[Calcified Amorphous Tumor Diagnosed After Stroke:Report of a Case].

Calcified amorphous tumor (CAT), a non-neoplastic tumor, is rare. Histopathologic features are the presence of calcified nodules in an amorphous background of fibrin. CAT is reported to be associated with renal dysfunction or hemodialysis, and possibly causes cerebral embolism. We report a case of CAT diagnosed after stroke. A 58-year-old male with a 2-year history of hemodialysis was diagnosed with an acute stroke, and was treated medically. Paralysis promptly improved, but transthoracic echocardiography revealed a tumor attached to the posterior mitral leaflet and dense mitral annular calcification. To prevent embolism due to the large tumor, we performed resection of the tumor. Pathological findings showed calcifications surrounded by amorphous fibrous tissue, indicating CAT. Postoperative course was uneventful.

PubChemQC B3LYP/6-31G*//PM6 Data Set: The Electronic Structures of 86 Million Molecules Using B3LYP/6-31G* Calculations.

The presented "PubChemQC B3LYP/6-31G*//PM6" data set is composed of the electronic properties of 85,938,443 molecules, encompassing a broad spectrum of molecules from essential compounds to biomolecules with a molecular weight up to 1000. These molecules account for 94.0% of the original PubChem Compound catalog as of August 29, 2016. The electronic properties, including orbitals, orbital energies, total energies, dipole moments, and other pertinent properties, were computed by using the B3LYP/6-31G* and PM6 methods. The data set, available in three formats, namely, GAMESS quantum chemistry program files, selected JSON output files, and a PostgreSQL database, provides researchers with the ability to query molecular properties. It is further subdivided into five subdata sets for more specific data. The first two subsets encompass molecules with carbon, hydrogen, oxygen, and nitrogen with molecular weights under 300 and 500, respectively. The third and fourth subsets incorporate molecules with carbon, hydrogen, nitrogen, oxygen, phosphorus, sulfur, fluorine, and chlorine, with molecular weights under 300 and 500, respectively. The fifth subset comprises molecules with carbon, hydrogen, nitrogen, oxygen, phosphorus, sulfur, fluorine, chlorine, sodium, potassium, magnesium, and calcium, with a molecular weight of under 500. The coefficients of determination for the highest occupied molecular orbital-lowest unoccupied molecular orbital energy gap range from 0.892 (for CHON500) to 0.803 (for the whole data set). These comprehensive results pave the way for applications in drug discovery and materials science, among others. The data sets can be accessed under the Creative Commons Attribution 4.0 International license at the following web address: https://nakatamaho.riken.jp/pubchemqc.riken.jp/b3lyp_pm6_datasets.html.

[Pulmonary Adenocarcinoma in Situ with Positive Findings in Pleural Lavage Cytology].

We report a rare case of positive findings in pleural lavage cytology(PLC) in the patient with pulmonary adenocarcinoma in situ (AIS). A 78-year-old woman was presented with a 30 mm pure groundglass nodule (GGN) in the left upper lobe on chest computed tomography (CT). After 2 years follow- up, thoracoscopic surgery was performed to resect the nodule. PLC was performed before pulmonary resection. Histopathological diagnosis was 25 mm AIS. However, PLC showed positive findings of malignant cells. CT examination at 1 year and 6 months postoperatively showed pleural dissemination findings and the patient died of lung cancer at 3 years and 2 months postoperatively. PLC's contribution to TNM staging has not yet been clarified. The positive findings in PLC and large size of pure GGN were considered likely to be poor prognostic indicators.

[Acute Coronary Syndrome in a Patient with Giant Coronary Artery Aneurysm:Report of a Case].

Coronary artery aneurysm is a rare entity defined as expansion more than 1.5 times of normal coronary artery in diameter. A 77-year-old male was admitted to our hospital with a diagnosis of acute coronary syndrome and a giant right coronary artery aneurysm. Coronary angiography showed occlusion of the right coronary artery and significant stenosis of left anterior descending artery and left circumflex artery. Enhanced computed tomography( CT) showed a right coronary artery aneurysm with a diameter of 38 mm. Urgent coronary artery bypass grafting and coronary artery ligation proximal and distal to the aneurysm were performed. His postoperative course was uneventful.

