Copy Number Variation of Age-Related Macular Degeneration Relevant Genes in the Korean Population

PURPOSE: Studies that analyzed single nucleotide polymorphisms (SNP) in various genes have shown that genetic factors are strongly associated with age-related macular degeneration (AMD) susceptibility. Copy number variation (CNV) may be an additional type of genetic variation that contributes to AMD pathogenesis. This study investigated CNV in 4 AMD-relevant genes in Korean AMD patients and control subjects. METHODS: Four CNV candidate regions located in AMD-relevant genes (VEGFA, ARMS2/HTRA1, CFH and VLDLR), were selected based on the outcomes of our previous study which elucidated common CNVs in the Asian populations. Real-time PCR based TaqMan Copy Number Assays were performed on CNV candidates in 273 AMD patients and 257 control subjects. RESULTS: The predicted copy number (PCN, 0, 1, 2 or 3+) of each region was called using the CopyCaller program. All candidate genes except ARMS2/HTRA1 showed CNV in at least one individual, in which losses of VEGFA and VLDLR represent novel findings in the Asian population. When the frequencies of PCN were compared, only the gain in VLDLR showed significant differences between AMD patients and control subjects (p = 0.025). Comparisons of the raw copy values (RCV) revealed that 3 of 4 candidate genes showed significant differences (2.03 vs. 1.92 for VEGFA, p<0.01; 2.01 vs. 1.97 for CFH, p<0.01; 1.97 vs. 2.01, p<0.01 for ARMS2/HTRA1). CONCLUSION: CNVs located in AMD-relevant genes may be associated with AMD susceptibility. Further investigations encompassing larger patient cohorts are needed to elucidate the role of CNV in AMD pathogenesis

M3FPolypSegNet: Segmentation Network with Multi-frequency Feature Fusion for Polyp Localization in Colonoscopy Images

Polyp segmentation is crucial for preventing colorectal cancer a common type of cancer. Deep learning has been used to segment polyps automatically, which reduces the risk of misdiagnosis. Localizing small polyps in colonoscopy images is challenging because of its complex characteristics, such as color, occlusion, and various shapes of polyps. To address this challenge, a novel frequency-based fully convolutional neural network, Multi-Frequency Feature Fusion Polyp Segmentation Network (M3FPolypSegNet) was proposed to decompose the input image into low/high/full-frequency components to use the characteristics of each component. We used three independent multi-frequency encoders to map multiple input images into a high-dimensional feature space. In the Frequency-ASPP Scalable Attention Module (F-ASPP SAM), ASPP was applied between each frequency component to preserve scale information. Subsequently, scalable attention was applied to emphasize polyp regions in a high-dimensional feature space. Finally, we designed three multi-task learning (i.e., region, edge, and distance) in four decoder blocks to learn the structural characteristics of the region. The proposed model outperformed various segmentation models with performance gains of 6.92% and 7.52% on average for all metrics on CVC-ClinicDB and BKAI-IGH-NeoPolyp, respectively.Comment: 5pages. 2023 IEEE International Conference on Image Processing (ICIP). IEEE, 202

Terminal fucosylation of haptoglobin in cancer-derived exosomes during cholangiocarcinoma progression

BackgroundCholangiocarcinoma (CCA) is a silent tumor with a high mortality rate due to the difficulty of early diagnosis and prediction of recurrence even after timely surgery. Serologic cancer biomarkers have been used in clinical practice, but their low specificity and sensitivity have been problematic. In this study, we aimed to identify CCA-specific glycan epitopes that can be used for diagnosis and to elucidate the mechanisms by which glycosylation is altered with tumor progression.MethodsThe serum of patients with various cancers was fractioned into membrane-bound and soluble components using serial ultracentrifugation. Lectin blotting was conducted to evaluate glycosylation. Proteins having altered glycosylation were identified using proteomic analysis and further confirmed using immunoblotting analysis. We performed HPLC, gene analysis, real-time cargo tracking, and immunohistochemistry to determine the origin of CCA glycosylation and its underlying mechanisms. Extracellular vesicles (EV) were isolated from the sera of 62 patients with CCA at different clinical stages and inflammatory conditions and used for glycan analysis to assess their clinical significance.ResultsThe results reveal that glycosylation patterns between soluble and membrane-bound fractions differ significantly even when obtained from the same donor. Notably, glycans with α1-3/4 fucose and β1-6GlcNAc branched structures increase specifically in membrane-bound fractions of CCA. Mechanically, it is primarily due to β-haptoglobin (β-Hp) originating from CCA expressing fucosyltransferase-3/4 (FUT 3/4) and N-acetylglucosaminyltransferase-V (MGAT5). Newly synthesized β-Hp is loaded into EVs in early endosomes via a KFERQ-like motif and then secreted from CCA cells to induce tumor progression. In contrast, β-Hp expressed by hepatocytes is secreted in a soluble form that does not affect CCA progression. Moreover, evaluation of EV glycosylation in CCA patients shows that fucosylation level of EV-Hp gradually increases with tumor progression and decreases markedly when the tumors are eliminated by surgery.ConclusionThis study suggests that terminal fucosylation of Hp in cancer-derived exosomes can be a novel glycan marker for diagnosis and prognosis of CCA. These findings highlight the potential of glycan analysis in different fractions of serum for biomarker discover for other diseases. Further research is needed to understand the role of fucosylated EVs on CCA progression

Measuring Complex Refractive Indices of a Nanometer-Thick Superconducting Film Using Terahertz Time-Domain Spectroscopy with a 10 Femtoseconds Pulse Laser

