TET2 and LILRB1 mutations are frequent in Epstein-Barr virus-positive diffuse large B-cell lymphoma especially in elderly patients.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) harboring Epstein-Barr virus (EBV) primarily occurs in patients who have underlying immunodeficiency or in elderly patients but is also reported in young, immunocompetent patients. The authors investigated the pathologic differences in EBV-positive DLBCL in these three groups of patients. METHODS: In total, 57 patients with EBV-positive DLBCL were included in the study; of these, 16 patients had associated immunodeficiency, 10 were young (younger than 50 years), and 31 were elderly (aged 50 years or older). Immunostaining for CD8, CD68, PD-L1, and EBV nuclear antigen 2, and panel-based next-generation sequencing was performed on formalin-fixed, paraffin-embedded blocks. RESULTS: Immunohistochemistry revealed EBV nuclear antigen 2 positivity in 21 of the 49 patients. The degree of CD8-positive and CD68-positive immune cell infiltration and PD-L1 expression did not differ significantly in each group. Extranodal site involvement was more common in young patients (p = .021). In mutational analysis, the genes with the highest mutation frequency were PCLO (n = 14), TET2 (n = 10), and LILRB1 (n = 10). For the TET2 gene, all 10 mutations were found in elderly patients (p = .007). Compared with a validation cohort, both TET2 and LILRB1 showed a higher mutation frequency in EBV-positive patients than in EBV-negative patients. CONCLUSIONS: EBV-positive DLBCL occurring in three different age and immune status groups showed similar pathologic characteristics. Notably, a high frequency of TET2 and LILRB1 mutations was characteristic of this disease in elderly patients. Further studies are needed to determine the role of TET2 and LILRB1 mutations in the development of EBV-positive DLBCL along with immune senescence. PLAIN LANGUAGE SUMMARY: Epstein-Barr virus-positive diffuse large B-cell lymphoma occurring in three different groups (immunodeficiency-associated, young, and elderly) showed similar pathologic characteristics. The frequency of TET2 and LILRB1 mutations was high in elderly patients with Epstein-Barr virus-positive diffuse large B-cell lymphoma.

Korean Red Ginseng Saponins Play an Anti-Inflammatory Role by Targeting Caspase-11 Non-Canonical Inflammasome in Macrophages.

We previously reported that Korean red ginseng (KRG) exerts an anti-inflammatory role through inhibiting caspase-11 non-canonical inflammasome in macrophages; however, the components responsible for the anti-inflammatory role remained unclear. This study explored the anti-inflammatory activity of the KRG saponin fraction (KRGSF) in caspase-11 non-canonical inflammasome-activated macrophages. KRGSF inhibited pyroptosis, pro-inflammatory cytokine secretion, and inflammatory mediator production in caspase-11 non-canonical inflammasome-activated J774A.1 cells. A mechanism study revealed that KRGSF-induced anti-inflammatory action was mediated via suppressing the proteolytic activation of caspase-11 and gasdermin D (GSDMD) in caspase-11 non-canonical inflammasome-activated J774A.1 cells. Moreover, KRGSF increased the survival of lethal septic mice. Taken together, these results reveal KRGSF-mediated anti-inflammatory action with a novel mechanism, by inhibiting caspase-11 non-canonical inflammasome in macrophages.

Chaperoning the major facilitator superfamily at single-molecule level.

In this issue of Structure, Blaimschein et al. elucidate the chaperoning function of the insertase YidC during the insertion and folding of the melibiose permease MelB. Their single-molecule forced unfolding approach reveals that YidC significantly reduces the misfolding and enhances the folding of helices near the interface of two folding cores.

The role of myofibroblasts in upregulation of S100A8 and S100A9 and the differentiation of myeloid cells in the colorectal cancer microenvironment.

