Publications by authors named "Daisuke Matsumoto"

101 Publications

Molecular Switch Engineering for Precise Genome Editing.

Bioconjug Chem 2021 Apr 7. Epub 2021 Apr 7.

Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi Minami-ku, Hiroshima, 734-8553, Japan.

Genome editing technology commenced in 1996 with the discovery of the first zinc-finger nuclease. Application of Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) associated protein 9 (Cas9) technology to genome editing of mammalian cells allowed researchers to use genome editing more easily and cost-effectively. However, one of the technological problems that remains to be solved is "off-target effects", which are unexpected mutations in nontarget DNA. One significant improvement in genome editing technology has been achieved with molecular/protein engineering. The key to this engineering is a "switch" to control function. In this review, we discuss recent efforts to design novel "switching" systems for precise editing using genome editing tools.
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http://dx.doi.org/10.1021/acs.bioconjchem.1c00088DOI Listing
April 2021

Social factors associated with reversing frailty progression in community-dwelling late-stage elderly people: An observational study.

PLoS One 2021 3;16(3):e0247296. Epub 2021 Mar 3.

Department of Physical Therapy, Faculty of Health Science, Kio University, Koryo, Kitakatsuragi-gun, Nara, Japan.

Frailty is considered to be a complex concept based mainly on physical vulnerability, but also vulnerabilities in mental/psychological and social aspects. Frailty can be reversible with appropriate intervention; however, factors that are important in recovering from frailty have not been clarified. The aim of the present study was to identify factors that help an individual reverse frailty progression and characteristics of individuals that have recovered from frailty. Community-dwelling people aged ≥75 years who responded to the Kihon Checklist (KCL) were enrolled in the study. The KCL consists of 25 yes/no questions in 7 areas: daily-life related activities, motor functions, nutritional status, oral functions, homebound, cognitive functions, and depressed mood. The number of social activities, degree of trust in the community, degree of interaction with neighbors, and subjective age were also evaluated. Frailty was assessed based on the number of checked items: 0-3 for robust, 4-7 for pre-frailty, and ≥8 for frailty. A total of 5050 participants were included for statistical analysis. At the time of the baseline survey in 2016, 18.7% (n = 942) of respondents had frailty, and the follow-up survey showed that the recovery rate from frailty within 2 years (median 24 months) was 31.8% (n = 300). Multiple logistic regression analysis showed that exercise-based social participation (odds ratio [OR] 2.0, 95% confidence interval [CI] 1.2-3.4; P<0.01) and self-rated health (OR 1.2, CI 1.0-1.5; P = 0.02) were related to reversing frailty progression. Principal component analysis indicated that the main factors constituting the first principal component (contribution rate, 18.3%) included items related to social capital, such as interaction with neighbors, trust in the community, and number of social participation activities. Our results demonstrate that exercise-based social participation and high self-rated health have associations with reversing frailty progression. Individuals that recovered from frailty are characterized by high individual-level social capital components (i.e., trust in community, interaction with neighbors, and social participation).
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0247296PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7928521PMC
March 2021

Cone-beam computed tomography versus computed tomography-guided ultrathin bronchoscopic diagnosis for peripheral pulmonary lesions: A propensity score-matched analysis.

Respirology 2021 Feb 21. Epub 2021 Feb 21.

Department of Thoracic and Endocrine Surgery and Oncology, Institute of Biomedical Sciences, The University of Tokushima Graduate School, Tokushima, Japan.

Background And Objective: CBCT-guided TBB using a UTB under VBN is a useful method for the diagnosis of peripheral small pulmonary lesions. CBCT-guided TBB using UTB under VBN has been used as an alternative to CT-guided TBB. However, the advantage of CBCT-guided TBB using UTB under VBN over CT-guided TBB is still unknown. This study aimed to compare the diagnostic yield of CT-guided TBB and CBCT-guided TBB using a propensity score-matched analysis.

Methods: Patients with peripheral pulmonary lesions ≤30 mm were included. Lesions whose bronchus could not be determined by CT were excluded. A UTB and biopsy forceps were advanced to the target bronchus under VBN, 2D-fluoroscopy and CT or CBCT. The CT-guided and CBCT-guided groups were matched for their propensity scores based on patient characteristics.

Results: We retrospectively reviewed 93 patients in the CT-guided group and 79 patients in the CBCT-guided group for this study. Furthermore, 48 distinct examination pairs were generated by propensity score matching. In the overall diagnostic yield, the CBCT-guided group showed better results (72.9%) than did the CT-guided group (47.9%) (P = 0.012). The median examination time lasted for 43 (IQR: 37-51) min in the CBCT-guided group and 50 (IQR: 43-62) min in the CT-guided group. The examination time in the CBCT-guided group was significantly shorter than that of the CT-guided group (P = 0.001).

Conclusion: CBCT-guided TBB had a better diagnostic yield and shorter examination time than did CT-guided TBB.
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http://dx.doi.org/10.1111/resp.14016DOI Listing
February 2021

Classifying the destination of right top pulmonary vein in 31 clinical cases.

Gen Thorac Cardiovasc Surg 2021 Feb 14. Epub 2021 Feb 14.

Department of Thoracic, Endocrine Surgery and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15, Kuramoto-cho, Tokushima, 770-8503, Japan.

Disruption in the flow of blood vessels is of great concern during thoracic surgery. Preoperative 3-dimensional computed tomography facilitates visualization of the exact location and course of blood vessels. The right posterior upper lobe segmental vein, known as the right top pulmonary vein (RTPV), is an anomalous vein beginning at the right upper lobe and running through the posterior surface of the intermediate bronchus. We clinically investigated 31 patients with RTPV who underwent lobectomy or total resection of the right lung in our hospital or related institutions. We classified the final destination of RTPV into four types. The RTPV flowed into the left atrium in 35.5% of cases, superior pulmonary vein in 9.7%, inferior pulmonary vein in 41.9%, and independently into V6 in 12.9%. An RTPV with a diameter ≥ 5 mm was considered a main drainage vein in S2. We should pay attention to the RTPV during right lung lobectomy.
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http://dx.doi.org/10.1007/s11748-021-01604-6DOI Listing
February 2021

Granulomatosis with polyangiitis presenting as a solitary renal mass: A case report with imaging and literature review.

