Publications by authors named "Hiroyuki Shimada"

568 Publications

Screening prefrailty in Japanese community-dwelling older adults with daily gait speed and number of steps via tri-axial accelerometers.

Sci Rep 2021 Sep 21;11(1):18673. Epub 2021 Sep 21.

Department of Preventive Gerontology, Center for Gerontology and Social Science, National Center for Geriatrics and Gerontology, 7-430 Morioka, Obu, Aichi, 474-8511, Japan.

Prefrailty is an intermediate stage between non-frailty and frailty. It is associated with an increased risk of progression to frailty, which makes it important to screen older adults for prefrailty at an early stage. This study verified whether daily gait speed and number of steps measured using a tri-axial accelerometer could be used to identify prefrailty. In total, 1692 Japanese community-dwelling older adults were divided into robust (n = 1032) and prefrail (n = 660) groups based on the Kihon Checklist, which is a self-administered questionnaire. Both daily gait speed and number of steps were measured for two weeks using tri-axial accelerometers. We also calculated the area under the ROC curve and the cut-off values for these parameters. Our results showed that the cut-off value for daily gait speed was 106.3 cm/s, while that for number of steps was 6342.2. In addition, we found that the combined assessment of both cut-off values was a more effective way to screen older adults with prefrailty status compared to either parameter alone. This is also considered an effective way to reduce national expenditures for daily care assistance.
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http://dx.doi.org/10.1038/s41598-021-98286-0DOI Listing
September 2021

Driving cessation and physical frailty in community-dwelling older adults: A longitudinal study.

Geriatr Gerontol Int 2021 Sep 16. Epub 2021 Sep 16.

Department of Preventive Gerontology, Center for Gerontology and Social Science, National Center for Geriatrics and Gerontology, Obu, Japan.

Aim: Physical frailty is a critical health problem that can increase the risk of adverse health outcomes in older adults. Driving cessation has been associated with negative outcomes such as disability. However, the relationship between physical frailty and driving cessation remains unclear. Thus, this study aimed to examine whether driving cessation is associated with physical frailty transition in community-dwelling older adults.

Methods: This prospective cohort study was performed in a community setting in Japan. Participants were 2934 older Japanese adults, classified into two groups according to their driving status: a driving group (drivers at baseline who continued driving at a 4-year follow-up) and a driving cessation group (drivers at baseline who ceased driving by 4-year follow-up). We examined the association between physical frailty transition and driving cessation over a 4-year period, using logistic regression analysis before and after imputation.

Results: In total, 3.9% of community-dwelling older adults had ceased driving by the 4-year follow-up. Rates for physical frailty transition in the driving and driving cessation groups were 4.6% and 17.1%, respectively (P < 0.001). In fully adjusted logistic regression analysis, when compared with driving, driving cessation independently affected physical frailty transition. The results were similar after multiple imputations.

Conclusions: Our findings indicated driving cessation was an independent risk factor associated with physical frailty transition in older adults. As physical frailty in older adults can contribute to negative health outcomes, including increased disability and mortality, preventing frailty has important public health implications. Geriatr Gerontol Int 2021; ••: ••-••.
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http://dx.doi.org/10.1111/ggi.14272DOI Listing
September 2021

An Overview of Social Participation in Older Adults: Concepts and Assessments.

Phys Ther Res 2021 13;24(2):85-97. Epub 2021 Jul 13.

Department of Physical Therapy, School of Health Sciences, Kyorin University, Japan.

In older adults, social participation is an important component of rehabilitation and health promotion. Several studies have attempted to describe the definition and concepts of social participation, and there were many outcomes to measure social participation. This overview provides information about representative social participation and related concepts that have been defined in the literature. A standardized definition of social participation has not been developed; commonly, recognition for social participation was proposed as focused on involvement in social activities that provide interaction with others in a society or community. Many instruments assess the various aspects of social participation. Because of operational definition and diversity in social participation, performance in social participation was adopted as an aspect of assessment. Further discussions are needed to clarify the definition of social participation and evaluate the instruments used to assess social participation for it to be useful for rehabilitation and health promotion. In doing so, determining and developing assessment and intervention based on the purpose or perspective of social participation in older adults with and without disabilities is important.
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http://dx.doi.org/10.1298/ptr.R0013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8419478PMC
July 2021

A case of bilateral pachychoroid disease: polypoidal choroidal vasculopathy in one eye and peripheral exudative hemorrhagic chorioretinopathy in contralateral eye.

BMC Ophthalmol 2021 Sep 4;21(1):320. Epub 2021 Sep 4.

Department of Ophthalmology, School of Medicine, Nihon University, 1-6 Surugadai, Kanda, Chiyodaku, 101-8309, Tokyo, Japan.

Background: We report a case of bilateral pachychoroid disease manifesting polypoidal choroidal vasculopathy (PCV) with punctate hyperfluorescent spot (PHS) in one eye, and peripheral exudative hemorrhagic choroidal retinopathy (PEHCR) with central serous chorioretinopathy (CSC) and PHS in the contralateral eye.

Case Presentation: A 51-year-old healthy woman presented with complaint of blurred vision in her right eye. Corrected visual acuity was 20/20 in the right and 24/20 in the left eye. Fundus examination was normal in the left eye. In the right eye, fundus finding of an orange-red nodular lesion and optical coherence tomography (OCT) finding of polypoidal lesions led to a diagnosis of PCV. Four aflibercept intravitreal injections were performed in her right eye. After treatment, indocyanine green angiography (ICGA) confirmed residual polypoidal lesions with branching vascular networks and PHS with choroidal vascular hyperpermeability. OCT showed PHS associated with small sharp-peaked retinal pigment epithelium (RPE) elevation in peripheral fundus and small RPE elevation in posterior fundus. Based on the above findings, PCV with PHS was finally diagnosed in the right eye. Posttreatment corrected visual acuity in the right eye was 20/20. She presented again 32 months later, with complaint of vision loss in her left eye. Left corrected visual acuity was 20/20, and fundus examination showed mild vitreous hemorrhage. Vitrectomy was performed. In temporal midperipheral fundus, fluorescein angiography revealed CSC, and OCT showed pachychoroid. ICGA depicted abnormal choroidal networks and PHS in peripheral fundus. Furthermore, polypoidal lesions were confirmed by OCT. Based on the above findings, PEHCR and CSC with PHS was finally diagnosed in the left eye. Postoperative corrected visual acuity in the left eye was 20/20, and aflibercept intravitreal injection was performed for prevention of recurrence of vitreous hemorrhage.

Conclusions: This is the first case report of PCV with PHS in one eye, and PEHCR with CSC and PHS in the contralateral eye. This case suggests that PCV, PEHCR, and CSC may be linked pathologies of pachychoroid spectrum disease.
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http://dx.doi.org/10.1186/s12886-021-02067-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8418046PMC
September 2021

Composite Neuroblastoma Metastatic to a Lymph Node: The Novel Histopathologic Diagnosis of a Unique Multiclonal Neoplasm.

