Prognostic value of signet-ring cell carcinoma proportion in undifferentiated gastric cancer: Implications for endoscopic treatment decisions.

Background: Poorly cohesive gastric carcinomas are classified based on the proportion of signet-ring cell carcinoma (SRCC) components. In surgically resected gastric cancer, SRCC is diagnosed when the signet-ring cell (SRC) component constitutes ≥ 50% of the entire tumor, whereas poorly cohesive carcinoma (PCC) not otherwise specified is diagnosed when the proportion of the SRC component is < 50% of the entire tumor. The SRCC proportion in PCC varies along the spectrum, and its prognostic significance in gastric cancer remains unclear.

Inhalation of dust accumulated on personal computer fans in the office may cause pathological effects by disrupting the metabolic activity of alveolar macrophages.

Considering that computer fans draw in dust from the office air, and that printers and copiers are typically placed near computers, we collected dust that accumulated on computer fans from three commercial personal computer centers to predict the health effects of inhaled office dust (OD). OD contained various types of microplastics and non-protein particles, and several hydrophilic elements were bound to the OD. When aspirated OD via the pharynx for 90 days, blood levels of IP and K significantly decreased in male mice, but not in female mice.

Dodecyldimethylamine oxide may induce lysosomal-associated cell death: Potential lipotoxicity.

Dodecyldimethylamine oxide (DDAO) is one of the most commonly used chemicals in household products, including spray types. We identified the potential toxicity mechanism using human bronchial epithelial cells. After 6 h of exposure, DDAO decreased cell viability (non-apoptotic cell death) and formed numerous small artificial vacuoles in the cytoplasm.

Immunogenomic characteristics and prognostic implications of terminally exhausted CD8 T cells in colorectal cancers.

Introduction: T-cell exhaustion is a major mechanism of immune evasion. Recently, the therapeutic and prognostic implications of progenitor exhausted T cells (Tpex) and terminally exhausted T cells (Ttex) have been explored in various cancer types. This study explored the immunogenomic characteristics and prognostic implications of Tpex and Ttex in colorectal cancers (CRCs).

Ensemble Learning Approaches for Automatic Detection of Chronic Kidney Disease Stages during Sleep.

This study investigates the use of ensemble learning methods for the automatic detection of chronic kidney disease (CKD) stages during sleep. We applied and evaluated four ensemble learning approaches-CatBoost, random forest, XGBoost, and LightGBM-to analyze polysomnography (PSG) data from 730 participants of the Cleveland Family Study (539 control subjects and 191 CKD patients). Our analysis involved extracting 1,210 phenotypic parameters from the PSG data, which enabled the classification of CKD into four stages: mild (stages 1 and 2), moderate (stage 3), severe (stage 4), and critical (stage 5).

Diagnostic challenges associated with adrenocortical neoplasms arising from adreno-hepatic fusion: a case report of two patients and a literature review.

Background: A right adrenal gland may present in the form of adreno-hepatic fusion (AHF), in which the adrenal cells are interspersed among the hepatocytes without septation. This rare, naturally-occurring phenomenon may be associated with preoperative misdiagnosis. We present two cases of adrenal tumor in patients with AHF that were misdiagnosed, despite thorough preoperative work-ups.

Didecyldimethylammonium chloride-induced lung fibrosis may be associated with phospholipidosis.

In the current study, we dosed didecyldimethylammonium chloride (DDAC) in mice by pharyngeal aspiration for 28 days or 90 days (weekly) and tried to elucidate the relationship between lamellar body formation and the lesions. When exposed for 28 days (0, 5, 10, 50, and 100 μg/head), all the mice in the 50 and 100 μg/head groups died since Day 2 after the third dosing (Day 16 after the first dosing). Edema, necrosis of bronchiolar and alveolar epithelium, and fibrinous exudate were observed in the lungs of all the dead mice, and chronic inflammatory lesions were observed in the lung tissues of alive mice.

The combination of CDX2 expression status and tumor-infiltrating lymphocyte density as a prognostic factor in adjuvant FOLFOX-treated patients with stage III colorectal cancers.

Background: Colorectal carcinomas (CRCs) with caudal-type homeobox 2 (CDX2) loss are recognized to pursue an aggressive behavior but tend to be accompanied by a high density of tumor-infiltrating lymphocytes (TILs). However, little is known about whether there is an interplay between CDX2 loss and TIL density in the survival of patients with CRC.