Comparison of Phenotypes in Subcutaneous Fat and Perivascular Adipose Tissue Surrounding the Saphenous Vein in Coronary Artery Bypass Grafting.

BACKGROUND: The saphenous vein (SV) is used as an essential conduit in coronary artery bypass grafting (CABG), but the long-term patency of SV grafts is a crucial issue. The use of the novel "no-touch" technique of harvesting the SV together with its surrounding tissue has been reported to result in good long-term graft patency of SV grafts. We recently showed that perivascular adipose tissue (PVAT) surrounding the SV (SV-PVAT) had lower levels of metaflammation and consecutive adipose tissue remodeling than did PVAT surrounding the coronary artery. However, the difference between SV-PVAT and subcutaneous adipose tissue (SCAT) remains unclear.Methods and Results: Fat pads were sampled from 55 patients (38 men, 17 women; mean [±SD] age 71±8 years) with coronary artery disease who underwent elective CABG. Adipocyte size was significantly larger in SV-PVAT than SCAT. The extent of fibrosis was smaller in SV-PVAT than SCAT. There were no significant differences between SCAT and SV-PVAT in macrophage infiltration area, quantified by antibodies for CD68, CD11c, and CD206, or in gene expression levels of metaflammation-related markers. Expression patterns of adipocyte developmental and pattern-forming genes differed between SCAT and SV-PVAT. CONCLUSIONS: The properties of SV-PVAT are close to, but not the same as, those of SCAT, possibly resulting from inherent differences in adipocytes. SV-PVAT has healthy expansion with less fibrosis in fat than SCAT.

A Case of Severe Aortic Stenosis after Aortic Valve Neocuspidization Using Autologous Pericardium (Ozaki Procedure).

A 56-year-old man with a history of left nephrectomy for Wilms' tumor on chronic hemodialysis underwent aortic valve neocuspidization using autologous pericardium (Ozaki procedure) for aortic stenosis (AS) due to a bicuspid aortic valve 6 years ago. The AS gradually progressed and a decrease in the left ventricular ejection fraction was observed. Because of this, we decided to perform reoperative aortic valve replacement using a mechanical valve. Intraoperative findings showed severe calcification at the site where the autologous pericardium was sutured to the annulus. However, the degeneration of the valve leaflets themselves was mild. While excellent mid-term results have been reported for the Ozaki procedure, the long-term results are still unclear. In this case, the annulus was severely calcified, which reduced the mobility of the leaflet. We report the first case of AS progression requiring reoperation in the long-term period after the Ozaki procedure.

Exploratory evaluation of an eye-tracking system in patients with advanced spinal muscular atrophy type I receiving nusinersen.

Objective: This study evaluated the feasibility of a matching-pair test using eye-tracking technology to assess nusinersen effectiveness in patients with advanced spinal muscular atrophy (SMA) type I. Methods: This prospective, observational study enrolled patients with 5q-SMA type I who had lost gross motor function. Three different levels of matching-pair tests were conducted using the eye-gaze system (My Tobii; TobiiDynavox Inc.) at baseline, and after 9 and 24 weeks of nusinersen treatment. The primary endpoint was the change from baseline in matching-pair test scores and response times (i.e., the time to answer matching-pair test) at 24 weeks from baseline. Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND), Pediatric Quality of Life inventory for patients with Neuromuscular Disease (PedsQL-NM) and Numerical Rating Scale (NRS) scores were also assessed as secondary endpoints. Analysis of ocular fixation was performed as an additional analysis. This study was registered at https://www.umin.ac.jp/ctr/ (UMIN000033935). Results: Seven patients (one male, six female) aged 5-21 years (median 11 years) were enrolled; all patients were bedridden and six patients were ventilated. All seven patients were able to conduct level 1 matching-pair tests at each assessment; five patients were also able to conduct levels 2 and 3. Two patients (those with the highest CHOP-INTEND scores) were able to complete all tests correctly within 60 s. There was a non-significant trend toward improvement in CHOP-INTEND, PedsQL-NM, and NRS scores over the 6-month period. There were no significant differences in the number of actions, errors, correct answers, or response times between baseline and Week 9 or 24 at any level. However, the result of an additional analysis suggests that detection of eye movement would be useful to evaluate for advanced SMA. Conclusions: Eye-tracking systems are possibly feasible for the assessment of treatment efficacy in patients with advanced SMA type I.