Radiol Case Rep 2021 Mar 17;16(3):736-741. Epub 2021 Jan 17.

Department of Radiology, Aichi Medical University, 1-1 Yazako Karimata, Yatomi City, Aichi 480-1195, Japan.

Granulomatosis with polyangiitis (GPA) manifests as necrotizing granulomatous inflammatory masses in the nasal cavity, paranasal sinuses, and lungs. However, a mass in the kidney is extremely rare. We herein report a case of GPA that presented as a solitary mass in the left kidney. The patient was a man in his 60s. A 2.5-cm solitary mass was incidentally discovered in the left kidney at another hospital and was followed-up. Eight months later, the mass had enlarged, and the patient visited our hospital for further examination and treatment. The mass was hypovascular, with unclear margins on contrast-enhanced computed tomography (CT). The signal of the mass was nonuniform and iso- to slightly hypo-intense on T2-weighted and diffusion-weighted magnetic resonance imaging (MRI). Enlarged para-aortic lymph nodes were also detected on the CT and MRI. Based on imaging, malignant tumors were suspected, and nephrectomy was performed. The pathological diagnosis was GPA. We performed a literature review of this rare renal manifestation and present a summary of reported imaging findings. If a hypovascular renal mass with an unclear margin can be found in those with GPA, unnecessary operations may be avoided by actively promoting renal biopsy.
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http://dx.doi.org/10.1016/j.radcr.2021.01.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815982PMC
March 2021

Impact of the Antithrombotic Effects of Prasugrel on Mid-Term Vascular Healing in Acute Coronary Syndrome vs. Stable Coronary Artery Disease.

Circ J 2021 Jan 8. Epub 2021 Jan 8.

Kobe University Graduate School of Medicine.

Background: The impact of antiplatelet drug effects on mid-term local arterial responses following percutaneous coronary intervention (PCI) remains uncertain. We evaluated the impact of the platelet reactivity of prasugrel on mid-term vascular healing between acute coronary syndrome (ACS) and stable coronary artery disease (CAD).Methods and Results:We conducted a prospective, 12-center study in 125 patients with ACS and 126 patients with stable CAD who underwent PCI with an everolimus-eluting stent (EES) and received dual antiplatelet therapy (DAPT) with prasugrel and aspirin. Serial optical coherence tomography (OCT) was performed immediately after PCI and at the 9-month follow-up to assess the association of P2Yreaction units (PRU) with the frequency of malapposed or uncovered struts and intrastent thrombi (IST). The incidence of abnormal mid-term OCT findings did not different between the ACS and CAD arms, regardless of clinical presentation, except that uncovered struts were more frequent in the ACS than CAD arm. PRU at PCI was significantly associated with the frequency of IST at follow-up, but not with uncovered and malapposed struts. PRU at PCI was the only independent predictor of IST detected at follow-up (odds ratio 1.009).

Conclusions: In patients undergoing EES implantation and receiving prasugrel, achieving an adequate antiplatelet effect at the time of stent implantation may regulate thrombus formation throughout the follow-up period.
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http://dx.doi.org/10.1253/circj.CJ-20-0872DOI Listing
January 2021

Genetic and histopathological analysis of transverse testicular ectopia without persistent Müllerian duct syndrome: two case reports.

J Med Case Rep 2020 Dec 1;14(1):233. Epub 2020 Dec 1.

Department of Pediatric Urology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan.

Background: Transverse testicular ectopia (TTE) is a rare anomaly in which both testes descend through a single inguinal canal into the same hemiscrotum. Although almost 20-50% of patients with TTE exhibit persistent Müllerian duct syndrome (PMDS) and many genetic analyses have been performed, no reports have described the genes contributing to TTE without PMDS. Here, we report two cases of TTE without PMDS using immunohistochemical staining and genetic analysis.

Case Presentation: Two Asian patients with TTE without PMDS were subjected to orchiopexy. We performed testicular biopsies during operation and obtained blood samples before the operation. Testicular tissues were stained for c-kit, placental alkaline phosphatase (PLAP), and undifferentiated embryonic cell transcription factor 1 (UTF1) to evaluate the presence of intratubular malignant germ cells. Additionally, we performed polymerase chain reaction-based direct sequencing to identify single nucleotide polymorphisms in genes associated with regression of the Müllerian duct and testicular descent (that is, anti-Müllerian hormone [AMH], AMH receptor 2 [AMHR2], insulin-like 3 [INSL3], and relaxin family peptide receptor 2 [RXFP2]). The three-dimensional structures of proteins were predicted using SWISS-MODEL. In immunohistochemical analysis, c-kit and UTF1 were positive, whereas PLAP was negative in three testicular tissue samples from the two patients. These features were also detected on the unaffected side. In variant analysis, common missense variants in the AMH gene (g.365G>T; c.165G>T; p.Ser49Ile [rs10407022]) were observed. All variants in INSL3 and RXFP2 genes were intronic or silent.

Conclusions: Because UTF1, a specific marker of spermatogonial stem cell activity, was expressed in both the affected and unaffected sides in the testicular tissues of two patients, the risk of malignancy may be high in these patients. Although the etiology of TTE without PMDS remains unclear, our variant analysis results were consistent with previous reports, and variants in the AMH gene (rs10407022) may contribute to the specific phenotype of TTE without PMDS.
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http://dx.doi.org/10.1186/s13256-020-02559-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7706043PMC
December 2020

Safe central venous catheters for esophageal cancer treatment.

J Med Invest 2020 ;67(3.4):298-303

Department of Thoracic, Endocrine Surgery and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.