Methods: Stage III CRC tissues were assessed for CDX2 loss using immunohistochemistry and analyzed for their densities of CD8 TILs in both intraepithelial (iTILs) and stromal areas using a machine learning-based analytic method.

The Potential of Molecular Remission: Tissue Neutrophil Elastase Is Better Than Histological Activity for Predicting Long-Term Relapse in Patients With Ulcerative Colitis in Endoscopic Remission.

Background: Growing interest exists in deep remission, beyond clinical and endoscopic remission, to enhance long-term prognosis in patients with ulcerative colitis (UC). Our study aimed to evaluate the risk of relapse according to tissue expression levels of calprotectin and neutrophil elastase (NE) in patients with quiescent UC.

Methods: Rectal biopsies were performed on 218 patients with UC in clinical and endoscopic remission.

Concomitant expression patterns of CDX2 and SATB2 as prognostic factors in stage III colorectal cancers.

CDX2 and SATB2 are often used as biomarkers for identification of colorectal origin in primary or metastatic adenocarcinomas. Loss of CDX2 or SATB2 expression has been associated with poor prognosis in patients with colorectal cancer (CRC). However, little is known regarding clinicopathological features, including prognosis, of CRCs with concomitant loss of CDX2 and SATB2.

Molecular Activity of Inflammation and Epithelial-Mesenchymal Transition in the Microenvironment of Ulcerative Colitis.

Background/aims: : The genetic expression in the active inflammatory regions is increased in ulcerative colitis (UC) with endoscopic activity. The aim of this study was to investigate the molecular activity of inflammation and tissue remodeling markers in endoscopically inflamed and uninflamed regions of UC.

Methods: : Patients with UC (n=47) and controls (n=20) were prospectively enrolled at the Seoul National University Bundang Hospital.

Intratumoral spatial heterogeneity of tumor-infiltrating lymphocytes is a significant factor for precisely stratifying prognostic immune subgroups of microsatellite instability-high colorectal carcinomas.

Although the density of tumor-infiltrating lymphocytes (TILs) is known to be linked to prognosis in various cancers, the prognostic impact and immunologic significance of the spatial heterogeneity of TILs have been rarely investigated. In this study, CD3+ and CD8+ TILs were quantified in independent cohorts (discovery, n = 73; and external validation, n = 93) of colorectal carcinomas (CRCs) with microsatellite instability-high (MSI-H) utilizing whole-slide image analysis of CD3/CD8 immunohistochemistry. The Shannon and Simpson indices, which measure intratumoral patch-to-patch evenness of TIL densities, were used to quantitatively assess the spatial heterogeneity of TILs in each case.

Lymphoproliferative disorder involving body fluid: diagnostic approaches and roles of ancillary studies.

Lymphocyte-rich effusions represent benign reactive process or neoplastic condition. Involvement of lymphoproliferative disease in body cavity is not uncommon, and it often causes diagnostic challenge. In this review, we suggest a practical diagnostic approach toward lymphocyte-rich effusions, share representative cases, and discuss the utility of ancillary tests.

Comprehensive clinicopathologic, molecular, and immunologic characterization of colorectal carcinomas with loss of three intestinal markers, CDX2, SATB2, and KRT20.

Caudal-type homeobox 2 (CDX2), special AT-rich sequence-binding protein 2 (SATB2), and keratin 20 (KRT20) are frequently used as intestinal epithelium-specific markers in immunohistochemical studies. However, subsets of colorectal carcinomas (CRCs) show loss of these markers. We analyzed The Cancer Genome Atlas data to explore molecular correlates of CDX2, SATB2, and KRT20 genes in 390 CRCs.

Combinatory statuses of tumor stromal percentage and tumor infiltrating lymphocytes as prognostic factors in stage III colorectal cancers.

Background And Aim: Tumor stroma and tumor-infiltrating lymphocytes (TILs) are major constituents of the tumor microenvironment, although they have different effects on the prognosis of patients with colorectal cancer (CRC). Combinatory statuses of tumor-stromal percentage (TSP) and TILs are expected to provide more powerful prognostic information but have never been studied in CRCs.

Methods: Stage III CRCs from patients (n = 487) treated with adjuvant chemotherapy were assessed for their TSP and CD3-TIL or CD8-TIL densities using computer-aided methodology.

A Novel Pyrazolo[3,4-]pyrimidine Induces Heme Oxygenase-1 and Exerts Anti-Inflammatory and Neuroprotective Effects.

