A Case of Sickle Cell Retinopathy With Retinal Artery Occlusion in African-Japanese Patients.

As globalization progresses, cases of sickle cell disease (SCD) are now being seen even in Japan, where SCD did not originally exist. SCD causes not only anemia but also peripheral blood flow obstruction, which can lead to systemic complications. This report represents a case of sickle cell retinopathy (SCR) in Japan discovered with the onset of retinal artery occlusion (RAO). The patient, a 20-year-old African-Japanese male, was being monitored for SCD at the Nagoya University Hospital, Pediatrics Department, Nagoya, Japan. Following a chest pain episode, he reported a loss of vision in his right eye and was referred to the ophthalmology department. Examination showed reduced visual acuity in the right eye 20/40 compared to the left 20/20. A Goldman visual field test indicated central vision loss in the right eye, and fundoscopic examination revealed yellow-white lesions centered on the macula and peripheral salmon-patch-like lesions in the right eye, with peripheral black sunburst-like lesions in the left eye. Optical coherence tomography (OCT) of the right eye showed inner retinal edema within the macula, suggesting an SCR accompanied by branch RAO. Six months later, he complained of further vision loss in his right eye. Examination and OCT revealed sub-inner limiting membrane hemorrhage in the right eye, suggesting worsening of the SCR. SCD is exceedingly rare among native Japanese but is likely to be encountered more frequently as globalization progresses. Even in countries where SCD has traditionally been rare, attention must be paid to the occurrence of severe SCR when managing SCD.

Assessment of Mild Cognitive Impairment Using CogEvo: A Computerized Cognitive Function Assessment Tool.

INTRODUCTION/OBJECTIVES: To assess the utility of the computerized cognitive function assessment tool, CogEvo, as a screening tool for mild cognitive impairment in primary care, we explored the relationship between CogEvo performance, age, and the severity of cognitive dysfunction evaluated by the Mini-Mental State Examination (MMSE). METHODS: The observational cross-sectional study included 209 individuals' data (mean age 79.4 ± 8.9 years). We conducted a correlation analysis between CogEvo and MMSE scores, compared the performance among the 3 cognitive function groups (MMSE ≥ 28 group; MMSE24-27 group; MMSE ≤ 23 group) using the MMSE cut-off, and evaluated CogEvo's predictive accuracy for cognitive dysfunction through ROC analysis. RESULTS: Both total CogEvo and MMSE scores significantly decreased with age. A significant positive correlation was observed between total CogEvo and MMSE scores, but a ceiling effect was detected in MMSE performance. Significant differences were observed in the total CogEvo score, including orientation and spatial cognitive function scores, among the 3 groups. CogEvo showed no educational bias. ROC analyses indicated moderate discrimination between the MMSE ≥ 28 group and the MMSE24-27 and MMSE ≤ 23 groups. CONCLUSIONS: The computer-administered CogEvo has the advantage of not exhibiting ceiling effects or educational bias like the MMSE, and was found to be able to detect age-related cognitive decline and impairment.

IgG4-related retroperitoneal fibrosis induced by nivolumab and ipilimumab in a patient with non-small cell lung cancer: A case report.

IgG4-related diseases are adverse events that occur after receiving treatment with immune checkpoint inhibitors (ICI). This study reports the first case of IgG4-related retroperitoneal fibrosis after the administration of chemotherapy with nivolumab and ipilimumab (NI therapy). An 80-year-old man developed lower abdominal pain eight months after NI therapy was initiated. Although the primary lesion maintained its reduced size on computed tomography, there was an increase in the soft tissue shadows intensity around the abdominal aorta, bladder, and seminal vesicles, suggesting retroperitoneal fibrosis. Blood tests showed elevated IgG4 levels. Computed tomography-guided biopsy of the retroperitoneum showed B cell-dominant lymphocyte infiltration consistent with IgG4-related retroperitoneal fibrosis and characteristic CD8-positive lymphocyte infiltration, suggestive of the involvement of cytotoxic T cells. Based on the clinical, imaging, and pathological findings, the patient was diagnosed with IgG4-related retroperitoneal fibrosis due to ICI. Immunotherapy discontinuation alone did not result in improvement; therefore, steroid therapy was initiated. In clinical practice, IgG4-related retroperitoneal fibrosis can occur as an immune-related adverse event when administering anti-PD-1 and anti-CTLA-4 antibodies for cancer immunotherapy. Early steroid therapy could be effective in controlling this immune-related adverse event.