Ann Clin Lab Sci 2021 Jul;51(4):573-579

Stanford University School of Medicine, Department of Pathology, Stanford, CA, USA

Objective: Composite neuroblastoma is a tumor composed of multiple tumoral clones within the neuroblastoma family. To date, establishing this unique histopathologic diagnosis has required the evaluation of the primary tumor mass. We report a case of composite neuroblastoma diagnosed by evaluation of a metastatic lymph node.

Methods: One abdominal lymph node involved by tumor was evaluated in a 6-year-old boy. The primary abdominal mass was not examined. Following histopathologic examination, clonality studies using comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH) were also performed.

Results: Two distinct tumor components were identified by histopathologic evaluation and classified as differentiating neuroblastoma (component A) and poorly differentiated neuroblastoma (component B). Based on the patient's age, each clone was further classified as Unfavorable Histology. The presence of these two different tumoral clones was confirmed by CGH and FISH.

Conclusion: This case affirms the histopathologic approach to evaluating composite tumors, as established by the International Neuroblastoma Pathology Classification (INPC) model for ganglioneuroblastoma, nodular tumors. Also, when both components are metastatic, this case demonstrates that composite tumors can be diagnosed by the evaluation of metastatic lesions alone. Finally, it supports the addition of composite neuroblastoma to a future version of the INPC.
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July 2021

Spatiotemporal gait characteristics and risk of mortality in community-dwelling older adults.

Maturitas 2021 Sep 24;151:31-35. Epub 2021 Jun 24.

Department of Preventive Gerontology, Center for Gerontology and Social Science, Research Institute, National Center for Geriatrics and Gerontology, 7-430, Morioka, Obu, Aichi 474-8511, Japan.

Gait is one of the best measures of physical function in older adults. The study examined the association between spatiotemporal gait variables and mortality among older adults. The participants were 4,298 older adults in the National Center for Geriatrics and Gerontology - Study of Geriatric Syndromes. At baseline we measured the following spatiotemporal gait variables: gait speed, stride length, cadence, and stride length variability. Demographic variables, medical conditions, cognitive function, and physical inactivity were also assessed at baseline. We obtained gait measurements over five trials using an electronic gait-measuring device mounted at the middle 2.4 m section of a 6.4 m straight and flat pathway, with 2 m allowed for acceleration and deceleration. Participants' usual gait speed was measured. Subsequent incident death was confirmed using administrative data. During follow-up (mean duration: 1,571 days), there were 185 incident deaths among participants. Low function on all gait variables increased risk of mortality (adjusted hazard ratio [95% confidence interval], gait speed: 1.83 [1.31-2.56], stride length: 1.85 [1.31-2.62], cadence: 1.60 [1.17-2.18], stride length variability: 1.50 [1.09-2.06]). In addition, mortality risk increased with the number of variables showing low gait function compared with normal gait function (p < .05). Slower gait speed, shorter stride length, lower cadence, and higher stride length variability were associated with increased mortality. Multifaceted gait analysis could be useful for evaluating mortality risk.
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http://dx.doi.org/10.1016/j.maturitas.2021.06.007DOI Listing
September 2021

Cataract Surgery by Intraoperative Surface Irrigation with 0.25% Povidone-Iodine.

J Clin Med 2021 Aug 16;10(16). Epub 2021 Aug 16.

Department of Ophthalmology, School of Medicine, Nihon University, 1-6 Surugadai, Kanda, Chiyodaku, Tokyo 101-8309, Japan.

Postoperative endophthalmitis after cataract surgery is typically caused by the patient's own conjunctival normal bacterial flora. A three-step approach is recommended to prevent endophthalmitis: (1) "border control" to prevent microorganisms from entering the eye by disinfecting the ocular surface is the most important measure; (2) bacteria that have gained access into the anterior chamber are reduced by irrigation; (3) bacteria remaining in the anterior chamber and vitreous at the end of surgery are controlled by antibacterial drugs. We have devised a method, "the Shimada technique", for irrigating the ocular surface with povidone-iodine, a disinfectant with potent microbicidal effect and established effective and safe concentrations for eye tissues. Povidone-iodine exhibits a bactericidal effect for a wide concentration range of 0.005-10%, but 0.1% povidone-iodine has the highest activity and requires the shortest time of only 15 s to achieve microbicidal effect. When used to irrigate the ocular surface every 20-30 s during cataract surgery, 0.25% povidone-iodine is conceivably diluted to around 0.1%. Irrigation with 0.25% povidone-iodine during cataract surgery significantly reduced bacteria contamination rate in the anterior chamber compared with saline ( = 0.0017) without causing corneal endothelial damage.
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http://dx.doi.org/10.3390/jcm10163611DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8397035PMC
August 2021

Predictivity of International Physical Activity Questionnaire Short Form for 5-Year Incident Disability Among Japanese Older Adults.

J Phys Act Health 2021 Aug 25:1-5. Epub 2021 Aug 25.

Background: This study aimed to examine whether physical activity measured using the International Physical Activity Questionnaire Short Form (IPAQ-SF) can predict incident disability in Japanese older adults.

Methods: Community-dwelling older adults participated in a prospective cohort survey. The time spent in moderate- to vigorous-intensity physical activity was assessed at the survey baseline using the IPAQ-SF. The participants were categorized into those who spent ≥150 minutes per week (physically active) or <150 minutes per week (physically inactive) in moderate- to vigorous-intensity physical activity. Incident disability was monitored through Long-Term Care Insurance certification during a follow-up lasting 5 years.

Results: Among the 4387 analyzable participants (mean age = 75.8 y, 53.5% female), the IPAQ-SF grouped 1577 (35.9%) and 2810 (64.1%) participants as those who were physically active and inactive, respectively. A log-rank test showed a significantly higher incidence of disability among the inactive group of participants (P < .001). The Cox proportional hazards model showed that physically inactive participants had a higher risk of incident disability than the physically active ones did, even after adjusting for covariates (hazard ratio, 1.24; 95% CI, 1.07-1.45, P < .001).

Conclusions: Older adults identified as physically inactive using the IPAQ-SF had a greater risk of developing disabilities than those identified as physically active. The IPAQ-SF seems to be appropriate to estimate the incidence risk of disability.
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http://dx.doi.org/10.1123/jpah.2021-0247DOI Listing
August 2021

A case of primary CNS embryonal rhabdomyosarcoma with PAX3-NCOA2 fusion and systematic meta-review.

J Neurooncol 2021 Sep 16;154(2):247-256. Epub 2021 Aug 16.

Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan.