[Coronary Aneurysm with Fistula].

We successfully treated two rare cases of coronary aneurysm with fistula. Case 1;A 65-year-old female referred to our hospital with the coronary aneurysm and fistula. Right coronary aneurysm with fistula leading to coronary sinus was observed. Coronary bypass surgery using a saphenous vein to #4PD was performed, and two right ventricle branches were reconstructed. Coronary aneurysm was resected. Case 2;A 46-year-old male was admitted with chest discomfort. Coronary aneurysm with fistula from the left main trunk to left ventricle was demonstrated. Ligation of the coronary artery aneurysm and suture closure of the entry site to the left ventricle was performed. Both patients had uneventful recovery.

[Third Tricuspid Valve Replacement:Report of a Case].

A 79-year-old man underwent tricuspid valve replacement (TVR) with a bovine pericardial bioprosthesis, Carpentier-Edwards Perimount (CEP), for tricuspid regurgitation 27 years earlier. Twenty-one years after the first operation, he underwent re-TVR with a bovine pericardial bioprosthesis, Magna Mitral Ease, due to prosthetic valve dysfunction. Since the prosthetic valve dysfunction progressed again, the third TVR was performed six years after the second operation. The findings of the resected bioprosthesis showed sclerosis of the septal cusp, and pannus formation between the septal and posterior cusps. For the third TVR, the porcine bioprosthesis Epic was used. Neither transvalvular nor perivalvular leakage was observed postoperatively, and the patient was discharged without any complications.

[Papillary Fibroelastoma Arising from the Left Atrial Wall:Report of a Case].

Papillary fibroelastoma (PFE) is a rare benign cardiac tumor generally arising from the valvular endocardium. We report an extremely rare case of PFE arising from the left atrial wall. A 70-year-old male patient was admitted to our hospital with a diagnosis of left atrial tumor. Echocardiography and enhanced computed tomography showed an approximately 14 mm mass on the left atrial wall. Moreover, the magnetic resonance imaging showed hyperintenseness on a T2-weighted image. We diagnosed the tumor as a myxoma. Intraoperatively, we found a mobile tumor on the left atrial wall. It had a sea anemone-like appearance and was suspected to be PFE. We performed the tumor resection including the left atrial wall. Histological examination confirmed PFE. His postoperative course was uneventful.

A pediatric case of transient periictal MRI abnormalities after repeated seizures.

BACKGROUND: Transient periictal MRI abnormalities (TPMA) are caused by seizures, and may completely or partially reverse within a few days following seizure. Although TPMA are usually observed in patients with status epilepticus (SE), they have also been rarely reported after isolated/recurrent seizures not fulfilling the criteria for SE. Herein, we present a case of a 1-year-old girl with TPMA. CASE: A 1-year-old girl with Apert syndrome and epilepsy showed MRI abnormalities in the cortico-subcortical areas of the left temporal, occipital and parietal lobes, as well as the left thalamus. These abnormalities showed as a hyperintense signal on diffusion-weighted imaging and a hypointense signal on apparent-diffusion coefficient maps. On follow-up MRI after 3 days, the abnormal signals were completely reversed. We confirmed TPMA after eliminating other possibilities. When treatment was withdrawn, the patient regained consciousness immediately and did not show any abnormality on subsequent MRI. CONCLUSION: TPMA may occur in young children; recognizing this possibility is important for making the diagnosis and conducting appropriate treatment. As a previous study revealed, the distribution of signal changes in cortico-subcortical areas and the ipsilateral thalamus may be a characteristic feature of TPMA.

