Exploring multi-omics and clinical characteristics linked to accelerated biological aging in Asian women of reproductive age: insights from the S-PRESTO study.

Background: Phenotypic age (PhenoAge), a widely used marker of biological aging, has been shown to be a robust predictor of all-cause mortality and morbidity in different populations. Existing studies on biological aging have primarily focused on individual domains, resulting in a lack of a comprehensive understanding of the multi-systemic dysregulation that occurs in aging.

Methods: PhenoAge was evaluated based on a linear combination of chronological age (CA) and 9 clinical biomarkers in 952 multi-ethnic Asian women of reproductive age.

Association of Acylcarnitines With Maternal Cardiometabolic Risk Factors Is Defined by Chain Length: The S-PRESTO Study.

Context: Due to the essential role of carnitine as an intermediary in amino acid, carbohydrate, and lipid metabolism, a detailed characterization of circulating and urinary carnitine concentrations will aid in elucidating the molecular basis of impaired maternal metabolic flexibility and facilitating timely intervention for expectant mothers.

Objective: To investigate the association of maternal plasma and urinary free carnitine and acylcarnitines with cardiometabolic risk factors.

Methods: Liquid chromatography tandem mass spectrometry-based quantification of free carnitine and acylcarnitines (C2-C18) was performed on 765 plasma and 702 urine samples collected at preconception, 26 to 28 weeks' pregnancy, and 3 months postpartum in the Singapore PREconception Study of long-Term maternal and child Outcomes (S-PRESTO) cohort study.

Dynamic altruistic cooperation within breast tumors.

Background: Social behaviors such as altruism, where one self-sacrifices for collective benefits, critically influence an organism's survival and responses to the environment. Such behaviors are widely exemplified in nature but have been underexplored in cancer cells which are conventionally seen as selfish competitive players. This multidisciplinary study explores altruism and its mechanism in breast cancer cells and its contribution to chemoresistance.

Plasma lipidomic profiling reveals metabolic adaptations to pregnancy and signatures of cardiometabolic risk: a preconception and longitudinal cohort study.

Background: Adaptations in lipid metabolism are essential to meet the physiological demands of pregnancy and any aberration may result in adverse outcomes for both mother and offspring. However, there is a lack of population-level studies to define the longitudinal changes of maternal circulating lipids from preconception to postpartum in relation to cardiometabolic risk factors.

Methods: LC-MS/MS-based quantification of 689 lipid species was performed on 1595 plasma samples collected at three time points in a preconception and longitudinal cohort, Singapore PREconception Study of long-Term maternal and child Outcomes (S-PRESTO).

Time-to-conception and clinical pregnancy rate with a myo-inositol, probiotics, and micronutrient supplement: secondary outcomes of the NiPPeR randomized trial.

Objective: To determine whether a combined myo-inositol, probiotics and micronutrient nutritional supplement impacts time-to-natural-conception and clinical pregnancy rates.

Design: Secondary outcomes of a double-blind randomized controlled trial.

Setting: Community recruitment.

A direct sequencing assay for pharmacogenetic testing of thiopurine-intolerant NUDT15 alleles in an Asian population.

Objective: The nucleoside diphosphate linked moiety X (Nudix)-Type motif 15 (NUDT15) enzyme is involved in thiopurine metabolism. Genetic variants in the NUDT15 gene result in decreased NUDT15 activity, which in addition to decreased thiopurine S-methyltransferase (TPMT) activity, contributes to thiopurine toxicity. Current standard approaches of NUDT15 genetic analysis have mainly been targeting several common variants.

The socioeconomic landscape of the exposome during pregnancy.

Background: While socioeconomic position (SEP) is consistently related to pregnancy and birth outcome disparities, relevant biological mechanisms are manifold, thus necessitating more comprehensive characterization of SEP-exposome associations during pregnancy.

Objectives: We implemented an exposomic approach to systematically characterize the socioeconomic landscape of prenatal exposures in a setting where social segregation was less distinct in a hypotheses-generating manner.

Methods: We described the correlation structure of 134 prenatal exogenous and endogenous sources (e.

Association of plasma kynurenine pathway metabolite concentrations with metabolic health risk in prepubertal Asian children.