Successful Chemotherapy for Diffuse Cystic Lung Metastases during Targeted Therapy with Osimertinib in a Patient with Non-Small-Cell Lung Cancer: A Literature Review and a Rare Case Report.

Introduction: Diffuse lung cysts occur owing to several diseases; however, diffuse cystic lung metastases are very rare in the case of lung cancer. We report a rare case of diffuse cystic lung metastases from lung adenocarcinoma and reviewed previously reported cases of cystic lung metastases for lung cancer and determined their characteristics. Case Presentation: A 78-year-old Japanese woman with advanced lung adenocarcinoma was positive for the epidermal growth factor receptor gene mutation exon 21 L858R and had been treated with osimertinib. She presented with multiple bilaterally positioned thin-walled lung cysts and pneumothorax. Lung cysts were diagnosed as cystic lung metastases from lung cancer, and carboplatin, pemetrexed, and pembrolizumab were subsequently administered. All cysts markedly decreased in size, and some disappeared. Conclusion: Effective treatment methods for cystic lung metastases from lung cancer have not been reported. To our knowledge, this is the first case of cystic lung metastases that were successfully treated with chemotherapy.

Variations in the Protein Hydration and Hydrogen-Bond Network of Water Molecules Induced by the Changes in the Secondary Structures of Proteins Studied through Near-Infrared Spectroscopy.

This study investigated how the secondary structural changes of proteins in aqueous solutions affect their hydration and the hydrogen-bond network of water molecules using near-infrared (NIR) spectroscopy. The aqueous solutions of three types of proteins, i.e., ovalbumin, ß-lactoglobulin, and bovine serum albumin, were denatured by heating, and changes in the NIR bands of water reflecting the states of hydrogen bonds induced via protein secondary structural changes were investigated. On heating, the intermolecular hydrogen bonds between water molecules as well as between water and protein molecules were broken, and protein molecules were no longer strongly bound by the surrounding water molecules. Consequently, the denaturation was observed to proceed depending on the thermodynamic properties of the proteins. When the aqueous solutions of proteins were cooled after denaturation, the hydrogen-bond network was reformed. However, the state of protein hydration was changed owing to the secondary structural changes of proteins, and the variation patterns were different depending on the protein species. These changes in protein hydration may be derived from the differences in the surface charges of proteins. The elucidation of the mechanism of protein hydration and the formation of the hydrogen-bond network of water molecules will afford a comprehensive understanding of the protein functioning and dysfunctioning derived from the structural changes in proteins.

Ultrahigh pressure-induced modification of morphology and performance of MOF-derived Cu@C electrocatalysts.

We report the pyrolysis of copper-containing metal-organic frameworks under high pressure and the effect of the applied pressure on the morphology and electrocatalytic performance toward the oxygen-related reactions of the products. The high-pressure and high-temperature (HPHT) syntheses were performed under 5, 2.5, 1, and 0.5 GPa, and the Cu@C products were obtained except for the 2.5 GPa experiment. Copper formed a shell-like nanostructure on the carbon matrices during the 0.5 GPa experiment, whereas copper formed sub-nanometer sized particles in the carbon matrices with the increasing pressure. It is considered that the transportation of copper atoms by outgassing during the pyrolysis affects the morphology. Electrochemical measurements revealed that all samples exhibited activity for the oxygen reduction reaction (ORR). The 0.5 GPa-treated product also exhibited the oxygen evolution reaction (OER). The overall ORR/OER performance of this product was excellent among Cu-based bifunctional materials even though it did not contain cocatalysts such as nitrogen-doped carbon or other metal elements. The Cu(iii) species in the nano-thick copper shell structure provided the active sites for the OER.

Validity and reliability of a computerized cognitive function evaluation battery (CogEvo) as a screening tool.