BACKGROUND/AIM: S100A8/A9 and myeloid cells in the tumor microenvironment play an important role in cancer invasion and progression, and the effect of tumor-infiltrated myofibroblasts on myeloid cells in the tumor microenvironment is relatively unknown. Accordingly, we investigated the role of myofibroblasts in the upregulation of S100A8/A9 as well as in the differentiation of myeloid cells in the colorectal cancer (CRC) microenvironment. MATERIALS AND METHODS: To investigate the interactions among cancer cells, myofibroblasts, and inflammatory cells in the microenvironment of CRC, we used 10 CRC cell lines, 18CO cells and THP-1 cells, which were co-cultured with each other or cultured in conditioned media (CM) of other cells. Expression of S100A8/A9 was evaluated via Western blot, immunohistochemical staining and immunofluorescence. The secreted factors from the cell lines were analyzed using cytokine antibody array. Flow cytometry analysis was performed to analyze the differentiation markers of myeloid cells. RESULTS: 18CO CM induced increased expression of S100A8/A9 in THP-1 cells. Increased expression of S100A8/A9 was noted in inflammatory cells of the peri- and intra-tumoral areas, along with myofibroblasts in colon cancer tissue. S100A8/A9-expressing inflammatory cells also exhibited CD68 expression in colon cancer tissue, and 18CO CM induced differentiation of THP-1 cells into myeloid-derived suppressor cells (MDSCs) or M2 macrophages expressing S100A8/A9. Significant amounts of IL-6 and IL-8 were detected in 18CO CM, compared to those in both controls and THP-1 CM, and tumor-infiltrated myofibroblasts expressed IL-8 in colon cancer tissue. Finally, neutralizing antibodies to IL-6 and IL-8 attenuated 18CO CM-induced increased expression of S100A8/A9. CONCLUSIONS: The upregulation of S100A8/A9 in tumor-infiltrated myeloid cells could be triggered by IL-6 and IL-8 released from myofibroblasts, and myofibroblasts might induce the differentiation of myeloid cells into S100A8/9-expressing MDSCs or M2 macrophages in the CRC microenvironment.

Cauda equina syndrome caused by pseudogout involving the lumbar intervertebral disc.

Calcium pyrophosphate dihydrate (CPPD) deposition disease, also known as pseudogout, is a disease that causes inflammatory arthropathy in peripheral joints, however, symptomatic involvement of the intervertebral disc is uncommon. Herein, we describe a 59-yr-old patient who presented with cauda equina syndrome. Magnetic resonance imaging of the patient showed an epidural mass-like lesion at the disc space of L4-L5, which was compressing the thecal sac. Biopsy of the intervertebral disc and epidural mass-like lesion was determined to be CPPD deposits. We reviewed previously reported cases of pseudogout involving the lumbar intervertebral disc and discuss the pathogenesis and treatment of the disease.

Histological features of differentiated dysplasia in the oral mucosa: a review of oral invasive squamous cell carcinoma cases diagnosed with benign or low-grade dysplasia on previous biopsies.

The diagnosis of oral squamous cell carcinoma is sometimes delayed. Recently, the concept of differentiated dysplasia in the oral mucosa was proposed, and we attempted to elucidate the histologic features of differentiated dysplasia in the oral mucosa. Two pathologists reviewed 38 small biopsy cases of patients diagnosed with benign to low-grade dysplasia in the first biopsy, but were diagnosed with invasive carcinoma after excisional biopsy within 2 years. Of these, 29 cases were suspected of having differentiated dysplasia, which histologically showed "abnormal variation in nuclear size and shape," "increased number and size of nucleoli," and "loss of polarity of basal cells." In addition to the features observed in classic dysplasia, "premature keratinization in single cells" and "loss of epithelial cell cohesion" were characteristically observed. These 2 findings were often observed only in the lower half of the epithelium, but not in the full layer of the epithelium. Histological findings of oral differentiated dysplasia were very similar to those of differentiated vulvar intraepithelial neoplasia. "Premature keratinization in single cells" and "loss of epithelial cell cohesion" are specific pathological findings of oral differentiated dysplasia. Oral differentiated dysplasia is considered as a part of the broad spectrum of oral dysplasia that exhibits morphological characteristics different from classic dysplasia rather than being a separate entity. The diagnosis of oral differentiated dysplasia is expected to reduce the delayed diagnosis and improve the prognosis and post-treatment quality of life of patients with oral cavity cancer.

