Structural variant allelic heterogeneity in MECP2 duplication syndrome provides insight into clinical severity and variability of disease expression.

Background: MECP2 Duplication Syndrome, also known as X-linked intellectual developmental disorder Lubs type (MRXSL; MIM: 300260), is a neurodevelopmental disorder caused by copy number gains spanning MECP2. Despite varying genomic rearrangement structures, including duplications and triplications, and a wide range of duplication sizes, no clear correlation exists between DNA rearrangement and clinical features. We had previously demonstrated that up to 38% of MRXSL families are characterized by complex genomic rearrangements (CGRs) of intermediate complexity (2 ≤ copy number variant breakpoints < 5), yet the impact of these genomic structures on regulation of gene expression and phenotypic manifestations have not been investigated.

Noninvasive Hepatic Steatosis and Fibrosis Indices Differentially Predict Mortality in the Adult Korean Population.

Background & Aims: Because the association of hepatic fibrosis and steatosis non-invasive indices with mortality remain controversial, their association with all-cause, cardiovascular-, cancer-, and liver-related mortality was evaluated in the Korean population.

Methods: In this registry-based, cohort study, data were retrieved from the Korea National Health and Nutrition Examination Survey and mortality data from the Korean Cause of Death data registry; 40,491 individuals followed-up for a median of 8.6 years.

Prognostic value of structural variants in early breast cancer patients.

Genomic analysis of structural variants(SVs) in breast cancer (BC) patients has been conducted, but the relationship between genomic alterations and BC prognosis remains unclear. We performed RNA sequencing of 297 early BC fresh-frozen tissues. We identified SVs using three tools (STAR.

Inverted triplications formed by iterative template switches generate structural variant diversity at genomic disorder loci.

The duplication-triplication/inverted-duplication (DUP-TRP/INV-DUP) structure is a complex genomic rearrangement (CGR). Although it has been identified as an important pathogenic DNA mutation signature in genomic disorders and cancer genomes, its architecture remains unresolved. Here, we studied the genomic architecture of DUP-TRP/INV-DUP by investigating the DNA of 24 patients identified by array comparative genomic hybridization (aCGH) on whom we found evidence for the existence of 4 out of 4 predicted structural variant (SV) haplotypes.

Break-induced replication underlies formation of inverted triplications and generates unexpected diversity in haplotype structures.

Background: The duplication-triplication/inverted-duplication (DUP-TRP/INV-DUP) structure is a type of complex genomic rearrangement (CGR) hypothesized to result from replicative repair of DNA due to replication fork collapse. It is often mediated by a pair of inverted low-copy repeats (LCR) followed by iterative template switches resulting in at least two breakpoint junctions . Although it has been identified as an important mutation signature of pathogenicity for genomic disorders and cancer genomes, its architecture remains unresolved and is predicted to display at least four structural variation (SV) haplotypes.

Comprehensive profiling of DNA methylation in Korean patients with colorectal cancer.

Alterations in DNA methylation play an important pathophysiological role in the development and progression of colorectal cancer. We comprehensively profiled DNA methylation alterations in 165 Korean patients with colorectal cancer (CRC), and conducted an in-depth investigation of cancer-specific methylation patterns. Our analysis of the tumor samples revealed a significant presence of hypomethylated probes, primarily within the gene body regions; few hypermethylated sites were observed, which were mostly enriched in promoter-like and CpG island regions.

Longitudinal multi-omics study of palbociclib resistance in HR-positive/HER2-negative metastatic breast cancer.

Background: Cyclin-dependent kinase 4/6 inhibitor (CDK4/6) therapy plus endocrine therapy (ET) is an effective treatment for patients with hormone receptor-positive/human epidermal receptor 2-negative metastatic breast cancer (HR+/HER2- MBC); however, resistance is common and poorly understood. A comprehensive genomic and transcriptomic analysis of pretreatment and post-treatment tumors from patients receiving palbociclib plus ET was performed to delineate molecular mechanisms of drug resistance.

Methods: Tissue was collected from 89 patients with HR+/HER2- MBC, including those with recurrent and/or metastatic disease, receiving palbociclib plus an aromatase inhibitor or fulvestrant at Samsung Medical Center and Seoul National University Hospital from 2017 to 2020.