 Introduction : Central venous catheter (CVC) use is essential for treating esophageal cancer. Peripherally inserted central catheters (PICC) are commonly used recently for improved patient comfort and safety. We compared centrally inserted central catheters (CICC) and PICC insertions and examined their safety. Methods : We retrospectively investigated complications at the catheter insertion and post-insertion for 199 patients' esophageal cancer treatment (CICC : 45, PICC : 154) from 2013 to 2018. In addition, we summarized the results of catheter tip culture. Results : No serious complications occurred at the catheter insertion in either group. The rate of complications at catheter insertion was 5.8% for PICC and 6.7% for CICC patients. Post-insertion complications were observed in 6.5% and 11.1% of patients with PICC and CICC, respectively, and this difference was not significant. The incidence of catheter-related blood stream infection (CRBSI) was significantly lower in PICC than CICC patients (0.3 vs. 1.8 / 1,000 catheter-days ; p = 0.029). Catheter-related thrombosis was observed in PICC : 0.5 and CICC : 0.6, and occlusion due to blood flow reversal was observed in PICC : 0.5 and CICC : 0.6. Conclusion : PICCs are safer and more effective than CICCs for the treatment of esophageal cancer, and reduce the incidence of CRBSI. We hope to standardize the insertion procedures, conventionalize techniques, and establish training systems. J. Med. Invest. 67 : 298-303, August, 2020.
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http://dx.doi.org/10.2152/jmi.67.298DOI Listing
January 2020

Heritability and Environmental Correlation of Phase Angle with Anthropometric Measurements: A Twin Study.

Int J Environ Res Public Health 2020 10 26;17(21). Epub 2020 Oct 26.

Center for Twin Research, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.

Bioelectrical impedance analysis (BIA)-derived phase angle (PhA) is a valuable parameter to assess physical health. However, the genetic and environmental aspects of PhA are not yet well understood. The present study aimed to estimate the heritability of PhA and investigate the relationships between PhA and anthropometric measurements. PhA and skeletal muscle mass index (SMI) were examined using multi-frequency BIA in 168 Japanese twin volunteers (54 males and 114 females; mean age = 61.0 ± 16.5 years). We estimated the narrow-sense heritability of these parameters and the genetic and environmental relationships between them using a genetic twin modeling. For the PhA, 51% (95% confidence interval: 0.33, 0.64) of the variance was explained by additive genetic effects, and 49% (95% confidence interval: 0.36, 0.67) was explained by unique environmental effects. The heritability of PhA was lower than the height, body weight, and body mass index. PhA shared almost no genetic variation with anthropometric measurements and SMI but shared an environmental variation (14%) with SMI. These findings suggest that the genes affecting PhA are different than those affecting anthropometric measurements and SMI. The correlation between PhA and SMI is caused by common environmental factors.
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http://dx.doi.org/10.3390/ijerph17217810DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7662672PMC
October 2020

A cell cycle-dependent CRISPR-Cas9 activation system based on an anti-CRISPR protein shows improved genome editing accuracy.

Commun Biol 2020 Oct 23;3(1):601. Epub 2020 Oct 23.

Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10 Kandasurugadai, Chiyoda-ku, Tokyo, 101-0062, Japan.

The development of genome editing systems based on the Cas9 endonuclease has greatly facilitated gene knockouts and targeted genetic alterations. Precise editing of target genes without off-target effects is crucial to prevent adverse effects in clinical applications. Although several methods have been reported to result in less off-target effects associated with the CRISPR technology, these often exhibit lower editing efficiency. Therefore, efficient, accurate, and innocuous CRISPR technology is still required. Anti-CRISPR proteins are natural inhibitors of CRISPR-Cas systems derived from bacteriophages. Here, the anti-CRISPR protein, AcrIIA4, was fused with the N terminal region of human Cdt1 that is degraded specifically in S and G, the phases of the cell cycle when homology-directed repair (HDR) is dominant. Co-expression of SpyCas9 and AcrIIA4-Cdt1 not only increases the frequency of HDR but also suppress off-targets effects. Thus, the combination of SpyCas9 and AcrIIA4-Cdt1 is a cell cycle-dependent Cas9 activation system for accurate and efficient genome editing.
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http://dx.doi.org/10.1038/s42003-020-01340-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7584632PMC
October 2020

Bronchioalveolar stem cells derived from mouse-induced pluripotent stem cells promote airway epithelium regeneration.

Stem Cell Res Ther 2020 10 2;11(1):430. Epub 2020 Oct 2.

Department of Thoracic and Endocrine Surgery and Oncology, Institute of Biomedical Sciences, The University of Tokushima Graduate School, 3-18-15, Kuramoto-cho, Tokushima, 770-8503, Japan.

Background: Bronchioalveolar stem cells (BASCs) located at the bronchioalveolar-duct junction (BADJ) are stem cells residing in alveoli and terminal bronchioles that can self-renew and differentiate into alveolar type (AT)-1 cells, AT-2 cells, club cells, and ciliated cells. Following terminal-bronchiole injury, BASCs increase in number and promote repair. However, whether BASCs can be differentiated from mouse-induced pluripotent stem cells (iPSCs) remains unreported, and the therapeutic potential of such cells is unclear. We therefore sought to differentiate BASCs from iPSCs and examine their potential for use in the treatment of epithelial injury in terminal bronchioles.

Methods: BASCs were induced using a modified protocol for differentiating mouse iPSCs into AT-2 cells. Differentiated iPSCs were intratracheally transplanted into naphthalene-treated mice. The engraftment of BASCs into the BADJ and their subsequent ability to promote repair of injury to the airway epithelium were evaluated.

Results: Flow cytometric analysis revealed that BASCs represented ~ 7% of the cells obtained. Additionally, ultrastructural analysis of these iPSC-derived BASCs via transmission electron microscopy showed that the cells containing secretory granules harboured microvilli, as well as small and immature lamellar body-like structures. When the differentiated iPSCs were intratracheally transplanted in naphthalene-induced airway epithelium injury, transplanted BASCs were found to be engrafted in the BADJ epithelium and alveolar spaces for 14 days after transplantation and to maintain the BASC phenotype. Notably, repair of the terminal-bronchiole epithelium was markedly promoted after transplantation of the differentiated iPSCs.

Conclusions: Mouse iPSCs could be differentiated in vitro into cells that display a similar phenotype to BASCs. Given that the differentiated iPSCs promoted epithelial repair in the mouse model of naphthalene-induced airway epithelium injury, this method may serve as a basis for the development of treatments for terminal-bronchiole/alveolar-region disorders.
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http://dx.doi.org/10.1186/s13287-020-01946-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7531137PMC
October 2020

Eating Alone at Each Meal and Associated Health Status among Community-Dwelling Japanese Elderly Living with Others: A Cross-Sectional Analysis of the KAGUYA Study.

Nutrients 2020 Sep 13;12(9). Epub 2020 Sep 13.

