Chromatin remodeling of histone H3 variants by DDM1 underlies epigenetic inheritance of DNA methylation.

Nucleosomes block access to DNA methyltransferase, unless they are remodeled by DECREASE in DNA METHYLATION 1 (DDM1LSH/HELLS), a Snf2-like master regulator of epigenetic inheritance. We show that DDM1 promotes replacement of histone variant H3.3 by H3.1. In ddm1 mutants, DNA methylation is partly restored by loss of the H3.3 chaperone HIRA, while the H3.1 chaperone CAF-1 becomes essential. The single-particle cryo-EM structure at 3.2 Å of DDM1 with a variant nucleosome reveals engagement with histone H3.3 near residues required for assembly and with the unmodified H4 tail. An N-terminal autoinhibitory domain inhibits activity, while a disulfide bond in the helicase domain supports activity. DDM1 co-localizes with H3.1 and H3.3 during the cell cycle, and with the DNA methyltransferase MET1Dnmt1, but is blocked by H4K16 acetylation. The male germline H3.3 variant MGH3/HTR10 is resistant to remodeling by DDM1 and acts as a placeholder nucleosome in sperm cells for epigenetic inheritance.

A crossbar array of magnetoresistive memory devices for in-memory computing.

Implementations of artificial neural networks that borrow analogue techniques could potentially offer low-power alternatives to fully digital approaches1-3. One notable example is in-memory computing based on crossbar arrays of non-volatile memories4-7 that execute, in an analogue manner, multiply-accumulate operations prevalent in artificial neural networks. Various non-volatile memories-including resistive memory8-13, phase-change memory14,15 and flash memory16-19-have been used for such approaches. However, it remains challenging to develop a crossbar array of spin-transfer-torque magnetoresistive random-access memory (MRAM)20-22,  despite the technology's practical advantages such as endurance and large-scale commercialization5. The difficulty stems from the low resistance of MRAM, which would result in large power consumption in a conventional crossbar array that uses current summation for analogue multiply-accumulate operations. Here we report a 64 × 64 crossbar array based on MRAM cells that overcomes the low-resistance issue with an architecture that uses resistance summation for analogue multiply-accumulate operations. The array is integrated with readout electronics in 28-nanometre complementary metal-oxide-semiconductor technology. Using this array, a two-layer perceptron is implemented to classify 10,000 Modified National Institute of Standards and Technology digits with an accuracy of 93.23 per cent (software baseline: 95.24 per cent). In an emulation of a deeper, eight-layer Visual Geometry Group-8 neural network with measured errors, the classification accuracy improves to 98.86 per cent (software baseline: 99.28 per cent). We also use the array to implement a single layer in a ten-layer neural network to realize face detection with an accuracy of 93.4 per cent.

Host immunomodulatory lipids created by symbionts from dietary amino acids.

Small molecules derived from symbiotic microbiota critically contribute to intestinal immune maturation and regulation1. However, little is known about the molecular mechanisms that control immune development in the host-microbiota environment. Here, using a targeted lipidomic analysis and synthetic approach, we carried out a multifaceted investigation of immunomodulatory α-galactosylceramides from the human symbiont Bacteroides fragilis (BfaGCs). The characteristic terminal branching of BfaGCs is the result of incorporation of branched-chain amino acids taken up in the host gut by B. fragilis. A B. fragilis knockout strain that cannot metabolize branched-chain amino acids showed reduced branching in BfaGCs, and mice monocolonized with this mutant strain had impaired colonic natural killer T (NKT) cell regulation, implying structure-specific immunomodulatory activity. The sphinganine chain branching of BfaGCs is a critical determinant of NKT cell activation, which induces specific immunomodulatory gene expression signatures and effector functions. Co-crystal structure and affinity analyses of CD1d-BfaGC-NKT cell receptor complexes confirmed the interaction of BfaGCs as CD1d-restricted ligands. We present a structural and molecular-level paradigm of immunomodulatory control by interactions of endobiotic metabolites with diet, microbiota and the immune system.

Prognosis after switching to electronic cigarettes following percutaneous coronary intervention: a Korean nationwide study.

