Verification of criterion-related validity of the evaluation method of postural stability using the frame subtraction method.

It is important to quantify the postural stability. The frame subtraction method can calculate the motions of a subject, and might be easier to implement, with lower costs. However, validity of the evaluation of postural stability using this method have not been validated yet. Therefore, the purpose of this study was to verify criterion-related validity of the frame subtraction scores and the center of pressure (COP) parameters during maintenance of single leg standing. Twenty two healthy young subjects participated in this study. Motion tasks comprised right leg standing with eyes open and closed. The total length of COP displacements (LNG), Root mean square (RMS) area, anterior - posterior (AP) range, medial - lateral (ML) range were recorded using the force plate. Simultaneously, the motion images were acquired with digital video cameras from the front and right sides. After the motion images were analyzed using the frame subtraction method, the frame subtraction scores (maximumsum of the frame subtraction score on each planethe frontal and sagittal planes) were measured. To confirm the validity, Spearman's rank correlation coefficient between the frame subtraction scores and the COP parameters was calculated. The sum of the frame subtraction score on the frontal plane was significantly correlated with all COP displacements in the single leg standing. The result of this study indicated that the frame subtraction method could be applied to the evaluation of balance task with postural sway such as maintenance of single leg standing. The frame subtraction method is low cost and easy owing to its marker-less systems

Long-term prognosis and DNA damage status after oral mucosal epithelial cell sheet transplantation following esophageal endoscopic submucosal dissection for squamous cell carcinoma: A case series

Autologous oral mucosal epithelial cell sheet (AOMECS) transplantation has recently been applied in human patients to prevent postprocedural stenosis following endoscopic submucosal dissection (ESD) for esophageal squamous cell carcinoma. However, the long-term safety of AOMECS transplantation remains unclear. We evaluated the long-term outcomes of 10 patients who participated in a clinical trial of AOMECS transplantation after esophageal ESD. Additionally, we assessed the local DNA damage response in the esophageal epithelium using p53 binding protein 1 (53BP1) immunofluorescence in post-AOMECS biopsy specimens. The median follow-up period was 118.5 months (range: 46–130 months). Two patients developed primary esophageal cancer near the AOMECS site and successfully underwent additional ESD. One patient developed lymph node metastasis and underwent chemotherapy. None of the patients died from the original disease, although one patient died from unrelated causes. The rate of abnormal 53BP1 nuclear foci, indicative of increased genome instability, increased with the progression of neoplasia in patients post AOMECS. Our case series suggests that AOMECS transplantation provides an acceptable long-term prognosis and 53BP1 foci may serve as a useful marker for assessing DNA instability in the post-AOMECS esophageal epithelium.Regenerative Therapy, 26, pp.557-563; 2024journal articl

Risk Factors and Long‐Term Prognosis for Coinfection of Nontuberculous Mycobacterial Pulmonary Disease and Chronic Pulmonary Aspergillosis: A Multicentre Observational Study in Japan

Background: Nontuberculous mycobacterial pulmonary disease (NTM-PD) is a chronic respiratory infection with increasing prevalence and mortality worldwide. Coinfection with chronic pulmonary aspergillosis (CPA) is a significant complication of NTM-PD, often complicating treatment and resulting in poor prognosis. Objective: In this multicentre, retrospective cohort study, we examined the epidemiology, comorbidities, risk factors for CPA coinfection and long-term prognosis of patients with NTM-PD infected with CPA in Japan. Methods: Patients aged ≥ 18 years with newly diagnosed NTM-PD who visited 18 hospitals between 2010 and 2017 in Kyushu, Japan, were included. Medical records were reviewed for patient characteristics, mycobacterial species, laboratory data, radiological features, Aspergillus coinfection and all-cause mortality rates. Risk factors for CPA coinfection were analysed using multiple logistic regression, and survival analysis was performed before and after propensity score matching with risk factors. Results: Among 1304 patients with NTM-PD, 45 (3.5%) were diagnosed with CPA, including 42 with chronic progressive pulmonary aspergillosis. The risk factors for CPA coinfection included male sex, chronic obstructive pulmonary disease, oral corticosteroid use and cavity formation. All-cause mortality was significantly higher in patients with NTM-PD with CPA than in those without CPA (log-rank test, p < 0.001; crude hazard ratio [HR], 3.98). Survival analysis after propensity score matching suggested CPA was an independent poor prognostic factor (log-rank test, p = 0.036; adjusted HR, 1.59). Conclusion: CPA is an independent poor prognostic factor in patients with NTM-PD. Clinicians must consider CPA when treating patients with NTM-PD, particularly those with high-risk factors, to ensure timely diagnosis and management.Mycoses, 68(6), art. no. e70083; 2025journal articl