Department of Physical Therapy, Faculty of Health Science, Kio University, 4-2-2 Umaminaka, Koryo-cho, Kitakatsuragi-gun, Nara 635-0832, Japan.

This cross-sectional study investigated the association between eating alone at each meal and health status, including functional capacity among community-dwelling Japanese elderly living with others. A self-administered questionnaire was mailed to all 8004 residents aged 65 or older, residing in the same Japanese town in March 2016. Eating alone was assessed by first asking whether participants ate three separate meals each day (i.e., breakfast, lunch, and dinner), and those who answered affirmatively were then asked how many people were usually present at each meal. Health status was assessed in terms of subjective health, medical history, care needs, body mass index, depression, and functional capacity. Data from 2809 respondents were analyzed. Those who reported not being in good subjective health and a history of hypertension were significantly more likely to eat alone at breakfast (odds ratio 1.27; 95% confidence interval 1.01-1.61, and 1.26; 1.06-1.49). Depressive symptoms and many subscales of functional capacity were also significantly associated with eating alone at breakfast, lunch, and dinner ( < 0.05). Many health status indicators were related to eating alone at each meal, especially breakfast.
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http://dx.doi.org/10.3390/nu12092805DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7551543PMC
September 2020

Effect of Care Capacity on Stroke Patients' Recovery in Activities of Daily Living: A Multi-Hospital Study.

J Stroke Cerebrovasc Dis 2020 Oct 31;29(10):105187. Epub 2020 Jul 31.

Department of Rehabilitation, Chubu Rosai Hospital, 1-10-6 Koumei, Minato-ku, Nagoya-city 455-8530, Aichi-ken, Japan. Electronic address:

Background: This study aimed to investigate whether care capacity for patients following stroke contributes to improved activities of daily living (ADL) at discharge from hospital based on the degree of stroke severity.

Design: Retrospective, observational, longitudinal study.

Setting: Acute phase hospitals.

Participants: From 2005 to 2011, 5006 patients with stroke at acute phase hospitals were registered in a database. There were 2501 individuals from 11 hospitals who met the following four criteria: (1) a pre-stroke modified Rankin Scale (mRS) score of 0-3; (2) admission to hospital within 7 days of suffering a stroke; (3) ischemic or hemorrhagic stroke; and (4) staying in hospital for 8-60 days.

Main Outcome Measures: The main outcome measure was the Functional Independence Measure (FIM, version 3.0) score at discharge. The FIM is an internationally used scale, which is used as an ADL outcome assessment scale for after rehabilitation.

Results: Among patients with stroke, those with care capacity had higher FIM scores at hospital discharge than did those without care capacity (unstandardized coefficient = 2.3, P = 0.015). Examination of this relationship by stroke severity showed that the FIM score at discharge was only significantly higher in patients who suffered from a moderate to severe stroke (unstandardized coefficient = 7.0, P = 0.040). No associations were observed in patients who suffered from minor, moderate, or severe stroke.

Conclusions: These results suggest that care capacity facilitates total recovery of the FIM, especially among patients who suffer from a moderate to severe stroke.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.105187DOI Listing
October 2020

Diagnosis of recurrence and follow-up using FDG-PET/CT for postoperative non-small-cell lung cancer patients.

Gen Thorac Cardiovasc Surg 2021 Feb 9;69(2):311-317. Epub 2020 Sep 9.

Department of Thoracic and Endocrine Surgery and Oncology, Institute of Health Biosciences, University of Tokushima Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan.

Background: There is currently no consensus regarding the best program for postoperative follow-up and surveillance after a curative resection for non-small-cell lung cancer (NSCLC) patients. We examined the diagnostic capability of F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) for detecting recurrence in postoperative NSCLC patients, and we evaluated the results of postoperative surveillance using FDG-PET/CT in asymptomatic patients.

Patients And Methods: Between 2005 and 2013, 496 FDG-PET/CT examinations were performed to detect recurrences for 187 NSCLC patients who had undergone potentially curative operations at our institution. Follow-up FDG-PET/CT was performed ≥ 1 × /year in principle in 172 asymptomatic patients without clinical or radiological evidence of recurrence, and the results were retrospectively reviewed.

Results: FDG-PET/CT correctly diagnosed recurrence in 46 of 47 (97.9%) patients and 68 of 69 (98.6%) recurrent sites. The following were obtained: 97.9% sensitivity, 97.1% specificity, 92.0% positive predictive value, 99.3% negative predictive value, and 97.3% accuracy. In six patients, other diseases were detected and treated appropriately. In asymptomatic patients, the detection rate of recurrence in the stage III group was significantly higher than the detection rates in the stage I and II groups, and FDG-PET/CT performed ≤ 3 years post-resection detected significantly more FDG-positive lesions compared to that performed after 4 years.

Conclusion: FDG-PET/CT is very useful for detecting recurrence in NSCLC patients after a potentially curative operation. It might be sufficient to perform follow-up FDG-PET/CT until 3 years post-resection for advanced-stage patients. Further randomized clinical trials are needed to determine whether the early detection of recurrences leads to better prognoses.
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http://dx.doi.org/10.1007/s11748-020-01477-1DOI Listing
February 2021

Worsening renal function during hospitalization in elderly patients with heart failure: an independent factor of activities of daily living decline.

Heart Vessels 2021 Jan 27;36(1):76-84. Epub 2020 Jul 27.

Department of Cardiovascular Medicine, Yodogawa Christian Hospital, Osaka, Japan.

