16 research outputs found

    A Difficult Differential Diagnosis of Acute Cholecystitis in a Patient With Steroid-induced Diabetes

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    An impairment of gallbladder motility due to autonomic neuropathy may cause cholestasis and result in gallbladder stone formation. Diabetes is one of risk factors for acute cholecystitis. Diabetes and steroid use are associated with the susceptibility to bacterial infections, we are apt to diagnose steroid-induced diabetic patients manifesting symptoms of cholecystitis as having acute bacterial infective cholecystitis. Here, we report a very rare steroid-induced diabetic patient complicated with gallbladder torsion-induced necrotizing cholecystitis due to a floating gallbladder

    Hotspots of De Novo Point Mutations in Induced Pluripotent Stem Cells

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    Summary: Induced pluripotent stem cells (iPSCs) are generated by direct reprogramming of somatic cells and hold great promise for novel therapies. However, several studies have reported genetic variations in iPSC genomes. Here, we investigated point mutations identified by whole-genome sequencing in mouse and human iPSCs in the context of epigenetic status. In contrast to disease-causing single-nucleotide polymorphisms, de novo point mutations introduced during reprogramming were underrepresented in protein-coding genes and in open chromatin regions, including transcription factor binding sites. Instead, these mutations occurred preferentially in structurally condensed lamina-associated heterochromatic domains, suggesting that chromatin organization is a factor that can bias the regional mutation rate in iPSC genomes. Mutation signature analysis implicated oxidative stress associated with reprogramming as a likely cause of point mutations. Altogether, our study provides deeper understanding of the mutational landscape of iPSC genomes, paving an important way toward the translation of iPSC-based cell therapy. : Yoshihara et al. show that de novo point mutations introduced during iPSC reprogramming preferentially occur in structurally condensed lamina-associated heterochromatic domains and exhibit an oxidative stress-induced DNA damage mutation signature. This study provides better characterization of iPSC mutations at the whole-genome level and accelerates the translation of iPSC-based cell therapies. Keywords: iPSCs, genomics, point mutation, epigenetics, heterochromatin, lamina-associated domains, iPSC-based cell therap

    Hotspots of De Novo Point Mutations in Induced Pluripotent Stem Cells

    No full text
    Induced pluripotent stem cells (iPSCs) are generated by direct reprogramming of somatic cells and hold great promise for novel therapies. However, several studies have reported genetic variations in iPSC genomes. Here, we investigated point mutations identified by whole-genome sequencing in mouse and human iPSCs in the context of epigenetic status. In contrast to disease-causing single-nucleotide polymorphisms, de novo point mutations introduced during reprogramming were underrepresented in protein-coding genes and in open chromatin regions, including transcription factor binding sites. Instead, these mutations occurred preferentially in structurally condensed lamina-associated heterochromatic domains, suggesting that chromatin organization is a factor that can bias the regional mutation rate in iPSC genomes. Mutation signature analysis implicated oxidative stress associated with reprogramming as a likely cause of point mutations. Altogether, our study provides deeper understanding of the mutational landscape of iPSC genomes, paving an important way toward the translation of iPSC-based cell therap

    Voxel-based statistical analysis and quantification of amyloid PET in the Japanese Alzheimer\u27s disease neuroimaging initiative (J-ADNI) multi-center study

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    Background: Amyloid PET plays a vital role in detecting the accumulation of in vivo amyloid-β (Aβ). The quantification of Aβ accumulation has been widely performed using the region of interest (ROI)-based mean cortical standardized uptake value ratio (mcSUVR). However, voxel-based statistical analysis has not been well studied. The purpose of this study was to examine the feasibility of analyzing amyloid PET scans by voxel-based statistical analysis. The results were then compared to those with the ROI-based mcSUVR. In total, 166 subjects who underwent 11C-PiB PET in the J-ADNI multi-center study were analyzed. Additionally, 18 Aβ-negative images were collected from other studies to form a normal database. The PET images were spatially normalized to the standard space using an adaptive template method without MRI. The mcSUVR was measured using a pre-defined ROI. Voxel- wise Z-scores within the ROI were calculated using the normal database, after which Z-score maps were generated. A receiver operating characteristic (ROC) analysis was performed to evaluate whether Z-sum (sum of the Z-score) and mcSUVR could be used to classify the scans into positive and negative using the central visual read as the reference standard. PET scans that were equivocal were regarded as positive. Results: Sensitivity and specificity were respectively 90.8% and 100% by Z-sum and 91.8% and 98.5% by mcSUVR. Most of the equivocal scans were subsequently classified by both Z-sum and mcSUVR as false negatives. Z-score maps correctly delineated abnormal Aβ accumulation over the same regions as the visual read. Conclusions: We examined the usefulness of voxel-based statistical analysis for amyloid PET. This method provides objective Z-score maps and Z-sum values, which were observed to be helpful as an adjunct to visual interpretation especially for cases with mild or limited Aβ accumulation. This approach could improve the Aβ detection sensitivity, reduce inter-reader variability, and allow for detailed monitoring of Aβ deposition

    An Individual with Gastric Schwannoma with Pathologically Malignant Potential Surviving Two Years after Laparoscopy-Assisted Partial Gastrectomy

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    Schwannomas are a kind of neurogenic tumor. They are generally benign and originate primarily from the central and peripheral nerve. They rarely develop in the gastrointestinal tract: gastric schwannomas make up 0.2% of gastric neoplasms. A malignant gastric schwannoma is a comparatively rare tumor, a few cases have been reported until now. We present the case of a 34-year-old male patient diagnosed during medical examination. The patient was treated with surgical resection, and 2 years passed without recurrence
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