with Strongyloides stercoralis, the species that causes most of the human strongyloidiasis cases. S. stercoralis can also infect non-human primates (NHPs), dogs and cats, rendering these animals putative sources for zoonotic human S. stercoralis infection. S. fuelleborni is normally found in old world NHPs but occasionally also infects humans, mainly in Africa. Dogs in southeast Asia carry at least two types of Strongyloides, only one of which appears to be shared with humans ("dog only" and "human and dog" types). For S. stercoralis with molecular taxonomic information, there is a strong sampling bias towards southeast and east Asia and Australia. In order to extend the geographic range of sampling, we collected human and dog derived Strongyloides spp. and hookworms from two locations in Bangladesh and subjected them to molecular taxonomic and genomic analysis based on nuclear and mitochondrial sequences. All hookworms found were Necator americanus. Contrary to earlier studies in Asia, we noticed a rather high incidence of S. fuelleborni in humans. Also in this study, we found the two types of S. stercoralis and no indication for genetic isolation from the southeast Asian populations. However, we found one genomically "dog only" type S. stercoralis in a human sample and we found two worms in a dog sample that had a nuclear genome of the "dog only" but a mitochondrial genome of the "human and dog" type. S. fuelleborni may play a more prominent role as a human parasite in certain places in Asia than previously thought. The introgression of a mitochondria haplotype into the "dog only" population suggests that rare interbreeding between the two S. stercoralis types does occur and that exchange of genetic properties, for example a drug resistance, between the two types is conceivable.

Incidence and Prognostic Values in Human Epidermal Growth Factor Receptor 2-Low Expression Metastatic Breast Cancer in Southeast Asian Population: A 10-Year Retrospective Study.

Breast cancer progression varies across molecular subtypes, and treatment options for human epidermal growth factor receptor 2 (HER2)-low expression tumors are limited compared with those of HER2 overexpression tumors. Comprehensive information regarding the epidemiology and clinical outcomes of metastatic HER2-low expression breast cancer in a Southeast Asian population is lacking. This retrospective cohort study was performed to analyze data from patients with de novo advanced breast cancer, including HER2 expression, tumor stage, and metastatic pattern. Statistical analyses, including chi-square tests and survival analyses, were used to compare HER2-low expression and HER2-negative groups. Of the 491 patients, 21.2% had HER2-low expression, 30% had HER2 overexpression, and 50% had HER2-negative expression. Among the hormone receptor (HR)-positive patients, 34% had HER2-low expression; in the triple-negative patients, the HER2-low incidence was 20.6%. No significant differences in clinical characteristics between HER2-low and HER2-negative groups were observed, except for more HR-positive patients in the HER2-low group. HER2-low patients had a longer overall survival (OS) than HER2-negative patients (43 v 23 months; hazard ratio, 0.7; P < .001), especially in HR-positive patients. After adjusting for HR status, HER2-low patients maintained improved outcomes. HR-positive HER2-low patients showed nonsignificant OS gains compared with HR-positive HER2-negative patients, regardless of first-line chemotherapy or endocrine therapy. This study revealed the incidence and clinical outcomes of HER2-low expression in de novo advanced breast cancer, suggesting favorable outcomes, particularly in HR-positive breast cancer. These findings may inform personalized treatment strategies. Further research into the mechanisms and implications of HER2-low expression in breast cancer is required.

Triglyceride-HDL index as a predictor of post-stroke outcomes: A retrospective analysis of 6,235 ischemic stroke patients from the Qatar Stroke Database

Objectives: In this study, we explored the Qatar stroke database to study the independent effect of sex- specific TG-HDL index on neurologic and cardiovascular outcomes following stroke in a predominantly Arab and Southeast Asian population. Methods: All patients admitted with acute ischemic stroke between 2014-2022 were included. TG-HDL index on admission was calculated and patients were stratified into sex-specific quartiles. We studied the 90-day modified Rankin Score (mRS), and 1-year major cardiac adverse events (MACE). Multivariate linear and binary logistic regression analyses were performed to identify the independent effect of TG-HDL index on short- and long-term outcomes. Results: A total of 6,235 stroke patients were identified. Overall, mean age was 55±13 years; 5,122 patients (82%) male; 1,989(32%) Arab; 1,628(26%) BMI ≥30; 3,526 (57%) diabetes mellitus; 4,598 (74%) hypertension, 3,158 (51%) dyslipidemia, and 1,876 (30%) smokers. The median TG levels were 1.5 (1.0-2.3), HDL levels 1.0 (0.8-1.2), and TG-HDL index was 1.5 (1.0-2.3). On long term follow-up, 120 (2%) had a recurrent stroke, 314 (5.1%) had MACE, 38 (0.6%) had post-stroke MI, and 37 (0.6%) had post-stroke cardiac revascularization procedures. On multivariate analyses, higher sex-specific TG-HDL index was independently associated with lower adjusted odds of severe stroke and lower inpatient mortality, and higher 1-year adjusted odds of post-stroke MI (p&lt;0.05). Conclusion: TG-HDL was strongly associated with in-patient mortality and long-term post-stroke cardiovascular outcomes but not long-term stroke recurrence. Our finding of an independently increased 1-year risk of post-stroke MI with higher TG-HDL index may warrant consideration of this index as a cardiac risk stratification tool for stroke patients.