This study aimed to clarify the effects of worsening renal function (WRF) during hospitalization on activities of daily living (ADL) at discharge of elderly heart failure (HF) patients. We included 323 consecutive patients hospitalized for HF who were prescribed phase I cardiac rehabilitation (CR) from November 2017 to April 2019. WRF was defined as a relative increase from baseline in serum creatinine of 25% or that in serum creatinine ≥ 0.3 mg/dL during hospitalization. The indices of ADL and physical function were the functional independence measure (FIM), short physical performance battery (SPPB) and 10-m comfortable gait speed as assessed at discharge. We compared background factors, clinical parameters, walking level before hospitalization, physical function, and FIM in two groups. Multiple regression analysis was performed with FIM at discharge as the dependent variable and items with P < 0.05 in bivariate correlation as independent variables. Ultimately, 160 patients were included and divided into the WRF group (n = 72) and non-WRF group (n = 88). FIM, SPPB, and 10-m comfortable walking speed were significantly lower in the WRF group. Moreover, even after adjustment for confounding factors (age, Hb, eGFR, CKD, GNRI, start day of standing), eGFR on admission (β = 0.12), WRF (β =  - 6.42) and walking level before hospitalization (β = - 10.00) were independent factors of ADL decline at discharge (adjusted R = 0.46). WRF during hospitalization of elderly HF patients was a factor affecting ADL decline at discharge along with walking level before hospitalization and renal function at admission.
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http://dx.doi.org/10.1007/s00380-020-01672-3DOI Listing
January 2021

Use of a prognostic risk score that aggregates the FDG-PET/CT SUVmax, tumor size, and histologic group for predicting the prognosis of pStage I lung adenocarcinoma.

Int J Clin Oncol 2020 Jun 4;25(6):1079-1089. Epub 2020 Mar 4.

Department of Thoracic and Endocrine Surgery and Oncology, Institute of Biomedical Sciences, The University of Tokushima Graduate School, 3-18-15, Kuramoto-cho, Tokushima, 770-8503, Japan.

Background: pStage I includes clinicopathologically diverse groups. This study aimed to identify the prognostic factors for pStage I lung adenocarcinoma.

Methods: We retrospectively reviewed 208 patients with pStage I adenocarcinomas who underwent curative resection in our institute between 2006 and 2013. The maximum standardized uptake value (SUVmax) on [F18]-fluoro-deoxy-D-glucose positron emission tomography-computed tomography (PET/CT) was evaluated. Adenocarcinomas were categorized into the following histologic groups: group 0 (minimally invasive adenocarcinoma and lepidic predominant adenocarcinoma), group 1 (papillary predominant adenocarcinoma), and group 2 (acinar predominant adenocarcinoma and all the remaining subtypes). We assessed the relationship between disease-free survival (DFS) and clinicopathological factors.

Results: Multivariate analysis of DFS demonstrated that SUVmax > 3.0 (p < 0.001), total tumor size > 20 mm (p = 0.016), and histologic groups (p < 0.05) were independent prognostic factors. The prognostic risk score (PRS) was calculated using the following equation: PRS = SUVmax (≤ 3.0: 0 point, > 3.0: 2 points) + total tumor size (≤ 20 mm: 0 point, > 20 mm: 1 point) + histologic group (group 0: 0 point, group 1: 1 point, group 2: 2 points). Patients were divided into the following three risk groups: low-risk (PRS 0-2 points, n = 136), intermediate-risk (PRS 3-4 points, n = 49), and high-risk groups (PRS 5 points, n = 13). The 5-year DFS rates were 93.2%, 50.6%, and 30.8% for the low-, intermediate-, and high-risk groups, respectively (p < 0.001).

Conclusions: The PRS aggregating the FDG-PET/CT SUVmax, total tumor size, and histologic group predicts the prognosis of pStage I lung adenocarcinoma.
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http://dx.doi.org/10.1007/s10147-020-01637-6DOI Listing
June 2020

Early and Mid-Term Vascular Responses to Optical Coherence Tomography-Guided Everolimus-Eluting Stent Implantation in Stable Coronary Artery Disease.

Can J Cardiol 2019 11 8;35(11):1513-1522. Epub 2019 Aug 8.

Iwate Medical University, Morioka, Japan.

Background: Analysis of pooled clinical data has shown the safety of 3 months of dual antiplatelet therapy with everolimus-eluting cobalt-chromium stents (Co-Cr EESs). This study evaluated early and mid-term vascular responses to Co-Cr EESs in patients with stable coronary artery disease.

Methods: The Multicenter Comparison of Early and Late Vascular Responses to Everolimus-Eluting Cobalt-Chromium Stent and Platelet Aggregation Studies in Patients With Stable Angina Managed as Elective Case (MECHANISM-Elective) study (NCT02014818) is a multicenter optical coherence tomography (OCT) registry. Enrolled patients were evaluated by OCT immediately after everolimus-eluting stent implantation were prospectively allocated to 1 month (n = 50) or 3 months (n = 50) OCT follow-up and then received a 12-month OCT evaluation. The incidences of intrastent thrombus (IS-Th) and irregular protrusion (IRP) were also assessed.

Results: The percentage of uncovered struts was 6.4% ± 10.3% at 1 month (P < 0.001 vs. postprocedure) and 0.5% ± 0.9% at 12 months (P < 0.001 vs. 1 month). The corresponding values in the 3-month cohort were 2.0% ± 2.5% (P < 0.001 vs. postprocedure) and 0.5% ± 1.5% (P < 0.001 vs. 3 months). The incidence of IS-Th was 32.7% at 1 month, 5.4% at 3 months, and 2.0% at 12 months. IRP was observed in 21.8% of patients post-EES but had totally resolved at 1, 3, and 12 months.

Conclusion: Early and mid-term vascular reactions after Co-Cr EES implantation in stable patients with coronary artery disease in the MECHANISM-Elective included dynamic resolution of IS-Th and IRP and rapid decrease in uncovered struts. Thus, EES may allow shortening of dual antiplatelet therapy duration less than 3 months in this patient subset.
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http://dx.doi.org/10.1016/j.cjca.2019.07.633DOI Listing
November 2019

TALEN-Based Chemically Inducible, Dimerization-Dependent, Sequence-Specific Nucleases.

Biochemistry 2020 01 21;59(2):197-204. Epub 2019 Oct 21.

Institute of Biomaterials and Bioengineering , Tokyo Medical and Dental University , 2-3-10 Kandasurugadai , Chiyoda-ku, Tokyo 101-0062 , Japan.

For precise genome editing, it is important to control the activity of sequence-specific nucleases. We have constructed a chemically inducible nuclease system based on the dimerization of FKBP and FRB domains in the presence of rapamycin and designated it as a chemically inducible dimerization (CID). The CID was designed to occur at the interlinker section between DNA binding domains and the FokI catalytic domain. Thus, induction of cleavage should occur quickly after addition of rapamycin because components of proteins are already in active form and located in the nucleus. This CID-dependent sequence-specific nuclease has potential to be applied for time-resolved analysis of the mutation induction mechanism in the genome.
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http://dx.doi.org/10.1021/acs.biochem.9b00798DOI Listing
January 2020

Thoracoscopic Oesophagectomy Using Prone Positioning for Oesophageal Cancer With Right Aortic Arch: A Case Report.

