Increased local DNA methylation disorder in AMLs with DNMT3A-destabilizing variants and its clinical implication.

The mechanistic link between the complex mutational landscape of de novo methyltransferase DNMT3A and the pathology of acute myeloid leukemia (AML) has not been clearly elucidated so far. Motivated by a recent discovery of the significance of DNMT3A-destabilizing mutations (DNMT3A) in AML, we here investigate the common characteristics of DNMT3A AML methylomes through computational analyses. We present that methylomes of DNMT3A AMLs are considerably different from those of DNMT3A AMLs in that they exhibit increased intratumor DNA methylation heterogeneity in bivalent chromatin domains.

Development of Marine-Degradable Poly(Ester Amide)s with Strong, Up-Scalable, and Up-Cyclable Performance.

Biodegradable polyesters provide an attractive alternative to non-degradable plastics but often encounter a tradeoff between biodegradability and mechanical properties because esters are rotational and lack hydrogen bonds. Conversely, natural polyamides, i.e.

Human immunodeficiency virus-1 induces host genomic R-loops and preferentially integrates its genome near the R-loop regions.

Although HIV-1 integration sites favor active transcription units in the human genome, high-resolution analysis of individual HIV-1 integration sites has shown that the virus can integrate into a variety of host genomic locations, including non-genic regions. The invisible infection by HIV-1 integrating into non-genic regions, challenging the traditional understanding of HIV-1 integration site selection, is more problematic because they are selected for preservation in the host genome during prolonged antiretroviral therapies. Here, we showed that HIV-1 integrates its viral genome into the vicinity of R-loops, a genomic structure composed of DNA-RNA hybrids.

Punishing "gender deviants"? Women born in the year of the white horse and college selectivity.

Belief in the Chinese zodiac, a cultural belief widely held in East Asian cultures, posits that people are fated to have different traits according to the zodiac animal attached to their birth year. As a white horse is culturally associated with masculine traits, Korean women born in the White Horse year are presumed to be argumentative, headstrong, and born with "too much" Yin energy. In this study, we analyze a nationally representative sample of Korean college graduates to examine whether and how being born in the White Horse year, thereby being chronically exposed to gender stereotype-violating stigma, affects women's higher educational attainment.

MicroRNA miR-199a-3p alleviates liver fibrosis by targeting CDK17 in activated hepatic stellate cells.

Liver fibrosis, a common feature of most chronic liver diseases, poses significant health risks and results from various etiologies. While microRNAs (miRNAs) have demonstrated promising anti-fibrotic potential through the direct regulation of target genes, their therapeutic mechanisms remain incompletely understood. In this study, we identified miR-199a, initially discovered in anti-liver fibrotic exosomes, as a key modulator that alleviates thioacetamide-induced liver fibrosis in a mouse model.

Unraveling the impact of lysosomal dysfunction on myeloproliferative neoplasm.

Background: Lysosomal dysfunction (LD) impacts cytokine regulation, inflammation, and immune responses, influencing the development and progression of cancer. Inflammation is implicated in the pathogenesis of myeloproliferative neoplasm (MPN). With a hypothesis that LD significantly contributes to MPN carcinogenesis by inducing abnormal inflammation, our objective was to elucidate the pathophysiological mechanisms of MPN arising from an LD background.

Human cytomegalovirus harnesses host L1 retrotransposon for efficient replication.

Genetic parasites, including viruses and transposons, exploit components from the host for their own replication. However, little is known about virus-transposon interactions within host cells. Here, we discover a strategy where human cytomegalovirus (HCMV) hijacks L1 retrotransposon encoded protein during its replication cycle.

Multi-layered knowledge graph neural network reveals pathway-level agreement of three breast cancer multi-gene assays.

Multi-gene assays have been widely used to predict the recurrence risk for hormone receptor (HR)-positive breast cancer patients. However, these assays lack explanatory power regarding the underlying mechanisms of the recurrence risk. To address this limitation, we proposed a novel multi-layered knowledge graph neural network for the multi-gene assays.

Effectiveness of lumbar motion style acupuncture treatment on inpatients with acute low back pain: A pragmatic, randomized controlled trial.

Background And Purpose: This parallel, single-center, pragmatic, randomized controlled study aimed to investigate the effectiveness and safety of motion style acupuncture treatment (MSAT; a combination of acupuncture and Doin therapy) to reduce pain and improve the functional disability of patients with acute low back pain (aLBP) due to road traffic accidents.

Materials And Methods: Ninety-six patients with aLBP admitted to the Haeundae Jaseng Hospital of Korean Medicine in South Korea due to traffic accidents were treated with integrative Korean medicine (IKM) with additional 3-day MSAT sessions during hospitalization (MSAT group, 48 patients) or without (control group, 48 patients), and followed up for 90 days.

Results: The mean numeric rating scale (NRS) scores of low back pain (LBP) of the MSAT and control groups were both 6.

Evaluation and optimization of sequence-based gene regulatory deep learning models.

Neural networks have emerged as immensely powerful tools in predicting functional genomic regions, notably evidenced by recent successes in deciphering gene regulatory logic. However, a systematic evaluation of how model architectures and training strategies impact genomics model performance is lacking. To address this gap, we held a DREAM Challenge where competitors trained models on a dataset of millions of random promoter DNA sequences and corresponding expression levels, experimentally determined in yeast, to best capture the relationship between regulatory DNA and gene expression.

A Prospective Sociocentric Study of 2 Entire Traditional Korean Villages: The Korean Social Life, Health, and Aging Project (KSHAP).