Superconducting thin films are widely applied in various fields, including switching devices, because of their phase transition behaviors in relation to temperature changes. Therefore, it is important to quantitatively determine the optical constant of a superconducting material in the thin-film state. We performed a terahertz time-domain spectroscopy, based on a 10 femtoseconds pulse laser, to measure the optical constant of a superconducting GdBa2Cu3O7-x (GdBCO) thin film in the terahertz region. We then estimated the terahertz refractive indices of the 70 nm-thick GdBCO film using a numerical extraction process, even though the film thickness was approximately 1/10,000 times smaller than the terahertz wavelength range of 200 mu m to 1 mm. The resulting refractive indices of the GdBCO thin film were consistent with the theoretical results using the two-fluid model. Our work will help to further understand the terahertz optical properties of superconducting thin films with thicknesses under 100 nm, as well as provide a standard platform for characterizing the optical properties of thin films without the need of Kramers-Kronig transformation at the terahertz frequencies

Replacing conventional battery electrolyte additives with dioxolone derivatives for high-energy-density lithium-ion batteries

Solid electrolyte interphases generated using electrolyte additives are key for anode-electrolyte interactions and for enhancing the lithium-ion battery lifespan. Classical solid electrolyte interphase additives, such as vinylene carbonate and fluoroethylene carbonate, have limited potential for simultaneously achieving a long lifespan and fast chargeability in high-energy-density lithium-ion batteries (LIBs). Here we report a next-generation synthetic additive approach that allows to form a highly stable electrode-electrolyte interface architecture from fluorinated and silylated electrolyte additives; it endures the lithiation-induced volume expansion of Si-embedded anodes and provides ion channels for facile Li-ion transport while protecting the Ni-rich LiNi0.8Co0.1Mn0.1O2 cathodes. The retrosynthetically designed solid electrolyte interphase-forming additives, 5-methyl-4-((trifluoromethoxy)methyl)-1,3-dioxol-2-one and 5-methyl-4-((trimethylsilyloxy)methyl)-1,3-dioxol-2-one, provide spatial flexibility to the vinylene carbonate-derived solid electrolyte interphase via polymeric propagation with the vinyl group of vinylene carbonate. The interface architecture from the synthesized vinylene carbonate-type additive enables high-energy-density LIBs with 81.5% capacity retention after 400 cycles at 1???C and fast charging capability (1.9% capacity fading after 100 cycles at 3???C)

A Successful Primary Percutaneous Coronary Intervention Twelve Days After a Cabrol Composite Graft Operation in Marfan Syndrome

The Cabrol procedure is one of several techniques used for re-implantation of a coronary artery. After replacement of the ascending aorta and aortic valve using a composite graft, second Dacron tube grafts are used for anastomosis between the ascending aortic graft and the coronary arteries. Ostial stenosis is one of the complications associated with the Cabrol operation. However, there have been no reported cases of acute thrombosis of a Cabrol graft. Here we report a case with acute ST elevation myocardial infarction due to thrombotic total occlusion of a right Cabrol graft-to-right coronary artery (RCA) twelve days after surgery in a patient with Marfan syndrome. He was successfully treated with primary percutaneous coronary intervention (PCI)

A case of hepatoblastoma misdiagnosed as combined hepatocellular carcinoma and cholangiocarcinoma in an adult

Hepatoblastoma usually occurs in children under the age of 2 years, with very few cases reported in adults. We experienced a case of adult hepatoblastoma in a 36-year-old female with chronic hepatitis B. She had experienced sudden onset abdominal pain. Her serum alpha-fetoprotein level was markedly elevated, and abdominal CT showed a 9-cm mass with internal hemorrhage in the right hepatic lobe with hemoperitoneum, so an emergency hepatic central bisectionectomy was performed. The initial histologic examination revealed that the mass mimicked combined hepatocellular carcinoma and cholangiocarcinoma with spindle-cell metaplasia of the cholangiocarcinoma element. Follow-up abdominal CT performed 3 months later showed a 5.5-cm metastatic mass in the left subphrenic area. Laparoscopic splenectomy with mass excision was performed, and hepatoblastoma was confirmed histologically. A histologic re-examination of previously obtained surgical specimens also confirmed the presence of hepatoblastoma. Metastatic hepatoblastoma was found at multiple sites of the abdomen during follow-up, and so chemotherapy with cisplatin, 5-fluorouracil (5-FU), and vincristine was applied, followed by carboplatin and doxorubicin. Despite surgery and postoperative chemotherapy, she died 12 months after symptom onset

Case report: Fatal insulin overdose in a dog with type 1 diabetes mellitus—characteristics and successful management

Administering more than 10 times the therapeutic dose of insulin is extremely rare in diabetic dogs and is life threatening with hypoglycemia and seizures if not accompanied by appropriate treatment. A 15-year-old, castrated male miniature poodle dog managed for diabetes presented with depression, disorientation, ataxia, and cluster seizures. The dog had been administered 11.1 U/kg of neutral protamine hegadorn (NPH) insulin (10 times the prescribed dose) 3 h before the onset of symptoms. Blood analysis revealed hypoglycemia, with a circulating glucose level of &lt;50 mg/dL. To treat the hypoglycemia-induced seizures, dextrose was repeatedly administered intravenously. Repeated generalized seizures were treated with anticonvulsants and intermittent mannitol. Since refractory hypoglycemia persisted 24 h after the insulin overdose, it was decided to proceed with glucagon treatment (15–30 ng/kg/min titrated to the blood glucose level after a loading dose of 50 ng/kg intravenous bolus infusion). After 37 h of glucagon treatment, blood glucose levels stabilized. After entering a hyperglycemic state, NPH insulin was administered to manage insulin-dependent diabetes mellitus. This is the first case documented of successful treatment with glucagon, anticonvulsants and intermittent mannitol for refractory hypoglycemia and seizure caused by fatal insulin overdose. Thus, it has great clinical value in veterinary medicine