Anticancer Res 2019 Jun;39(6):3207-3211

Department of Gastroenterological Surgery, Tokushima Red Cross Hospital, Tokushima, Japan.

Background/aim: Right aortic arch (RAA) is a rare abnormality of the aortic arch that forms a vascular ring. Oesophageal cancer (EC) accompanied with RAA is even rarer, and in such cases, it is very important to understand the anatomical structure in the upper mediastinum in order to perform a safe and curative operation.

Patients And Methods: A 67-year-old man who presented with pharyngeal discomfort was admitted to our hospital. Further examinations revealed advanced thoracic EC accompanied with RAA and aortic diverticulum.

Results: After neoadjuvant chemotherapy, we successfully and safely performed thoracoscopic oesophagectomy and lymphadenectomy using the prone positioning.

Conclusion: There exist only a few reports of thoracoscopic oesophagectomy for EC with RAA. Sufficient preoperative preparation and sharing an adequate strategy for the surgical approach with the surgical team are definitely necessary. Although the thoracoscopic approach for EC with RAA is useful, more considerations are needed for some issues.
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http://dx.doi.org/10.21873/anticanres.13460DOI Listing
June 2019

Transbronchial Biopsy Using an Ultrathin Bronchoscope Guided by Cone-Beam Computed Tomography and Virtual Bronchoscopic Navigation in the Diagnosis of Pulmonary Nodules.

Respiration 2019;98(4):321-328. Epub 2019 May 23.

Department of Thoracic, Endocrine Surgery and Oncology, Institute of Health Bioscience, The University of Tokushima Graduate School, Tokushima, Japan.

Background: Transbronchial biopsy is a safe diagnostic approach for patients with peripheral pulmonary lesions; however, the diagnostic yield is low.

Objectives: This study was conducted to evaluate the feasibility and diagnostic yield of transbronchial biopsy using the combination of an ultrathin bronchoscope, virtual bronchoscopic navigation (VBN), and cone-beam computed tomography (CBCT).

Methods: Patients with peripheral pulmonary lesions, no >30 mm, with the responsible bronchus, were prospectively included. An ultrathin bronchoscope and biopsy forceps were advanced to the target bronchus under VBN, 2D-fluoroscopy, and CBCT. We categorized the CBCT findings before biopsy into 3 types according to positions of the target lesion and forceps (CBCT target-forceps sign). In type A, the forceps reached the inside of the target lesion. In type C, the forceps could not reach the lesion. When the CBCT findings could not be categorized into either type A or C, the sign was categorized as type B.

Results: Although the target lesions were invisible by conventional C-arm fluoroscopy in 29 patients, CBCT visualized all 40 lesions. The overall diagnostic yield was 90.0%, and diagnostic yields for malignant and benign lesions were 92.0 and 86.7%, respectively. Diagnostic yields for CBCT target-forceps sign types A, B, and C were 100, 75.0, and 0%, respectively. Four undiagnosed patients proceeded to other diagnostic procedures based on the CBCT target-forceps sign (type B: n = 2, type C: n = 2) and were correctly diagnosed without delay.

Conclusions: Transbronchial biopsy using an ultrathin bronchoscope guided by CBCT and VBN showed a very high yield in the diagnosis of pulmonary nodules.
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http://dx.doi.org/10.1159/000500228DOI Listing
September 2020

Factors delaying the progress of early rehabilitation of elderly Japanese patients with heart failure.

Aging Clin Exp Res 2020 Mar 10;32(3):399-406. Epub 2019 May 10.

Department of Cardiovascular Medicine, Yodogawa Christian Hospital, Osaka, Japan.

Background: Although intervention with early cardiac rehabilitation (CR) is recommended for elderly patients treated for acute heart failure (HF), there are patients in whom the progress of early CR will be delayed. The aim of this study was to clarify factors related to the progress of early CR.

Methods: We enrolled 180 Japanese inpatients aged ≥ 65 years with HF in the present retrospective cohort study. We set a short-term goal of 30 m of walking at 1 week after the start of early CR. We divided the patients into two groups according to whether this goal was achieved (Achievement group, n = 124) or not (Non-achievement group, n = 56) and compared patients' characteristics and clinical parameters.

Results: There was a significant difference (p < 0.05) between the groups for age, length of hospital stay, Functional Independence Measure at discharge, walking level before hospitalization, rate of co-existence of diabetes mellitus, chronic renal failure, orthopedic disease, use of diuretics, creatinine, Prognostic Nutritional Index, hemoglobin, C-reactive protein, and estimated glomerular filtration rate (eGFR). Furthermore, logistic regression analysis showed that walking level before hospitalization (odds ratio [OR]: 3.144, p = 0.0001) and eGFR (OR: 0.971, p = 0.009) were factors related to the inability to achieve the short-term goal.

Conclusion: Our findings suggest that walking level before hospitalization and renal function on admission are factors related to delayed progress in early CR of elderly Japanese patients with HF.
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http://dx.doi.org/10.1007/s40520-019-01213-7DOI Listing
March 2020

Acase of advanced colon cancer arising from a colonic graft foran esophago-bronchial fistula : A case report.

J Med Invest 2019 ;66(1.2):190-193

Department of General Surgery, JA Kochi Kouseiren, Kochi Japan.

Neoplasm of a colonic graft after esophageal reconstruction is rare. We treated a colon cancer patient who developed malignancy in a colonic graft after esophagectomy and reconstruction through a retrosternal route. A male had undergone esophagectomy in his 50s due to a benign esophago-bronchial fistula. His dysphagia became exacerbated 20 years later, and further examinations showed a circumferential tumor on the esophagocolonic anastomosis. He underwent resection of the colonic graft adenocarcinoma with median sternotomy after neoadjuvant chemotherapy. Gastric tube reconstruction was performed through a retrosternal route. This report should be informative in terms of making decisions from an initial reconstruction to follow-up and choosing a therapeutic strategy for colonic graft cancer in the future. J. Med. Invest. 66 : 190-193, February, 2019.
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http://dx.doi.org/10.2152/jmi.66.190DOI Listing
December 2019

Indocyanine green fluorescence imaging for resection of pulmonary metastasis of hepatocellular carcinoma.

