Carrier Frequency and Incidence of -Associated Polyposis Based on Database Analysis in East Asians and Koreans.

Background: -associated polyposis is an autosomal recessive disorder associated with an increased lifetime risk of colorectal cancer and a moderately increased risk of ovarian, bladder, breast, and endometrial cancers. We analyzed the carrier frequency and estimated the incidence of -associated polyposis in East Asian and Korean populations, for which limited data were previously available.

Methods: We examined 125,748 exomes from the gnomAD database, including 9,197 East Asians, and additional data from 5,305 individuals in the Korean Variant Archive and 1,722 in the Korean Reference Genome Database.

Exact Decoding of a Sequentially Markov Coalescent Model in Genetics.

In statistical genetics, the sequentially Markov coalescent (SMC) is an important family of models for approximating the distribution of genetic variation data under complex evolutionary models. Methods based on SMC are widely used in genetics and evolutionary biology, with significant applications to genotype phasing and imputation, recombination rate estimation, and inferring population history. SMC allows for likelihood-based inference using hidden Markov models (HMMs), where the latent variable represents a genealogy.

Guidance for Triangulating Data and Estimates of HIV Prevalence Among Pregnant Women and Coverage of PMTCT Using the Spectrum AIDS Impact Module.

Background: Most countries use the Spectrum AIDS Impact Module (Spectrum-AIM), antenatal care routine HIV testing, and antiretroviral treatment data to estimate HIV prevalence among pregnant women. Nonrepresentative program data may lead to inaccurate estimates of HIV prevalence and treatment coverage for pregnant women.

Setting: One hundred fifty-four countries and subnational locations across 126 countries.

Guidance for triangulating data and estimates of HIV prevalence among pregnant women and coverage of PMTCT using the Spectrum AIDS Impact Module.

Background: Most countries use the Spectrum AIDS Impact Module (Spectrum-AIM), antenatal care routine HIV testing, and antiretroviral treatment data to estimate HIV prevalence among pregnant women. Non-representative programme data may lead to inaccurate estimates HIV prevalence and treatment coverage for pregnant women.

Setting: 154 locations in 126 countries.

Familial chylomicronemia syndrome: case reports of siblings with deletions of the GPIHBP1 gene.

Background: Familial chylomicronemia syndrome (FCS) is a rare monogenic form of severe hypertriglyceridemia, caused by mutations in genes involved in triglyceride metabolism. Herein, we report the case of a Korean family with familial chylomicronemia syndrome caused by compound heterozygous deletions of glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1).

Case Presentation: A 4-year-old boy was referred for the evaluation of severe hypertriglyceridemia (3734 mg/dL) that was incidentally detected 4 months prior.

KCNJ3 is a novel candidate gene for autosomal dominant pure hereditary spastic paraplegia identified using whole genome sequencing.

Hereditary spastic paraplegia (HSP) is a group of familial diseases characterized by progressive corticospinal tract degeneration. Clinically, patients present with lower-limb spasticity and weakness. To date, more than 80 genetic HSP types have been identified.

Progranulin haploinsufficiency mediates cytoplasmic TDP-43 aggregation with lysosomal abnormalities in human microglia.

Background: Progranulin (PGRN) haploinsufficiency due to progranulin gene (GRN) variants can cause frontotemporal dementia (FTD) with aberrant TAR DNA-binding protein 43 (TDP-43) accumulation. Despite microglial burden with TDP-43-related pathophysiology, direct microglial TDP-43 pathology has not been clarified yet, only emphasized in neuronal pathology. Thus, the objective of this study was to investigate TDP-43 pathology in microglia of patients with PGRN haploinsufficiency.

Differentiation, maturation, and collection of THP-1-derived dendritic cells based on a PEG hydrogel culture platform.

Purpose: Dendritic cell (DC) is a spearhead responsible for immune response and surrounded by extracellular matrix in three-dimensional (3D) tissue. Nevertheless, conventional DC culture has relied on suspension or two-dimensional (2D) tissue culture plate (TCP)-based culture system. This culture condition often fails to recapitulate the physiological behavior of DC in real tissue.