BACKGROUND AND AIMS: Despite the increasing popularity of electronic cigarettes (E-cigarettes), the prognostic impact of switching to E-cigarettes in smokers with coronary artery disease who have undergone percutaneous coronary intervention (PCI) remains unclear. METHODS: Using a nationwide cohort from the Korean National Health Insurance database, 17 973 adults (≥20 years) identified as smokers (based on a health screening examination within 3 years before PCI) who underwent health screening within 3 years after PCI were enrolled to determine changes in smoking habits. Patients were classified as continued combustible cigarette users, successful quitters, or switchers to E-cigarettes. The group switching to E-cigarettes was further divided into dual users (using both combustible and E-cigarettes) and those exclusively using E-cigarettes. Primary outcomes included major adverse cardiac events (MACEs), a composite of all-cause death, spontaneous myocardial infarction, and repeat revascularization. RESULTS: Among the total population, 8951 patients (49.8%) continued using combustible cigarettes, 1694 (9.4%) were switched to E-cigarettes, and 7328 (40.7%) successfully quit smoking after PCI. During a median follow-up of 2.4 years, the cumulative incidence of MACE was lower among E-cigarette switchers (10%) or quitters (13.4%) than among continued combustible cigarette users (17%). When continued combustible cigarette users were used as the reference, the multivariable-adjusted hazard ratios with 95% confidence intervals for MACE were 0.82 (0.69-0.98) for switchers to E-cigarettes and 0.87 (0.79-0.96) for successful quitters. Compared with dual users, entirely switching to E-cigarettes was associated with a significantly lower MACE risk (hazard ratio 0.71; 95% confidence interval 0.51-0.99). CONCLUSIONS: Among smokers who underwent PCI for coronary artery disease, switching to E-cigarette use (particularly complete transition) or quitting smoking was associated with reduced MACE risk than with continued combustible cigarette use. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT06338761.

Randomized, Double-Blind, Active-Controlled Phase 3 Study to Evaluate Efficacy and Safety of Zastaprazan Compared With Esomeprazole in Erosive Esophagitis.

INTRODUCTION: Zastaprazan is a potent potassium-competitive acid blocker developed to treat gastroesophageal reflux disease. The aim of this study was to evaluate the efficacy and safety of zastaprazan compared with esomeprazole in patient with erosive esophagitis (EE). METHODS: A phase III, multicenter, randomized, double-blind, noninferiority clinical study was conducted with 300 subjects with confirmed EE. Subjects were randomized to receive zastaprazan 20 mg or esomeprazole 40 mg once daily up to 8 weeks. The primary end point was the cumulative proportion of subject with healed EE confirmed by endoscopy at week 8. The secondary end points included the healing rate at week 4, symptom response, and quality of life assessment. Safety profiles and serum gastrin levels were also assessed. RESULTS: In the full analysis set, the cumulative healing rate at week 8 were 97.92% (141/144) for zastaprazan and 94.93% (131/138) ( P = 0.178) for esomeprazole. The healing rate at week 4 in the zastaprazan group was higher than the esomeprazole group (95.14% [137/144] vs 87.68% [121/138]; P = 0.026). There was no significant difference between groups in healing rates (the per-protocol set) at week 8 and week 4, symptom responses, quality of life assessments, and safety profiles. In addition, serum gastrin levels increased during treatment in both groups, with a significant difference between the 2 groups ( P = 0.047), but both decreased after treatment. DISCUSSION: An 8-week therapy of zastaprazan 20 mg is noninferior to esomeprazole 40 mg in subjects with predominantly low-grade EE. The healing rate at week 4 appears to be higher for zastaprazan than esomeprazole.

Applicability of selected reaction monitoring for precise screening tests.