Purpose: Primary central nervous system (CNS) rhabdomyosarcoma is a rare mesenchymal tumor predominantly seen in children and associated with a poor outcome. We report a case of primary CNS rhabdomyosarcoma with PAX3-NCOA2 fusion and present a systematic meta-review of primary CNS rhabdomyosarcoma to characterize this rare tumor.

Methods: We present the case of a 6-year-old boy with primary CNS rhabdomyosarcoma in the posterior fossa. In a systematic meta-review, we compare the demographic data of primary CNS rhabdomyosarcoma with data of rhabdomyosarcoma at all sites from the SEER database and analyze clinical factors associated with survival outcome.

Results: Our patient underwent gross total resection and received vincristine, actinomycin-D, cyclophosphamide with early introduction of concurrent focal radiation and remained alive with no evidence of disease for 2 years after the end of therapy. Histopathological review revealed embryonal-type rhabdomyosarcoma, and whole-transcriptome analysis revealed PAX3 (EX6)-NCOA2 (EX12) fusion. In all, 77 cases of primary CNS rhabdomyosarcoma were identified through the meta-review. The demographic data of primary CNS rhabdomyosarcoma were similar to data of rhabdomyosarcoma at all sites. Overall and event-free survival outcomes were available for 64 and 56 patients, respectively, with a 3-year OS of 29.0% and a 3-year EFS of 25.7%. The group that received trimodal treatment exhibited better survival outcomes, with a 3-year OS of 57.4% and a 3-year EFS of 46.3%.

Conclusions: Primary CNS rhabdomyosarcoma shares common histological, molecular, and demographic features with non-CNS rhabdomyosarcoma. A trimodal treatment approach with early introduction of radiation therapy may result in favorable survival outcomes.
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http://dx.doi.org/10.1007/s11060-021-03823-6DOI Listing
September 2021

Computer use and cognitive decline among Japanese older adults: A prospective cohort study.

Arch Gerontol Geriatr 2021 Jul 18;97:104488. Epub 2021 Jul 18.

Department of Preventive Gerontology, Center for Gerontology and Social Science, National Center for Geriatrics and Gerontology Research Institute, Obu City, Japan.

Introduction: This study aimed to examine the prospective association between computer use and cognitive decline among community-dwelling Japanese older adults, considering the characteristics of computer users.

Methods: This four-year prospective cohort study was conducted in Obu, Japan. Participants who were cognitive intact at Wave 1 (2011-2012) were followed through the study period. Cognitive decline was defined as scoring below the standard threshold in at least one of four neuropsychological tests at Wave 2 (2015-2016). The association between computer use at Wave 1 and cognitive decline was examined using logistic regression for complete samples (n = 2010, 52.5% female, mean 71.0 ± 4.7 years) and imputed samples (n = 3435, 51.8% female, mean 71.5 ± 5.3 years).

Results: The computer use group had a reduced adjusted odds ratio (aOR) of cognitive decline, after adjustment for covariates, in both the complete and imputed samples (complete samples: aOR 0.71, 95% confidence interval [CI] 0.52-0.97, p = 0.030; imputed samples: aOR 0.67, 95% CI 0.51-0.88, p < 0.003). Stratified analysis of both samples showed that computer users with ≥ 10 years' education, a GDS score of < 6, or a walking speed of ≥ 1.0m/s, showed reduced aOR for cognitive decline (aOR 0.61 to 0.69, p < 0.05). Those with < 10 years of education years, GDS scores ≥ 6 of GDS, or walking speed < 1.0m/s did not show significant association.

Conclusion: Computer use is longitudinally associated with protected cognitive function, based on computer user characteristics.
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http://dx.doi.org/10.1016/j.archger.2021.104488DOI Listing
July 2021

The Multi-Domain Intervention Trial in Older Adults With Diabetes Mellitus for Prevention of Dementia in Japan: Study Protocol for a Multi-Center, Randomized, 18-Month Controlled Trial.

Front Aging Neurosci 2021 12;13:680341. Epub 2021 Jul 12.

Center for Comprehensive Care and Research on Memory Disorders, National Center for Geriatrics and Gerontology, Obu, Japan.

The Japan-Multi-domain Intervention Trial for Prevention of Dementia in Older Adults with Diabetes (J-MIND-Diabetes) is an 18-month, multi-centered, open-labeled, randomized controlled trial designed to identify whether multi-domain intervention targeting modifiable risk factors for dementia could prevent the progression of cognitive decline among older adults with type 2 diabetes mellitus (T2DM). This manuscript describes the study protocol for the J-MIND-Diabetes trial. Subjects of this trial will comprise a total of 300 T2DM outpatients aged 70-85 years with mild cognitive impairment. Subjects will be centrally randomized into intervention and control groups at a 1:1 allocation ratio using the stratified permuted-block randomization methods. The intervention group will participate in multi-domain intervention programs aimed at: (1) management of metabolic and vascular risk factors; (2) physical exercise and self-monitoring of physical activity; (3) nutritional guidance; and (4) social participation. The control group will receive usual T2DM care and general instructions on dementia prevention. The primary and secondary outcomes will be assessed at baseline, at 6- and 18-month follow-up. The primary outcome is change from baseline at 18 months in a global composite score combining several neuropsychological domains, including global cognitive function, memory, attention, executive function, processing speed and language. Secondary outcomes include: (1) cognitive changes in neuropsychological tests; (2) changes in geriatrics assessments; (3) metabolic control and diabetic complications; (4) changes in blood and urinary markers. This trial will be the first trial to demonstrate the effectiveness of multi-domain intervention in preventing cognitive decline in older adults with T2DM at increased risk of dementia in Japan. UMIN000035911; Registered on the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) 18 February 2019. (https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000040908).
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http://dx.doi.org/10.3389/fnagi.2021.680341DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8312849PMC
July 2021

The Association of Sleep Habits and Advancing Age in Japanese Older Adults: Results from the National Center for Geriatrics and Gerontology Study of Geriatric Syndromes.

Gerontology 2021 Jul 28:1-5. Epub 2021 Jul 28.

Department of Preventive Gerontology, Center for Gerontology and Social Science, National Center for Geriatrics and Gerontology, Obu, Japan.

Background: The association of sleep habits with "advancing age among older adults" is not fully understood.

Objectives: The purpose of the present study was to examine the association of sleep habits with advancing age among community-dwelling older adults in Japan.

Methods: A total of 18,005 older people (mean age: 73.2 ± 6.0 years; 8,070 men and 9,935 women) from the National Center for Geriatrics and Gerontology Study of Geriatric Syndromes were analyzed. Participants were asked in face-to-face interviews about the times they usually go to bed, fall asleep, wake-up, and get up. The amount of time spent in bed and self-reported sleep duration were then calculated from the differences between these times. As other parameters, the subjects were also asked about sleep latency, time spent in bed after waking up, number of nocturnal awakenings, and duration of napping in a typical day.