Hybrid strategy of drug-eluting stent and drug-coated balloon in the treatment of de novo coronary artery disease: 1-year clinical outcomes.

The hybrid strategy of drug-eluting stent (DES) and drug-coated balloon (DCB) has been increasingly accepted for the treatment of de novo coronary artery disease. However, data regarding the clinical outcome of this practice in a Southeast Asian population are limited. We aimed to investigate the safety and clinical outcome of this hybrid strategy (DES and DCB) in the treatment of de novo coronary artery disease. The primary endpoint was target lesion failure (TLF) in the DES/DCB-treated segment at 12 months. TLF is defined as the composite of cardiac death, target vessel myocardial infarction (TVMI) and ischaemia-driven target lesion revascularisation (ID-TLR) in the DES- and/or DCB-treated segment. A total of 401 patients with 458 lesions were treated with the hybrid strategy at the National Heart Institute (IJN), Kuala Lumpur, Malaysia, from 1 July 2021 to 30 June 2022, were retrospectively enrolled in the study. A total of 38 patients (9.5%) were lost to subsequent follow-up, and the remaining 363 patients (90.5%) were included in the outcome analysis. Clinical outcomes at 1 year were analysed. In all, 219 lesions (47.8%) involved the left anterior descending artery, 146 lesions (31.9%) involved the right coronary artery, and 57 lesions (12.4%) involved the left circumflex artery. In all, 87 lesions (19%) were bifurcation lesions. A total of 8 patients (2.2%) had TLF, of whom 3 patients (0.83%) had TVMI, 3 patients (0.83%) had ID-TLR, and 2 patients (0.6%) experienced cardiac death. Four patients died of a non-cardiac cause at 1-year follow-up. A hybrid strategy of DES and DCB for the treatment of de novo coronary artery lesions appears to be feasible and clinically safe according to the 1-year outcomes.

Pilot robotic mastectomy in Singapore (PRoMiSing I) study: first safety and feasibility prospective cohort trial in South East Asia.

Robotic mastectomy has been performed worldwide since 2015. The advantages of the robotic approach in nipple-sparing mastectomy have been proven with better visualization and preservation of blood supply to the nipple-areolar complex, with a lower incidence of necrosis. It also allows smaller incisions for both mastectomy and immediate breast reconstruction. To date, no centers in Singapore and Southeast Asia offer robotic mastectomy. We believe that robotic mastectomy is a feasible and safe technique that our population can utilize. This study aimed to ascertain the surgical outcomes and perform a learning curve analysis in patients undergoing robotic mastectomy in a multi-ethnic South East Asian population. A single-arm prospective pilot study of eligible patients aged 21-70 years old with early breast cancer or high-risk patients indicated for risk-reducing mastectomy who were eligible and consented to robotic mastectomy were enrolled in this trial from December 22, 2022 to December 15, 2023. A total of 29 consecutive robotic mastectomies were performed. The mean total operative time was 95±10.2min. The average blood loss was 5.7±1.9ml, and the average length of stay was 1.05 days. The mean mastectomy specimen weight was 251g, and there was no conversion to conventional mastectomy in any case. Furthermore, there were no 30-day morbidity or complications in terms of wound infection requiring intervention, flap, and nipple-areolar complex necrosis, and postoperative hematoma/bleeding requiring intervention. This study contributes to the current evidence that robotic mastectomy is a safe and feasible option and could prove to be a great alternative to conventional mastectomy. Further prospective trials examining the long-term oncological outcomes of robotic mastectomy will be performed to establish the oncologic safety of this technique in breast cancer treatment.