Novel In-Frame Deletion Variant in a Family With Intellectual Developmental Disorder With Speech Delay and Dysmorphic Facies.

Objectives: Intellectual developmental disorder with speech delay, autism, and dysmorphic facies (IDDSADF) is caused by heterozygous (MIM# 604910) variants on chromosome 19q13. This study aimed to identify and describe the clinical features of a Korean family with maternally inherited speech delay and intellectual and developmental disability to elucidate the underlying genetic mechanism.

Methods: We conducted whole-exome sequencing and confirmatory Sanger sequencing on the proband, the mother, and unaffected grandparents with wild-type genotypes.

Carrier frequency and incidence of alpha-mannosidosis: population database-based study-focus on the East Asian and Korean population.

Alpha-mannosidosis caused by mutations in the gene is a rare genetic disorder characterized by physical abnormalities and intellectual disabilities. The objective of this study was to analyze the carrier frequency and estimated incidence of alpha-mannosidosis in East Asian populations, as limited data exists on its incidence in this group. In this study, a total of 125,748 exomes from the gnomAD database was analyzed.

Age-associated mortality is partially mediated by TERT promoter mutation status in differentiated thyroid carcinoma.

Background: Age at diagnosis (AAD) and telomerase reverse transcriptase (TERT) promoter mutations are prognostic factors in differentiated thyroid carcinoma (DTC), and the prevalence of the mutations increases with AAD. Considering this correlation, we investigated whether an interaction between AAD and the mutations is present and whether the mutation mediates the effect of AAD on the mortality rate in DTC.

Methods: The study included 393 patients with DTC who were followed-up after thyroidectomy at a single medical center in Korea from 1994 to 2004.

Effect of Matrix Stiffness and Hepatocyte Growth Factor on Small Cell Lung Cancer Cells in Decellularized Extracellular Matrix-Based Hydrogels.

Small cell lung cancer (SCLC) is one of lethal cancers resulting in very low 5-year-survival rate. Although its clinical treatment largely relies on chemotherapy, SCLC cell physiology in three-dimenstional (3D) matrix has been less explored. In this work, the tumor microenvironment is reconstructed with decellularized porcine pulmonary extracellular matrix (dECM) with hyaluronic acid.

Identification of two novel COL3A1 variants in patients with vascular Ehlers-Danlos syndrome.

Background: Vascular Ehlers-Danlos syndrome (vEDS) is an autosomal dominant disease caused by aberrations in COL3A1, which encodes type III collagen. Sanger sequencing has limitations for diagnosis since exon deletion/duplication and splicing alterations are not uncommon in COL3A1. We report 2 patients with vEDS who were not diagnosed by conventional Sanger sequencing.

Differential Diagnosis of Pulmonary Veno-Occlusive Disease and/or Pulmonary Capillary Hemangiomatosis after Identification of Two Novel Variants by Whole-Exome Sequencing.

Background: Pulmonary veno-occlusive disease (PVOD) and/or pulmonary capillary hemangiomatosis (PCH) are rare causes of pulmonary hypertension. Pulmonary arterial hypertension (PAH) and PVOD/PCH are clinically similar, but there is a risk of drug-induced pulmonary edema when PCH patients receive the PAH therapy. Therefore, early diagnosis of PVOD/PCH is important.

Carrier frequency and incidence of aromatic L-amino acid decarboxylase deficiency: a gnomAD-based study.

Background: Aromatic L-amino acid decarboxylase (AADC) deficiency is an autosomal recessive neurotransmitter metabolism disorder and is clinically characterized by infancy hypotonia, ophthalmic crisis, and developmental delay. With the emergence of gene therapy for AADC deficiency, accurate prediction of AADC deficiency is required. This study aimed to analyze the carrier frequency and expected incidence of AADC deficiency using exome data from the Genome Aggregation Database (gnomAD).

Role of NCKAP1 in the Defective Phagocytic Function of Microglia-Like Cells Derived from Rapidly Progressing Sporadic ALS.