Background: The tryptophan-kynurenine (KYN) pathway is linked to obesity-related systemic inflammation and metabolic health. The pathway generates multiple metabolites, with little available data on their relationships to early markers of increased metabolic disease risk in children. The aim of this study was to examine the association of multiple KYN pathway metabolites with metabolic risk markers in prepubertal Asian children.

The Kynurenine Pathway Metabolites in Cord Blood Positively Correlate With Early Childhood Adiposity.

Context: The kynurenine pathway generates metabolites integral to energy metabolism, neurotransmission, and immune function. Circulating kynurenine metabolites positively correlate with adiposity in children and adults, yet it is not known whether this relationship is present already at birth.

Objective: In this prospective longitudinal study, we investigate the relationship between cord blood kynurenine metabolites and measures of adiposity from birth to 4.

Multicenter study on the genetics of glomerular diseases among southeast and south Asians: Deciphering Diversities - Renal Asian Genetics Network (DRAGoN).

Multinational studies have reported monogenic etiologies in 25%-30% of children with steroid-resistant nephrotic syndrome. Such large studies are lacking in Asia. We established Deciphering Diversities: Renal Asian Genetics Network (DRAGoN) and aimed to describe the genetic and clinical spectrums in Asians.

Genetic Link Determining the Maternal-Fetal Circulation of Vitamin D.

Vitamin D is an essential micronutrient whose demand is heightened during pregnancy to support the growth of the fetus. Furthermore, the fetus does not produce vitamin D and hence relies exclusively on the supply of maternal vitamin D through the placenta. Vitamin D inadequacy is linked with pregnancy complications and adverse infant outcomes.

A novel de novo androgen receptor nonsense mutation in a sex-reversed 46,XY infant.

An infant with 46,XY karyotype, and unambiguous female phenotype was found to have testes in the inguinal regions. Capillary sequencing of the androgen receptor (AR) gene identified a hemizygous de novo mutation (NM_000044.6:c.

A De Novo Mosaic Variant Causing Sporadic X-Linked Hypophosphatemic Rickets in a 2-Year-Old Girl.

Pathogenic variants in the gene are causative of X-linked hypophosphatemic rickets (XLH). We present a case of a 2-year-old girl with hypophosphatemic rickets with genu varum and short stature without any family history of XLH. Next generation sequencing of the gene identified a splice donor variant, NM_000444.

Laboratory Verification of a and Massively Parallel Sequencing Assay from Wet Bench to Bioinformatics for Germline DNA Analysis.

 A robust genetic test for and genes is necessary for the diagnosis, prognosis, and treatment of patients with hereditary breast and ovarian cancer. We evaluated a commercial amplicon-based massively parallel sequencing (MPS) assay, BRCA MASTR Plus on the MiSeq platform, for germline genetic testing.  This study was performed on 31 DNA from cell lines and proficiency testing samples to establish the accuracy of the assay.

Validation of the Hemochromatosis (2SNP+) Direct EUROArray Assay for the Molecular Diagnosis of -Related Hereditary Hemochromatosis.

Two missense variants in the gene, c.845G>A (p.Cys282Tyr) and c.

Genetic testing of GCK-MODY identifies a novel pathogenic variant in a Chinese boy with early onset hyperglycemia.

Glucokinase-maturity-onset diabetes of the young (GCK-MODY or MODY 2), caused by a heterozygous inactivating variant in the ( gene, is a common form of MODY. Here, we present a case of GCK-MODY in a young Chinese boy, his sister and his father with a novel pathogenic variant in exon 8 of the gene, NM_000162.5:c.

Paper-Based MicroRNA Expression Profiling from Plasma and Circulating Tumor Cells.

Background: Molecular characterization of circulating tumor cells (CTCs) holds great promise for monitoring metastatic progression and characterizing metastatic disease. However, leukocyte and red blood cell contamination of routinely isolated CTCs makes CTC-specific molecular characterization extremely challenging.

Methods: Here we report the use of a paper-based medium for efficient extraction of microRNAs (miRNAs) from limited amounts of biological samples such as rare CTCs harvested from cancer patient blood.