Results: The results of the Jonckheere-Terpstra test showed that all sleep parameters shifted to an earlier time (going to bed, falling asleep, waking up, and getting out of bed), longer duration (sleep duration, time spent in bed, sleep latency, time spent in bed after waking up, and napping), or more nocturnal awakenings with advancing age (all p < 0.01). Among the men, the time of waking up was not significantly associated with age, while among the women, the time of getting up was not significantly associated with age.

Conclusion: These results from a large cohort show the age-related trends of sleep habits in community-dwelling older adults in Japan. Our results revealed that a longer duration and earlier timing of sleep are associated with advancing age.
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http://dx.doi.org/10.1159/000516387DOI Listing
July 2021

Revised Neuroblastoma Risk Classification System: A Report From the Children's Oncology Group.

J Clin Oncol 2021 Jul 28:JCO2100278. Epub 2021 Jul 28.

Department of Pediatrics, Children's Hospital of Philadelphia and Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.

Purpose: Treatment planning for children with neuroblastoma requires accurate assessment of prognosis. The most recent Children's Oncology Group (COG) risk classification system used tumor stage as defined by the International Neuroblastoma Staging System. Here, we validate a revised classifier using the International Neuroblastoma Risk Group Staging System (INRGSS) and incorporate segmental chromosome aberrations (SCA) as an additional genomic biomarker.

Methods: Newly diagnosed patients enrolled on the COG neuroblastoma biology study ANBL00B1 between 2007 and 2017 with known age, International Neuroblastoma Staging System, and INRGSS stage were identified (N = 4,832). Tumor status, ploidy, SCA status (1p and 11q), and International Neuroblastoma Pathology Classification histology were determined centrally. Survival analyses were performed for combinations of prognostic factors used in COG risk classification according to the prior version 1, and to validate a revised algorithm (version 2).

Results: Most patients with locoregional tumors had excellent outcomes except for those with image-defined risk factors (INRGSS L2) with amplification (5-year event-free survival and overall survival: 76.3% ± 5.8% and 79.9% ± 5.5%, respectively) or patients age ≥ 18 months with L2 nonamplified tumors with unfavorable International Neuroblastoma Pathology Classification histology (72.7% ± 5.4% and 82.4% ± 4.6%), which includes the majority of L2 patients with SCA. For patients with stage M (metastatic) and MS (metastatic, special) disease, genomic biomarkers affected risk group assignment for those < 12 months () or 12-18 months (, histology, ploidy, and SCA) of age. In a retrospective analysis of patient outcome, the 5-year event-free survival and overall survival using COG version 1 were low-risk: 89.4% ± 1.1% and 97.9% ± 0.5%; intermediate-risk: 86.1% ± 1.3% and 94.9% ± 0.8%; high-risk: 50.8% ± 1.4% and 61.9% ± 1.3%; and using COG version 2 were low-risk: 90.7% ± 1.1% and 97.9% ± 0.5%; intermediate-risk: 85.1% ± 1.4% and 95.8% ± 0.8%; high-risk: 51.2% ± 1.4% and 62.5% ± 1.3%, respectively.

Conclusion: A revised 2021 COG neuroblastoma risk classifier (version 2) that uses the INRGSS and incorporates SCAs has been adopted to prospectively define COG clinical trial eligibility and treatment assignment.
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http://dx.doi.org/10.1200/JCO.21.00278DOI Listing
July 2021

A phase 2 study of nilotinib in pediatric patients with CML: long-term update on growth retardation and safety.

Blood Adv 2021 07;5(14):2925-2934

Clinical Research for Holistic Management in Pediatric Hematology and Oncology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

The phase 2, open-label study (DIALOG) of nilotinib in pediatric patients with Philadelphia chromosome-positive chronic myelogenous leukemia (CML) met its coprimary end points, showing sustained nilotinib efficacy in patients with newly diagnosed (ND) or imatinib/dasatinib resistant/intolerant (R/I) CML. This update assessed growth and safety profiles in patients who had completed ≥48, 28-day treatment cycles of nilotinib 230 mg/m2 twice daily, or previously discontinued the study. Height was assessed regularly and reported using standard deviation scores (SDSs) based on World Health Organization growth charts. All data were summarized descriptively (cutoff, 6 March 2019). Overall, 33 patients in the R/I cohort and 25 patients in the ND cohort received nilotinib. Each cohort showed a negative slope in height SDS over the course of the study, indicating attenuated growth rates during nilotinib treatment: overall median change from baseline in height SDS after 48 cycles was -0.54 SDS (range, - 1.6 to 0.4) and -0.91 SDS (-1.4 to -0.1) in R/I and ND cohorts, respectively. Patients in the R/I cohort were shorter at baseline than those in the ND cohort, and remained so throughout the study. The most common all-cause adverse events were increased blood bilirubin (53.4%), headache (46.6%), pyrexia (37.9%), and increased alanine transferase (36.2%). Apart from the impact on growth, the safety profile of nilotinib was generally consistent with previous reports. This study was registered on www.clinicaltrials.gov at #NCT01844765.
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http://dx.doi.org/10.1182/bloodadvances.2020003759DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8341357PMC
July 2021

Randomized Phase II Trial of MIBG Versus MIBG, Vincristine, and Irinotecan Versus MIBG and Vorinostat for Patients With Relapsed or Refractory Neuroblastoma: A Report From NANT Consortium.

J Clin Oncol 2021 Jul 16:JCO2100703. Epub 2021 Jul 16.

Department of Pediatrics, UCSF Benioff Children's Hospital and UCSF School of Medicine, San Francisco, CA.

Purpose: I-metaiodobenzylguanidine (MIBG) is an active radiotherapeutic for neuroblastoma. The primary aim of this trial was to identify which of three MIBG regimens was likely associated with the highest true response rate.

Patients And Methods: Patients 1-30 years were eligible if they had relapsed or refractory neuroblastoma, at least one MIBG-avid site, and adequate autologous stem cells. Patients received MIBG 18 mCi/kg on day 1 and autologous stem cell on day 15. Patients randomly assigned to arm A received only MIBG; patients randomly assigned to arm B received intravenous vincristine on day 0 and irinotecan daily on days 0-4; patients randomly assigned to arm C received vorinostat (180 mg/m/dose) orally once daily on days 1 to 12. The primary end point was response after one course by New Approaches to Neuroblastoma Therapy criteria. The trial was designed with 105 patients to ensure an 80% chance that the arm with highest response rate was selected.

Results: One hundred fourteen patients were enrolled, with three ineligible and six unevaluable, leaving 105 eligible and evaluable patients (36 in arm A, 35 in arm B, and 34 in arm C; 55 boys; and median age 6.5 years). After one course, the response rates (partial response or better) on arms A, B, and C were 14% (95% CI, 5 to 30), 14% (5 to 31), and 32% (18 to 51). An additional five, five, and four patients met New Approaches to Neuroblastoma Therapy Minor Response criteria on arms A, B, and C, respectively. On arms A, B, and C, rates of any grade 3+ nonhematologic toxicity after first course were 19%, 49%, and 35%.

