Co-transcriptional methylations of histone H3 at lysines 4 and 36, highly conserved methyl marks from yeast to humans, have profound roles in regulation of histone acetylation. These modifications function to recruit and/or activate distinct histone acetyltransferases (HATs) or histone deacetylases (HDACs). Whereas H3K4me3 increases acetylation at promoters via multiple HATs, H3K4me2 targets Set3 HDAC to deacetylate histones in 5' transcribed regions. In 3' regions of genes, H3K36me2/3 facilitates deacetylation by Rpd3S HDAC and slows elongation. Despite their important functions in deacetylation, no strong effects on global gene expression have been seen under optimized or laboratory growth conditions. Instead, H3K4me2-Set3 HDAC and Set2-Rpd3S pathways primarily delay the kinetics of messenger RNA (mRNA) and long noncoding RNA (lncRNA) induction upon environmental changes. A majority of mRNA genes regulated by these pathways have an overlapping lncRNA transcription either from an upstream or an antisense promoter. Surprisingly, the distance between mRNA and lncRNA promoters seems to specify the repressive effects of the two pathways. Given that co-transcriptional methylations and acetylation have been linked to many cancers, studying their functions in a dynamic condition or during cancer progression will be much more important and help identify novel genes associated with cancers.
Acetylation ; Gene Expression* ; Histone Acetyltransferases ; Histone Deacetylases ; Histones* ; Humans ; Kinetics ; Methylation* ; RNA, Long Noncoding ; RNA, Messenger ; Yeasts

Women undergo various physical changes because of hormonal changes occurring after menopause. Some representative changes caused by the reduction in estrogen levels in these women are dyslipidemia, abnormal lipoprotein levels, obesity, weight gain, and changes in body fat distribution. A characteristic of women approaching menopause is the shift of fat from their hips and thighs to their abdomen. Notably, fat accumulation is common in internal organs, resulting in male-pattern obesity among women approaching menopause; therefore, these women require more exercise therapy than premenopausal women to prevent and treat obesity. To the best of our knowledge, no effective exercise therapy guidelines have been established for postmenopausal women; therefore, I aimed to suggest more effective diet and exercise therapies for postmenopausal women with obesity. For this purpose, I organized the diet and exercise protocol by collaborating with an obstetrician and a researcher specializing in sports medicine; further, this protocol was actually applied to all participants. The results indicated that the protocol is effective in reducing weight; however, joint pain was commonly noted in participants who dropped out of the program. Based on the evaluation of joint pain, this study found that it is necessary to perform exercise therapy by avoiding weight-bearing activities and reinforcing personalized joint strengthening exercises because reduced estrogen level is an important factor exacerbating arthritis in postmenopausal women.

Background: Malaria elimination strategies in the Republic of Korea (ROK) have decreased malaria incidence but face challenges due to delayed case detection and response. To improve this, machine learning models for predicting malaria, focusing on high-risk areas, have been developed. Methods: The study targeted the northern region of ROK, near the demilitarized zone, using a 1-km grid to identify areas for prediction. Grid cells without residential buildings were excluded, leaving 8,425 cells. The prediction was based on whether at least one malaria case was reported in each grid cell per month, using spatial data of patient locations. Four algorithms were used: gradient boosted (GBM), generalized linear (GLM), extreme gradient boosted (XGB), and ensemble models, incorporating environmental, sociodemographic, and meteorological data as predictors. The models were trained with data from May to October (2019–2021) and tested with data from May to October 2022. Model performance was evaluated using the area under the receiver operating characteristic curve (AUROC). Results: The AUROC of the prediction models performed excellently (GBM = 0.9243, GLM = 0.9060, XGB = 0.9180, and ensemble model = 0.9301). Previous malaria risk, population size, and meteorological factors influenced the model most in GBM and XGB. Conclusion Machine-learning models with properly preprocessed malaria case data can provide reliable predictions. Additional predictors, such as mosquito density, should be included in future studies to improve the performance of models.