Aim: The aim of this study was to determine the validity and reliability of cognitive function evaluation battery, CogEvo, a recently developed computerized cognitive function evaluation battery, as a screening tool for decreased cognitive function. Methods: The study sample comprised 123 (age: 57-97 years) community-dwelling elderly people. They were required to perform five CogEvo tasks and complete two questions-based neuropsychological tests, including the Mini-Mental State Examination, so that the correlations could be analyzed. The validity and reliability of CogEvo were examined using factor analysis, MacDonald's omega reliability coefficient, logistic regression analysis, and receiver operating characteristic curve analysis. Results: Exploratory factor analysis revealed the orientation/spatial cognitive function (orientation and spatial cognition) and attention/executive function (attention, memory, and execution) factors. Structural validity was supported by confirmatory factor analysis. All two-factor-based subtasks showed adequate internal consistency (MacDonald's omega ≥0.6). The total CogEvo score and two-factor scores were significantly correlated with neuropsychological test results. Based on the total CogEvo score, the cognitively normal and cognitive decline groups were identified by receiver operating characteristic curve analysis with a moderate predictive performance. The cognitive decline group was well identified using the orientation/spatial cognitive function factor. Conclusions: CogEvo is a valid and reliable screening tool for cognitive function evaluation. It proved useful in the early identification of cognitive decline in our study sample.

Mixed Infection of Cytomegalovirus and Pulmonary Nocardiosis Caused by Nocardia elegans Diagnosed Using Nanopore Sequencing Technology.

A 69-year-old woman who had undergone renal transplantation and was receiving sulfamethoxazole/trimethoprim (ST) developed pulmonary nocardiosis. To our knowledge, this is the first report of the identification of Nocardia elegans using nanopore sequencing, supported by 16S rDNA capillary sequencing findings. Chest computed tomography performed after ST initiation revealed significant improvement of the pulmonary shadows compared to previous findings. We herein report the value of nanopore sequencing for rapid identification of rare pathogens, such as Nocardia elegans. Furthermore, our findings suggest that Nocardia may infect even patients receiving ST, which is currently the most effective prophylactic drug.

Synthesis of catalysts with fine platinum particles supported by high-surface-area activated carbons and optimization of their catalytic activities for polymer electrolyte fuel cells.

Herein, we demonstrated that carbon-supported platinum (Pt/C) is a low-cost and high-performance electrocatalyst for polymer electrolyte fuel cells (PEFCs). The ethanol reduction method was used to prepare the Pt/C catalyst, which was realized by an effective matching of the carbon support and optimization of the Pt content for preparing a membrane electrode assembly (MEA). For this, the synthesis of Pt/C catalysts with different Pt loadings was performed on two different carbons (KB1600 and KB800) as new support materials. Analysis of the XRD pattern and TEM images showed that the Pt nanoparticles (NPs) with an average diameter of ca. 1.5 nm were uniformly dispersed on the carbon surface. To further confirm the size of the NPs, the coordination numbers of Pt derived from X-ray absorption fine structure (XAFS) data were used. These results suggest that the NP size is almost identical, irrespective of Pt loading. Nitrogen adsorption-desorption analysis indicated the presence of mesopores in each carbon. The BET surface area was found to increase with increasing Pt loading, and the value of the BET surface area was as high as 1286 m2 gcarbon -1. However, after 40 wt% Pt loading on both carbons, the BET surface area was decreased due to pore blockage by Pt NPs. The oxidation reduction reaction (ORR) activity for Pt/KB1600, Pt/KB800 and commercial Pt/C was evaluated by Koutecky-Levich (K-L) analysis, and the results showed first-order kinetics with ORR. The favourable surface properties of carbon produced Pt NPs with increased density, uniformity and small size, which led to a higher electrochemical surface area (ECSA). The ECSA value of the 35 wt% Pt/KB1600 catalyst was 155.0 m2 gpt -1 higher than that of the Pt/KB800 and commercial Pt/C (36.7 wt%) catalysts. A Higher ECSA indicates more available active sites for catalyst particles. The single cell test with MEA revealed that the cell voltage in the high current density regions depends on the BET surface area, and the durability of the 35 wt% Pt/KB1600 catalyst was superior to that of the 30 wt% Pt/KB800 and commercial Pt/C (46.2 wt%) catalysts. This suggests that an optimal ratio of Pt to Pt/KB1600 catalyst provides adequate reaction sites and mass transport, which is crucial to the PEFC's high performance.

RNA-hydrolyzing activity of metallo-ß-lactamase IMP-1.

Metallo-ß-lactamases (MBLs) hydrolyze a wide range of ß-lactam antibiotics. While all MBLs share a common αß/ßα-fold, there are many other proteins with the same folding pattern that exhibit different enzymatic activities. These enzymes, together with MBLs, form the MBL superfamily. Thermotoga maritima tRNase Z, a tRNA 3' processing endoribonuclease of MBL-superfamily, and IMP-1, a clinically isolated MBL, showed a striking similarity in tertiary structure, despite low sequence homology. IMP-1 hydrolyzed both total cellular RNA and synthetic small unstructured RNAs. IMP-1 also hydrolyzed pre-tRNA, but its cleavage site was different from those of T. maritima tRNase Z and human tRNase Z long form, indicating a key difference in substrate recognition. Single-turnover kinetic assays suggested that substrate-binding affinity of T. maritima tRNase Z is much higher than that of IMP-1.