The anti-oxidant enzyme heme oxygenase-1 (HO-1) is known to exert anti-inflammatory effects. From a library of pyrazolo[3,4-]pyrimidines, we identified a novel compound KKC080096 that upregulated HO-1 at the mRNA and protein levels in microglial BV-2 cells. KKC080096 exhibited anti-inflammatory effects via suppressing nitric oxide, interleukin-1β (IL-1β), and iNOS production in lipopolysaccharide (LPS)-challenged cells.

Targeted next-generation sequencing-based detection of microsatellite instability in colorectal carcinomas.

In the present study, we developed a computational method and panel markers to assess microsatellite instability (MSI) using a targeted next-generation sequencing (NGS) platform and compared the performance of our computational method, mSILICO, with that of mSINGS to detect MSI in CRCs. We evaluated 13 CRC cell lines, 84 fresh and 119 formalin-fixed CRC tissues (including 61 MSI-high CRCs and 155 microsatellite-stable CRCs) and tested the classification performance of the two methods on 23, 230, and 3,154 microsatellite markers. For the fresh tissue and cell line samples, mSILICO showed a sensitivity of 100% and a specificity of 100%, regardless of the number of panel markers, whereas for the formalin-fixed tissue samples, mSILICO exhibited a sensitivity of up to 100% and a specificity of up to 100% with three differently sized panels ranging from 23 to 3154.

Utility of Apical Lung Assessment on Computed Tomography Angiography as a COVID-19 Screen in Acute Stroke.

Background And Purpose: Evaluation of the lung apices using computed tomography angiography of the head and neck during acute ischemic stroke (AIS) can provide the first objective opportunity to screen for coronavirus disease 2019 (COVID-19).

Methods: We performed an analysis assessing the utility of apical lung exam on computed tomography angiography for COVID-19-specific lung findings in 57 patients presenting with AIS. We measured the diagnostic accuracy of apical lung assessment alone and in combination with patient-reported symptoms and incorporate both to propose a COVID-19 era AIS algorithm.

Differential immune microenvironmental features of microsatellite-unstable colorectal cancers according to Fusobacterium nucleatum status.

It has been suggested that Fusobacterium nucleatum (Fn) may differentially impact tumor immune responses according to microsatellite instability (MSI) status in colorectal cancers (CRCs). We aimed to reveal the detailed relationship between intratumoral Fn and immune microenvironmental features in MSI-high CRCs. A total of 126 MSI-high CRCs were subjected to analyses for intratumoral Fn DNA load using quantitative PCR and for densities of tumor-infiltrating immune cells, including CD3 T cells, CD4 T cells, CD8 T cells, FoxP3 T cells, CD68 macrophages, CD163 macrophages, and CD177 neutrophils, at invasive margin (IM) and center of tumor (CT) areas using computational image analysis of immunohistochemistry.

A novel pyrazolo [3,4-d] pyrimidine, KKC080106, activates the Nrf2 pathway and protects nigral dopaminergic neurons.

The transcription factor nuclear factor-erythroid 2-related factor-2 (Nrf2) is known to induce neuroprotective and anti-inflammatory effects and is considered to be an excellent molecular target for drugs related to neurodegenerative disease therapy. Nrf2 activators previously tested in clinical trials were electrophilic, causing adverse effects due to non-selective and covalent modification of cellular thiols. In order to circumvent this issue, we constructed and screened a chemical library consisting of 241 pyrazolo [3,4-d] pyrimidine derivatives and discovered a novel, non-electrophilic compound: 1-benzyl-6-(methylthio)-N-(1-phenylethyl)-1H-pyrazolo[3,4-d]pyrimidine-4-amine (KKC080106).

Aberrant Tonic Inhibition of Dopaminergic Neuronal Activity Causes Motor Symptoms in Animal Models of Parkinson's Disease.

Current pharmacological treatments for Parkinson's disease (PD) are focused on symptomatic relief, but not on disease modification, based on the strong belief that PD is caused by irreversible dopaminergic neuronal death. Thus, the concept of the presence of dormant dopaminergic neurons and its possibility as the disease-modifying therapeutic target against PD have not been explored. Here we show that optogenetic activation of substantia nigra pars compacta (SNpc) neurons alleviates parkinsonism in acute PD animal models by recovering tyrosine hydroxylase (TH) from the TH-negative dormant dopaminergic neurons, some of which still express DOPA decarboxylase (DDC).