BACKGROUND: The clinical presentation and course of Langerhans cell histiocytosis (LCH) are variable, ranging from an isolated, spontaneously remitting bone lesion to multisystem disease with risk organ involvement. Treatment of LCH ranges from a wait-and-see attitude to intensive multidrug therapy and, in some cases, bone marrow transplantation. It is necessary to develop an objective score for assessing disease activity in patients with LCH. We propose a new clinical scoring system to evaluate disease activity at diagnosis that can predict the clinical outcomes of LCH and correlate it with clinical courses. METHODS: Clinical data, obtained from children diagnosed with LCH at Asan Medical Center and Hanyang University Hospital between March 1998 and February 2009, were studied retrospectively. The scoring system was developed according to the basic biological data, radiological findings, and physical findings and applied to a database containing information on 133 patients. RESULTS: The median age of the 133 patients (74 male, 59 female) was 52 months (range, 0.6-178 months), and LCH was diagnosed based on CD1a positivity. At diagnosis, the score distributions were highly asymmetrical: the score was between 1 and 2 in 75.9% of cases, 3-6 in 15.8%, and greater than 6 in 8.3%. Initial scores above 6 were highly predictive of reactivation and late complications. CONCLUSION: This new LCH disease activity score provides an objective tool for assessing disease severity, both at diagnosis and during follow-up.
Bone Marrow Transplantation ; Child ; Follow-Up Studies ; Histiocytosis ; Histiocytosis, Langerhans-Cell ; Humans ; Langerhans Cells ; Male ; Retrospective Studies

BACKGROUND: Few scales are currently available to evaluate changes in hand volume. We aimed to develop a hand grading scale for quantitative assessments of dorsal hand volume with additional consideration of changes in skin texture; to validate and prove the precision and reproducibility of the new scale; and to demonstrate the presence of clinically significant differences between grades on the scale. METHODS: Five experienced plastic surgeons developed the Hand Volume Rating Scale (HVRS) and rated 91 images. Another five plastic surgeons validated the scale using 50 randomly selected images. Intra- and inter-rater agreement was calculated using the weighted kappa statistic and intraclass correlation coefficients (ICCs). Paired images were also evaluated to verify whether the scale reflected clinical differences. RESULTS: The intra-rater agreement was 0.95 (95% confidence interval, 0.922–0.974). The interrater ICCs were excellent (first rating, 0.94; second rating, 0.94). Image pairs that differed by 1, 2, and 3 grades were considered to contain clinically relevant differences in 80%, 100%, and 100% of cases, respectively, while 84% of image pairs of the same grade were found not to show clinically relevant differences. This confirmed that the scale of the HVRS corresponded to clinically relevant distinctions. CONCLUSIONS: The scale was proven to be precise, reproducible, and reflective of clinical differences.
Asian Continental Ancestry Group ; Hand ; Humans ; Plastics ; Rejuvenation ; Skin ; Skin Aging ; Surgeons ; Weights and Measures

Objectives: This study aimed to analyze trends in the timely diagnosis of malaria cases over the past 10 years in relation to the utilization of different types of healthcare facilities. Methods: The study included 3,697 confirmed and suspected cases of malaria reported between January 1, 2013, and December 31, 2022, in the national integrative disease and healthcare management system. Some cases lacking a case report or with information missing from the case report were excluded from the analysis. A generalized linear model with a Poisson distribution was constructed to estimate rate ratios and 95% confidence intervals adjusted for other variables, such as distance. Results: When cases involving diagnosis >5 days after symptom onset in confirmed patients (5DD) were examined according to the type of healthcare facility, the rate ratio of 5DD cases was found to be higher for public health facilities than for tertiary hospitals. Specifically, the rate ratio was higher when the diagnosis was established at a tertiary hospital, even after a participant had visited primary or secondary hospitals. In an analysis adjusted for the distance to each participant’s healthcare facility, the results did not differ substantially from the results of the crude analysis. Conclusion It is imperative to improve the diagnostic capabilities of public facilities and raise awareness of malaria at primary healthcare facilities for effective prevention and control.

Objective: To elucidate whether clinical features and the weighted genetic risk score (wGRS) were associated with the presence of lupus nephritis (LN). Methods: We retrospectively divided patients with systemic lupus erythematosus (SLE, n=1,078) into biopsy-proven LN (n=507) and non-LN groups (non-LN, n=571). Baseline clinical features, serologic markers, and the wGRS were collected. The wGRS was calculated from 112 non-human leukocyte antigen (non-HLA) loci and HLA-DRβ1 amino acid haplotypes for SLE. Associations among clinical features, wGRS, and the presence of LN were identified. Results: In the multivariate analysis, patients with LN were younger at diagnosis (odds ratio [OR]=0.97, p＜0.001), had more pleuritis (OR=2.44, p＜0.001) and pericarditis (OR=1.62, p=0.029), had a higher detection rate of anti-double stranded deoxyribonucleic acid (anti-dsDNA antibodies, OR=2.22, p＜0.001), anti-Smith antibodies (anti-Sm antibodies, OR=1.70, p=0.002), low level of complement (OR=1.37, p=0.043) and absence of antiphospholipid antibodies (aPL antibodies, OR=1.60, p=0.002), and had higher wGRS (OR=1.16, p=0.012). Mediation analysis suggested that anti-Sm antibodies and low complement could be mediators in the relationship between high wGRS and the presence of LN. Conclusion Onset age, pleuritis, pericarditis, several serologic markers, and wGRS were associated with the presence of LN. Anti-Sm antibodies and low complement appeared to mediate the indirect relationship between wGRS and the presence of LN.