Risk Factors and Long-Term Prognosis for Coinfection of Nontuberculous Mycobacterial Pulmonary Disease and Chronic Pulmonary Aspergillosis: A Multicentre Observational Study in Japan

Background Nontuberculous mycobacterial pulmonary disease (NTM-PD) is a chronic respiratory infection with increasing prevalence and mortality worldwide. Coinfection with chronic pulmonary aspergillosis (CPA) is a significant complication of NTM-PD, often complicating treatment and resulting in poor prognosis. Objective In this multicentre, retrospective cohort study, we examined the epidemiology, comorbidities, risk factors for CPA coinfection and long-term prognosis of patients with NTM-PD infected with CPA in Japan. Methods Patients aged ≥ 18 years with newly diagnosed NTM-PD who visited 18 hospitals between 2010 and 2017 in Kyushu, Japan, were included. Medical records were reviewed for patient characteristics, mycobacterial species, laboratory data, radiological features, Aspergillus coinfection and all-cause mortality rates. Risk factors for CPA coinfection were analysed using multiple logistic regression, and survival analysis was performed before and after propensity score matching with risk factors. Results Among 1304 patients with NTM-PD, 45 (3.5%) were diagnosed with CPA, including 42 with chronic progressive pulmonary aspergillosis. The risk factors for CPA coinfection included male sex, chronic obstructive pulmonary disease, oral corticosteroid use and cavity formation. All-cause mortality was significantly higher in patients with NTM-PD with CPA than in those without CPA (log-rank test, p < 0.001; crude hazard ratio [HR], 3.98). Survival analysis after propensity score matching suggested CPA was an independent poor prognostic factor (log-rank test, p = 0.036; adjusted HR, 1.59). Conclusion CPA is an independent poor prognostic factor in patients with NTM-PD. Clinicians must consider CPA when treating patients with NTM-PD, particularly those with high-risk factors, to ensure timely diagnosis and management

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

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Verification of reliability and validity of motion analysis systems during bilateral squat using human pose tracking algorithm

Background: The human tracking algorithm called OpenPose can detect joint points and calculate joint angles. However, the reliability and validity of OpenPose have not been clarified yet. Research question: Are there the enough reliability and validity of OpenPose based motion analysis? Methods: 20 healthy young subjects participated in this study. The motion task was a bilateral squat. The joint angles of the trunk, hip, knee, and ankle were calculated using OpenPose and VICON. Kinematic measurements by three-dimensional motion analysis devices were recorded using VICON. Simultaneously, the images were taken with a digital camera from the right side. After the images were processed with OpenPose, joint angles were calculated from estimated joint points. To confirm the test-retest reliability within device, intraclass correlation coefficients [ICC (1, 3)] were calculated. To confirm the validity, linear regression analysis and ICC (2, 1) between the data obtained by OpenPose and VICON were calculated. Furthermore, the agreement between the data obtained by OpenPose and VICON was assessed by Bland-Altman analysis. Results: ICCs (1, 3) of the data obtained by OpenPose and VICON were almost perfect. There were significant associations between the data obtained by OpenPose and VICON. ICCs (2, 1) between the data obtained by OpenPose and VICON were almost perfect or substantial for trunk, knee and ankle joints, and fair on the hip joint. There were fixed biases on knee and ankle joints, and proportional biases on trunk and hip joint. Significance: OpenPose based motion analysis is reliable and has the advantage of being low cost and easier to operate than conventional methods. In future, to consider the clinical utility of OpenPose, it is necessary to identify the error between the true values indicating actual joint movement and data obtained by OpenPose with its correction for fixed and proportional biases