INTRODUCTION: The proactive identification of diseases through screening tests has long been endorsed as a means to preempt symptomatic onset. However, such screening endeavors are fraught with complications, such as diagnostic inaccuracies, procedural risks, and patient unease during examinations. These challenges are amplified when screenings for multiple diseases are administered concurrently. Selected Reaction Monitoring (SRM) offers a unique advantage, allowing for the high-throughput quantification of hundreds of analytes with minimal interferences. AREAS COVERED: Our research posits that SRM-based assays, traditionally tailored for single-disease biomarker profiling, can be repurposed for multi-disease screening. This innovative approach has the potential to substantially alleviate time, labor, and cost demands on healthcare systems and patients alike. Nonetheless, there are formidable methodological hurdles to overcome. These include difficulties in detecting low-abundance proteins and the risk of model overfitting due to the multiple functionalities of single proteins across different disease spectrums - issues especially pertinent in blood-based assays where detection sensitivity is constrained. As we move forward, technological strides in sample preparation, online extraction, throughput, and automation are expected to ameliorate these limitations. EXPERT OPINION: The maturation of mass spectrometry's integration into clinical laboratories appears imminent, positioning it as an invaluable asset for delivering highly sensitive, reproducible, and precise diagnostic results.

Impact of smoking reduction on lung cancer risk in patients with COPD who smoked fewer than 30 pack-years: a nationwide population-based cohort study.

BACKGROUND: The effects of smoking reduction on the incidence of lung cancer in patients with chronic obstructive pulmonary disease (COPD) are not well known. This study aimed to investigate the effects of changes in smoking habits after COPD diagnosis on lung cancer development in patients who smoked less than 30 pack-years. METHODS: This nationwide retrospective cohort study included 16,832 patients with COPD who smoked less than 30 pack-years at the time of COPD diagnosis. Based on changes in smoking habits in the health screening examination data, smokers were categorized into three groups: quitters, reducers, and sustainers. The primary outcome was the risk of lung cancer development, which was estimated using the Cox proportional hazards model. We also modelled the amount of smoking reduction as a continuous variable. RESULTS: During a median follow-up of 4 years, the cumulative incidence of lung cancer was the highest among sustainers, followed by reducers and quitters. Compared with sustainers, reducers (adjusted HR 0.74, 95% CI:0.56-0.98) and quitters (adjusted HR 0.78, 95% CI:0.64-0.96) had a significantly lower risk of lung cancer. Incidence of lung cancer showed a decreasing trend with a decreasing amount of smoking (P for linearity < 0.01). CONCLUSIONS: In patients with COPD who smoked less than 30 pack-years, smoking reduction and cessation lowered the risk of lung cancer.

Longitudinal BMI change and outcomes in Chronic Obstructive Pulmonary Disease: a nationwide population-based cohort study.

BACKGROUND: The association between longitudinal body mass index (BMI) change and clinical outcomes in patients with chronic obstructive pulmonary disease (COPD) has not fully investigated. METHODS: This retrospective cohort study included 116,463 COPD patients aged ≥ 40, with at least two health examinations, one within 2 years before and another within 3 years after COPD diagnosis (January 1, 2014, to December 31, 2019). Associations between BMI percentage change with all-cause mortality, primary endpoint, and initial severe exacerbation were assessed. RESULTS: BMI decreased > 5% in 14,728 (12.6%), while maintained in 80,689 (69.2%), and increased > 5% in 21,046 (18.1%) after COPD diagnosis. Compared to maintenance group, adjusted hazard ratio (aHR) for all-cause mortality was 1.70 in BMI decrease group (95% CI:1.61, 1.79) and 1.13 in BMI increase group (95% CI:1.07, 1.20). In subgroup analysis, decrease in BMI showed a stronger effect on mortality as baseline BMI was lower, while an increase in BMI was related to an increase in mortality only in obese COPD patients with aHRs of 1.18 (95% CI: 1.03, 1.36). The aHRs for the risk of severe exacerbation (BMI decrease group and increase group vs. maintenance group) were 1.30 (95% CI:1.24, 1.35) and 1.12 (95% CI:1.07, 1.16), respectively. CONCLUSIONS: A decrease in BMI was associated with an increased risk of all-cause mortality in a dose-dependent manner in patients with COPD. This was most significant in underweight patients. Regular monitoring for weight loss might be an important component for COPD management.