Validation Study of QSAR/DNN Models Using the Competition Datasets.

Since the QSAR/DNN model showed predominant predictive performance over other conventional methods in the Kaggle QSAR competition, many artificial neural network (ANN) methods have been applied to drug and material discovery. Appearance of artificial intelligence (AI), which is combined various general purpose ANN platforms with large-scale open access chemical databases, has attracting great interest and expectation in a wide range of molecular sciences. In this study, we investigate various DNN settings in order to reach a high-level of predictive performance comparable to the champion team of the competition, even with a general purpose ANN platform, and introduce the Meister setting for constructing a good QSAR/DNNs model. Here, we have used the most commonly available DNN model and constructed many QSAR/DNN models trained with various DNN settings by using the 15 datasets employed in the competition. As a result, it was confirmed that we can constructed the QSAR/DNN model that shows the same level of R2 performance as the champion team. The difference from the DNN setting recommended by the champion team was to reduce the mini-batch size. We have also explained that the R2 performance of each target depends on the molecular activity type, which is related to the complexity of biological mechanisms and chemical processes observed in molecular activity measurements.

Comparative metabolomics of Japanese Black cattle beef and other meats using gas chromatography-mass spectrometry.

Progress in metabolomic analysis now allows the evaluation of food quality. This study aims to identify the metabolites in meat from livestock using a metabolomic approach. Using gas chromatography-mass spectrometry (GC/MS), many metabolites were reproducibly detected in meats, and distinct differences between livestock species (cattle, pigs, and chickens) were indicated. A comparison of metabolites between tissues types (muscle, intramuscular fat, and intermuscular fat) in marbled beef of Japanese Black cattle revealed that most metabolites are abundant in the muscle tissue. Several metabolites (medium-chain fatty acids, etc.) involved in triacylglycerol synthesis were uniquely detected in fat tissue. Additionally, the results of multivariate analysis suggest that GC/MS analysis of metabolites can distinguish between cattle breeds. These results provide useful information for the analysis of meat quality using GC/MS-based metabolomic analysis.ABBREVIATIONS: GC/MS: gas chromatography-mass spectrometry; NMR: nuclear magnetic resonance; MS: mass spectrometry; IS: 2-isopropylmalic acid; MSTFA: N-Methyl-N-trimethylsilyltrifluoroacetamide; CV: coefficient of variation; TBS: Tris-buffered saline; MHC: myosin fast type; PCA: principal component analysis; OPLS-DA: orthogonal partial least-squares discriminant analysis; O2PLS: two-way orthogonal partial least-squares.

Structure and properties of the egg mass of the ommastrephid squid Todarodes pacificus.

The Japanese flying squid, Todarodes pacificus, is thought to spawn neutrally buoyant egg masses that retain a specific location in the water column by floating at the interface between water layers of slightly different densities. It is important to understand the physical process that determines the vertical distribution of the egg masses to predict their horizontal drift in relation to embryo survival and subsequent recruitment. Here, mesocosm experiments were conducted in a 300 m3 tank by creating a thermally stratified (17-22°C) water column to obtain egg masses. A cage net methodology was developed to sustain egg masses for detailed observation. We measured the density of the egg masses of T. pacificus, and used this information to infer the vertical distribution patterns of the egg masses at the spawning grounds (Tsushima Strait, Japan). When measured separately, the density of the outer jelly of each egg mass was 2.7 σ units higher than that of the surrounding water. The outer jelly and the specific gravity of embedded individual eggs (~1.10) cause the egg masses to have very slight negative buoyancy relative to the water in which they are formed. Analysis of the vertical profile of the spawning ground showed that water density (σθ) increased sharply at ~30 m depth; thus, egg masses might settle above the pycnocline layer. In conclusion, we suggest that T. pacificus egg masses might retain their location in the water column by floating at the interface between water layers of slightly different densities, which happen to be above the pycnocline layer (actual depth varies seasonally/annually) in the Tsushima Strait between Korea and Japan.