Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.esmorw.2024.100072

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Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.clcc.2024.04.001

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Publishing type：Research paper (scientific journal)   Publisher：Wiley  

Abstract

The molecular mechanisms associated with spaceflight‐induced biological adaptations that may affect many healthy tissue functions remain poorly understood. In this study, we analyzed temporal changes in the serum proteome of six astronauts during prolonged spaceflight missions using quantitative comprehensive proteome analysis performed with the data‐independent acquisition method of mass spectrometry (DIA‐MS). All six astronauts participated in a spaceflight mission for approximately 6 months and showed a decreasing trend in T‐scores at almost all sites where dual‐energy X‐ray absorptiometry scans were performed. DIA‐MS successfully identified 624 nonredundant proteins in sera and further quantitative analysis for each sampling point provided information on serum protein profiles closely related to several time points before (pre‐), during (in‐), and after (post‐) spaceflight. Changes in serum protein levels between spaceflight and on the ground suggest that abnormalities in bone metabolism are induced in astronauts during spaceflight. Furthermore, changes in the proteomic profile occurring during spaceflight suggest that serum levels of bone metabolism‐related proteins, namely ALPL, COL1A1, SPP1, and POSTN, could serve as highly responsive indicators of bone metabolism status in spaceflight missions. This study will allow us to accelerate research to improve our understanding of the molecular mechanisms of biological adaptations associated with prolonged spaceflight.

DOI： 10.1002/pmic.202300328

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Authorship：Lead author   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.esmogo.2023.08.006

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Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.esmorw.2023.100005

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Publishing type：Research paper (scientific journal)   Publisher：Wiley  

Abstract

Objective

The aim of the present study was to investigate which treatment, neoadjuvant chemoradiotherapy (NAC‐RT) with S‐1 or combination neoadjuvant chemotherapy with gemcitabine and S‐1 (NAC‐GS), is more promising as neoadjuvant treatment (NAT) for resectable pancreatic cancer in terms of effectiveness and safety.

Methods

In the NAC‐RT with S‐1 group, the patients received a total radiation dose of 50.4 Gy in 28 fractions with oral S‐1. In the NAC‐GS group, the patients received intravenous gemcitabine at a dose of 1000 mg/m² with oral S‐1 for two cycles. The primary endpoint was the 2‐year progression‐free survival (PFS) rate. The trial was registered with the UMIN Clinical Trial Registry as UMIN000014894.

Results

From April 2014 to April 2017, a total of 103 patients were enrolled. After exclusion of one patient because of ineligibility, 51 patients were included in the NAC‐RT with S‐1 group, and 51 patients were included in the NAC‐GS group in the intention‐to‐treat analysis. The 2‐year PFS rate was 45.0% (90% confidence interval [CI]: 33.3%–56.0%) in the NAC‐RT with S‐1 group and 54.9% (42.8%–65.5%) in the NAC‐GS group (p = .350). The 2‐year overall survival rate was 66.7% in the NAC‐RT with S‐1 group and 72.4% in the NAC‐GS group (p = .300). Although leukopenia and neutropenia rates were significantly higher in the NAC‐GS group than in the NAC‐RT with S‐1 group (p = .023 and p < .001), other adverse events of NAT and postoperative complications were comparable between the two groups.

Conclusion

Both NAC‐RT with S‐1 and NAC‐GS are considered promising treatments for resectable pancreatic cancer.

DOI： 10.1002/jhbp.1353

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Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

Abstract

Gravity-dependent physical processes strongly affect the ability of elderly people to maintain musculoskeletal health by reducing muscle atrophy and increasing bone mineral density, thereby increasing quality of life. A need therefore exists to identify molecules in the musculoskeletal system that are responsive to gravitational loading and to establish an objective indicator for the maintenance of healthy musculoskeletal systems. Here, we performed an integrated assessment of the results of soleus muscle proteomic analyses in three model mouse experiments under different gravity environments (hypergravity, hindlimb unloading, and spaceflight). Myl6b, Gpd1, Fbp2, Pvalb, and Actn3 were shown to be gravity-responsive muscle proteins, and alterations in the levels of these proteins indicated changes in muscle fiber type to slow-twitch type due to gravity loading. In addition, immunoblotting and enzyme-linked immunosorbent assays revealed that Pvalb levels in the sera of hindlimb-unloaded mice and osteoporosis patients were higher than in control subjects, suggesting that Pvalb levels might be useful to objectively evaluate soleus muscle atrophy and bone loss.