Vulnerability to shear stress caused by altered peri-endothelial matrix is a key feature of Moyamoya disease.

Moyamoya disease (MMD) is characterized by progressive bilateral stenotic changes in the terminal portion of the internal carotid arteries. Although RNF213 was identified as a susceptibility gene for MMD, the exact pathogenesis remains unknown. Immunohistochemical analysis of autopsy specimens from a patient with MMD revealed marked accumulation of hyaluronan and chondroitin sulfate (CS) in the thickened intima of occlusive lesions of MMD. Hyaluronan synthase 2 was strongly expressed in endothelial progenitor cells in the thickened intima. Furthermore, MMD lesions showed minimal staining for CS and hyaluronan in the endothelium, in contrast to control endothelium showing positive staining for both. Glycosaminoglycans of endothelial cells derived from MMD and control induced pluripotent stem cells demonstrated a decreased amount of CS, especially sulfated CS, in MMD. A computational fluid dynamics model showed highest wall shear stress values in the terminal portion of the internal carotid artery, which is the predisposing region in MMD. Because the peri-endothelial extracellular matrix plays an important role in protection, cell adhesion and migration, an altered peri-endothelial matrix in MMD may contribute to endothelial vulnerability to wall shear stress. Invading endothelial progenitor cells repairing endothelial injury would produce excessive hyaluronan and CS in the intima, and cause vascular stenosis.

PubChemQC PM6: Data Sets of 221 Million Molecules with Optimized Molecular Geometries and Electronic Properties.

We report on optimized molecular geometries and electronic properties calculated by the PM6 method for 94.0% of the 91.6 million molecules cataloged in PubChem Compounds retrieved on August 29, 2016. In addition to neutral states, we also calculated those for cationic, anionic, and spin flipped electronic states of 56.2%, 49.7%, and 41.3% of the molecules, respectively. Thus, the grand total of the PM6 calculations amounted to 221 million. We compared the resulting molecular geometries with B3LYP/6-31G* optimized geometries for 2.6 million molecules. The root-mean-square deviations in bond length and bond angle were approximately 0.016 Å and 1.7°, respectively. Then, using linear regression to examine the HOMO energy levels E(HOMO) in the B3LYP and PM6 calculations, we found that EB3LYP(HOMO) = 0.876EPM6(HOMO) + 1.975 (eV) and calculated the coefficient of determination to be 0.803. Likewise, we examined the LUMO energy levels and found EB3LYP(LUMO) = 1.069EPM6(LUMO) - 0.420 (eV); the coefficient of determination was 0.842. We also generated four subdata sets, each of which was composed of molecules with molecular weights less than 500. Subdata set i contained C, H, O and N, ii contained C, H, N, O, P, and S, iii contained C, H, N, O, P, S, F, and Cl, and iv contained C, H, N, O, P, S, F, Cl, Na, K, Mg, and Ca. The data sets are available at http://pubchemqc.riken.jp/pm6_datasets.html under a Creative Commons Attribution 4.0 International license.

DNA methylation analysis of multiple imprinted DMRs in Sotos syndrome reveals IGF2-DMR0 as a DNA methylation-dependent, P0 promoter-specific enhancer.

