The Clinical Landscape of Circulating Tumor DNA in Gastrointestinal Malignancies

Technologies for genomic analyses have revealed more details in cancer biology and have changed standard treatments for cancer, including the introduction of targeted gene-specific therapy. Currently, liquid biopsies are increasingly being utilized in clinical trials and research settings to analyze circulating tumor DNA (ctDNA) from peripheral blood. Several studies have shown the potential of ctDNA in the screening, prognostication, molecular profiling, and monitoring of gastrointestinal malignancies. Although limitations continue to exist in the use of ctDNA, such as method standardization, the sensitivity, concordance with tumor tissue, and regulatory issues, this field offers promising benefits for cancer treatment. A deeper understanding of tumor biology via ctDNA analyses and ctDNA-guided clinical trials will lead to the increasing use of ctDNA in clinical practice in the near future; this development will result in the improvement of outcomes among patients with gastrointestinal malignancies

Text-Guided Scene Sketch-to-Photo Synthesis

We propose a method for scene-level sketch-to-photo synthesis with text guidance. Although object-level sketch-to-photo synthesis has been widely studied, whole-scene synthesis is still challenging without reference photos that adequately reflect the target style. To this end, we leverage knowledge from recent large-scale pre-trained generative models, resulting in text-guided sketch-to-photo synthesis without the need for reference images. To train our model, we use self-supervised learning from a set of photographs. Specifically, we use a pre-trained edge detector that maps both color and sketch images into a standardized edge domain, which reduces the gap between photograph-based edge images (during training) and hand-drawn sketch images (during inference). We implement our method by fine-tuning a latent diffusion model (i.e., Stable Diffusion) with sketch and text conditions. Experiments show that the proposed method translates original sketch images that are not extracted from color images into photos with compelling visual quality

Atomizing Performance of Non-Heating Fog Machine

The paper deals with the closed-spaced atomizing performance of a non-haeting fog machine which was extensively used for protection in a vinyl greenhouse. The electrode near the nozzle of this machine could spray with electrostatic charge, which makes it possible to check through the atomizing performance with or without electrostatic charge. The test results showed that:(1) particles within a size of 10 ～ 30μm could be dispersed extensively;(2) electrostatic charge could make spray particle size smaller and make atomization and adherability to back side of our copper test plate better than that of spray particles without electrostatic charge.本文はビニールハウス内の防除用として広く使われている常温煙霧機について，ビニールハウス内で噴霧し，噴霧された微細粒子をミラーコート紙およびアースした銅板上に捕捉して拡大し粒径と粒数を求めて，常温煙霧機の微粒化性能を明らかにした．供試機はノズル出口の近傍に帯電用の電極を持ち，静電散布が可能という常温煙霧機であり，噴霧粒子を帯電させた場合とさせなかった場合について微粒化性能を調べた．試験結果によって，常温煙霧機の微粒化性能が明らかになり，10～30μmの揃った粒子が広く拡散していることがわかった．また，噴霧粒子を帯電させた場合は，粒径が若干小さくなり，微粒化が良くなることがわかった．裏面への付着性も良くなることが確かめられ

Radiosynthesis and in vivo evaluation of two imidazopyridineacetamides, [11C]CB184 and [11C]CB190, as a PET tracer for 18 kDa translocator protein: direct comparison with [11C](R)-PK11195