Microglia plays a key role in determining the progression of amyotrophic lateral sclerosis (ALS), yet their precise role in ALS has not been identified in humans. This study aimed to identify a key factor related to the functional characteristics of microglia in rapidly progressing sporadic ALS patients using the induced microglia model, although it is not identical to brain resident microglia. After confirming that microglia-like cells (iMGs) induced by human monocytes could recapitulate the main signatures of brain microglia, step-by-step comparative studies were conducted to delineate functional differences using iMGs from patients with slowly progressive ALS [ALS(S), n = 14] versus rapidly progressive ALS [ALS(R), n = 15].

Proteolytically degradable PEG hydrogel matrix mimicking tumor immune microenvironment for 3D co-culture of lung adenocarcinoma cells and macrophages.

Tumor-associated macrophages and monocytes are the major stromal cell types found in the tumor immune microenvironment (TIME), which modulates tumor progression, invasion, and chemoresistance. To address the need for an three-dimensional tumor model for understanding the complex cellular interactions within the TIME, we propose a TIME-mimetic co-culture matrix composed of photo-crosslinked poly(ethylene glycol) hydrogels mimicking the characteristics of the tumor and stroma. Desmoplasia-mimetic microgels encapsulating lung adenocarcinoma cells (A549) were embedded with monocyte- or macrophage-type U937 cells in normal stroma-mimetic hydrogel, increasing the proximity between the two cell types.

The Diagnostic Yield and Difficulties of Utilizing Soft-clipped Read Clusters Encountered in Clinical Exome Sequencing.

Background: Despite the wide use of next generation sequencing, there are still many difficulties in detecting structural variants. A split read is one of the clues of structural variants and is represented as a soft-clipped read in the raw sequencing data. Considering that most of the breakpoints of structural variants reside in non-coding regions, split read information has not been routinely used in exome sequencing or targeted panel sequencing.

Integrative modeling of tumor genomes and epigenomes for enhanced cancer diagnosis by cell-free DNA.

Multi-cancer early detection remains a key challenge in cell-free DNA (cfDNA)-based liquid biopsy. Here, we perform cfDNA whole-genome sequencing to generate two test datasets covering 2125 patient samples of 9 cancer types and 1241 normal control samples, and also a reference dataset for background variant filtering based on 20,529 low-depth healthy samples. An external cfDNA dataset consisting of 208 cancer and 214 normal control samples is used for additional evaluation.

Structural Characteristics and Properties of Cocoon and Regenerated Silk Fibroin from Different Silkworm Strains.

Silk has attracted the attention of researchers as a biomedical and cosmetic material because of its good biocompatibility and cytocompatibility. Silk is produced from the cocoons of silkworms, which have various strains. In this study, silkworm cocoons and silk fibroins (SFs) were obtained from ten silkworm strains, and their structural characteristics and properties were examined.

Selection Criteria for Completion Thyroidectomy in Follicular Thyroid Carcinoma Using Primary Tumor Size and TERT Promoter Mutational Status.

Background: A stepwise surgical approach with hemithyroidectomy and completion thyroidectomy was used to achieve definite characterization of follicular thyroid carcinoma (FTC). Choosing appropriate candidates for completion thyroidectomy has been controversial.

Objective: The aim of this study was to clarify the selection criteria for completion thyroidectomy using telomerase reverse transcriptase (TERT) promoter mutation.

Development and performance evaluation of an artificial intelligence algorithm using cell-free DNA fragment distance for non-invasive prenatal testing (aiD-NIPT).

With advances in next-generation sequencing technology, non-invasive prenatal testing (NIPT) has been widely implemented to detect fetal aneuploidies, including trisomy 21, 18, and 13 (T21, T18, and T13). Most NIPT methods use cell-free DNA (cfDNA) fragment count (FC) in maternal blood. In this study, we developed a novel NIPT method using cfDNA fragment distance (FD) and convolutional neural network-based artificial intelligence algorithm (aiD-NIPT).