Conclusion: Vorinostat and MIBG is likely the arm with the highest true response rate, with manageable toxicity. Vincristine and irinotecan do not appear to improve the response rate to MIBG and are associated with increased toxicity.
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http://dx.doi.org/10.1200/JCO.21.00703DOI Listing
July 2021

Identification of Disability Risk in Addition to Slow Walking Speed in Older Adults.

Gerontology 2021 Jul 14:1-10. Epub 2021 Jul 14.

Centre for Gerontology and Social Science, National Centre for Geriatrics and Gerontology, Obu, Japan.

Introduction: A cutoff speed of 1.0 m/s for walking at a comfortable pace is critical for predicting future functional decline. However, some older adults with walking speeds below the cutoff point maintain an independent living. We aimed to identify specific predictors of disability development in older adults with slow walking speeds in contrast to those with a normal walking speed.

Methods: This prospective cohort study on 12,046 community-dwelling independent Japanese older adults (mean age, 73.6 ± 5.4 years) was conducted between 2011 and 2015. Participants were classified into slow walking speed (comfortable walking speed slower than 1.0 m/s) and normal walking speed (speed of 1.0 m/s or faster) groups and followed up to assess disability incidence for 24 months after baseline assessments. Cox proportional hazards regression models were used to identify predictors of disability development in the slow and normal walking groups.

Results: Overall, 26.8% of participants had a slow walking speed. At follow-up, 17.3% and 5.1% of participants in the slow and normal walking groups, respectively, developed disability (p < 0.01). Cox regression models revealed that age (hazard ratio 1.07, 95% confidence interval 1.05-1.09), walking speed (0.12, 0.07-0.22), grip strength (0.97, 0.95-0.99), Parkinson's disease (4.65, 2.59-8.33), word list memory-immediate recognition score (0.90, 0.85-0.97), word list memory-delayed recall score (0.94, 0.89-1.00), Symbol Digit Substitution Test (SDST) score (0.98, 0.96-0.99), and 15-item Geriatric Depression Scale (GDS) score (1.04, 1.01-1.07) were significantly associated with disability incidence in the slow walking group. In the normal walking group, age, grip strength, depression, diabetes, cognition, GDS score, and reduced participation in outdoor activity were significantly associated with disability incidence; however, there was no significant association with walking speed.

Conclusions: Decreased walking speeds have considerably greater impact on disability development in older adults with a slow walking speed than in those with a normal walking speed. Health-care providers should explore modifiable factors for reducing walking speed; they should also encourage improvement of risk factors such as muscle weakness and depression to reduce disability risk in older adults with slow walking speeds.
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http://dx.doi.org/10.1159/000516966DOI Listing
July 2021

Life Satisfaction and the Relationship between Mild Cognitive Impairment and Disability Incidence: An Observational Prospective Cohort Study.

Int J Environ Res Public Health 2021 06 19;18(12). Epub 2021 Jun 19.

Department of Preventive Gerontology, Center for Gerontology and Social Science, National Center for Geriatrics and Gerontology, 7-430 Morioka-cho, Obu 474-8511, Japan.

The relationship between the incidence of disability and cognitive function has been clarified, but whether life satisfaction is related to this relationship is unclear. Therefore, the purpose of this study was to clarify whether life satisfaction is related to the relationship between the incidence of disability and mild cognitive impairment. We included 2563 older adults from the National Center for Geriatrics and Gerontology-Study of Geriatric Syndromes. Baseline measurements included cognitive, life satisfaction, and demographic characteristics. Life satisfaction was measured using the Life Satisfaction Scale, which was stratified into three levels based on the score: lower, moderate, and higher. Associations between disability incidence and mild cognitive impairment were examined for each group according to life satisfaction, and monthly assessment for disability was monitored through long-term care insurance certification for at least 2 years from the baseline. At a 35.5-month mean follow-up, 150 participants had developed a disability. The potential confounding factors adjusted hazard for incidence of disability in the group with lower life satisfaction was 1.88 (CI: 1.05-3.35; = 0.034) for mild cognitive impairment. Mild cognitive impairment was associated with disability incidence, and the effect was more pronounced among older adults with lower life satisfaction.
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http://dx.doi.org/10.3390/ijerph18126595DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8296376PMC
June 2021

Absolute Cardiovascular Disease Risk Is Associated With the Incidence of Non-amnestic Cognitive Impairment in Japanese Older Adults.

Front Aging Neurosci 2021 14;13:685683. Epub 2021 Jun 14.

Center for Gerontology and Social Science, National Center for Geriatrics and Gerontology, Obu, Japan.

Background: The estimated absolute cardiovascular disease (CVD) risk level is known to be a useful surrogate marker for future cognitive impairment; however, evidence regarding its predictive validity in terms of cognitive subtypes is limited. We aimed to examine subtype-dependent differences in the associations between absolute CVD risk and the incidence of cognitive impairment in a community-dwelling older Japanese cohort.

Methods And Results: This study comprised 1,641 cognitively intact older Japanese participants without CVDs at baseline. We estimated absolute CVD risk using WHO region-specific risk estimation charts and included age, sex, diabetes mellitus, smoking, systolic blood pressure, and total cholesterol at baseline, and the CVD risk level was stratified into the three following risk categories: low (<10%), moderate (10 to <20%), and high (≥20%). Objective cognitive screening was performed using a multicomponent neurocognitive test at baseline and follow-up, and the incidence of cognitive impairment over 48 ± 2 months was determined. The incidence of cognitive impairment in low-, moderate-, and high-CVD risk participants was 1.2, 3.0, and 5.4%, respectively, for amnestic subtypes and 5.8, 10.1, and 14.0%, respectively, for non-amnestic subtypes. After adjusting for potential confounding factors, the absolute CVD risk level was significantly associated with non-amnestic impairment but not with amnestic impairment.

Conclusions: The absolute CVD risk estimated using region-specific risk estimation charts in old age is useful to predict incidence of cognitive impairment. Strategies to screen populations at risk of cognitive impairment and to prevent progression to dementia should be cognitive subtype-specific.
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http://dx.doi.org/10.3389/fnagi.2021.685683DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236854PMC
June 2021

Sleep duration and progression to sarcopenia in Japanese community-dwelling older adults: a 4 year longitudinal study.

J Cachexia Sarcopenia Muscle 2021 Aug 30;12(4):1034-1041. Epub 2021 Jun 30.

Department of Preventive Gerontology, Center for Gerontology and Social Science, National Center for Geriatrics and Gerontology, Obu, Japan.