Objective: We report synthesis of two carbon-11 labeled imidazopyridines TSPO ligands, [11C]CB184 and [11C]CB190, for PET imaging of inflammatory process along with neurodegeneration, ischemia or brain tumor. Biodistribution of these compounds was compared with that of [11C]CB148 and [11C](R)-PK11195. Methods: Both [11C]CB184 and [11C]CB190 having 11C-methoxyl group on an aromatic ring were readily prepared using [11C]methyl triflate. Biodistribution and metabolism of the compounds were examined with normal mice. An animal PET study using 6-hydroxydopamine treated rats as a model of neurodegeneration was pursued for proper estimation of feasibility of the radioligands to determine neuroinflammation process. Results: [11C]CB184 and [11C]CB190 were obtained via O-methylation of corresponding desmethyl precursor using [11C]methyl triflate in radiochemical yield of 73 % (decay-corrected). In vivo validation as a TSPO radioligand was carried out using normal mice and lesioned rats. In mice, [11C]CB184 showed more uptake and specific binding than [11C]CB190. Metabolism studies showed that 36 % and 25 % of radioactivity in plasma remained unchanged 30 min after intravenous injection of [11C]CB184 and [11C]CB190, respectively. In the PET study using rats, lesioned side of the brain showed significantly higher uptake than contralateral side after i.v. injection of either [11C]CB184 or [11C](R)-PK11195. Indirect Logan plot analysis revealed distribution volume ratio (DVR) between the two sides which might indicate lesion-related elevation of TSPO binding. The DVR was 1.15 ± 0.10 for [11C](R)-PK11195 and was 1.15 ± 0.09 for [11C]CB184. Conclusion: The sensitivity to detect neuroinflammation activity was similar for [11C]CB184 and [11C](R)-PK11195

Surgical Outcomes of Posterior Short Segment Fixation for Thoracolumbar Burst Fractures: A Study of Patients Treated without Vertebroplasty

There is no widespread agreement regarding the treatment of thoracolumbar burst fractures. While performing posterior short segment fixation of thoracolumbar burst fractures, we evaluated therapeutic outcomes in patients treated with screw insertion into fractured vertebral bodies without vertebroplasty. We also investigated the limitations associated with the treatment of burst fractures when vertebroplasty is not performed. Twenty-one of 51 patients with thoracolumbar burst fractures who were treated surgically in Ohta Nishinouchi Hospital were evaluated in the present study. These patients underwent posterior short segment fixation with screw insertion into the fractured vertebral bodies (only pedicle screws were inserted one level above and one level below the fractured vertebral bodies) without vertebroplasty. Vertebral angles were measured before surgery, immediately after surgery, and at the final follow-up examination. Changes in vertebral angles were compared and analyzed. The mean vertebral angles before and after surgery and at the final follow-up examination were 15.4°, 6.6°, and 9.1°, respectively. The mean postoperative correction loss was 2.5°. The therapeutic outcomes of posterior short segment fixation with screw insertion into fractured vertebral bodies without vertebroplasty were generally favorable

The Novel Monoclonal Antibody 9F5 Reveals Expression of a Fragment of GPNMB/Osteoactivin Processed by Furin-like Protease(s) in a Subpopulation of Microglia in Neonatal Rat Brain

To differentiate subtypes of microglia (MG), we developed a novel monoclonal antibody, 9F5, against one subtype (type 1) of rat primary MG. The 9F5 showed high selectivity for this cell type in Western blot and immunocytochemical analyses and no cross‐reaction with rat peritoneal macrophages (Mφ). We identified the antigen molecule for 9F5: the 50‐ to 70‐kDa fragments of rat glycoprotein nonmetastatic melanoma protein B (GPNMB)/osteoactivin, which started at Lys170. In addition, 9F5 immunoreactivity with GPNMB depended on the activity of furin‐like protease(s). More important, rat type 1 MG expressed the GPNMB fragments, but type 2 MG and Mφ did not, although all these cells expressed mRNA and the full‐length protein for GPNMB. These results suggest that 9F5 reactivity with MG depends greatly on cleavage of GPNMB and that type 1 MG, in contrast to type 2 MG and Mφ, may have furin‐like protease(s) for GPNMB cleavage. In neonatal rat brain, amoeboid 9F5+ MG were observed in specific brain areas including forebrain subventricular zone, corpus callosum, and retina. Double‐immunοstaining with 9F5 antibody and anti‐Iba1 antibody, which reacts with MG throughout the CNS, revealed that 9F5+ MG were a portion of Iba1+ MG, suggesting that MG subtype(s) exist in vivo. We propose that 9F5 is a useful tool to discriminate between rat type 1 MG and other subtypes of MG/Mφ and to reveal the role of the GPNMB fragments during developing brain

