Objectives: Early hemorrhage detection in intensive care units (ICUs) enables timely intervention and reduces the risk of irreversible outcomes. In this study, we aimed to develop a machine learning model to predict hemorrhage by learning the patterns of continuously changing, real-world clinical data. Methods: We used the Medical Information Mart for Intensive Care databases (MIMIC-III and MIMIC-IV). A recurrent neural network was used to predict severe hemorrhage in the ICU. We developed three machine learning models with an increasing number of input features and levels of complexity: model 1 (11 features), model 2 (18 features), and model 3 (27 features). MIMIC-III was used for model training, and MIMIC-IV was split for internal validation. Using the model with the highest performance, external verification was performed using data from a subgroup extracted from the eICU Collaborative Research Database. Results: We included 5,670 ICU admissions, with 3,150 in the training set and 2,520 in the internal test set. A positive correlation was found between model complexity and performance. As a measure of performance, three models developed with an increasing number of features showed area under the receiver operating characteristic (AUROC) curve values of 0.61–0.94 according to the range of input data. In the subgroup extracted from the eICU database for external validation, an AUROC value of 0.74 was observed. Conclusions Machine learning models that rely on real clinical data can be used to predict patients at high risk of bleeding in the ICU.

High-riding right brachiocephalic and subclavian arteries are often asymptomatic and rare vascular variations. We present a patient with high-riding right brachiocephalic and subclavian arteries that caused compressive pharyngeal and cervical esophageal dysphagia. An 82-year-old woman presented to our hospital with dysphagia that worsened with solid food. A pulsatile lump was observed on the right neck side. A videofluoroscopic swallowing study showed a deviated food bolus movement anterolaterally from the normal vertical pharyngoesophageal transition, with a filling defect in the lower pharynx through the upper esophagus. Neck computed tomography (CT) showed high-riding right brachiocephalic and subclavian arteries and a tortuous right common carotid artery located adjacent to the trachea in the cervical area. The cervical midline structures were deviated to the left neck side. A neck mass with vascular variation should be considered as a cause of dysphagia that worsens with solid food; CT should be considered to determine its cause.

Breast cancer is a heterogeneous disease, and its subtypes are characterized by hormone receptor and human epidermal growth factor receptor 2 (HER2) expression status. “HER2-low” tumors, which exhibit a low level of HER2 expression (immunohistochemistry 1+ or 2+ without gene amplification), were conventionally considered not amenable to anti-HER2 targeting agents based on the results of a phase III trial of trastuzumab. However, this perspective is being challenged by the emergence of novel anti-HER2 antibody-drug conjugates, such as trastuzumab-deruxtecan. These innovative therapies have demonstrated remarkable efficacy against HER2-low breast cancer, shedding new light on a previously overlooked category of breast cancer. Such promising results highlight the need for in-depth investigations of the biology and prognostic implications of HER2-low tumors. In this review, we comprehensively summarize the current evidence surrounding this topic and highlight areas that warrant further exploration and research in the future.

Mitochondrial deficits or altered expressions of microRNAs are associated with the pathogenesis of various diseases, and microRNA-operated control of mitochondrial activity has been reported. Using a retrovirus-mediated short-hairpin RNA (shRNA) system, we observed that miR-24-mediated H2AX knockdown (H2AX-KD) impaired both mitochondria and the insulin signaling pathway. The overexpression of miR-24 decreased mitochondrial H2AX and disrupted mitochondrial function, as indicated by the ATP content, membrane potential and oxygen consumption. Similar mitochondrial damage was observed in shH2AX-mediated specific H2AX-KD cells. The H2AX-KD reduced the expression levels of mitochondrial transcription factor A (TFAM) and mitochondrial DNA-dependent transcripts. H2AX-KD mitochondria were swollen, and their cristae were destroyed. H2AX-KD also blocked the import of precursor proteins into mitochondria and the insulin-stimulated phosphorylation of IRS-1 (Y632) and Akt (S473 and T308). The rescue of H2AX, but not the nuclear form of ΔC24-H2AX, restored all features of miR-24- or shH2AX-mediated impairment of mitochondria. Hepatic miR-24 levels were significantly increased in db/db and ob/ob mice. A strong feedback loop may be present among miR-24, H2AX, mitochondria and the insulin signaling pathway. Our findings suggest that H2AX-targeting miR-24 may be a novel negative regulator of mitochondrial function and is implicated in the pathogenesis of insulin resistance.
Adenosine Triphosphate ; Animals ; Insulin Resistance ; Insulin* ; Membrane Potentials ; Mice ; MicroRNAs ; Mitochondria* ; Oxygen Consumption ; Phosphorylation ; RNA ; Transcription Factors