Identification of a Novel Long Non-coding RNA, lnc-ATMIN-4:2, and its Clinicopathological and Prognostic Significance in Advanced Gastric Cancer.

BACKGROUND/AIM: Long non-coding RNAs (lncRNAs) are emerging as significant regulators of gene expression and a novel promising biomarker for cancer diagnosis and prognosis. This study identified a novel, differentially expressed lncRNA in advanced gastric cancer (AGC), Inc-ATMIN-4:2, and evaluated its clinicopathological and prognostic significance. PATIENTS AND METHODS: Whole transcriptome sequencing was performed to identify differentially expressed lncRNAs in AGC tissue samples. We also analyzed lnc-ATMIN-4:2 expression in 317 patients with AGC using RNA in situ hybridization. RESULTS: High (>30 dots) lnc-ATMIN-4:2 expression significantly correlated with younger age, poorly differentiated histology, diffuse type, deeper invasion depth, perineural invasion, lymph node metastasis, and higher stage group. In addition, high lnc-ATMIN-4:2 expression was significantly associated with worse overall survival in patients with AGC. CONCLUSION: This study elucidated the significance of lncRNAs in AGC and indicated the value of lnc-ATMIN-4:2 expression as a predictive biomarker for the overall survival of patients with AGC.

Cyclooxygenase-2-expressing macrophages in human pterygium co-express vascular endothelial growth factor.

PURPOSE: To evaluate cyclooxygenase-2 (COX-2) expression and to characterize COX-2-expressing stromal cells in human pterygium. METHODS: Primary pterygium tissue of Korean patients (eight males and nine females) was analyzed. The clinical characteristics were classified, and immunohistochemical staining using primary antibodies against cyclooxygenease-2, vascular endothelial growth factor-A, cluster of differentiation (CD)68, CD3, CD20, and leukocyte common antigen was performed. RESULTS: COX-2 expression was detected in all pterygium tissues evaluated (17 primary pterygia). Diffuse expression of COX-2 in the epithelial layer was observed in nine samples. Infiltration of strongly positive COX-2 cells into the epithelial layer was a more common observation than diffuse epithelial COX-2 expression. Scattered COX-2-expressing cells in the stromal layer were found in all samples. Some COX-2-positive cells were found within microvessels. In addition to stromal COX-2-expressing cells, a few vascular endothelial cells strongly expressed COX-2; however most of the vessels were negative for COX-2 expression. Stromal COX-2-expressing cells were positive for the macrophage marker CD68 and co-expressed vascular endothelial growth factor. COX-2 expression in normal conjunctiva was not observed in seven control samples. CONCLUSIONS: These COX-2- and vascular endothelial growth factor-expressing macrophages may have relevance to the pathogenesis of pterygium.

Protease imaging of human atheromata captures molecular information of atherosclerosis, complementing anatomic imaging.

