Evaluation of the Relationship Between Cognitive Impairment, Glycometabolism, and Nicotinic Acetylcholine Receptor Deficits in a Mouse Model of Alzheimer's Disease

PURPOSE: In patients with Alzheimer's disease (AD), the loss of cerebral nicotinic acetylcholine receptors (nAChRs) that are implicated in higher brain functions has been reported. However, it is unclear if nAChR deficits occur in association with cognitive impairments. The purpose of this study was to assess the relationship between nAChR deficits and cognitive impairments in a mouse model of AD (APP/PS2 mice). PROCEDURES: The cognitive abilities of APP/PS2 and wild-type mice (aged 2-16 months) were evaluated using the novel object recognition test. Double-tracer autoradiography analyses with 5-[125I]iodo-A-85380 ([125I]5IA: α4β2 nAChR imaging probe) and 2-deoxy-2-[18F]fluoro-D-glucose were performed in both mice of different ages. [123I]5IA-single-photon emission tomography (SPECT) imaging was also performed in both mice at 12 months of age. Furthermore, each age cohort was investigated for changes in cognitive ability and expression levels of α7 nAChRs and N-methyl-D-aspartate receptors (NMDARs). RESULTS: No significant difference was found between the APP/PS2 and wild-type mice at 2-6 months of age in terms of novel object recognition memory; subsequently, however, APP/PS2 mice showed a clear cognitive deficit at 12 months of age. [125I]5IA accumulation decreased in the brains of 12-month-old APP/PS2 mice, i.e., at the age at which cognitive impairments were first observed; this result was supported by a reduction in the protein levels of α4 nAChRs using Western blotting. nAChR deficits could be noninvasively detected by [123I]5IA-SPECT in vivo. In contrast, no significant changes in glycometabolism, expression levels of α7 nAChRs, or NMDARs were associated with cognitive impairments in APP/PS2 mice. CONCLUSION: A decrease in cerebral α4β2 nAChR density could act as a biomarker reflecting cognitive impairments associated with AD pathology

Development and characterization of a 68Ga-labeled A20FMDV2 peptide probe for the PET imaging of αvβ6 integrin-positive pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is known to be one of the most lethal cancers. Since the majority of patients are diagnosed at an advanced stage, development of a detection method for PDAC at an earlier stage of disease progression is strongly desirable. Integrin αVβ6 is a promising target for early PDAC detection because its expression increases during precancerous changes. The present study aimed to develop an imaging probe for positron emission tomography (PET) which targets αVβ6 integrin-positive PDAC. We selected A20FMDV2 peptide, which binds specifically to αvβ6 integrin, as a probe scaffold, and 68Ga as a radioisotope. A20FMDV2 peptide has not been previously labeled with 68Ga. A cysteine residue was introduced to the N-terminus of the probe at a site-specific conjugation of maleimide-NOTA (mal-NOTA) chelate. Different numbers of glycine residues were also introduced between cysteine and the A20FMDV2 sequence as a spacer in order to reduce the steric hindrance of the mal-NOTA on the binding probe to αVβ6 integrin. In vitro, the competitive binding assay revealed that probes containing a 6-glycine linker ([natGa]CG6 and [natGa]Ac-CG6) showed high affinity to αVβ6 integrin. Both probes could be labeled by 67/68Ga with high radiochemical yield (>50%) and purity (>98%). On biodistribution analysis, [67Ga]Ac-CG6 showed higher tumor accumulation, faster blood clearance, and lower accumulation in the surrounding organs of pancreas than did [67Ga]CG6. The αVβ6 integrin-positive xenografts were clearly visualized by PET imaging with [68Ga]Ac-CG6. The intratumoral distribution of [68Ga]Ac-CG6 coincided with the αVβ6 integrin-positive regions detected by immunohistochemistry. Thus, [68Ga]Ac-CG6 is a useful peptide probe for the imaging of αVβ6 integrin in PDAC

Development of a novel artificial intelligence algorithm to detect pulmonary nodules on chest radiography