The Korean Social Life, Health, and Aging Project (KSHAP) was a multidisciplinary prospective study conducted in South Korea that measured various health biomarkers from blood, hair, and brain magnetic resonance imaging, and we examined their associations with sociocentric (global) social network data of older adults in 2 entire villages (or cohorts). Cohort K included participants aged 60 years or older, and cohort L included participants aged 65 years or older. We performed a baseline survey involving 814 of the 860 individuals (94.

Characterization of Mechanical Properties and Grain Size of Stainless Steel 316L via Metal Powder Injection Molding.

The metal powder injection molding process is completed by mixing a metal powder and a binder, performing an injection molding and degreasing process, and then performing a sintering process for high density. The disadvantage of metal powder injection molding is that defects occurring during the process affect mechanical properties, which are worse in mechanical properties than in products manufactured by cold-rolling. In this study, the mechanical properties and microstructure of stainless steel 316L manufactured by the metal powder injection molding process were analyzed.

Characterization of radiation-resistance mechanism in Spirosoma montaniterrae DY10 in terms of transcriptional regulatory system.

To respond to the external environmental changes for survival, bacteria regulates expression of a number of genes including transcription factors (TFs). To characterize complex biological phenomena, a biological system-level approach is necessary. Here we utilized six computational biology methods to infer regulatory network and to characterize underlying biologically mechanisms relevant to radiation-resistance.

Metheor: Ultrafast DNA methylation heterogeneity calculation from bisulfite read alignments.

Phased DNA methylation states within bisulfite sequencing reads are valuable source of information that can be used to estimate epigenetic diversity across cells as well as epigenomic instability in individual cells. Various measures capturing the heterogeneity of DNA methylation states have been proposed for a decade. However, in routine analyses on DNA methylation, this heterogeneity is often ignored by computing average methylation levels at CpG sites, even though such information exists in bisulfite sequencing data in the form of phased methylation states, or methylation patterns.

Learning the histone codes with large genomic windows and three-dimensional chromatin interactions using transformer.

The quantitative characterization of the transcriptional control by histone modifications has been challenged by many computational studies, but most of them only focus on narrow and linear genomic regions around promoters, leaving a room for improvement. We present Chromoformer, a transformer-based, three-dimensional chromatin conformation-aware deep learning architecture that achieves the state-of-the-art performance in the quantitative deciphering of the histone codes in gene regulation. The core essence of Chromoformer architecture lies in the three variants of attention operation, each specialized to model individual hierarchy of transcriptional regulation involving from core promoters to distal elements in contact with promoters through three-dimensional chromatin interactions.

Risk Stratification for Breast Cancer Patient by Simultaneous Learning of Molecular Subtype and Survival Outcome Using Genetic Algorithm-Based Gene Set Selection.

Patient stratification is a clinically important task because it allows us to establish and develop efficient treatment strategies for particular groups of patients. Molecular subtypes have been successfully defined using transcriptomic profiles, and they are used effectively in clinical practice, e.g.

Colistin-degrading proteases confer collective resistance to microbial communities during polymicrobial infections.

Background: The increasing prevalence of resistance against the last-resort antibiotic colistin is a significant threat to global public health. Here, we discovered a novel colistin resistance mechanism via enzymatic inactivation of the drug and proposed its clinical importance in microbial communities during polymicrobial infections.

Results: A bacterial strain of the Gram-negative opportunistic pathogen Stenotrophomonas maltophilia capable of degrading colistin and exhibiting a high-level colistin resistance was isolated from the soil environment.

Optimum Urine Cotinine and NNAL Levels to Distinguish Smokers from Non-Smokers by the Changes in Tobacco Control Policy in Korea from 2008 to 2018.

Introduction: We examined the age- and sex-specific distributions of biomarkers of tobacco smoke exposure to determine the optimal cutoffs to distinguish smokers from non-smokers over the last 10 years in Korea, during which smoking prevalence and secondhand smoke (SHS) exposure declined due to changes in tobacco control policy.

Methods: We analyzed data from the Korea National Health and Nutrition Examination Survey on creatinine-adjusted urinary cotinine (2008-2018; 33 429 adults: 15 653 males and 17 776 females) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL; 2016-2018; 6337 adults: 3091 males and 3246 females). We determined the optimal cutoffs and confidence intervals (CIs) to distinguish smokers from non-smokers using receiver operator characteristic curve analysis and bootstrapping (1000 resamples).

Knowledge-guided artificial intelligence technologies for decoding complex multiomics interactions in cells.

Cells survive and proliferate through complex interactions among diverse molecules across multiomics layers. Conventional experimental approaches for identifying these interactions have built a firm foundation for molecular biology, but their scalability is gradually becoming inadequate compared to the rapid accumulation of multiomics data measured by high-throughput technologies. Therefore, the need for data-driven computational modeling of interactions within cells has been highlighted in recent years.

Eco-friendly erucamide-polydimethylsiloxane coatings for marine anti-biofouling.

Marine biofouling of ship hulls and ocean structures causes enormous economic losses due to increased frictional drag. Thus, efforts have been exerted worldwide to eliminate biofouling. In addition, a strong demand exists for the development of a cost-effective and eco-friendly anti-biofouling coating technology.

Chemoenzymatic valorization of agricultural wastes into 4-hydroxyvaleric acid via levulinic acid.

Given that (i) levulinic acid (LA) is one of the most significant platform chemicals derived from biomass and (ii) 4-hydroxyvaleric acid (4-HV) is a potential LA derivative, the aim of this study is to achieve chemoenzymatic valorization of LA, which was obtained from agricultural wastes, to 4-HV. The thermochemical process utilized agricultural wastes (i.e.