Background: Identifying factors that contribute to the development of sarcopenia in older adults is a public health priority. Although several studies have examined the association between sleep duration and sarcopenia, additional evidence is needed to reveal the causality of this association, especially from a longitudinal study. The purpose of the present study was to examine whether sleep duration was associated with the progression to sarcopenia and its subcomponents among community-dwelling older adults in Japan.

Methods: A total of 3918 older community-dwelling people (mean age: 73.2 ± 6.0 years, 51.8% female) included in the National Center for Geriatrics and Gerontology Study of Geriatric Syndromes were analysed. Sleep duration was assessed using a self-reported questionnaire. Logistic regression analysis was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) of progression of sarcopenia at Wave 2 (4 years later), according to the three categories of sleep duration [short: ≤6.0 h, medium: 6.1-8.9 h (control), & long: ≥9.0 h)] at Wave 1.

Results: The numbers in each group in the second wave among the total sample were as follows: short 403 (10.3%), medium 2877 (73.4%), and long 638 (16.3%). Significant associations with the progression of sarcopenia were found in the long sleep duration group compared with the medium one, even after adjustment for other covariates (OR 1.66, 95% CI: 1.02-2.69, P = 0.040). Long sleep duration was significantly associated with slow gait (OR: 1.55, 95% CI: 1.17-2.06, P = 0.002) and low grip strength (OR: 1.34, 95% CI: 1.00-1.78, P = 0.047) but was not associated with low muscle mass (OR: 1.33, 95% CI: 0.74-2.38, P = 0.343).

Conclusions: This study revealed that long sleep duration was associated with an increased risk of progression to sarcopenia among older adults.
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http://dx.doi.org/10.1002/jcsm.12735DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8350197PMC
August 2021

Correlates of improvement in the care need levels of older adults with disabilities: a two-year follow-up study.

J Phys Ther Sci 2021 Jun 18;33(6):466-471. Epub 2021 Jun 18.

Center for Gerontology and Social Science, National Center for Geriatrics and Gerontology, Japan.

[Purpose] This study examined the effect of motor functioning, cognitive functioning, and activities of daily living on improvements in care need levels of older adults requiring low-level care at baseline in Japan's Long-Term Care Insurance system. We aimed to link our findings to a proposal for effective measures toward improving care need levels. [Participants and Methods] This retrospective cohort study included 11,585 individuals aged 65 years and above who received personal care and used day-care services continuously for two or more years starting from the baseline assessment. Participants showing an improvement in their care need level from baseline to two years were included in the improved group, and those who maintained or declined from the baseline level were included in the maintained/deteriorated group. [Results] The mental status questionnaire and sub-scores for the Functional Independence Measure, including those for self-care, continence, and social cognition, were significantly correlated with improvements in care need levels. [Conclusion] Conducting a detailed evaluation of these factors is important for gauging the progress of the care need levels of older adults.In addition, it is important for physiotherapists to provide non-rehabilitation professionals with advice and guidance on their assessment methods and remedies.
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http://dx.doi.org/10.1589/jpts.33.466DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8219599PMC
June 2021

Nanoengineering of cathode layers for solid oxide fuel cells to achieve superior power densities.

Nat Commun 2021 Jun 25;12(1):3979. Epub 2021 Jun 25.

Research Institute for Energy Conservation, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki, Japan.

Solid oxide fuel cells (SOFCs) are power-generating devices with high efficiencies and considered as promising alternatives to mitigate energy and environmental issues associated with fossil fuel technologies. Nanoengineering of electrodes utilized for SOFCs has emerged as a versatile tool for significantly enhancing the electrochemical performance but needs to overcome issues for integration into practical cells suitable for widespread application. Here, we report an innovative concept for high-performance thin-film cathodes comprising nanoporous LaSrCoO cathodes in conjunction with highly ordered, self-assembled nanocomposite LaSrCoFeO (lanthanum strontium cobalt ferrite) and CeGdO (gadolinia-doped ceria) cathode layers prepared using pulsed laser deposition. Integration of the nanoengineered cathode layers into conventional anode-supported cells enabled the achievement of high current densities at 0.7 V reaching ~2.2 and ~4.7 A/cm at 650 °C and 700 °C, respectively. This result demonstrates that tuning material properties through an effective nanoengineering approach could significantly boost the electrochemical performance of cathodes for development of next-generation SOFCs with high power output.
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http://dx.doi.org/10.1038/s41467-021-24255-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8233395PMC
June 2021

Effects of Aerobic, Resistance, or Combined Exercise Training Among Older Adults with Subjective Memory Complaints: A Randomized Controlled Trial.

J Alzheimers Dis 2021 ;82(2):701-717

Institute of Innovation for Future Society, Nagoya University, Nagoya, Aichi, Japan.

Background: Physical exercise is suggested to be effective for preventing cognitive decline in older adults, but the relative efficacy of different types of exercise have yet to be clarified.

Objective: This single-blinded randomized controlled trial was designed to investigate the differential effects of aerobic exercise training (AT), resistance exercise training (RT), and combined exercise training (CT) on cognition in older adults with subjective memory complaints (SMC).

Methods: Community-dwelling older adults with SMC (n = 415; mean age = 72.3 years old) were randomly assigned to one of the four groups: AT, RT, CT, or control group. The study consisted of two phases: a 26-week intervention and a 26-week follow-up. The participants were evaluated at baseline, 26 weeks (postintervention), and 52 weeks (follow-up). The primary outcome of this study was memory function, which was assessed using the Logical Memory II subtest of the Wechsler Memory Scale-Revised (WMS-R) score. The secondary outcomes included global cognitive function, verbal fluency, working memory, processing speed, and executive functions.

Results: Intention-to-treat analysis by a mixed-effect model repeated measure showed that the AT group had significantly improved performance on the WMS-R Logical Memory II test (2.74 [1.82-3.66] points) than the control group (1.36 [0.44-2.28] points) at the postintervention assessment (p = 0.037). The effect was more pronounced in those without amnesia than those with amnesia. No significant improvement was observed in the RT and CT groups.

Conclusion: This study suggests that AT intervention can improve delayed memory in community-dwelling older adults, particularly in individuals without objective memory decline.
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http://dx.doi.org/10.3233/JAD-210047DOI Listing
September 2021

Association between Kihon check list score and geriatric depression among older adults from ORANGE registry.

PLoS One 2021 4;16(6):e0252723. Epub 2021 Jun 4.

Advanced Research Center for Geriatric and Gerontology, Akita University, Akita, Japan.

Objective: Older adults in Japan are tackling health-related challenges brought by comprehensive geriatric symptoms, such as physical and cognitive problems and social-psychological issues. In this nationwide study, we mainly focused on the Kihon checklist (KCL) as certificated necessity of long-term care for Japanese older adults and investigated whether the KCL score was associated with geriatric depression. In addition, we aimed to identify critical factors that influence the relationship between the KCL score and geriatric depression.

