U-Shape Pillar Strip for 3D Cell-Lumped Organoid Model (3D-COM) Mimicking Lung Cancer Hypoxia Conditions in High-Throughput Screening (HTS).

Hypoxia is a representative tumor characteristic associated with malignant progression in clinical patients. Engineered in vitro models have led to significant advances in cancer research, allowing for the investigation of cells in physiological environments and the study of disease mechanisms and processes with enhanced relevance. In this study, we propose a U-shape pillar strip for a 3D cell-lumped organoid model (3D-COM) to study the effects of hypoxia on lung cancer in a high-throughput manner. We developed a U-pillar strip that facilitates the aggregation of PDCs mixed with an extracellular matrix to make the 3D-COM in 384-plate array form. The response to three hypoxia-activated prodrugs was higher in the 3D-COM than in the 2D culture model. The protein expression of hypoxia-inducible factor 1 alpha (HIF-1α) and HIF-2α, which are markers of hypoxia, was also higher in the 3D-COM than in the 2D culture. The results show that 3D-COM better recapitulated the hypoxic conditions of lung cancer tumors than the 2D culture. Therefore, the U-shape pillar strip for 3D-COM is a good tool to study the effects of hypoxia on lung cancer in a high-throughput manner, which can efficiently develop new drugs targeting hypoxic tumors.

The impact of statin treatment duration on the risk of new-onset diabetes mellitus and recurrent vascular events in ischemic stroke patients: a linked data analysis.

INTRODUCTION: Although statin therapy reduces cardiovascular events, statin use is associated with the risk of new-onset diabetes mellitus (NODM). Using a linked dataset, we evaluated the effect of statin treatment on vascular outcomes and NODM development in patients with ischemic stroke. METHODS: From the dataset, we identified 20,250 patients with acute ischemic stroke who had neither a prior history of DM nor a previous history of statin use before the index stroke. Patients were divided into statin users and non-users. The outcomes were NODM and vascular outcomes, including recurrent ischemic stroke and acute myocardial infarction (AMI). RESULTS: Of the 20,250 patients, 13,706 (67.7%) received statin treatment after the index stroke. For the risk of NODM, a time-response relationship was observed between the use of statins and NODM; a longer post-stroke follow-up duration substantially increased the risk of NODM. Among those with ischemic stroke exceeding 3 years, statin users had an approximately 1.7-fold greater risk of NODM than statin non-users. Statin therapy significantly reduced the risk of recurrent ischemic stroke by 54% (HR 0.46, 95% CI, 0.43-0.50, P < 0.001) across all stroke subtypes. CONCLUSION: Statin therapy following ischemic stroke increased the occurrence of NODM in patients over a period of 3 years. Despite the increased risk of NODM, statin therapy shows a beneficial effect in reducing major cardiovascular events such as recurrent ischemic stroke and AMI in patients with ischemic stroke.

Indoor particulate matter induces epigenetic changes in companion atopic dogs.

The prevalence of atopic dermatitis (AD) is increasing and environmental factors are receiving attention as contributing causes. Indoor air pollutants (IAPs), especially particulate matter (PM) can alter epigenetic markers, DNA methylation (DNAm). Although DNAm-mediated epigenetic changes have been reported to modulate the pathogenesis of AD, their role at high risk of exposure to PM is still unclear. The study investigated the effects of exposure to IAPs in the development of AD and epigenetic changes through DNAm in companion atopic dogs that share indoor environment with their owners. Dogs were divided into two groups: AD (n = 47) and controls (n = 21). The IAPs concentration in each household was measured for 48 h, and a questionnaire on the residential environment was completed in all dogs. Eighteen dogs with AD and 12 healthy dogs were selected for DNAm analysis. In addition, clinical and immunological evaluations were conducted. The concentrations of PM2.5, PM10, and volatile organic compounds (VOCs) were significantly higher in the AD group. Moreover, there were more significant methylation differences in the LDLRAD4, KHSRP, and CTDSP2 genes in connection with PM10 in AD group compared to the controls. The degree of methylation of the LDLRAD4 and CTDSP2 genes was also correlated with related protein productions. The present study revealed that exposure to high indoor PM can cause epigenetic development of AD by methylation of the LDLRAD4, KHSRP, and CTDSP2 genes in dogs. Under the concept of "One Health," improving indoor environments should be considered to prevent the development of AD.

Multiple Antiplatelet Therapy in Ischemic Stroke Already on Antiplatelet Agents Based on the Linked Big Data for Stroke.