Purpose: Three years of adjuvant imatinib is the standard treatment for resected gastrointestinal stromal tumors (GISTs) with rupture, but the recurrence rate is prominently high. We aimed to investigate the efficacy and safety of 5-year adjuvant imatinib compared with 3-year treatment in patients with a ruptured GIST following surgical resection. Materials and Methods: A total of 51 patients were included in the analysis. The assessment of GIST rupture was based on Nishida’s classification. Twenty patients who were diagnosed before November 2013 were treated with 5 years of imatinib, and 31 patients who were diagnosed after November 2013 were treated with 3 years of imatinib. We retrospectively compared the clinical outcomes of the two groups. Results: Baseline characteristics and the incidence of the adverse events were generally comparable between the two groups. During a median follow-up duration of 43.8 months and 104.2 months in the 3- and 5-year group, 8 and 9 patients had a disease recurrence, respectively. The 5-year group showed better recurrence-free survival (RFS) than the 3-year group. In multivariate analysis, low mitotic index was a significant independent favorable prognostic factor for RFS, while 5-year imatinib treatment was marginally associated with a favorable RFS. Conclusion Five years of adjuvant imatinib treatment in patients with ruptured GIST was associated with favorable survival outcomes with manageable toxicity profiles. Our findings warrant validation and confirmation in future studies.

OBJECTIVE: To elucidate the association between non-specific low back pain (NSLBP) and spinal X-ray findings in Korean farmers: Farmers' Cohort for Agricultural Work-Related Musculoskeletal disorders (FARM) study. METHODS: A total of 835 farmers (391 males, 444 females; mean age, 56.6±7.4 years) without red-flag signs of specific LBP were recruited. Presence of LBP more than one week or once a month with more than moderate degree of pain severity during the last year was assessed with a binary questionnaire (yes or no). Spinal degenerative changes were classified into disc height change (DHC) of L4-5 and L5-S1 (grade 0–5) and osteophyte formation of L5 (grade 0–5) by a radiologist based on X-ray findings. Additionally, spondylolisthesis, scoliosis and spondylolysis were assessed. RESULTS: General prevalence of NSLBP was 40.7%, revealing a higher incidence of NSLBP in female and younger farmers compared to male and older farmers (χ²=23.3, p<0.001; χ²=4.54, p<05, respectively). Among X-ray findings, DHC (L5–S1) grade 4 revealed significantly higher relative risk of NSLBP compared to grade 0 (odds ratio, 5.00; 95% confidence interval, 2.05–12.20) after adjusting age and sex, while other X-ray findings were not associated with NSLBP. CONCLUSION: The NSLBP of Korean farmers was significantly related to lumbar disc degenerative changes, suggesting clinical usefulness of X-ray findings in assessing LBP in farmers.
Agriculture* ; Cohort Studies ; Farmers* ; Female ; Humans ; Incidence ; Low Back Pain* ; Male ; Osteoarthritis ; Osteophyte ; Prevalence ; Radiography ; Scoliosis ; Spine ; Spondylolisthesis ; Spondylolysis

The purpose of this study was proposed to identify the association of trunk body composition with spinal bone mineral density (BMD) in Korean male and female farmers. A total of 523 Korean farmers (259 males, 44 premenopausal females, and 220 postmenopausal females) were recruited. Computed tomography scans were acquired at the mid-L4 vertebral level, and total trunk muscle mass (TMM, cm3), back muscle mass (BMM), and abdominal wall muscle mass (AMM), total trunk fat mass (TFM), visceral fat mass (VFM), and subcutaneous fat mass (SFM) were assessed. Spinal BMD (g/cm2) was estimated from dual-energy X-ray absorptiometry at the L4 level. In terms of muscle mass, spinal BMD was significantly correlated with all the components of the trunk muscle mass (r = 0.171-0.360; P < 0.05, P < 0.001) in female farmers, while only with AMM (r = 0.181; P < 0.01) in male farmers. In terms of fat mass, spinal BMD was significantly correlated with all components of the trunk fat mass (r = 0.142-0.424; P < 0.05, P < 0.001) in male and premenopausal female farmers, while only with VFM (r = 0.132; P < 0.05) in postmenopausal females. Adjusted multivariate regression analysis showed that AMM in male and post-menopausal female farmers was closely associated with spinal BMD. There may be positive associations between trunk muscle and fat mass and spinal BMD with sexual dimorphism, and abdominal wall muscle mass was an explanatory variable closely related to spinal BMD in Korean farmers. Registered at the Clinical Research Information Service (CRIS, http://cris.nih.go.kr), number KCT0000829.
Abdominal Wall ; Absorptiometry, Photon ; Adipose Tissue ; Back Muscles ; Body Composition* ; Bone Density* ; Cohort Studies* ; Farmers ; Female* ; Humans ; Information Services ; Intra-Abdominal Fat ; Male* ; Sex Characteristics ; Spine ; Subcutaneous Fat