Differences in Cognitive Trajectories of Dementia: Comparison of Alzheimer's Disease Dementia and Dementia with Lewy Bodies in a Korean Patient Cohort.

INTRODUCTION: Prediction of the dementia progression is important for patient management. We aimed to investigate the cognitive trajectories of Alzheimer's disease dementia (ADD) and dementia with Lewy bodies (DLB) according to the initial structural change measured by comprehensive visual rating scales (CVRS). METHODS: We retrospectively included the patients who initially visited the Dementia Clinic of Chonnam National University Hospital between 2010 and 2012. All patients underwent dementia workup including neuropsychological battery (Seoul Neuropsychological Screening Battery, SNSB). We recruited the participant who underwent SNSB annually for 3 years successively. A total of 136 patients of ADD and 63 patients of DLB were included for analysis. We analyzed the decline pattern of the cognitive profile according to the initial brain structural changes. RESULTS: The general cognitive trajectories between ADD and DLB patients were not different. However, DLB patients showed more rapid decline of cognitive function in language and related function, visual memory function, and frontal executive function. The scores were lower in participants with DLB with the lesser atrophy group in attention, visuospatial function, and frontal executive function. In analysis of the cognitive trajectories, the visual memory domain declined rapidly in the DLB with lesser atrophy group compared with the ADD with lesser atrophy group. CONCLUSION: We founded that the differences in the visual cognitive profile in ADD and DLB patients in serial follow-up of neuropsychological tests. It is prominent in the mild structural change group of ADD and DLB.

Effectiveness of Early Thiopurine Use in Korean Patients With Moderate-to-Severe Ulcerative Colitis: A Prospective Multicenter Cohort (MOSAIK) Study.

BACKGROUND: Thiopurines play an important role in the management of steroid-refractory and steroid-dependent ulcerative colitis. However, the effectiveness of the early use of thiopurines in ulcerative colitis remains controversial. MATERIALS AND METHODS: In this multicenter prospective cohort (MOSAIK) study, we divided patients with ulcerative colitis into those who underwent early (within 6 mo of diagnosis) and late (6 mo after diagnosis) thiopurine therapy to determine the effectiveness of early thiopurine treatment. The primary outcome was the cumulative rate of clinical relapse (Mayo score >2 points). Multivariate Cox proportional hazards regression was used to identify independent clinical factors associated with the outcomes. RESULTS: Overall, 333 patients with moderate-to-severe ulcerative colitis were included. Of the 118 patients treated with thiopurines, 65 (55.1%) and 53 (44.9%) received thiopurine therapy within and after 6 months of diagnosis. The cumulative use rate of thiopurines was 38.9% at 3 years after diagnosis. The median initial dose of thiopurines was 0.7 mg/kg (0.3 to 2.0); the median maintenance dose was 1.1 mg/kg (0.3 to 2.4). The cumulative rate of clinical relapse was not significantly different between patients who started thiopurine therapy within 6 months of diagnosis and those who started therapy 6 months after diagnosis (P=0.712). The presence of extraintestinal manifestations (hazard ratio: 4.674, 95% CI: 1.210-18.061, P=0.025) independently predicted an increased risk of clinical relapse. CONCLUSIONS: Patients with ulcerative colitis who received early thiopurine therapy did not differ significantly in terms of clinical relapse compared with those who received late therapy.

Comprehensive Immunohistochemical Analysis of Mesonephric Marker Expression in Low-grade Endometrial Endometrioid Carcinoma.