BACKGROUND: Optimal antiplatelet strategy for patients with ischemic stroke who were already on single antiplatelet therapy (SAPT) remains to be elucidated. This study aimed to evaluate the effect of different antiplatelet regimens on vascular and safety outcomes at 1 year after non-cardioembolic stroke in patients previously on SAPT. METHODS: We identified 9,284 patients with acute non-cardioembolic ischemic stroke that occurred on SAPT using linked data. Patients were categorized into three groups according to antiplatelet strategy at discharge: 1) SAPT; 2) dual antiplatelet therapy (DAPT); and 3) triple antiplatelet therapy (TAPT). One-year outcomes included recurrent ischemic stroke, composite outcomes (recurrent ischemic stroke, myocardial infarction, intracerebral hemorrhage, and death), and major bleeding. RESULTS: Of 9,284 patients, 5,565 (59.9%) maintained SAPT, 3,638 (39.2%) were treated with DAPT, and 81 (0.9%) were treated with TAPT. Multiple antiplatelet therapy did not reduce the risks of 1-year recurrent stroke (DAPT, hazard ratio [HR], 1.08, 95% confidence interval [CI], 0.92-1.27, P = 0.339; TAPT, HR, 0.71, 95% CI, 0.27-1.91, P = 0.500) and 1-year composite outcome (DAPT, HR, 1.09, 95% CI, 0.68-1.97, P = 0.592; TAPT, HR, 1.46, 95% CI, 0.68-1.97, P = 0.592). However, the TAPT groups showed an increased risk of major bleeding complications (DAPT, HR, 1.23, 95% CI, 0.89-1.71, P = 0.208; TAPT, HR, 4.65, 95% CI, 2.01-10.74, P < 0.001). CONCLUSION: Additional use of antiplatelet agents in patients with non-cardioembolic ischemic stroke who were already on SAPT did not reduce the 1-year incidence of vascular outcomes, although it increased the risk of bleeding complications.

Dynamic change of neutrophil-to-lymphocyte ratio and symptomatic intracerebral hemorrhage after endovascular recanalization therapy.

OBJECTIVES: The neutrophil-to-lymphocyte ratio (NLR) is a known marker of systemic inflammation. Recent studies demonstrated its applicability as a marker of poor prognosis for stroke patients. In this study, we evaluated the relationship between dynamic changes in the NLR and sICH in patients with successful recanalization following ERT. MATERIALS AND METHODS: This study included 128 patients with acute ischemic stroke who underwent successful ERT between January 2013 and November 2019. We evaluated the NLR pre-ERT (at admission) and post-ERT (at 24-36 h after ERT). The symptomatic ICH and miserable outcomes at 3 months after ERT were analyzed as outcomes. sICH was defined as type-2 parenchymal hematoma with neurological deterioration (defined as National Institute of Health Stroke Scale score ≥4). Moreover, a modified Rankin Scale score of 5-6 at 3 months was considered a miserable outcome. RESULTS: Among the included patients, sICH occurred in 12 (9.4%). The sICH group had significantly higher post-ERT NLR (P < 0.001) and ∆NLR (calculated as the difference between pre-ERT NLR and post-ERT NLR) (P = 0.004). In the multivariate analysis, the post-ERT NLR was independently associated with sICH (odds ratio [OR], 1.166; 95% confidence interval [CI], 1.041-1.306; P = 0.008) and miserable outcome at 3 months (OR, 1.101; 95% CI, 1.002-1.210; P = 0.045). CONCLUSIONS: This study demonstrated that temporal elevation of the NLR is associated with sICH events after successful ERT in patients with acute ischemic stroke. The temporal variation in NLR may help to identify high-risk patients with sICH after ERT.

Decoding 'Maximum Entropy' Deconvolution.

For over five decades, the mathematical procedure termed "maximum entropy" (M-E) has been used to deconvolve structure in spectra, optical and otherwise, although quantitative measures of performance remain unknown. Here, we examine this procedure analytically for the lowest two orders for a Lorentzian feature, obtaining expressions for the amount of sharpening and identifying how spurious structures appear. Illustrative examples are provided. These results enhance the utility of this widely used deconvolution approach to spectral analysis.

Role of the A-Site Cation in Low-Temperature Optical Behaviors of APbBr3 (A = Cs, CH3NH3).

APbBr3 (A = Cs, CH3NH3) are prototype halide perovskites having bandgaps of 2.30-2.35 eV at room temperature, rendering their apparent color nearly identical (bright orange but opaque). Upon optical excitation, they emit bright photoluminescence (PL) arising from carrier recombination whose spectral features are also similar. At 10 K, however, the apparent color of CsPbBr3 becomes transparent yellow, whereas that of CH3NH3PbBr3 does not change significantly due to the presence of an indirect Rashba gap. With increasing the excitation level, evolution of the PL spectra, which are excitonic at 10 K, reveals the emergence of P-band emission arising from inelastic exciton-exciton scattering. Based on the spectral location of the P-band, exciton binding energies are determined to be 21.6 ± 2.0 and 38.3 ± 3.0 meV for CsPbBr3 and CH3NH3PbBr3, respectively. Intriguingly, upon further increase in the exciton density, electron-hole plasma appears in CsPbBr3 as evidenced by both red-shift and broadening of the PL. This phase, however, does not occur in CH3NH3PbBr3 presumably due to polaronic effects. Although the A-site cation is believed not to directly impact optical properties of APbBr3, our results underscore its critical role, which destines different high-density phases and apparent color at low temperatures.