Methods: This survey was a cross-sectional observational study design, performed from 2013 to 2019. A total of 8,760 participants aged 65 years and over were recruited from five cohorts in Japan, consisting of 6,755 persons in Chubu, 1,328 in Kanto, 481 in Kyushu, 49 in Shikoku and 147 in Tohoku. After obtaining informed consent from each participant, assessments were conducted, and outcomes were evaluated according to the ORANGE protocol. We collected data on demographics, KCL, physical, cognitive and mental evaluations. To clarify the relationship between the KCL and geriatric depression or critical factors, a random intercept model of multi-level models was estimated using individual and provincial variables depending on five cohorts.

Results: The KCL score was correlated with depression status. Moreover, the results of a random intercept model showed that the KCL score and geriatric depression were associated, and its association was affected by provincial factors of slow walking speed, polypharmacy and sex difference.

Conclusions: These results suggest that provincial factors of low walking performance, polypharmacy and sex difference (female) might be clinically targeted to improve the KCL score in older adults.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0252723PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8177620PMC
June 2021

A safety and feasibility trial of I-MIBG in newly diagnosed high-risk neuroblastoma: A Children's Oncology Group study.

Pediatr Blood Cancer 2021 Oct 24;68(10):e29117. Epub 2021 May 24.

UCSF Benioff Children's Hospital, University of California San Francisco School of Medicine, San Francisco, California.

Introduction: I-meta-iodobenzylguanidine ( I-MIBG) is effective in relapsed neuroblastoma. The Children's Oncology Group (COG) conducted a pilot study (NCT01175356) to assess tolerability and feasibility of induction chemotherapy followed by I MIBG therapy and myeloablative busulfan/melphalan (Bu/Mel) in patients with newly diagnosed high-risk neuroblastoma.

Methods: Patients with MIBG-avid high-risk neuroblastoma were eligible. After the first two patients to receive protocol therapy developed severe sinusoidal obstruction syndrome (SOS), the trial was re-designed to include an I-MIBG dose escalation (12, 15, and 18 mCi/kg), with a required 10-week gap before Bu/Mel administration. Patients who completed induction chemotherapy were evaluable for assessment of I-MIBG feasibility; those who completed I-MIBG therapy were evaluable for assessment of I-MIBG + Bu/Mel feasibility.

Results: Fifty-nine of 68 patients (86.8%) who completed induction chemotherapy received I-MIBG. Thirty-seven of 45 patients (82.2%) evaluable for I-MIBG + Bu/Mel received this combination. Among those who received I-MIBG after revision of the study design, one patient per dose level developed severe SOS. Rates of moderate to severe SOS at 12, 15, and 18 mCi/kg were 33.3%, 23.5%, and 25.0%, respectively. There was one toxic death. The I-MIBG and I-MIBG+Bu/Mel feasibility rates at the 15 mCi/kg dose level designated for further study were 96.7% (95% CI: 83.3%-99.4%) and 81.0% (95% CI: 60.0%-92.3%).

Conclusion: This pilot trial demonstrated feasibility and tolerability of administering I-MIBG followed by myeloablative therapy with Bu/Mel to newly diagnosed children with high-risk neuroblastoma in a cooperative group setting, laying the groundwork for a cooperative randomized trial (NCT03126916) testing the addition of I-MIBG during induction therapy.
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http://dx.doi.org/10.1002/pbc.29117DOI Listing
October 2021

Comparison of electrochemical impedance spectra for electrolyte-supported solid oxide fuel cells (SOFCs) and protonic ceramic fuel cells (PCFCs).

Sci Rep 2021 May 19;11(1):10622. Epub 2021 May 19.

Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, Sendai, Miyagi, 980-8577 , Japan.

Protonic ceramic fuel cells (PCFCs) are expected to achieve high power generation efficiency at intermediate temperature around 400-600 °C. In the present work, the distribution of relaxation times (DRT) analysis was investigated in order to deconvolute the anode and cathode polarization resistances for PCFCs supported on yttria-doped barium cerate (BCY) electrolyte in comparison with solid oxide fuel cells (SOFCs) supported on scandia-stabilized zirconia (ScSZ) electrolyte. Four DRT peaks were detected from the impedance spectra measured at 700 °C excluding the gas diffusion process for ScSZ and BCY. The DRT peaks at 5 × 10-1 × 10 Hz and 1 × 10-2 × 10 Hz were related to the hydrogen oxidation reaction at the anode and the oxygen reduction reaction at the cathode, respectively, for both cells. The DRT peak at 2 × 10-1 × 10 Hz depended on the hydrogen concentration at the anode for ScSZ, while it was dependent on the oxygen concentration at the cathode for BCY. Compared to ScSZ, steam was produced at the opposite electrode in the case of BCY, which enhanced the cathode polarization resistance for PCFCs.
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http://dx.doi.org/10.1038/s41598-021-90211-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8134428PMC
May 2021

Clinical Relevance of CD4 Cytotoxic T Cells in High-Risk Neuroblastoma.

Front Immunol 2021 22;12:650427. Epub 2021 Apr 22.

Department of Anatomy and Cell Biology, College of Medicine, University of Illinois at Chicago, Chicago, IL, United States.

Neuroblastoma is the most common extracranial childhood solid tumor. The majority of high-risk neuroblastoma is resistant/refractory to the current high intensity therapy, and the survival of these patients remains poor for the last three decades. To effectively treat these extremely unfavorable neuroblastomas, innovative immunotherapy approaches would be the most promising. In this article, we discuss the identity of tumor-infiltrating effector cells and immunosuppressive cells in high-risk neuroblastoma. Neuroblastoma is unique in that it expresses little or no classical HLA Class I and II. In contrast, high-risk neuroblastomas express the stress-responsive non-classical Class I, HLA-E molecule. HLA-E is the ligand of activating receptors NKG2C/E that are expressed on memory NK cells, CD8+T cells and CD4 CTLs. By examining a comprehensive RNA-seq gene expression dataset, we detected relatively high levels of expression in high-risk neuroblastoma tissues. The majority of CD4+ cells were CD3+, and thus they were likely tumor-associated CD4+T cells. In addition, high-level of both CD4 and NKG2C/E expression was associated with prolonged survival of the high-risk neuroblastoma patients, but CD8 levels were not, further suggesting that the CD4+ NKG2C/E+ T cells or CD4 CTL conferred cytotoxicity against the neuroblastoma cells. However, this T cell mediated- "protective effect" declined over time, in part due to the progressive formation of immunosuppressive tumor microenvironment. These observations suggest that to improve survival of high-risk neuroblastoma patients, it is essential to gain insights into how to enhance CD4 CTL cytotoxicity and control the immunosuppressive tumor microenvironment during the course of the disease.
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http://dx.doi.org/10.3389/fimmu.2021.650427DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8101497PMC
April 2021

Participation in Social Activities and Relationship between Walking Habits and Disability Incidence.