Background: In this study, we aimed to develop a novel artificial intelligence (AI) algorithm to support pulmonary nodule detection, which will enable physicians to efficiently interpret chest radiographs for lung cancer diagnosis. Methods: We analyzed chest X-ray images obtained from a health examination center in Fukushima and the National Institutes of Health (NIH) Chest X-ray 14 dataset. We categorized these data into two types: type A included both Fukushima and NIH datasets, and type B included only the Fukushima dataset. We also demonstrated pulmonary nodules in the form of a heatmap display on each chest radiograph and calculated the positive probability score as an index value. Results: Our novel AI algorithms had a receiver operating characteristic (ROC) area under the curve (AUC) of 0.74, a sensitivity of 0.75, and a specificity of 0.60 for the type A dataset. For the type B dataset, the respective values were 0.79, 0.72, and 0.74. The algorithms in both the type A and B datasets were superior to the accuracy of radiologists and similar to previous studies. Conclusions: The proprietary AI algorithms had a similar accuracy for interpreting chest radiographs when compared with previous studies and radiologists. Especially, we could train a high quality AI algorithm, even with our small type B data set. However, further studies are needed to improve and further validate the accuracy of our AI algorithm

Histological and Nuclear Medical Comparison of Inflammation After Hemostasis with Non-Thermal Plasma and Thermal Coagulation

The objective of this study is to examine the invasiveness of hemostasis by non-thermal plasma (NTP) compared with hemostasis by thermal coagulation (TC). The inflammation recovery process after hemostasis by TC and NTP was compared by using histological methods and nuclear medical molecular imaging. The necrotic areas in the NTP group disappeared after 5 days, whereas they remained 15 days after hemostasis in the TC group. The accumulation of 2-deoxy-2-[F-18] fluoro-D-glucopyranose (F-18-FDG), which reflects the existence of inflammatory cells, was higher in the TC group than in the NTP group on day 15. Thus, this study indicates that hemostasis by NTP is less inflammatory than TC. This report is the first to evaluate inflammation that occurred after hemostasis with medical devices noninvasively

Transonic Dislocation Propagation in Diamond

The motion of line defects (dislocations) has been studied for over 60 years but the maximum speed at which they can move is unresolved. Recent models and atomistic simulations predict the existence of a limiting velocity of dislocation motions between the transonic and subsonic ranges at which the self-energy of dislocation diverges, though they do not deny the possibility of the transonic dislocations. We use femtosecond x-ray radiography to track ultrafast dislocation motion in shock-compressed single-crystal diamond. By visualizing stacking faults extending faster than the slowest sound wave speed of diamond, we show the evidence of partial dislocations at their leading edge moving transonically. Understanding the upper limit of dislocation mobility in crystals is essential to accurately model, predict, and control the mechanical properties of materials under extreme conditions