Effectiveness of radiologist training in improving reader agreement for Lung-RADS 4X categorization.

OBJECTIVES: To identify the agreement on Lung CT Screening Reporting and Data System 4X categorization between radiologists and an expert-adjudicated reference standard and to investigate whether training led to improvement of the agreement measures and diagnostic potential for lung cancer. METHODS: Category 4 nodules in the Korean Lung Cancer Screening Project were identified retrospectively, and each 4X nodule was matched with one 4A or 4B nodule. An expert panel re-evaluated the categories and determined the reference standard. Nineteen radiologists were asked to determine the presence of CT features of malignancy and 4X categorization for each nodule. A review was performed in two sessions, and training material was given after session 1. Agreement on 4X categorization between radiologists and the expert-adjudicated reference standard and agreement between radiologist-assessed 4X categorization and lung cancer diagnosis were evaluated. RESULTS: The 48 expert-adjudicated 4X nodules and 64 non-4X nodules were evenly distributed in each session. The proportion of category 4X decreased after training (56.4% ± 16.9% vs. 33.4% ± 8.0%; p < 0.001). Cohen's κ indicated poor agreement (0.39 ± 0.16) in session 1, but agreement improved in session 2 (0.47 ± 0.09; p = 0.03). The increase in agreement in session 2 was observed among inexperienced radiologists (p < 0.05), and experienced and inexperienced reviewers exhibited comparable agreement performance in session 2 (p > 0.05). All agreement measures between radiologist-assessed 4X categorization and lung cancer diagnosis increased in session 2 (p < 0.05). CONCLUSION: Radiologist training can improve reader agreement on 4X categorization, leading to enhanced diagnostic performance for lung cancer. KEY POINTS: • Agreement on 4X categorization between radiologists and an expert-adjudicated reference standard was initially poor, but improved significantly after training. • The mean proportion of 4X categorization by 19 radiologists decreased from 56.4% ± 16.9% in session 1 to 33.4% ± 8.0% in session 2. • All agreement measures between the 4X categorization and lung cancer diagnosis increased significantly in session 2, implying that appropriate training and guidance increased the diagnostic potential of category 4X.

NUT Midline Carcinoma of the Lung: Computed Tomography Findings in 10 Patients.

OBJECTIVE: The aim of the study was to evaluate computed tomography (CT) findings of pulmonary NUT midline carcinoma. METHODS: We assessed clinical and CT features of pulmonary NUT carcinoma in 10 consecutive patients (M:F, 7:3; mean, 39 years). RESULTS: The primary tumors (size range, 15-65 mm) manifested as either a peripheral tumor (5/10) or a central tumor (5/10). All tumors showed relatively low-attenuation at contrast-enhanced CT (mean net enhancement, 26 HU). Associated CT findings were metastatic hilar or mediastinal lymphadenopathy (8/10), ipsilateral pleural seeding with malignant pleural effusion (2/10), and distant metastasis (2/10). Five patients with low tumor-node-metastasis stages after optimal treatment showed no evidence of disease (50%) for 6 to 35 months. CONCLUSIONS: Pulmonary NUT carcinoma presented as a peripheral or a central lung mass showing mild degree of contrast enhancement, frequent metastatic regional lymphadenopathy, affecting relatively young adults. Although known to be highly aggressive, an early diagnosis in low TNM stages can lead to a favorable prognosis.

Classification of Diffuse Glioma Subtype from Clinical-Grade Pathological Images Using Deep Transfer Learning.

Diffuse gliomas are the most common primary brain tumors and they vary considerably in their morphology, location, genetic alterations, and response to therapy. In 2016, the World Health Organization (WHO) provided new guidelines for making an integrated diagnosis that incorporates both morphologic and molecular features to diffuse gliomas. In this study, we demonstrate how deep learning approaches can be used for an automatic classification of glioma subtypes and grading using whole-slide images that were obtained from routine clinical practice. A deep transfer learning method using the ResNet50V2 model was trained to classify subtypes and grades of diffuse gliomas according to the WHO's new 2016 classification. The balanced accuracy of the diffuse glioma subtype classification model with majority voting was 0.8727. These results highlight an emerging role of deep learning in the future practice of pathologic diagnosis.