DOI： 10.1038/s41598-023-42875-8

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Other Link： https://www.nature.com/articles/s41598-023-42875-8

Authorship：Lead author   Publishing type：Research paper (scientific journal)   Publisher：MDPI AG  

Clinical studies often collect longitudinal and time-to-event data for each subject. Joint modeling is a powerful methodology for evaluating the association between these data. The existing models, however, have not sufficiently addressed the problem of missing data, which are commonly encountered in longitudinal studies. In this paper, we introduce a novel joint model with shared random effects for incomplete longitudinal data and time-to-event data. Our proposed joint model consists of three submodels: a linear mixed model for the longitudinal data, a Cox proportional hazard model for the time-to-event data, and a Cox proportional hazard model for the time-to-dropout from the study. By simultaneously estimating the parameters included in these submodels, the biases of estimators are expected to decrease under two missing scenarios. We estimated the proposed model by Bayesian approach, and the performance of our method was evaluated through Monte Carlo simulation studies.

DOI： 10.3390/math10193656

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Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

Abstract

Corticosteroids use in coronavirus disease 2019 (COVID-19) is controversial, especially in mild to severe patients who do not require invasive/noninvasive ventilation. Moreover, many factors remain unclear regarding the appropriate use of corticosteroids for COVID-19. In this context, this multicenter, retrospective, propensity score–matched study was launched to evaluate the efficacy of systemic corticosteroid administration for hospitalized patients with COVID-19 ranging in the degree of severity from mild to critically-ill disease. This multicenter, retrospective study enrolled consecutive hospitalized COVID-19 patients diagnosed January–April 2020 across 30 institutions in Japan. Clinical outcomes were compared for COVID-19 patients who received or did not receive corticosteroids, after adjusting for propensity scores. The primary endpoint was the odds ratio (OR) for improvement on a 7-point ordinal score on Day 15. Of 1092 COVID-19 patients analyzed, 118 patients were assigned to either the corticosteroid and non-corticosteroid group, after propensity score matching. At baseline, most patients did not require invasive/noninvasive ventilation (85.6% corticosteroid group vs. 89.8% non-corticosteroid group). The odds of improvement in a 7-point ordinal score on Day 15 was significantly lower for the corticosteroid versus non-corticosteroid group (OR, 0.611; 95% confidence interval [CI], 0.388–0.962; p = 0.034). The time to improvement in radiological findings was significantly shorter in the corticosteroid versus non-corticosteroid group (hazard ratio [HR], 1.758; 95% CI, 1.323–2.337; p < 0.001), regardless of baseline clinical status. The duration of invasive mechanical ventilation was shorter in corticosteroid versus non-corticosteroid group (HR, 1.466; 95% CI, 0.841–2.554; p = 0.177). Of the 106 patients who received methylprednisolone, the duration of invasive mechanical ventilation was significantly shorter in the pulse/semi-pulse versus standard dose group (HR, 2.831; 95% CI, 1.347–5.950; p = 0.006). In conclusion, corticosteroids for hospitalized patients with COVID-19 did not improve clinical status on Day 15, but reduced the time to improvement in radiological findings for all patients regardless of disease severity and also reduced the duration of invasive mechanical ventilation in patients who required intubation.

Trial registration: This study was registered in the University hospital Medical Information Network Clinical Trials Registry on April 21, 2020 (ID: UMIN000040211).

DOI： 10.1038/s41598-021-90246-y

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Other Link： https://www.nature.com/articles/s41598-021-90246-y

Event date： 2023.5 - 2023.6

Presentation type：Poster presentation  

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Event date： 2022.9

Presentation type：Oral presentation (general)  

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Event date： 2021.7

Presentation type：Poster presentation  

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Event date： 2021.3

Presentation type：Poster presentation  

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Event date： 2020.9

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