J Thorac Dis 2019 Mar;11(3):944-949

Department of Thoracic and Endocrine Surgery and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.

Background: Indocyanine green (ICG) accumulates in hepatocellular carcinoma (HCC), and tumor fluorescence can be observed under irradiation with near infrared light (NIR). This study investigated the clinical utility of ICG fluorescence imaging during resection of pulmonary metastases of HCC.

Methods: From April 2010 to June 2018, six patients with suspected pulmonary metastasis of HCC were enrolled prospectively. Prior to surgery, all patients underwent the ICG hepatic function test following intravenous administration of ICG (0.5 mg/kg body weight). During surgery, metastatic HCC was identified by observation of ICG fluorescence, allowing assessment of the surgical margin. Tumor fluorescence was also evaluated on cut sections.

Results: A total of 11 metastatic HCCs were resected in six patients at nine operations. Eight lesions were removed by wedge resection and 3 lesions were managed by lobectomy. During surgery, tumor fluorescence could be confirmed through the visceral pleura in 6 out of 7 lesions treated by wedge resection, while NIR irradiation was difficult for 1 lesion. For these 6 lesions, the median distance from the tumor to the visceral pleura and the median surgical margin were 0 mm (range, 0-2 mm) and 14 mm (range, 11-17 mm), respectively. When cut sections were examined, all tumors emitted fluorescence. All lesions were histologically confirmed to be metastatic HCC.

Conclusions: In patients with pulmonary metastasis of HCC, ICG fluorescence imaging is useful for identifying the tumor and securing its margin when the lesion is peripheral and wedge resection is planned.
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http://dx.doi.org/10.21037/jtd.2019.01.107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6462673PMC
March 2019

The difference between self-perceived and chronological age in the elderly may correlate with general health, personality and the practice of good health behavior: A cross-sectional study.

Arch Gerontol Geriatr 2019 Jul - Aug;83:13-19. Epub 2019 Mar 11.

Department of Nurse, Faculty of Health Science, Kio University, 4-2-2 Koryo, Kitakatsuragi-gun, Nara, Japan; Health Promotion Center, Kio University, 4-2-2 Koryo, Kitakatsuragi-gun, Nara, Japan.

Background And Objective: For the elderly, maintaining a young self-perceived age has a positive impact on physical and mental health. The purpose of this study was to investigate the impact of the discrepancy between self-perceived age and chronological age in regards to physical activity, instrumental activities of daily living, functional capacity, personality, general self-efficacy, depressive symptoms, and disease burden.

Methods: Participants were 3094 older adults from 2015 baseline data of the Keeping Active across Generations Uniting the Youth and the Aged study. The questionnaire was mailed to 8004 elderly people aged 65 years or older. Of the 3871 people who returned the questionnaire (collection rate, 48.3%), 3094 subjects were analyzed in this study (female, 52%). The questionnaire included aspects of physical activity, instrumental activity of daily living, functional capacity, personality traits, general self-efficacy, depressive symptoms, history of falls, fear of falling, communication with young people, medical history, and self-perceived age, as well as basic characteristics such as age, sex, living alone or not, and educational history.

Results: Regression analysis showed that the presence of high self-rated health, personality traits of extraversion and openness to experience, higher general self-efficacy, and the presence of fear of falling were positively associated with a younger self-perceived age.

Conclusions: The results identified personality and psychological factors related to of self-perceived age in community-dwelling elderly people. Therefore, changes in personality traits and subjective health accompanying aging affect the self-perceived age, which may also affect the extension of healthy life expectancy.
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http://dx.doi.org/10.1016/j.archger.2019.03.009DOI Listing
March 2020

Impact of dual antiplatelet therapy with adjusted-dose prasugrel on mid-term vascular response in patients undergoing elective percutaneous coronary intervention with everolimus-eluting stents.

Heart Vessels 2019 Jun 1;34(6):936-947. Epub 2019 Jan 1.

Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, 6500017, Japan.

The impact of dual antiplatelet therapy (DAPT) with adjusted-dose (3.75 mg/day) prasugrel for Japanese patients has not been fully investigated in terms of local arterial healing following the elective percutaneous coronary intervention (PCI). The ROUTE-01 elective study was a prospective, 12-center and single-arm registry that enrolled 123 patients who underwent elective PCI with everolimus-eluting stents (EESs) under DAPT with a combination of adjusted-dose prasugrel and aspirin. Serial optical coherence tomography (OCT) was performed at the index PCI and 9-month follow-up to assess the relationship between in-stent thorombus (IST) and residual platelet reactivity measuring platelet reactivity unit (PRU). The patients were classified as extensive, intermediate, and poor metabolizers by cytochrome P450 2C19 (CYP2C19) loss-of-function polymorphisms. The prevalence of IST was 9.0% by 9-month OCT, with no difference amongst the three groups (p = 0.886). The incidences of malapposed and uncovered struts were not different among the groups. PRU was not statistically different among the groups. In multivariate logistic regression analysis, the independent predictor for IST on 9-month OCT was irregular protrusion (odds ratio = 8.952, p = 0.037) on post-PCI OCT, not CYP2C19 loss-of-function polymorphisms. An adequate anti-thrombotic effect with an acceptable incidence of IST was observed irrespective of CYP2C19 loss-of-function polymorphisms. Our data suggests that adjusted-dose prasugrel and aspirin is a feasible treatment option in Japanese patients treated with EESs in elective PCI.
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http://dx.doi.org/10.1007/s00380-018-1322-2DOI Listing
June 2019

Efficient and Orthogonal Transcription Regulation by Chemically Inducible Artificial Transcription Factors.

Biochemistry 2018 11 2;57(45):6452-6459. Epub 2018 Nov 2.

Institute of Biomaterials and Bioengineering , Tokyo Medical and Dental University , 2-3-10 Kandasurugadai , Chiyoda-ku, Tokyo 101-0062 , Japan.