Immunohistochemical markers shown to be useful in identifying/confirming mesonephric/mesonephric-like differentiation (MLD markers) include thyroid transcription factor (TTF1), GATA-binding protein 3 (GATA3), and cluster of differentiation 10 (CD10). Only a few studies have examined the expression levels of MLD markers in endometrial endometrioid carcinomas (EECs). This study aimed to analyze the frequency and pattern of MLD marker expression in low-grade EECs. We performed immunostaining for the detection of TTF1, GATA3, and CD10 expression in 50 low-grade EEC tissue samples and evaluated their staining proportion and intensity. Nine tumors (18.0%) expressed at least one MLD marker in varying proportions and intensities, and 2 of these tumors were positive for 2 MLD markers (TTF1/GATA3 and GATA3/CD10, respectively). Three (6.0%) tumors showed moderate-to-strong nuclear TTF1 immunoreactivity in ≤5% of the tumor cells. Five tumors (10.0%) had at least moderate nuclear GATA3 staining, and three of them displayed a staining proportion of ≥15%. Three tumors (6.0%) were focal (mean proportion, 15%) but strongly positive for CD10. Our findings indicate that a subset of EEC can express one or more MLD markers with varying staining proportions and intensities. Given that a diagnosis of uterine mesonephric-like adenocarcinoma should be established based on a combination of characteristic histologic features, unique immunophenotypes, and confirmed molecular findings, pathologists should not exclude EEC based only on the presence of focal immunoreactivity for MLD markers. Awareness of the atypical expression patterns of MLD markers in EEC helps pathologists avoid misdiagnosing EEC as a uterine mesonephric-like adenocarcinoma.

Risk Factors Affecting Clinical Outcomes of Low-risk Early-stage Human Papillomavirus-Associated Endocervical Adenocarcinoma Treated by Surgery Alone: Application of Silva Pattern.

This study aimed to report the clinical outcomes and risk factors for survival of patients with low-risk early-stage human papillomavirus-associated (HPVA) endocervical adenocarcinoma (EAC) treated with surgery alone. This retrospective study obtained the clinicopathological data of patients with early-stage HPVA EAC who underwent surgery between 2012 and 2018. The Silva pattern of invasion was determined by reviewing pathology slides. Locoregional recurrence-free survival (RFS), RFS, and overall survival were calculated, and the risk factors for survival were analyzed. One hundred seventeen patients with a median follow-up of 5.2 years (0.5-9.7 yr) were included. The most common histologic type was usual (94/117, 80.3%). The Silva pattern was A in 79 patients (67.5%), B in 30 (25.6%), and C in 8 (6.8%). The 5-year locoregional RFS, RFS, and overall survival rates were 92.4%, 87.8%, and 97.2%, respectively. The presence of intermediate-risk factors and Silva pattern C were significantly associated with worse survival. Based on these findings, patients were categorized into 2 groups: Group 1 (Silva pattern A or Silva pattern B without intermediate-risk factors) and Group 2 (Silva pattern B with intermediate-risk factors or Silva pattern C ). Group 2 showed significantly worse outcomes than Group 1, including the 5-year locoregional RFS (98.6% vs 68.0%), RFS (96.4% vs 54.6%), and overall survival (100.0% vs 86.5%). In conclusion, surgery alone for early-stage HPVA EAC resulted in favorable outcomes. Consideration of the Silva pattern, in addition to well-known risk factors, could help in precise risk group stratification of low-risk, early-stage HPVA EAC.

Futile recanalization after endovascular treatment in acute ischemic stroke with large ischemic core.

BACKGROUND: Endovascular therapy (EVT) is the treatment of choice for acute ischemic stroke (AIS) with large vessel occlusion. However, in many patients, successful EVT recanalization does not correspond to a clinical improvement, called futile recanalization (FR). We aimed to identify stroke risk factors and patient characteristics associated with FR in AIS with large core infarct (LCI). METHODS: A total of 137 patients with AIS with LCI treated by EVT at a single stroke center were retrospectively included from January 2016 to June 2023. LCI was defined by Diffusion-Weighted Imaging-Alberta Stroke Program Early Computed Tomography Score (DWI-ASPECT) < 6. Patient age, sex, modified Rankin Scale (mRS), National Institutes of Health Stroke Scale (NIHSS), time to treatment, risk factors, and radiologic findings were collected, and potential associations with FR were analyzed. FR was defined as successful reperfusion with modified Thrombolysis in Cerebral Infarction (mTICI) ≥ 2b but without functional independence at 90 days (mRS ≥ 3). A multivariate logistic regression analysis was conducted on the clinical characteristics of patients, based on the presence or absence of FR, and the factors influencing FR. RESULTS: Of 137 patients, 120 showed successful recanalization (mTICI ≥ 2b). All patients were divided into FR (n = 80) and no FR (n = 40) groups. Older age (odds ratio [OR] 1.052, 95% confidence interval [CI] 1.002-1.105; p = 0.041), the higher the initial NIHSS score (OR 1.181, 95% CI 1.037-1.344; p = 0.012), and prior intravenous plasminogen activator (OR 0.310, 95% CI 0.118-0.813, p = 0.017) were independent influencing factors of FR. CONCLUSIONS: The older age, the higher the initial NIHSS, and not receiving intravenous plasminogen activator were independently associated with FR in AIS with LCI. These factors could identify poor responders to EVT recanalization.