OBJECTIVE: There is hope that molecular imaging can identify vulnerable atherosclerotic plaques. However, there is a paucity of clinical translational data to guide the future development of this field. Here, we cross-correlate cathepsin-B or matrix metalloproteinase-2/-9 molecular optical imaging data of human atheromata or emboli with conventional imaging data, clinical data, and histopathologic data. METHODS AND RESULTS: Fifty-two patients undergoing carotid endarterectomy (41 atheromata) or carotid stenting (15 captured emboli) were studied with protease-activatable imaging probes. We show that protease-related fluorescent signal in carotid atheromata or in emboli closely reflects the pathophysiologic alterations of plaque inflammation and statin-mediated therapeutic effects on plaque inflammation. Inflammation-related fluorescent signal was observed in the carotid bifurcation area and around ulcero-hemorrhagic lesions. Pathologically proven unstable plaques had high cathepsin-B-related fluorescent signal. The distribution patterns of the mean cathepsin-B imaging signals showed a difference between the symptomatic vs asymptomatic plaque groups. However, the degree of carotid stenosis or ultrasonographic echodensity was weakly correlated with the inflammatory proteolytic enzyme-related signal, suggesting that molecular imaging yields complimentary new information not available to conventional imaging. CONCLUSIONS: These results could justify and facilitate clinical trials to evaluate the use of protease-sensing molecular optical imaging in human atherosclerosis patients.

Comparison of Next-Generation Sequencing and Fluorescence In Situ Hybridization for Detection of Segmental Chromosomal Aberrations in Neuroblastoma.

The aim of this study was to compare next-generation sequencing (NGS) with the traditional fluorescence in situ hybridization (FISH) for detecting segmental chromosomal aberrations (SCAs) such as 1p deletion, 11q deletion and 17q gain, which are well-known predictive markers for adverse outcome in neuroblastoma. The tumor tissue obtained from 35 patients with neuroblastoma was tested by FISH and targeted NGS, which is specially designed to detect copy number alterations across the entire chromosomal region in addition to mutations in 353 cancer-related genes. All chromosomal copy number alterations were analyzed using the copy number variation plot derived from targeted NGS. FISH was performed to detect 1p deletion, 11q deletion and 17q gain. The copy numbers of 1p, 11q, and 17q obtained via NGS were correlated with those acquired via FISH. The SCAs determined by NGS were matched with those by FISH. Most 17q gain of mismatched cases detected by NGS alone showed a subsegmental gain of 17q. FISH revealed 11q deletion and 17q gain in a few tumor cells of two cases, which were not detected by NGS. NGS can be a sensitive complementary and alternative method to the conventional FISH for detecting SCAs.

3'-UTR Polymorphisms in Thymidylate Synthase with Colorectal Cancer Prevalence and Prognosis.

Colorectal cancer (CRC) is the third most common type of cancer and the second leading cause of cancer-related mortality in Western countries. Polymorphisms in one-carbon metabolism and angiogenesis-related genes have been shown to play important roles in tumor development, progression, and metastasis for many cancers, including CRC. Moreover, recent studies have reported that polymorphisms in specific microRNA (miRNA)-binding regions, which are located in the 3'-untranslated region (UTR) of miRNA-regulated genes, are present in a variety of cancers. Here, we investigated the association between two thymidylate synthase (TYMS or TS) 3'-UTR polymorphisms, 1100T>C [rs699517] and 1170A>G [rs2790], and CRC susceptibility and progression in Korean patients. A total of 450 CRC patients and 400 healthy controls were enrolled in this study, and genotyping at the TS locus was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) or TaqMan allelic discrimination assays. We found that TS 1170A>G genotypes, as well as the TS 1100T-1170G and 1100C-1170A haplotypes, are strongly associated with CRC. The TS 1100TC+CC type was associated with a poor survival (OS and RFS) rate. In addition, levels of the TS 1100C and TS 1170G allele were found to be significantly increased in CRC tissue. Our study provides the first evidence for 3'-UTR variants in TS genes as potential biomarkers of CRC prognosis and prevention.

The role of macrophage migration inhibitory factor in ocular surface disease pathogenesis after chemical burn in the murine eye.

