Virtual imaging-guided RAPN

Objectives : To evaluate whether virtual partial nephrectomy images could help surgeons identify vascular and collecting system around tumors during actual surgery. Materials & methods : We retrospectively analyzed 36 patients who underwent robot-assisted partial nephrectomy (RAPN) between 2016 and 2017. Virtual partial nephrectomy images were created from preoperative CT images using computer software, and then analyzed. For analysis, blood vessels and collecting system portions within a 5-mm-thick safety margin around the tumor were examined. During analysis, we predicted whether targeted vasculature around the tumor would require clipping or suturing during surgery, and also whether the collecting system would require opening during resection. Surgical outcomes for virtual partial nephrectomy analyses and actual RAPNs were compared and analyzed for sensitivity and specificity. Results : In 36 cases, 119 arteries and 100 veins were targeted on virtual partial nephrectomy images. Arterial suturing or clipping for hemostasis showed a sensitivity and specificity of 83.3% and 84.5%, respectively. For veins, the sensitivity and specificity were 39.1% and 92.2%, respectively. Collecting system opening prediction sensitivity was 85.7%, and specificity was 65.2%. Conclusion : Virtual partial nephrectomy imaging is useful for RAPN planning, particularly regarding arteries and the collecting system. It is hoped that techniques for visualizing veins will improve

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

Graphene oxide coating facilitates the bioactivity of scaffold material for tissue engineering

Carbon-based nanomaterials are being investigated for biomedical applications. Graphene oxide (GO), a monolayer of carbon, holds promise as a tissue engineering substrate due to its unique physicochemical properties. The aim of this study was to evaluate the effect of a GO coating on cell proliferation and differentiation in vitro. We also assessed the bioactivities of collagen scaffolds coated with different concentrations of GO in rats. The results showed that GO affects both cell proliferation and differentiation, and improves the properties of collagen scaffolds. Subcutaneous implant tests showed that low concentrations of GO scaffold enhances cell in-growth and is highly biodegradable, whereas high concentrations of GO coating resulted in adverse biological effects. Consequently, scaffolds modified with a suitable concentration of GO are useful as a bioactive material for tissue engineering

RAPN suturing technique for complex tumors

Objectives: To compare the postoperative outcomes of robot-assisted partial nephrectomy when only the inner layer is sutured (single-layer technique with soft coagulation) with those when sutures are placed in the inner and outer layers (double-layer technique) in patients with and without complex renal tumors. Methods: This retrospective three-institution study included 371 patients with renal tumors who underwent robot-assisted partial nephrectomy with a double-layer technique or a single-layer technique with soft coagulation. Tumors that were cT1b, completely embedded, located in the renal portal, or had a RENAL score of ≥10 were considered complex. Relevant data were collected from hospital records. Propensity score matching was performed to minimize selection bias. Results: Propensity score matching created 83 patient pairs with non-complex tumors and 32 with complex tumors. Regardless of tumor complexity, there was no significant difference in operation time, console time, warm ischemia time, positive surgical margin rate, or length of hospital stay between the double-layer and single-layer groups. Although Clavien–Dindo grade I–II urinomas not requiring intervention were significantly more common in the single-layer group regardless of tumor complexity, there was no significant between-group difference in the rate of decline in renal function or grade III–IV complications. Conclusion: Single-layer suturing with soft coagulation achieves renal function and perioperative outcomes comparable to those of double-layer suturing regardless of complexity

Biological Response to Nanostructure of Carbon Nanotube/titanium Composite Surfaces

Titanium (Ti) is frequently used as a biomaterial in dental and orthopedic implants and in bone fixation devices. Effective modification of the Ti surface plays a crucial role in improving biocompatibility. Carbon nanotubes (CNTs) are among the most interesting nanomaterials due to their unique properties. In this study, we fabricated CNT-Ti composite surfaces by annealing Ti plates covered by different sized CNTs (Nanocyl NC 7000, 9.5 nm diameter and VGCF-H, 150 nm diameter). The properties of these surfaces were examined by scanning electron microscopy, X-ray diffraction, energy dispersive X-ray spectroscopy, raman spectroscopy, contact angle measurement and osteoblast-like cell seeding. In addition, samples were implanted into the subcutaneous tissue of rats. The three-dimensional nanostructures of CNTs and creation of titanium carbide were evident on the Ti surfaces, suggesting that the CNTs were well-anchored onto the Ti plates. CNT modification promoted desirable cell behavior, including cell spreading and proliferation, especially on the Nanocyl-modified surface. Inflammatory response was rarely observed on the Nanocyl surface, but macrophage-like giant cells were frequently observed on the VGCF-H surface. Therefore, the nanomorphology of narrow diameter CNTs provides a CNT-Ti composite surface with good biocompatibility