Increased cardiovascular disease risk among adolescents and young adults with gastric cancer.

BACKGROUND: Previous studies have investigated cardiovascular disease (CVD) risks in cancer patients, but there is limited knowledge concerning the CVD risk in adult and young adolescent (AYA) survivors of gastric cancer. OBJECTIVES: This study aims to investigate the incidence of CVD in AYA gastric cancer survivors, analyzing it by treatment type and identifying associated risk factors. METHODS: We conducted a retrospective cohort study using Korean National Health Insurance Service data collected from 2006 to 2019. Propensity score matching (1:3, caliper < 0.1) was performed using the variables age, sex, income, residential area, and presence of comorbidities, and we classified participants into gastric cancer (n = 6562) and non-cancer control (n = 19,678) groups. Cox regression models were used to calculate hazard ratios (HRs) for CVD incidence. The study assessed CVD incidence by cancer treatment and identified risk factors through multivariable Cox regression. RESULTS: During a median 6.5-year follow-up, AYA gastric cancer survivors consistently exhibited greater CVD incidence. Their risk of CVD was significantly elevated compared to that of controls (HR, 1.18; 95% confidence interval [CI] 1.05-1.33). In particular, deep vein thrombosis (HR, 3.93; 95% CI 3.06-14.67) and pulmonary embolism (HR, 6.58; 95% CI 3.06-14.67) risks were notably increased. Chemotherapy was associated with an increased risk of stroke, heart failure, atrial fibrillation, deep vein thrombosis, and pulmonary embolism. Hypertension (HR, 1.58; 95% CI 1.10-2.26) and dyslipidemia (HR, 1.46; 95% CI 1.06-2.20) emerged as risk factors for CVD development. CONCLUSION: This study reports elevated risks of CVD in AYA gastric cancer survivors and emphasizes the need for vigilant monitoring of CVD in this population.

Selenoprotein W engages in overactive osteoclast differentiation in multiple myeloma.

BACKGROUND: Patients with multiple myeloma exhibit malignant osteolytic bone disease due to excessive osteoclast formation and function. We recently identified that osteoclastogenic stimulator selenoprotein W (SELENOW) is upregulated via ERK signaling and downregulated via p38 signaling during receptor activator of nuclear factor (NF)-κΒ ligand (RANKL)-induced osteoclast differentiation. In the intrinsic physiological process, RANKL-induced downregulation of SELENOW maintains proper osteoclast differentiation; in contrast, forced overexpression of SELENOW leads to overactive osteoclast formation and function. METHODS AND RESULTS: We observed that SELENOW is highly expressed in multiple myeloma-derived peripheral blood mononuclear cells (PBMCs) and mature osteoclasts when compared to healthy controls. Also, the level of tumor necrosis factor alpha (TNFα), a pathological osteoclastogenic factor, is increased in the PBMCs and serum of patients with multiple myeloma. ERK activation by TNFα was more marked and sustained than that by RANKL, allowing SELENOW upregulation. Excessive expression of SELENOW in osteoclast progenitors and mature osteoclasts derived from multiple myeloma facilitated efficient nuclear translocation of osteoclastogenic transcription factors NF-κB and NFATc1, which are favorable for osteoclast formation. CONCLUSION: Our findings suggest a possibility that feedforward signaling of osteoclastogenic SELENOW by TNFα derived from multiple myeloma induces overactive osteoclast differentiation, leading to bone loss during multiple myeloma.