Germination of photoblastic lettuce seeds is regulated via the control of endogenous physiologically active gibberellin content, rather than of gibberellin responsiveness

Phytochrome regulates lettuce (Lactuca sativa L. cv. Grand Rapids) seed germination via the control of the endogenous level of bioactive gibberellin (GA). In addition to the previously identified LsGA20ox1, LsGA20ox2, LsGA3ox1, LsGA3ox2, LsGA2ox1, and LsGA2ox2, five cDNAs were isolated from lettuce seeds: LsCPS, LsKS, LsKO1, LsKO2, and LsKAO. Using an Escherichia coli expression system and functional assays, it is shown that LsCPS and LsKS encode ent-copalyl diphosphate synthase and ent-kaurene synthase, respectively. Using a Pichia pastoris system, it was found that LsKO1 and LsKO2 encode ent-kaurene oxidases and LsKAO encodes ent-kaurenoic acid oxidase. A comprehensive expression analysis of GA metabolism genes using the quantitative reverse transcription polymerase chain reaction suggested that transcripts of LsGA3ox1 and LsGA3ox2, both of which encode GA 3-oxidase for GA activation, were primarily expressed in the hypocotyl end of lettuce seeds, were expressed at much lower levels than the other genes tested, and were potently up-regulated by phytochrome. Furthermore, LsDELLA1 and LsDELLA2 cDNAs that encode DELLA proteins, which act as negative regulators in the GA signalling pathway, were isolated from lettuce seeds. The transcript levels of these two genes were little affected by light. Lettuce seeds in which de novo GA biosynthesis was suppressed responded almost identically to exogenously applied GA, irrespective of the light conditions, suggesting that GA responsiveness is not significantly affected by light in lettuce seeds. It is proposed that lettuce seed germination is regulated mainly via the control of the endogenous content of bioactive GA, rather than the control of GA responsiveness

Impact of insulin resistance on subclinical left ventricular dysfunction in normal weight and overweight/obese japanese subjects in a general community

Background Insulin resistance carries increased risk of heart failure, although the pathophysiological mechanisms remain unclear. LV global longitudinal strain (LVGLS) assessed by speckle-tracking echocardiography has emerged as an important tool to detect early LV systolic abnormalities. This study aimed to investigate the association between insulin resistance and subclinical left ventricular (LV) dysfunction in a sample of the general population without overt cardiac disease. Methods We investigated 539 participants who voluntarily underwent extensive cardiovascular health check including laboratory test and speckle-tracking echocardiography. Glycemic profiles were categorized into 3 groups according to homeostatic model assessment of insulin resistance (HOMA-IR): absence of insulin resistance (HOMA-IR  − 16.65%). Results Forty-five (8.3%) participants had DM and 66 (12.2%) had abnormal HOMA-IR. LV mass index and E/e′ ratio did not differ between participants with and without abnormal HOMA-IR, whereas abnormal HOMA-IR group had significantly decreased LVGLS (− 17.6 ± 2.6% vs. − 19.7 ± 3.1%, p < 0.05). The prevalence of impaired LVGLS was higher in abnormal HOMA-IR group compared with normal HOMA-IR group (42.4% vs. 14.0%) and similar to that of DM (48.9%). In multivariable analyses, glycemic abnormalities were significantly associated with impaired LVGLS, independent of traditional cardiovascular risk factors and pertinent laboratory and echocardiographic parameters [adjusted odds ratio (OR) 2.38, p = 0.007 for abnormal HOMA-IR; adjusted OR 3.02, p = 0.003 for DM]. The independent association persisted even after adjustment for waist circumference as a marker of abdominal adiposity. Sub-group analyses stratified by body mass index showed significant association between abnormal HOMA-IR and impaired LVGLS in normal weight individuals (adjusted OR 4.59, p = 0.001), but not in overweight/obese individuals (adjusted OR 1.62, p = 0.300). Conclusions In the general population without overt cardiac disease, insulin resistance carries independent risk for subclinical LV dysfunction, especially in normal weight individuals

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