PURPOSE: To evaluate the role of macrophage migration inhibitory factor (MIF) in the wound healing process following severe chemical burns to the ocular surface. METHODS: Chemical burning of the ocular surface was induced in mice (C57BL/6) via the application of 0.1 M NaOH. Macrophage migration inhibitory factor (MIF), tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß) mRNA expression in the ocular surface and lacrimal gland was evaluated via real-time reverse transcription PCR on days 2, 7, and 30 after induction of the chemical burn. The expression of MIF protein in the ocular surface and lacrimal gland was evaluated via western blot analysis. Immunohistochemical staining was conducted to detect MIF and vasculoendothelial growth factor in the cornea during the wound healing process. The angiogenic role of MIF was further evaluated using an 8-0 polyglactin suture technique to induce corneal neovascularization. RESULTS: MIF, TNF-α, and IL-1ß mRNA expression were elevated significantly in the ocular surface up to day 30 after chemical burn induction. TNF-α alone was elevated in the lacrimal gland. MIF protein elevation was confirmed via western blot analysis, and the spatial similarity of MIF and VEGF expression in the cornea was noted during the wound healing process. 8-0 polyglactin sutures soaked in MIF induced significantly higher numbers of new vessels on the mouse cornea after 7 days (p=0.003, Mann-Whitney test). CONCLUSIONS: These findings indicate that MIF performs a crucial role in wound healing on the ocular surface after the induction of chemical burns.

Pancreatic Hemangioma Suspected of Neuroendocrine Tumor.

Adult pancreatic hemangioma is an extremely rare disease, with only 22 cases reported since 1939. Pancreatic hemangioma has no specific symptoms, diagnostic imaging, or laboratory findings, making it difficult to be clinically suspected and diagnosed. The majority are confirmed after surgery. In this report, a 61-year-old woman presented with melena and showed multiple small hyper-vascular lesions in the pancreas. A pancreatic neuroendocrine tumor was suspected, and the patient underwent a distal pancreatectomy. The pathology examination and immunohistochemical study revealed a pancreatic hemangioma.

Morule-like features in pulmonary adenocarcinoma associated with epidermal growth factor receptor mutations: two case reports with targeted next-generation sequencing analysis.

Morules, or morule-like features, can be identified in benign and malignant lesions in various organs. Morular features are unusual in pulmonary adenocarcinoma cases with only 26 cases reported to date. Here, we describe two cases of pulmonary adenocarcinoma with morule-like features in Korean women. One patient had a non-mucinous-type adenocarcinoma in situ and the other had an acinarpredominant adenocarcinoma with a micropapillary component. Both patients showed multiple intra-alveolar, nodular, whorled proliferative foci composed of atypical spindle cells with eosinophilic cytoplasm. Targeted next-generation sequencing was performed on DNA extracted from formalin-fixed paraffin-embedded samples of the tumors. Results showed unusual epidermal growth factor receptor (EGFR) mutations, which are associated with drug resistance to EGFR tyrosine kinase inhibitors, revealing the importance of identifying morule-like features in pulmonary adenocarcinoma and the need for additional study, since there are few reported cases.

BRCA1-associated protein 1 expression and prognostic role in prostate adenocarcinoma.

Purpose: As prostate cancer (PCa) is the second most commonly diagnosed cancer worldwide, finding novel markers for prognosis is crucial. BRCA1-associated protein 1 (BAP-1), a nuclear-localized deubiquitinating enzyme, has been reported in several human cancers. However, its prognostic role in PCa remains unknown. Herein, we assessed the prognostic and clinicopathologic significance of BAP-1 in PCa. Materials and Methods: Seventy surgical specimens from radical prostatectomy cases were examined. Two cores per case were selected for construction of tissue microarrays (TMAs). After the exclusion of two cases because of tissue sparsity, BAP-1 immunohistochemical expression was evaluated in 68 cases of formalin-fixed, paraffin-embedded TMA tissue blocks. The immunohistochemical stain was scored according to proportion of nuclear staining: negative (<10% of tumor cells) or positive (≥10% of tumor cells). Results: BAP-1 expression was negative in 30 cases (44.1%) and positive in 38 cases (55.9%). Positive BAP-1 expression was more common in pT3b disease than in pT2 (p=0.038). A high preoperative prostate-specific antigen level was correlated with BAP-1 expression (p=0.014). Age, lymphovascular invasion, perineural invasion, and grade group were not significantly correlated with BAP-1 expression. Patients with positive BAP-1 expression showed significantly shorter disease-free survival (p=0.013). Additionally, BAP-1 was an independent prognostic factor of PCa (p=0.035; hazard ratio, 9.277; 95% confidence interval, 1.165-73.892). Conclusions: Our study findings showed an association of BAP-1 expression with poor PCa prognosis and suggest a potential role for BAP-1 as a prognostic biomarker for PCa.