Anticoagulants Are a Risk Factor for Delayed Bleeding after Colorectal Endoscopic Submucosal Dissection: A HASID Multicenter Study.

INTRODUCTION: Delayed bleeding is an important adverse event following colorectal endoscopic submucosal dissection (ESD). However, whether anticoagulants are risk factors for delayed bleeding after colorectal ESD remains debatable. METHODS: We retrospectively analyzed 1,708 patients who underwent colorectal ESDs between January 2015 and December 2020 at five academic medical centers in South Korea. We aimed to identify the risk factors for delayed bleeding in patients after colorectal ESD and, in particular, to evaluate the effect of anticoagulants. RESULTS: Delayed bleeding occurred in 40 of 1,708 patients (2.3%). The risk factors for delayed bleeding were antithrombotic agents (odds ratio [OR], 6.155; 95% confidence interval [CI], 3.201-11.825; p < 0.001), antiplatelet agents (OR, 4.609; 95% CI, 2.200-9.658; p < 0.001), anticoagulants (OR, 8.286; 95% CI, 2.934-23.402; p < 0.001), and tumor location in the rectum (OR, 2.055; 95% CI, 1.085-3.897; p = 0.027). In the analysis that excluded patients taking antiplatelet agents, the delayed bleeding rate was higher in patients taking anticoagulants (1.6% no antithrombotic agents vs. 12.5% taking anticoagulants, p < 0.001). There was no difference in the delayed bleeding rate (4.2% direct oral anticoagulants vs. 25.0% warfarin, p = 0.138) or clinical outcomes according to the type of anticoagulant used. CONCLUSIONS: Anticoagulants use was a risk factor for delayed bleeding after colorectal ESD, and there was no difference in the risk of delayed bleeding based on the type of anticoagulant used. Colorectal ESD in patients receiving anticoagulants requires careful observation and management for delayed bleeding.

Effect of Ishige okamurae Extract on Osteoclastogenesis In Vitro and In Vivo.

We demonstrated the effect of Ishige okamurae extract (IOE) on the receptor activator of nuclear factor-κB ligand (RANKL)-promoted osteoclastogenesis in RAW 264.7 cells and confirmed that IOE inhibited RANKL-induced tartrate-resistant acid phosphatase (TRAP) activity and osteoclast differentiation. IOE inhibited protein expression of TRAP, metallopeptidase-9 (MMP-9), the calcitonin receptor (CTR), and cathepsin K (CTK). IOE treatment suppressed the expression of activated T cell cytoplasmic 1 and activator protein-1, thus controlling the expression of osteoclast-related factors. Moreover, IOE significantly reduced RANKL-phosphorylated extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK). It also reduced the RANKL-induced phosphorylation of NF-κB and nuclear translocation of p65. IOE inhibited Dex-induced bone loss and osteoclast-related gene expression in zebrafish larvae. HPLC analysis shows that IOE consists of 3.13% and 3.42% DPHC and IPA, respectively. Our results show that IOE has inhibitory effects on osteoclastogenesis in vitro and in vivo and is a potential therapeutic for osteoporosis.

Optimal Antithrombotic Therapy Beyond 1-Year After Coronary Revascularization in Patients With Atrial Fibrillation.

BACKGROUND: Currently, non-vitamin K-antagonist oral anticoagulant (NOAC) monotherapy has been suggested as the optimal antithrombotic therapy for atrial fibrillation (AF) beyond one year after coronary revascularization. The aim of this study was to compare the outcomes between NOAC monotherapy and NOAC plus antiplatelet combination therapy using real-world data. METHODS: Between 2015 and 2020, patients with AF who had received NOACs beyond one year after coronary revascularization were enrolled from Korean national insurance data. We emulated a pragmatic sequence of trials between the NOAC monotherapy and the antiplatelet combination therapy followed by propensity score matching. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCEs), a composite of all-cause death, myocardial infarction, and stroke. RESULTS: Among 206,407 person-trials from 4,465 individuals, we compared 3,275 pairs of the monotherapy and the matched combination therapy. During a median follow-up of 1.24 years, the incidence rate of MACCE was 19.4% and 20.0% per patient-year in the monotherapy group and the antiplatelet combination group, respectively (hazard ratio [HR], 0.96; 95% confidence interval [CI], 0.88-1.05; P = 0.422). Compared with the antiplatelet combination group, the monotherapy group had a significantly lower incidence rate of major bleeding, defined as intracranial bleeding or gastrointestinal bleeding requiring hospitalization (2.8% vs. 3.6% per patient-year; HR, 0.78; 95% CI, 0.62-0.97; P = 0.024). CONCLUSION: As an antithrombotic therapy for AF beyond one year after coronary revascularization, NOAC monotherapy was associated with a similar risk of MACCE and a lower risk of major bleeding compared to NOAC plus antiplatelet combination therapy.