COPD 急性増悪後1 年間における再入院に関連する入院中の因子

研究論文Original Articles【目的】本研究の目的は，COPD 急性増悪患者を対象に，退院後1 年間の再入院に関連する因子を明らかにすることであった．【方法】対象は2014 年4 月から2016 年9 月にCOPD 急性増悪の診断で入院し，退院後1 年間の追跡が可能な46 例（平均年齢78.0 ± 8.0 歳）であった．退院後1 年間の再入院の有無で2 群に分け，入院時のデータを電子カルテより収集し，分析を行った．【結果】再入院群は15 例，非再入院群は31 例であった．2 群間の比較では過去の増悪歴（60% vs 29%,p=0.04）に有意差があり，理学療法開始までの日数（5.0 ± 3.0 日vs 3.4 ± 1.7 日，p=0.07）は有意差がなかった．多重ロジスティック回帰分析の結果，過去の増悪歴（OR：4.45，95%CI：1.09-18.2）と理学療法開始までの日数（OR：1.41，95%CI：1.03-1.93）が退院後1 年間の再入院と関連していた．【結論】本研究の結果，急性増悪後の理学療法介入開始の遅延は，退院後1 年間の再入院リスクを増加させる可能性が示唆された．急性増悪後早期の理学療法介入は，再入院の予防に有効である可能性がある．Purpose　The purpose of this study was to clarify the factors related to readmission for one year after discharge in patients hospitalized with acute exacerbations of chronic obstructive pulmonary disease（ COPD）.Method　Among patients who were admitted with a diagnosis of acute exacerbation of COPD between April 2014 and September 2016, 46 patients （mean age 78.0 ± 8.0 years old） who could be followed-up for one year after discharge were evaluated. The subjects were divided into two groups based on whether or not they were re-hospitalized within one year after being discharged, and data from the time of the first admission was collected from their electronic medical records and analyzed.Result　15 patients were included in the readmission group and 31 patients in the non-readmission group. There was a significant difference in previous history of exacerbations （60% vs. 29%, p = 0.04） between the two groups, and a borderline difference in the number of days to commencement of physical therapy （5.0 ± 3.0 days vs. 3.4 ± 1.7, p = 0.07）. Multiple logistic regression analysis revealed that previous history of exacerbations（ OR: 4.45, 95% CI: 1.09 - 18.2） and the number of days to commencing physical therapy （OR: 1.41, 95% CI: 1.03 - 1.93） were related to readmission rate.Conclusion　The findings of this study suggest that a delay in the start of physical therapy after acute exacerbation of COPD might increase the risk of readmission for one year after discharge of the patient from the hospital. Early physical therapy intervention after acute exacerbation of COPD might be effective in preventing readmission due to further exacerbations

Demonstration of a spherical plasma mirror for the counter-propagating kilojoule-class petawatt LFEX laser system

A counter-propagating laser-beam platform using a spherical plasma mirror was developed for the kilojoule-class petawatt LFEX laser. The temporal and spatial overlaps of the incoming and redirected beams were measured with an optical interferometer and an x-ray pinhole camera. The plasma mirror performance was evaluated by measuring fast electrons, ions, and neutrons generated in the counter-propagating laser interaction with a Cu-doped deuterated film on both sides. The reflectivity and peak intensity were estimated as ∼50% and ∼5 × 1018 W/cm2, respectively. The platform could enable studies of counter-streaming charged particles in high-energy-density plasmas for fundamental and inertial confinement fusion research.Kojima S., Abe Y., Miura E., et al. Demonstration of a spherical plasma mirror for the counter-propagating kilojoule-class petawatt LFEX laser system. Optics Express 30, 43491 (2022); https://doi.org/10.1364/oe.475945

OryzaExpress: An Integrated Database of Gene Expression Networks and Omics Annotations in Rice

Similarity of gene expression profiles provides important clues for understanding the biological functions of genes, biological processes and metabolic pathways related to genes. A gene expression network (GEN) is an ideal choice to grasp such expression profile similarities among genes simultaneously. For GEN construction, the Pearson correlation coefficient (PCC) has been widely used as an index to evaluate the similarities of expression profiles for gene pairs. However, calculation of PCCs for all gene pairs requires large amounts of both time and computer resources. Based on correspondence analysis, we developed a new method for GEN construction, which takes minimal time even for large-scale expression data with general computational circumstances. Moreover, our method requires no prior parameters to remove sample redundancies in the data set. Using the new method, we constructed rice GENs from large-scale microarray data stored in a public database. We then collected and integrated various principal rice omics annotations in public and distinct databases. The integrated information contains annotations of genome, transcriptome and metabolic pathways. We thus developed the integrated database OryzaExpress for browsing GENs with an interactive and graphical viewer and principal omics annotations (http://riceball.lab.nig.ac.jp/oryzaexpress/). With integration of Arabidopsis GEN data from ATTED-II, OryzaExpress also allows us to compare GENs between rice and Arabidopsis. Thus, OryzaExpress is a comprehensive rice database that exploits powerful omics approaches from all perspectives in plant science and leads to systems biology