Complete Response of Isolated Para-aortic Lymph Node Recurrence from Rectosigmoid Cancer Treated by Chemoradiation Therapy with Capecitabine/Oxaliplatin plus Bevacizumab: A Case Report

Para-aortic lymph node recurrence is a rare type of metastasis from colorectal cancer, and no treatment has yet been established. Here, we report on a case of isolated para-aortic lymph node metastasis from rectosigmoid cancer that showed complete response to chemoradiation therapy with capecitabine/oxaliplatin plus bevacizumab. A 58-year-old woman underwent high anterior resection for rectosigmoid cancer in 2009. Para-aortic lymph node recurrence occurred in 2011. She underwent radiation therapy (50 Gy) and 8 courses of capecitabine/oxaliplatin plus bevacizumab. Abdominal computed tomography and positron emission tomography with 18-fluorodeoxyglucose did not reveal any para-aortic lymph node recurrence after chemoradiation therapy. Hence, this case was interpreted as a complete response. No recurrence was noted 6 months after the complete response. Chemoradiation therapy with capecitabine/oxaliplatin plus bevacizumab is likely to be effective in treating patients with para-aortic lymph node recurrence

Medial meniscus posterior root repair decreases posteromedial extrusion of the medial meniscus during knee flexion

Background Medial meniscus (MM) medial extrusion in the coronal plane does not always improve, even after repair. This study aimed to determine the extent of posteromedial extrusion of the MM during knee flexion before and after MM pullout repair using three-dimensional magnetic resonance imaging (MRI). Methods Data from 14 patients (mean age, 63.4 years; 86% female) who had undergone MM pullout repair at the current institution between August 2017 and October 2018 were retrospectively reviewed. The MRIs were performed pre-operatively and ≥ 3 months postoperatively. Three-dimensional MRIs of the tibial surface and MM were evaluated using Tsukada's measurement method before and after pullout repair. The expected center of MM posterior root attachment (point A), the point on the extruded edge of the MM farthest away from point A (point E), and the point of intersection of a line through the posteromedial corner of the medial tibial plateau and a line connecting points A and E (point I) were identified. Subsequently, the pre-operative and postoperative AE and IE distances were calculated and compared. Results Point E was laterally shifted by the pullout repair, whereas point I showed no significant change. The postoperative IE distance (6.7 mm) was significantly shorter than the pre-operative one (9.1 mm, P < 0.01). The postoperative AE distance (29.3 mm) was significantly shorter than the pre-operative one (31.5 mm, P < 0.01). Conclusions The AE and IE distances significantly decreased after MM posterior root repair, suggesting that transtibial pullout repair may be useful in reducing posteromedial extrusion of the MM

Transtibial pullout repair of medial meniscus posterior root tear restores physiological rotation of the tibia in the knee-flexed position

BACKGROUND: Medial meniscus posterior root tear (MMPRT) results in joint overloading and degenerative changes in the knee. Favorable clinical outcomes have been reported after transtibial pullout repair of MMPRT. To date, however, in vivo tibial rotational changes before and after root repair remain poorly understood. The purpose of this study was to investigate postoperative changes in tibial rotation following MMPRT pullout repair. HYPOTHESIS: Pathological external rotation of the tibia in the knee-flexed position is caused by MMPRT and is reduced after transtibial pullout repair. PATIENTS AND METHODS: Fifteen patients who underwent MMPRT pullout repair and 7 healthy volunteers were included. Magnetic resonance imaging examinations were performed in the 10° and 90° knee-flexed positions. The angles between the surgical epicondylar axis and a line between the medial border of the patellar tendon and the apex of the medial tibial spine were measured. Baseline was defined as a line lying at a right angle to the other, and a value was positive and negative when the tibia rotated internally and externally, respectively. RESULTS: In the volunteer's normal knees, tibial internal rotation was +1.00°±3.27° at 10° flexion and +4.14°±3.46° at 90° flexion. In the MMPRT preoperative knees, tibial internal rotation was +1.07°±3.01° at 10° flexion and +1.27°±2.96° at 90° flexion. In the postoperative knees, tibial internal rotation was +1.60°±2.85° at 10° flexion and +4.33°±2.89° at 90° flexion. DISCUSSION: This study demonstrates discontinuity of the MM posterior root may induce a pathological external rotation of the tibia during knee flexion and that MMPRT pullout repair reduces the pathological external rotation of the tibia in the knee-flexed position