BACKGROUND: Molecular epidemiological typing of Neisseria gonorrhoeae is crucial for monitoring the spread of resistant strains. As reference strains can be used for laboratory internal quality control, we genetically characterised the American Type Culture Collection (ATCC) gonococcal strains by Neisseria gonorrhoeae multiantigen sequence typing (NG-MAST) and porB sequence typing using public multilocus sequence typing (PubMLST). METHODS: Eight ATCC gonococcal reference strains (ATCC 19424, ATCC 31426, ATCC 35541, ATCC 43069, ATCC 43070, ATCC 49226, ATCC 49926, and ATCC 49981) from Culti-Loops (Thermo Fisher Scientific, USA) were cultured. After DNA extraction, porB and tbpB were amplified and sequenced. Sequence types (STs) and allele numbers were each determined by NG-MAST (http://www.ng-mast.net) and porB sequence typing using PubMLST (http://pubmlst.org/neisseria/porB/). RESULTS: ATCC 19424 was identified as ST 266 by NG-MAST, and as Allele 946 by PubMLST. ATCC31426 was assigned a novel ST by NG-MAST, and was assigned Allele 958 with 1.2% mismatch by PubMLST. ATCC 35541 was identified as ST 12 by NG-MAST, and as Allele 624 by PubMLST. ATCC 43069 and ATCC 43070 were both identified as ST 681 by NG-MAST, and as Allele 984 by PubMLST. ATCC 49226 was identified as ST 1572 by NG-MAST, and as Allele 2110 by PubMLST. ATCC 49926 and ATCC 49981 were both identified as ST 16496 by NG-MAST, and as Allele 928 by PubMLST. CONCLUSIONS: The ST data obtained for ATCC gonococcal reference strains by NG-MAST and porB sequence typing using PubMLST can be used for quality assurance of molecular epidemiological typing in clinical microbiological laboratories.
Alleles ; DNA ; Multilocus Sequence Typing ; Neisseria gonorrhoeae ; Neisseria ; Quality Control

OBJECTIVE: To determine the socio-demographic, psychologic, hematologic, or other relevant factors associated with hand grip strength in Korean farmers. METHODS: A total of 528 healthy Korean farmers were enrolled. Hand grip strength was measured in both hands using a hydraulic dynamometer. Socio-demographic characteristics were assessed and anthropometric measurements were obtained. Psycho-cognitive measurements such as sleep quality (Pittsburgh Sleep Quality Index) and Go/No-Go test response time were conducted. In addition to physical measurements, serologic parameters including insulin-like growth factor 1 were measured. The factors associated with hand grip strength were analyzed using multiple linear regression analysis after adjusting for age, height, and weight. RESULTS: The mean hand grip strength was associated with the Pittsburgh Sleep Quality Index total score (β=-0.12, p=0.01), the Go/No-Go test response time (β=-0.18, p=0.001), vitamin D (β=0.12, p=0.02), and insulin-like growth factor 1 levels (β=0.1, p=0.045). In female farmers, hand grip strength was only associated with the Pittsburgh Sleep Quality Index total score (β=-0.32, p < 0.001). CONCLUSION: The results of this study demonstrate that hand grip strength was associated with sleep quality and attention in Korean farmers.
Agriculture* ; Farmers ; Female ; Hand Strength* ; Hand* ; Humans ; Insulin-Like Growth Factor I ; Linear Models ; Reaction Time ; Vitamin D

Objective: To investigate whether lumbar lordosis (LL) and lumbar segmental lordosis (LSL) are related to sex, age, low back pain (LBP), and lumbar disc space narrowing (DSN). Methods: A total of 569 farmers were recruited. In lateral spine radiograph, LL (L1–L5) and LSL (L1, L2, L3, L4, and L5) were measured using Cobb’s method. The differences in LSL values (ΔLSL) according to the presence or absence of a DSN were calculated as LSLDSN – LSLnoDSN for each DSN level. Results: In male, the lateral spine radiograph showed significantly greater L4-LSL and L5-LSL and smaller L1-LSL and L2-LSL compared to female. LLs in the 50–59 and ≥60 years age groups were significantly smaller compared to those in the <50 years age group. In subjects with LBP, LL and L4-LSL were significantly smaller than in those without. The ΔLSLs at the disc level with DSN showed the greatest decrease: L1-ΔLSL (Δ-3.99°), L2-ΔLSL (Δ-3.31°), L3-ΔLSL (Δ-2.87°), L4-ΔLSL (Δ-3.31°), and L5-ΔLSL (Δ-4.44°) in L1/2, L2/3, L3/4, L4/5, and L5/S1 DSN, respectively. Conversely, distant ΔLSLs were inversely increased: L1-LSL (Δ0.75°) with L4/5 DSN and L2-LSL (Δ0.94°) with L5/S1 DSN. Conclusion Sagittal plane alignment was significantly associated with sex, age, LBP, and DSN. LSLs around the levels of DSN were decreased, and there was compensational increase of LSL distant to the DSN to maintain the overall LL.