Molecular imaging of cathepsin B proteolytic enzyme activity reflects the inflammatory component of atherosclerotic pathology and can quantitatively demonstrate the antiatherosclerotic therapeutic effects of atorvastatin and glucosamine.

Inflammation in atherosclerotic plaques causes plaque vulnerability and rupture, leading to thromboembolic complications. Cathepsin B (CatB) proteases secreted by macrophages play a major role in plaque inflammation. We used a CatB-activatable near-infrared fluorescence (NIRF) imaging agent to demonstrate the inflammatory component in mice atheromata and the atherosclerosis- modulating effects of atorvastatin or glucosamine treatments. Apolipoprotein E knockout mice (n = 35) were fed normal chow, a Western diet, a Western diet + atorvastatin, a Western diet + glucosamine, or a Western diet + atorvastatin + glucosamine for 14 weeks. Twenty-four hours after the intravenous injection of a CatB-activatable probe, ex vivo NIRF imaging of the aortas and brains was performed, followed by histology. The CatB-related signal, observed in the aortas but not in the cerebral arteries, correlated very well with protease activity and the presence of macrophages on histology. Animals on Western diets could be distinguished from animals on a normal diet. The antiatherosclerotic effects of atorvastatin and glucosamine could be demonstrated, with reduced CatB-related signal compared with untreated animals. Plaque populations were heterogeneous within individuals, with some plaques showing a high and others a lower CatB-related signal. These differences in signal intensity could not be predicted by visual inspection of the plaques but did correlate with histologic evidence of inflammation in every case. This suggests that vulnerable inflamed plaques can be identified by optical molecular imaging.

Simultaneous adrenal pheochromocytoma and sarcoidosis.

A 48-year-old man presented for evaluation of general weakness. Because he had a history of excessive alcohol use, an abdominal computed tomography scan was obtained, which revealed a left adrenal mass. Hormonal evaluation showed elevated levels of urinary catecholamines. Bilateral hilar lymphadenopathy was detected on a chest radiograph. The suspected diagnosis was asymptomatic pheochromocytoma with sarcoidosis. We performed a mediastinoscopic lymph node biopsy, which was followed by endoscopic adrenalectomy. Histologic tissue analysis confirmed an adrenal pheochromocytoma and sarcoid granulomas in the mediastinal lymph nodes. This case highlights the difficulty in determining the appropriate work up of patients presenting with an adrenal incidentaloma and concomitant systemic disease.

Long noncoding RNA HOTTIP overexpression: A potential prognostic biomarker in prostate cancer.