A model relating transpiration for Japanese cedar and cypress plantations with stand structure

Previous studies have revealed that changes in forest structure due to management (e.g., thinning, aging, and clearcutting) could affect the forest water balance. However, there are unexplained variability in changes in the annual water balance with changing structure among different sites. This is the case even when analyzing data for specific species/regions. For a more advanced and process-based understanding of changes in the water balance with changing forest structure, we examined transpiration (E) observed using the sap-flux method for 14 Japanese cedar and cypress plantations with various structure (e.g., stem density and diameter) in Japan and surrounding areas and developed a model relating E with structural parameters. We expressed E using the simplified Penman–Monteith equation and modeled canopy conductance (G[c]) as a product of reference G[c] (G[cref]) when vapor pressure deficit is 1.0 kPa and functions expressing the responses of G[c] to meteorological factors. We determined G[cref] and parameters of the functions for the sites separately. E observed for the 14 sites was not reproduced well by the model when using mean values of G[cref] and the parameters among the sites. However, E observed for the sites was reproduced well when using G[cref] determined for each site and mean values of the parameters of the functions among the sites, similar to the case when using G[cref] and the parameters of the functions determined for each site. These results suggest that considering variations in G[cref] among the sites was important to reproduce variations in E, but considering variations in the parameters of the functions was not. Our analysis revealed that G[cref] linearly related with the sapwood area on a stand scale (A) and that Alinearly related with stem density (N) and powers of the mean stem diameter (d[m]). Thus, we proposed a model relating E with A (or N and d[m]), where G[cref] was calculated from A (or N and d[m]) and the parameters of the functions were assumed to be the mean values among the sites. This model estimates changes in Ewith changing structure from commonly available data (N and d[m]), and therefore helps improve our understanding of the underlying processes of the changes in the water balance for Japanese cedar and cypress plantations

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

G-RMSD: Root Mean Square Deviation Based Method for Three-dimensional Molecular Similarity Determination

We present the Generalized Root Mean Square Deviation (G-RMSD) method. G-RMSD is an optimization method to calculate the minimal RMSD value of two atomic structures by optimal superimposition. The method is not restricted to systems with an equal number of atoms or a unique atom matching and can handle any type of chemical structure, including transition states and non-valence bond structures. It requires only Cartesian coordinates for the structures, but can also include further information, i.e. atom and bond types. Applications of G-RMSD to the classification of alpha-D-glucose conformers and 3D partial structure search using a dataset containing equilibrium (EQ), dissociation channel (DC), and transition state (TS) structures are demonstrated. We find that G-RMSD allows for a successful classification and mapping for a wide variety of molecular structures.</div

G-RMSD: Root Mean Square Deviation Based Method for Three-dimensional Molecular Similarity Determination

We present the Generalized Root Mean Square Deviation (G-RMSD) method. G-RMSD is an optimization method to calculate the minimal RMSD value of two atomic structures by optimal superimposition. G-RMSD is not restricted to systems with an equal number of atoms to compare or a unique atom mapping between two molecules. The method can handle any type of chemical structures, including transition states and structures which cannot be explained only with valence bond (VB) theory (non-VB structures). It requires only Cartesian coordinates for the structures. Further information, i.e. atom- and bond types can also be included. Applications of G-RMSD to the classification of α-D-glucose conformers and 3D partial structure search using a dataset containing equilibrium (EQ), dissociation channel (DC), and transition state (TS) structures are demonstrated. We find that G-RMSD allows for a successful classification and mapping for a wide variety of molecular structures