J Clin Med 2021 Apr 27;10(9). Epub 2021 Apr 27.

Department of Preventive Gerontology, Center for Gerontology and Social Science, National Center for Geriatrics and Gerontology, 7-430 Morioka-cho, Aichi, Obu City 474-8511, Japan.

Identifying the relationship between physical and social activity and disability among community-dwelling older adults may provide important information for implementing tailored interventions to prevent disability progression. The aim of this study was to determine the effect of the number of social activities on the relationship between walking habits and disability incidence in older adults. We included 2873 older adults (mean age, 73.1 years; SD, ±5.9 years) from the National Center for Geriatrics and Gerontology-Study of Geriatric Syndromes. Baseline measurements, including frequencies of physical and social activities, health conditions, physical function, cognitive function, metabolic parameters, and other potential disability risk factors (for example, the number of years of education); monthly assessment for disability was monitored through long-term care insurance certification for at least 2 years from baseline. During a mean follow-up of 35.1 months (SD, 6.4 months), 133 participants developed disability. The disability incidence was 19.0 and 27.9 per 1000 person-years for participants who walked more (≥3 times per week) and less (≤3 times per week) frequently, respectively. The potential confounding factor-adjusted disability hazard ratio was 0.67 (95% confidence interval, 0.46 to 0.96; = 0.030). The relationship between habitual walking and the number of social activities was statistically significant ( = 0.004). The reduction of disability risk by walking was greater among participants with fewer social activities. Habitual walking was associated with disability incidence, with a more pronounced effect among older adults who were less likely to engage in social activities.
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http://dx.doi.org/10.3390/jcm10091895DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8123784PMC
April 2021

Cortical Thickness, Volume, and Surface Area in the Motoric Cognitive Risk Syndrome.

J Alzheimers Dis 2021 ;81(2):651-665

Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA.

Background: The motoric cognitive risk (MCR) syndrome is a pre-clinical stage of dementia characterized by slow gait and cognitive complaint. Yet, the brain substrates of MCR are not well established.

Objective: To examine cortical thickness, volume, and surface area associated with MCR in the MCR-Neuroimaging Consortium, which harmonizes image processing/analysis of multiple cohorts.

Methods: Two-hundred MRIs (M age 72.62 years; 47.74%female; 33.17%MCR) from four different cohorts (50 each) were first processed with FreeSurfer 6.0, and then analyzed using multivariate and univariate general linear models with 1,000 bootstrapped samples (n-1; with resampling). All models adjusted for age, sex, education, white matter lesions, total intracranial volume, and study site.

Results: Overall, cortical thickness was lower in individuals with MCR than in those without MCR. There was a trend in the same direction for cortical volume (p = 0.051). Regional cortical thickness was also lower among individuals with MCR than individuals without MCR in prefrontal, insular, temporal, and parietal regions.

Conclusion: Cortical atrophy in MCR is pervasive, and include regions previously associated with human locomotion, but also social, cognitive, affective, and motor functions. Cortical atrophy in MCR is easier to detect in cortical thickness than volume and surface area because thickness is more affected by healthy and pathological aging.
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http://dx.doi.org/10.3233/JAD-201576DOI Listing
September 2021

Frailty and driving status associated with disability: a 24-month follow-up longitudinal study.

BMJ Open 2021 04 15;11(4):e042468. Epub 2021 Apr 15.

Department of Preventive Gerontology, Center for Gerontology and Social Science, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan.

Objectives: To examine the relationship of driving status and frailty with disability in older adults.

Design: A prospective study.

Setting And Participants: The study included 8533 participants (mean age: 72.0±6.1 years (range: 60-98 years), women: 54.1%) in a community setting.

Measures: Driving status and frailty were assessed at baseline. The clinical definition of frailty was used according to the Japanese Cardiovascular Health Study index. Disability was prospectively determined using a record of Japanese long-term care insurance (LTCI).

Results: During the follow-up period (mean duration: 23.5 months), 58 (0.7%) participants were regarded as moving out of the city, 80 (0.9%) participants had died and 311 (3.6%) participants were certified by LTCI. The proportion of disability was 1.3% among the not-frail group and 5.3% among the frail group. The proportion of disability was 2.5% in participants who were currently driving and 7.5% in those not driving. Based on frailty status and driving, participants were further classified into four groups: not frail and currently driving (n=2945), not frail and not driving (n=642), frail and currently driving (n=3598) and frail and not driving (n=1348). Compared with older adults who are not frail and driving, the combined status of frail and not driving (adjusted HR: 2.28; 95% CI: 1.47 to 3.52) and frail and driving (HR: 1.91; 95% CI: 1.30-2.81) were risk factors for disability.

Conclusions: Not driving and frail were associated with a risk of disability in community-dwelling older adults.
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http://dx.doi.org/10.1136/bmjopen-2020-042468DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055122PMC
April 2021

Development of a Questionnaire to Evaluate Older Adults' Total Sedentary Time and Sedentary Time With Cognitive Activity.

J Geriatr Psychiatry Neurol 2021 Apr 12:8919887211006468. Epub 2021 Apr 12.

Department of Preventive Gerontology, Center for Gerontology and Social Science, 221156National Center for Geriatrics and Gerontology, Japan.

This study aimed to develop a questionnaire for evaluating total sedentary time (ST) and ST with cognitive activity, and to examine the association between ST and cognitive function among Japanese older adults. The questionnaire to evaluate ST comprised 12 items regarding behavior in specific settings, including 8 items on ST with cognitive activity, in a usual week. Older adults aged ≥75 years who participated in a health check-up assessing cognitive function completed the developed questionnaire and subsequently wore an accelerometer and recorded a diary of ST with cognitive activity for a week as validity measures. Cognitive function was assessed with neuropsychological tests covering 4 domains: memory, attention, executive function, and processing speed. Fifty-two participants were included in the validity analysis. Spearman's correlation coefficient indicated fair-to-good agreement between the questionnaire-measured and the diary-measured time for ST with cognitive activity (r = 0.59, p < 0.001), but this was not the case for total ST. Bland-Altman plots showed that the questionnaire-measured total ST contained proportional bias (r = 0.51, p < 0.001). Multiple regression analysis (n = 49) showed longer questionnaire-measured ST with cognitive activity was significantly associated with better neuropsychological test scores (attention: β = -0.38, p = 0.025; executive function: β = -0.46, p = 0.003; and processing speed: β = 0.31, p = 0.041), while total ST was not associated with better cognitive performance. The developed questionnaire showed acceptable validity to measure ST with cognitive activity, which was found to be protectively associated with cognitive function.
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http://dx.doi.org/10.1177/08919887211006468DOI Listing
April 2021
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