HOXA transcript at the distal tip (HOTTIP) is a long noncoding RNA (lncRNA), which is >200 nucleotides in length. HOTTIP expression has been demonstrated to play a crucial oncogenic role in cancer pathogenesis, and is said to be associated with poor human cancer prognosis. In prostate cancer, HOTTIP has been identified as an oncogene, but its clinicopathologic significance remains unclear. Array-based qRT-PCR was used to investigate lncRNA levels in 10 pairs of prostate cancer tissues and non-neoplastic parenchyma. Tissue microarray (TMA) was constructed using a total of 70 surgically resected prostatic adenocarcinoma tissues obtained from the Korea University Anam Hospital from 2009 to 2013. HOTTIP expression was determined by RNA in situ hybridization(ISH) and was correlated with clinicopathologic features. Increased HOTTIP expression was observed in all available prostate cancer tissue specimens compared with that in paired normal tissue. High HOTTIP expression was positively associated with bad clinicopathologic features, including higher pathologic T stage (p < 0.001), presence of extraprostatic extension (p < 0.001), seminal vesicle invasion (p < 0.001), perineural invasion (p < 0.001), and the tumor involvement of resection margin (p = 0.044). In particular, significantly increased HOTTIP expression was observed in specimens from patients in the high or very high-risk group, according to the 2018 National Comprehensive Cancer Network (NCCN) guidelines (p < 0.001). Also, patients with high HOTTIP expression showed poorer overall survival than those with low expression. In conclusion, we analytically validated the poor prognostic significance of HOTTIP overexpression and its association with bad clinicopathologic features, and present HOTTIP as a potential prognostic biomarker in prostate cancer.

High Yes-associated protein 1 with concomitant negative LATS1/2 expression is associated with poor prognosis of advanced gastric cancer.

The Hippo pathway is a tumour-suppressive pathway and its inactivation is known to be associated with progression and metastasis of various cancers. LATS1/2 (large tumour suppressor homolog 1 and 2), YAP1 (Yes-associated protein 1), and TEAD4 (TEA domain-containing sequence-specific transcription factors 4) are core components of the Hippo pathway, and their prognostic roles have not yet been studied in advanced gastric cancers (AGCs). A total of 318 surgically resected AGCs were retrieved. Immunolabelling for LATS1/2, YAP1 and TEAD4 was compared with clinicopathological factors including patients' survival. High expression of YAP1 and TEAD4 was identified in 108 (34.0%) and 131 (41.2%) cases, respectively, and 223 (70.1%) cases were negative for LATS1/2 expression. High YAP1 expression was significantly correlated with the presence of perineural invasion (p=0.032). High YAP1 and high TEAD4 expressions were significantly associated with poor overall survival (p<0.001 and p=0.003, respectively), and negative LATS1/2 expression was also associated with poor overall survival (p=0.002). Combined expression of YAP1highLATS1/2neg showed the worst overall survival (p<0.001). Expression of YAP1high (HR=2.938; 95% CI 1.726-4.998; p<0.001), LATS1/2neg (HR=0.371; 95% CI 0.181-0.758; p=0.007), and combined YAP1highLATS1/2neg (HR=13.785; 95% CI 3.245-58.554; p<0.001) were independent poor prognostic factors of AGC patients. Combined or individual expression of YAP1, LATS1/2, and TEAD4 can be used as prognostic markers of AGC patients.

Effects of wire-type and mesh-type anode current collectors on performance and electrochemistry of microbial fuel cells.

Carbon-based material is commonly used for anodes in MFCs, but its low conductivity often limits anodic performance. Application of corrosion-resistive current collector to carbon-based anode can be a promising strategy for increasing the anodic performance. In this study, it was hypothesized increasing metal current collector improved anodic performance. Two different carbon-felt anodes with titanium wires (CF-W) or stainless steel mesh (CF-M) as a current collector were tested in a single chamber MFC. In the short-term tests such as polarization and impedance tests, CF-M with the larger current collector area (21.7 cm2) had 33% higher maximum power (2311 mW/m2), 81% lower anodic resistance (3 Ω), and 92% lower anodic impedance (1.1 Ω). However, in the long-term tests, CF-W with the smaller current collector area (0.6 cm2) showed higher performance in power and current generation, COD removal, and CE (51%, 10%, 11%, and 5% higher, respectively) and produced 41% higher net current in cyclic voltagramm (20.0 mA vs. 14.2 mA). This result shows that larger current collector is advantageous in short-term performance and disadvantageous in long-term performance, because the larger current collector is good for current collection, but interferes with mass transfer and microbial growth.