Haploinsufficiency of NSD1, which dimethylates histone H3 lysine 36 (H3K36), causes Sotos syndrome (SoS), an overgrowth syndrome. DNMT3A and DNMT3B recognizes H3K36 trimethylation (H3K36me3) through PWWP domain to exert de novo DNA methyltransferase activity and establish imprinted differentially methylated regions (DMRs). Since decrease of H3K36me3 and genome-wide DNA hypomethylation in SoS were observed, hypomethylation of imprinted DMRs in SoS was suggested. We explored DNA methylation status of 28 imprinted DMRs in 31 SoS patients with NSD1 defect and found that hypomethylation of IGF2-DMR0 and IG-DMR in a substantial proportion of SoS patients. Luciferase assay revealed that IGF2-DMR0 enhanced transcription from the IGF2 P0 promoter but not the P3 and P4 promoters. Chromatin immunoprecipitation-quantitative PCR (ChIP-qPCR) revealed active enhancer histone modifications at IGF2-DMR0, with high enrichment of H3K4me1 and H3 lysine 27 acetylation (H3K27ac). CRISPR-Cas9 epigenome editing revealed that specifically induced hypomethylation at IGF2-DMR0 increased transcription from the P0 promoter but not the P3 and P4 promoters. NSD1 knockdown suggested that NSD1 targeted IGF2-DMR0; however, IGF2-DMR0 DNA methylation and IGF2 expression were unaltered. This study could elucidate the function of IGF2-DMR0 as a DNA methylation dependent, P0 promoter-specific enhancer. NSD1 may play a role in the establishment or maintenance of IGF2-DMR0 methylation during the postimplantation period.

Comprehensive methylation analysis of imprinting-associated differentially methylated regions in colorectal cancer.

BACKGROUND: Imprinted genes are regulated by DNA methylation at imprinting-associated differentially methylated regions (iDMRs). Abnormal expression of imprinted genes is implicated in imprinting disorders and tumors. In colorectal cancer (CRC), methylation and imprinting status of the IGF2/H19 domain have been studied. However, no comprehensive methylation analysis of iDMRs in CRC has been reported. Furthermore, the relationship between iDMR methylation status and other methylation-related issues, such as CpG island methylator phenotype (CIMP) and long interspersed element-1 (LINE-1) methylation, remains unclear. RESULTS: We analyzed the methylation status of 38 iDMRs in 106 CRC patients. We also investigated CIMP, LINE-1 methylation, KRAS and BRAF gene mutations, and loss of imprinting (LOI) of IGF2. We further examined the relationship between these factors and clinicopathological factors. The overall trend in iDMR methylation was towards hypermethylation, and iDMRs could be grouped into three categories: susceptible, resistant, and intermediate-to-aberrant methylation. The susceptible and resistant iDMRs consisted of all types of iDMR (gametic and somatic, maternally and paternally methylated). Hypermethylation of multiple iDMRs (HyMiD)-positive status was statistically associated with CIMP-positive status, but not associated with mutations in the BRAF and KRAS genes. HyMiD-positive status was inversely associated with LINE-1 methylation. Among four iDMRs within the IGF2/H19 domain, IGF2-DMR0 hypomethylation occurred most frequently, but was not associated with IGF2 LOI. Finally, we statistically calculated predictive prognostic scores based on aberrant methylation status of three iDMRs. CONCLUSION: In CRC tissues, some iDMRs were susceptible to hypermethylation independent of the type of iDMR and genomic sequence. Although HyMiD-positive status was associated with CIMP-positive status, this was independent of the BRAF and KRAS pathways, which are responsible for CIMP. Since IGF2-DMR0 hypomethylation and aberrant methylation of other iDMRs within the IGF2/H19 domain were not associated with IGF2 LOI, dysfunction of any of the molecular components related to imprinting regulation may be involved in IGF2 LOI. The prognostic score calculated based on aberrant methylation of three iDMRs has potential clinical applications as a prognostic predictor in patients. Further study is required to understand the biological significance of, and mechanisms behind, aberrant methylation of iDMRs and IGF2 LOI in CRCs.

[Pulmonary Non-tuberculous Mycobacteriosis Complicated with Pulmonary Large Cell Neuroendocrine Carcinoma;Report of a Case].

A 64-year-old man with pulmonary non-tuberculous mycobacteriosis(pulmonary NTM) who had been treated by antituberculous chemotherapy, developed a new nodule of 8 mm in size in the segment 3 of the right upper lobe. The cavity of 4.0 cm in size in the segment 1+2 of the left upper lobe due to Mycobacterium avium infection was preexisted. Radiologically, new nodule of the right lung was suspected to be lung cancer. Left upper lobe apical trisegmentectomy was performed at first. Three months later, enlarging of the right lung nodule with increased fluoro-2-deoxy-D-glucose(FDG) activity was noted, and the diagnosis of lung cancer was made by transbronchial lung biopsy(TBLB). Then, right upper lobectomy with systematic nodal dissection were performed.