Objective: To elucidate whether clinical features and the weighted genetic risk score (wGRS) were associated with the presence of lupus nephritis (LN). Methods: We retrospectively divided patients with systemic lupus erythematosus (SLE, n=1,078) into biopsy-proven LN (n=507) and non-LN groups (non-LN, n=571). Baseline clinical features, serologic markers, and the wGRS were collected. The wGRS was calculated from 112 non-human leukocyte antigen (non-HLA) loci and HLA-DRβ1 amino acid haplotypes for SLE. Associations among clinical features, wGRS, and the presence of LN were identified. Results: In the multivariate analysis, patients with LN were younger at diagnosis (odds ratio [OR]=0.97, p＜0.001), had more pleuritis (OR=2.44, p＜0.001) and pericarditis (OR=1.62, p=0.029), had a higher detection rate of anti-double stranded deoxyribonucleic acid (anti-dsDNA antibodies, OR=2.22, p＜0.001), anti-Smith antibodies (anti-Sm antibodies, OR=1.70, p=0.002), low level of complement (OR=1.37, p=0.043) and absence of antiphospholipid antibodies (aPL antibodies, OR=1.60, p=0.002), and had higher wGRS (OR=1.16, p=0.012). Mediation analysis suggested that anti-Sm antibodies and low complement could be mediators in the relationship between high wGRS and the presence of LN. Conclusion Onset age, pleuritis, pericarditis, several serologic markers, and wGRS were associated with the presence of LN. Anti-Sm antibodies and low complement appeared to mediate the indirect relationship between wGRS and the presence of LN.

Entecavir (Baraclude®) is an oral antiviral drug used for the treatment of HBV. Entecavir is a reverse transcriptase inhibitor which prevents the HBV from multiplying. Most common adverse reactions caused by entecavir are headache, fatigue, dizziness, and nausea. Until now, there has been no report of peripheral neuropathy as a side effect associated with entecavir treatment. Herein, we report a case of peripheral neuropathy which probably occurred after treatment with entecavir in a hepatitis B patient. The possibility of the occurrence of this side effect should be carefully taken into consideration when a patient takes a high dose of entecavir for a long period of time or has risk factors for neuropathy at the time of initiating entecavir therapy.
Administration, Oral ; Antiviral Agents/*adverse effects/therapeutic use ; Brain/diagnostic imaging ; Drug Therapy, Combination ; Duloxetine Hydrochloride/therapeutic use ; Glucocorticoids/therapeutic use ; Guanine/adverse effects/*analogs & derivatives/therapeutic use ; Hepatitis B, Chronic/drug therapy ; Humans ; Male ; Middle Aged ; Polyneuropathies/*diagnosis/drug therapy/etiology ; Prednisolone/therapeutic use ; Pregabalin/therapeutic use ; Tomography, X-Ray Computed

OBJECTIVE: To develop guidelines and recommendations to prevent and treat glucocorticoid-induced osteoporosis (GIOP) in Korea. METHODS: The Korean Society for Bone and Mineral Research and the Korean College of Rheumatology developed this guideline based on Guidance for the Development of Clinical Practice Guidelines version 1.0 established by the National Evidence-Based Healthcare Collaborating Agency. This guideline was developed by adapting previously-published guidelines, and a systematic review and quality assessment were conducted. RESULTS: This guideline applies to adults aged 19 years or older who are using or plan to use glucocorticoids (GCs), but does not include children and adolescents. An initial assessment of fracture risk should be performed within 6 months of initial GC use. Fracture risk should be estimated using FRAX (Fracture Risk Assessment Tool) with adjustments for GC dose, previous osteoporotic fracture history, and bone mineral density (BMD) results. All patients taking more than 2.5 mg/day prednisolone or equivalent for more than 3 months are recommended to take adequate calcium and vitamin D. Patients at moderate to high fracture risk should be treated with additional osteoporosis medication. All patients continuing GC therapy should receive an annual BMD measurement, vertebral X-ray, and fracture risk assessment using FRAX. When a treatment failure is suspected, switching to another drug should be considered. CONCLUSION: This guideline is intended to provide guidance for clinicians in prevention and treatment of GIOP.
Adolescent ; Adult ; Bone Density ; Calcium ; Child ; Denosumab ; Diphosphonates ; Evidence-Based Practice ; Glucocorticoids ; Humans ; Korea ; Miners ; Osteoporosis* ; Osteoporotic Fractures ; Prednisolone ; Rheumatology ; Risk Assessment ; Teriparatide ; Treatment Failure ; Vitamin D