Benefits and harms of normal saline instillation before endotracheal suctioning in mechanically ventilated adult patients in intensive care units: A systematic literature review and meta-analysis.

Objectives: This systematic review aimed to identify the effects of normal saline instillation before endotracheal suctioning on clinical outcomes in critically ill patients on a mechanical ventilator.

Research Methodology: This review was based on the guidelines of the National Evidence-based Healthcare Collaborating Agency in Korea and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. Six electronic databases were searched for relevant literature.

Fibrosis-4 Index Predicts Long-Term All-Cause, Cardiovascular and Liver-Related Mortality in the Adult Korean Population.

Background & Aims: Associations between hepatic fibrosis and mortality remain to be fully elucidated in large population-based studies. This study aimed to evaluate the associations of the fibrosis-4 index (FIB-4) with all-cause, cardiovascular, cancer, and liver-related mortality in the adult Korean population without viral hepatitis.

Methods: Baseline data were retrieved from the Korea National Health and Nutrition Examination Survey, and mortality data were retrieved from the Korean Cause of Death data registry.

Associations between School Lunch and Obesity in Korean Children and Adolescents Based on the Korea National Health and Nutrition Examination Survey 2017-2019 Data: A Cross-Sectional Study.

Obesity in children and adolescents is a serious global problem. In Korea, approximately 35% of students' daily nutrient intake is from school lunch (SL), and all schools provide SL. However, the association between SL and obesity remains controversial.

Evaluation of Allergenicity on a ω-5 Gliadin-Deficient Cultivar in Wheat-Dependent Exercise-Induced Anaphylaxis.

Purpose: ω-5 gliadin is the major allergen that causes wheat-dependent exercise-induced anaphylaxis (WDEIA). Recently, a missing mutant wheat cultivar at 1B chromosome and closely linked was bred. This cultivar (ω5D) has a deficiency in ω-5 and γ-gliadins as well as some low-molecular-weight glutenins.

Genetic Aspects of Small for Gestational Age Infants Using Targeted-Exome Sequencing and Whole-Exome Sequencing: A Single Center Study.

Background: The etiology of small for gestational age (SGA) is multifactorial and includes maternal/uterine-placental factors, fetal epigenetics, and genetic abnormalities. We evaluated the genetic causes and diagnostic effectiveness of targeted-panel sequencing (TES) or whole-exome sequencing (WES) in SGA infants without a known cause.

Methods: A prospective study was conducted on newborn infants born with a birth weight of less than the 10th percentile for gestational age between January 2019 and December 2020 at the Pusan National University Hospital.

Molecular Subtypes Based on Genomic and Transcriptomic Features Correlate with the Responsiveness to Immune Checkpoint Inhibitors in Metastatic Clear Cell Renal Cell Carcinoma.

Clear cell renal cell carcinoma (ccRCC) has been reported to be highly immune to and infiltrated by T cells and has angiogenesis features, but the effect of given features on clinical outcomes followed by immune checkpoint inhibitors (ICIs) in ccRCC has not been fully characterized. Currently, loss of function mutation in , a PBAF-complex gene frequently mutated in ccRCC, is associated with clinical benefit from ICIs, and is considered as a predictive biomarker for response to anti-PD-1 therapy. However, functional mechanisms of mutation regarding immunotherapy responsiveness are still poorly understood.

Exploratory analysis of biomarkers associated with clinical outcomes from the study of palbociclib plus endocrine therapy in premenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer.

Background: Palbociclib plus endocrine therapy (ET) demonstrated significant progression-free survival (PFS) benefit in Young Pearl, a randomized phase ll trial comparing palbociclib + ET versus capecitabine in premenopausal women with hormone receptor positive, HER2 negative metastatic breast cancer (MBC). This exploratory analysis investigated potential biomarkers of palbociclib plus ET on PFS.

Patients And Methods: Of 178 patients randomized (92 palbociclib plus ET; 86 capecitabine), we performed targeted sequencing (141 patients) and whole transcriptome sequencing (165 patients) using baseline tumor samples to examine genomic alteration in relation to drug response on PFS.