[A Case of Locally Advanced Sigmoid Colon Cancer Occupying the Pelvis with Successful Total Posterior Pelvic Exenteration after Triplet Chemotherapy].

We report a case of locally advanced colon cancer that directly invaded the rectum wall and uterus resulting in huge mass in the whole pelvis that we could successfully made complete radical resection of the whole tumor without exposing the tumor to the surgical margin after the triplet chemotherapy. The patient was a 57-year-old woman complaining of anus pain, melena, fever, and weight loss. Although swelling of the regional lymph node was observed, no distant metastasis was found resulting in clinical diagnosis of Stage Ⅲb. However, oncologically safe complete resection seemed difficult; thus, chemotherapy( 3 courses of FOLFOX followed by 3 courses of FOLFOXIRI plus bevacizumab)was administered. As a result, significant tumor reduction was observed; therefore, the tumor was completely resected with posterior pelvic exenteration. Final staging was ypT4bypN0M0(ypStage Ⅱ). Eight courses of CapeOX was administered as adjuvant chemotherapy.

[Anterior Mediastinal Myxoid Liposarcoma Detected by Chest Computed Tomogram in the Patient with Pneumothorax].

A 57-year-old woman visited our hospital with left chest pain. Chest computed tomography (CT) scanning showed left pneumothorax with apical bullae and a nodular shadow in the left anterior mediastinum accidentally. However, a week later, we could not detect a mediastinal shadow on chest CT image after healing of left pneumothorax. Video assisted thoracoscopic surgery was scheduled in order to remove bullae and evaluate an anterior mediastinal lesion. The mediastinal lesion was tumorous and resected with around pericardial fat tissue. Pathological diagnosis was a myxoid liposarcoma of 15×10mm in size without infiltration into the surrounding tissue. The postoperative course was uneventful without recurrence 6 months later.

Differences in the Genotype Frequency of the RNF213 Variant in Patients with Familial Moyamoya Disease in Kyushu, Japan.

The p.R4810K (rs11273543, c.14429G > A) variant of the RNF213 gene is associated with increased risk of Moyamoya disease (MMD), which is an idiopathic progressive intracranial vascular steno-occlusive disease, in Asian populations. Numerous variant association studies for this MMD variant have been performed in Japan to date. Since another genetic study that utilized approximately 140,000 single nucleotide polymor (SNPs) has indicated that there still are genetic differences among mainland Japanese, there is a possibility that the variant distribution in patients with MMD and normal individuals varies between different Japanese regions. Additionally, the majority of variant association studies have used Sanger sequencing, which is labor-intensive, time-consuming, and costly. In this study, we analyzed the frequency of the variant genotype in patients with MMD and normal individuals in Kyushu using pyrosequencing, which is an accurate, cost-effective, and automated method. We found differences in the genotype frequencies in familial patients from Kyushu and normal populations in Tohoku compared with west Japan, which suggested that there were differences in the frequency of the variant among different regions in Japan.

Extraction of Knowledge from the Topographic Attentive Mapping Network and its Application in Skill Analysis of Table Tennis.

The Topographic Attentive Mapping (TAM) network is a biologically-inspired classifier that bears similarities to the human visual system. In case of wrong classification during training, an attentional top-down signal modulates synaptic weights in intermediate layers to reduce the difference between the desired output and the classifier's output. When used in a TAM network, the proposed pruning algorithm improves classification accuracy and allows extracting knowledge as represented by the network structure. In this paper, sport technique evaluation of motion analysis modelled by the TAM network was discussed. The trajectory pattern of forehand strokes of table tennis players was analyzed with nine sensor markers attached to the right upper arm of players. With the TAM network, input attributes and technique rules were extracted in order to classify the skill level of players of table tennis from the sensor data. In addition, differences between the elite player, middle level player and beginner were clarified; furthermore, we discussed how to improve skills specific to table tennis from the view of data analysis.