The DNA-binding specificity of genome editing tools can be applied to gene regulation. Recently, multiple artificial transcription factors (ATFs) were shown to synergistically and efficiently regulate gene expression. Chemically triggered protein associations are useful for functional regulation at specific timings. A combination of several inducible protein association systems could enable the regulation of multiple genes at different loci with independent timing. We applied the FKBP-rapamycin-FRB and GAI-gibberellin-GID systems for gene regulation using multiple TALEs and dCas9. By the combined use of currently available systems, reporter gene assays were performed; the results indicated that gene expression was regulated by rapamycin or gibberellin in the presence of the FRB or GAI effector domains, respectively. Furthermore, the activation of endogenous genes was differentially regulated by the system. This success suggests the usability of the chemically inducible multiple ATFs for the time-dependent regulation of multiple genes, such as the case for cellular phenomena that are dependent on the programmable timing of expression and the differential expression of multiple genes.
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http://dx.doi.org/10.1021/acs.biochem.8b00741DOI Listing
November 2018

Benefits of a novel concept of home-based exercise with the aim of preventing aspiration pneumonia and falls in frail older women: a pragmatic controlled trial.

BMJ Open Sport Exerc Med 2016 10;2(1):e000127. Epub 2016 Jun 10.

Nara Medical University Department of Public Heath , Health Management and Policy , Kashihara , Japan.

Aim: To investigate whether home-based exercise with the aim of preventing aspiration pneumonia and accidental falls improves swallowing-related and physical functions in community-dwelling frail older women.

Methods: Participants were 266 community-dwelling frail older women in a long-term care prevention class (mean (SD): age 75 (5) years). Participants were allocated to either an intervention group or a control group. In the intervention group, participants were asked to perform, at least three times a week for 6 months, a home-based exercise programme that was specifically developed to prevent aspiration pneumonia and accidental falls. Control group participants were instructed to perform general stretching exercises only. Voluntary peak cough flow and lip closure force were measured as swallowing-related functions. Static and dynamic balance function, lower limb strength and flexibility were measured as secondary outcomes. Intervention effects were determined using t tests; effect sizes were calculated using Cohen's d.

Results: Voluntary peak cough flow in the intervention group was significantly greater than in the control group (p<0.01, d=0.5). However, lip closure force did not differ between groups. Regarding physical function, results of the Timed Up and Go Test (p<0.05, d=0.4), Chair Stand Test (p<0.01, d=0.4), maximal knee extension strength (p<0.05, d=0.4), and Sit and Reach Test (p<0.05, d=0.3) showed greater improvement in the intervention group.

Conclusions: Specifically developed home-based exercise as described in this study is simple and can be performed briefly. Improvements in voluntary peak cough flow and physical function indicate the possible usefulness of such exercise in preventing falls and aspiration pneumonia in community-dwelling frail older adults.

Trial Registration Number: UMIN Clinical Trials Registry (UMIN-CTR): UMIN000014880.
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http://dx.doi.org/10.1136/bmjsem-2016-000127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5117083PMC
June 2016

DNA aptamers against FokI nuclease domain for genome editing applications.

Biosens Bioelectron 2017 Jul 22;93:26-31. Epub 2016 Nov 22.

Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, 2-24-16 Naka-cho, Koganei, Tokyo 184-8588, Japan. Electronic address:

Genome editing with site-specific nucleases (SSNs) can modify only the target gene and may be effective for gene therapy. The main limitation of genome editing for clinical use is off-target effects; excess SSNs in the cells and their longevity can contribute to off-target effects. Therefore, a controlled delivery system for SSNs is necessary. FokI nuclease domain (FokI) is a common DNA cleavage domain in zinc finger nuclease (ZFN) and transcription activator-like effector nuclease. Previously, we reported a zinc finger protein delivery system that combined aptamer-fused, double-strand oligonucleotides and nanoneedles. Here, we report the development of DNA aptamers that bind to the target molecules, with high affinity and specificity to the FokI. DNA aptamers were selected in six rounds of systematic evolution of ligands by exponential enrichment. Aptamers F6#8 and #71, which showed high binding affinity to FokI (K=82nM, 74nM each), showed resistance to nuclease activity itself and did not inhibit nuclease activity. We immobilized the ZFN-fused GFP to nanoneedles through these aptamers and inserted the nanoneedles into HEK293 cells. We observed the release of ZFN-fused GFP from the nanoneedles in the presence of cells. Therefore, these aptamers are useful for genome editing applications such as controlled delivery of SSNs.
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http://dx.doi.org/10.1016/j.bios.2016.11.042DOI Listing
July 2017

Case of sarcomatoid carcinoma occurring in a patient with Werner syndrome.

J Dermatol 2016 Nov 14;43(11):1362-1364. Epub 2016 Apr 14.

Department of Dermatology, Federation of National Public Service Personnel Mutual Aid Associations, Hamanomachi Hospital, Fukuoka, Japan.

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http://dx.doi.org/10.1111/1346-8138.13399DOI Listing
November 2016

Direct observation of electrically induced Pauli paramagnetism in single-layer graphene using ESR spectroscopy.

Sci Rep 2016 10 12;6:34966. Epub 2016 Oct 12.

Division of Materials Science, University of Tsukuba, Tsukuba, Ibaraki 305-8573, Japan.

Graphene has been actively investigated as an electronic material owing to many excellent physical properties, such as high charge mobility and quantum Hall effect, due to the characteristics of a linear band structure and an ideal two-dimensional electron system. However, the correlations between the transport characteristics and the spin states of charge carriers or atomic vacancies in graphene have not yet been fully elucidated. Here, we show the spin states of single-layer graphene to clarify the correlations using electron spin resonance (ESR) spectroscopy as a function of accumulated charge density using transistor structures. Two different electrically induced ESR signals were observed. One is originated from a Fermi-degenerate two-dimensional electron system, demonstrating the first observation of electrically induced Pauli paramagnetism from a microscopic viewpoint, showing a clear contrast to no ESR observation of Pauli paramagnetism in carbon nanotubes (CNTs) due to a one-dimensional electron system. The other is originated from the electrically induced ambipolar spin vanishments due to atomic vacancies in graphene, showing a universal phenomenon for carbon materials including CNTs. The degenerate electron system with the ambipolar spin vanishments would contribute to high charge mobility due to the decrease in spin scatterings in graphene.
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http://dx.doi.org/10.1038/srep34966DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5059738PMC
October 2016