Additive Effects of Exercise or Nutrition Intervention in a 24-Month Multidisciplinary Treatment with a Booster Intervention for Children and Adolescents with Overweight or Obesity: The ICAAN Study.

This study compared the effects of a real-world multidisciplinary intervention with additional exercise or nutritional elements and investigated the effectiveness of a booster intervention after weight regain. A total of 242 children and adolescents (age- and sex-specific body mass index [BMI] ≥ 85th percentile, mean age: 10.82 years, 60% male) were allocated to three groups: usual care, exercise, or nutrition.

Metabolomic Signatures for the Effects of Weight Loss Interventions on Severe Obesity in Children and Adolescents.

Childhood obesity has increased worldwide, and many clinical and public interventions have attempted to reduce morbidity. We aimed to determine the metabolomic signatures associated with weight control interventions in children with obesity. Forty children from the "Intervention for Children and Adolescent Obesity via Activity and Nutrition (ICAAN)" cohort were selected according to intervention responses.

Clinical and Laboratory Findings of Nosocomial Sepsis in Extremely Low Birth Weight Infants According to Causative Organisms.

Background: nosocomial sepsis remains a significant source of morbidity and mortality in extremely low birth weight (ELBW) infants. Early and accurate diagnosis is very important, but it is difficult due to the similarities in clinical manifestation between the causative microorganisms. We tried to identify the differences between causative microorganisms in clinical and laboratory findings and to help choose antibiotics, when sepsis was suspected in ELBW infants.

Changes in Plasma Choline and the Betaine-to-Choline Ratio in Response to 6-Month Lifestyle Intervention Are Associated with the Changes of Lipid Profiles and Intestinal Microbiota: The ICAAN Study.

Trimethylamine -oxide (TMAO) and its precursors, including choline, betaine, and L-carnitine, are gut microbiota-related metabolites associated with the risk of obesity. We aimed (1) to comprehensively examine whether the changes in plasma TMAO and its precursors induced by lifestyle intervention are associated with the improvements in plasma metabolic parameters; and (2) to identify the fecal microbiome profiles and nutrient intakes associated with these metabolites and metabolic index. Data from 40 participants (obese children and adolescents) having the plasma metabolites data related to the changes in BMI z-scores after 6-month lifestyle intervention were analyzed.

Genomic profile of MYCN non-amplified neuroblastoma and potential for immunotherapeutic strategies in neuroblastoma.

Background: MYCN amplification is the most important genomic feature in neuroblastoma (NB). However, limited studies have been conducted on the MYCN non-amplified NB including low- and intermediate-risk NB. Here, the genomic characteristics of MYCN non-amplified NB were studied to allow for the identification of biomarkers for molecular stratification.

Clinical implications of HER2 mRNA expression and intrinsic subtype in refractory HER2-positive metastatic breast cancer treated with pan-HER inhibitor, poziotinib.

Introduction: We explored clinical implication of intrinsic molecular subtype in human epidermal growth factor receptor 2 (HER2) + metastatic breast cancer (BC) with pan-HER inhibitor from a phase II clinical trial of poziotinib in refractory HER2+BC patients.

Methods: For this translational research correlated with phase II clinical trial, we performed an nCounter expression assay, using gene panel including 50 genes for PAM50 prediction and targeted deep sequencing.

Results: From 106 participants, we obtained 97 tumor tissues and analyzed gene expression in 91 of these samples.

Clinical Characteristics and Exploratory Genomic Analyses of Germline BRCA1 or BRCA2 Mutations in Breast Cancer.

gBRCA1/2 mutations increase the incidence of breast cancer by interrupting the homologous recombination repair (HRR) pathway. Although gBRCA1 and gBRCA2 breast cancer have similar clinical profiles, different molecular characteristics have been observed. In this study, we conducted comprehensive genomic analyses and compared gBRCA1/2 breast cancer.

Evidence-based customized nutritional intervention improves body composition and nutritional factors for highly-adherent children and adolescents with moderate to severe obesity.

Background/objectives: Evidence-based customized nutritional interventions are required for effective treatment of moderate to severe obese children and adolescents.

Subjects/methods: Sixty six (64.1% of 103) of the eligible participants who joined the usual care or physical activity group in the clinic were involved in 16-week intervention.