Contemporary Statistics of Acute Ischemic Stroke and Transient Ischemic Attack in 2021: Insights From the CRCS-K-NIH Registry.

This report presents the latest statistics on the stroke population in South Korea, sourced from the Clinical Research Collaborations for Stroke in Korea-National Institute for Health (CRCS-K-NIH), a comprehensive, nationwide, multicenter stroke registry. The Korean cohort, unlike western populations, shows a male-to-female ratio of 1.5, attributed to lower risk factors in Korean women. The average ages for men and women are 67 and 73 years, respectively. Hypertension is the most common risk factor (67%), consistent with global trends, but there is a higher prevalence of diabetes (35%) and smoking (21%). The prevalence of atrial fibrillation (19%) is lower than in western populations, suggesting effective prevention strategies in the general population. A high incidence of large artery atherosclerosis (38%) is observed, likely due to prevalent intracranial arterial disease in East Asians and advanced imaging techniques. There has been a decrease in intravenous thrombolysis rates, from 12% in 2017-2019 to 10% in 2021, with no improvements in door-to-needle and door-to-puncture times, worsened by the coronavirus disease 2019 pandemic. While the use of aspirin plus clopidogrel for non-cardioembolic stroke and direct oral anticoagulants for atrial fibrillation is well-established, the application of direct oral anticoagulants for non-atrial fibrillation cardioembolic strokes in the acute phase requires further research. The incidence of early neurological deterioration (13%) and the cumulative incidence of recurrent stroke at 3 months (3%) align with global figures. Favorable outcomes at 3 months (63%) are comparable internationally, yet the lack of improvement in dependency at 3 months highlights the need for advancements in acute stroke care.

The Influence of Fatigue, Recovery, and Environmental Factors on the Body Stability of Construction Workers.

In the construction industry, falls, slips, and trips (FST) account for 42.3% of all accidents. The primary cause of FST incidents is directly related to the deterioration of workers' body stability. To prevent FST-related accidents, it is crucial to understand the interaction between physical fatigue and body stability in construction workers. Therefore, this study investigates the impact of fatigue on body stability in various construction site environments using Dynamic Time Warping (DTW) analysis. We conducted experiments reflecting six different fatigue levels and four environmental conditions. The analysis process involves comparing changes in DTW values derived from acceleration data obtained through wearable sensors across varying fatigue levels and construction environments. The results reveal the following changes in DTW values across different environments and fatigue levels: for non-obstacle, obstacle, water, and oil conditions, DTW values tend to increase as fatigue levels rise. In our experiments, we observed a significant decrease in body stability against external environments starting from fatigue Levels 3 or 4 (30% and 40% of the maximum failure point). In the non-obstacle condition, the DTW values were 9.4 at Level 0, 12.8 at Level 3, and 23.1 at Level 5. In contrast, for the oil condition, which exhibited the highest DTW values, the values were 10.5 at Level 0, 19.1 at Level 3, and 34.5 at Level 5. These experimental results confirm that the body stability of construction workers is influenced by both fatigue levels and external environmental conditions. Further analysis of recovery time, defined as the time it takes for body stability to return to its original level, revealed an increasing trend in recovery time as fatigue levels increased. This study quantitatively demonstrates through wearable sensor data that, as fatigue levels increase, workers experience decreased body stability and longer recovery times. The findings of this study can inform individual worker fatigue management in the future.