Publications by authors named "Yoshiyuki Watanabe"

357 Publications

Gut microbiota, determined by dietary nutrients, drive modification of the plasma lipid profile and insulin resistance.

iScience 2021 May 16;24(5):102445. Epub 2021 Apr 16.

First Department of Internal Medicine, Faculty of Medicine, Academic Assembly, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.

The gut microbiota metabolizes the nutrients to produce various metabolites that play crucial roles in host metabolism. However, the links between the microbiota established by different nutrients and the microbiota-influenced changes in the plasma lipids remain unclear. Diets rich in cornstarch, fructose, branched chain amino acids, soybean oil (SO), or lard established a unique microbiota and had influence on glucose metabolism, which was partially reproduced by transferring the microbiota. Comparison of plasma lipidomic analysis between germ-free and colonized mice revealed significant impacts of the microbiota on various lipid classes, and of note, the microbiota established by the SO diet, which was associated with the greatest degree of glucose intolerance, caused the maximum alteration of the plasma lipid profile. Thus, the gut microbiota composed of dietary nutrients was associated with dynamic changes in the lipids potentially having differential effects on glucose metabolism.
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http://dx.doi.org/10.1016/j.isci.2021.102445DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105675PMC
May 2021

Effective Control of Brain Metastases Irrespective of Distance from Isocenter in Single-isocenter Multitarget Stereotactic Radiosurgery.

Anticancer Res 2021 May;41(5):2575-2581

Department of Radiology, Shiga University of Medical Science, Otsu, Japan.

Background/aim: Few previous studies have evaluated the effectiveness of single-isocenter multitarget (SIMT) stereotactic radiosurgery (SRS) in clinical practice.

Patients And Methods: Gross tumor volumes of 113 metastases in 13 patients were measured by contrast-enhanced magnetic resonance imaging. Prescribed doses were set at 20-24 Gy. Based on tumor reduction rates (TRRs) measured before and after SIMT SRS, tumor shrinkage effect was categorized into four grades; almost disappeared: TRR=1, decreased: 0.3≤TRR<1, stable: -0.2
Results: Median survival time was 17 months, with 63.7%, 11.5% and 12.4% of metastases corresponded to almost disappeared, decreased and stable, respectively. No significant difference was found in the distribution for TRRs among 3 groups.

Conclusion: Good local control of multiple brain metastases was demonstrated by SIMT SRS, irrespective of distance from the isocenter.
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http://dx.doi.org/10.21873/anticanres.15036DOI Listing
May 2021

Effect of Neurofeedback Facilitation on Poststroke Gait and Balance Recovery: A Randomized Controlled Trial.

Neurology 2021 May 20;96(21):e2587-e2598. Epub 2021 Apr 20.

From the Department of Neurology (M.M., Y.S.), Kawasaki Medical School, Kurashiki; Departments of Neurology (M.M., H.O., Y.K., K.K., H.M.) and Radiology (Y.W.), Osaka University Graduate School of Medicine, Suita; Neurorehabilitation Research Institute (H.F., Y.H., I.M.), Morinomiya Hospital, Osaka; Division of Clinical Neuroengineering (N.H.), Osaka University Global Center for Medical Engineering and Informatics, Suita; and Department of Rehabilitation (N.H.), Toyama University, Japan.

Objective: To test the hypothesis that supplementary motor area (SMA) facilitation with functional near-infrared spectroscopy-mediated neurofeedback (fNIRS-NFB) augments poststroke gait and balance recovery, we conducted a 2-center, double-blind, randomized controlled trial involving 54 Japanese patients using the 3-meter Timed Up and Go (TUG) test.

Methods: Patients with subcortical stroke-induced mild to moderate gait disturbance more than 12 weeks from onset underwent 6 sessions of SMA neurofeedback facilitation during gait- and balance-related motor imagery using fNIRS-NFB. Participants were randomly allocated to intervention (28 patients) or placebo (sham: 26 patients). In the intervention group, the fNIRS signal contained participants' cortical activation information. The primary outcome was TUG improvement 4 weeks postintervention.

Results: The intervention group showed greater improvement in the TUG test (12.84 ± 15.07 seconds, 95% confidence interval 7.00-18.68) than the sham group (5.51 ± 7.64 seconds, 95% confidence interval 2.43-8.60; group difference 7.33 seconds, 95% CI 0.83-13.83; = 0.028), even after adjusting for covariates (group × time interaction; = 4.50, = 0.030, partial η = 0.083). Only the intervention group showed significantly increased imagery-related SMA activation and enhancement of resting-state connectivity between SMA and ventrolateral premotor area. Adverse effects associated with fNIRS-mediated neurofeedback intervention were absent.

Conclusion: SMA facilitation during motor imagery using fNIRS neurofeedback may augment poststroke gait and balance recovery by modulating the SMA and its related network.

Classification Of Evidence: This study provides Class III evidence that for patients with gait disturbance from subcortical stroke, SMA neurofeedback facilitation improves TUG time (UMIN000010723 at UMIN-CTR; umin.ac.jp/english/).
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http://dx.doi.org/10.1212/WNL.0000000000011989DOI Listing
May 2021

Generation and characterization of a Meflin-CreERT2 transgenic line for lineage tracing in white adipose tissue.

PLoS One 2021 24;16(3):e0248267. Epub 2021 Mar 24.

First Department of Internal Medicine, University of Toyama, Toyama-shi, Toyama, Japan.

Meflin (Islr) expression has gained attention as a marker for mesenchymal stem cells, but its function remains largely unexplored. Here, we report the generation of Meflin-CreERT2 mice with CreERT2 inserted under the Meflin gene promoter to label Meflin-expressing cells genetically, thereby enabling their lineages to be traced. We found that in adult mice, Meflin-expressing lineage cells were present in adipose tissue stroma and had differentiated into mature adipocytes. These cells constituted Crown-like structures in the adipose tissue of mice after high-fat diet loading. Cold stimulation led to the differentiation of Meflin-expressing lineage cells into beige adipocytes. Thus, the Meflin-CreERT2 mouse line is a useful new tool for visualizing and tracking the lineage of Meflin-expressing cells.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0248267PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7990287PMC
March 2021

Efficacy of endovascular intratumoral embolization for meningioma: assessment using dynamic susceptibility contrast-enhanced perfusion-weighted imaging.

J Neurointerv Surg 2021 Mar 15. Epub 2021 Mar 15.

Neurosurgery, Osaka University School of Medicine Graduate School of Medicine, Suita, Japan.

Background: In preoperative embolization for intracranial meningioma, endovascular intratumoral embolization is considered to be more effective for the reduction of tumorous vascularity than proximal feeder occlusion. In this study, we aimed to reveal different efficacies for reducing tumor blood flow in meningiomas by comparing endovascular intratumoral embolization and proximal feeder occlusion using dynamic susceptibility contrast-enhanced perfusion-weighted imaging (DSC-PWI).

Methods: 28 consecutive patients were included. DSC-PWI was performed before and after embolization for intracranial meningiomas. Normalized tumor blood volume (nTBV) of voxels of interest of whole tumors were measured from the DSC-PWI data before and after embolization. ΔnTBV% was compared between the cases that received intratumoral embolization and proximal feeder occlusion.

Results: ΔnTBV% in the intratumoral embolization group (42.4±29.8%) was higher than that of the proximal feeder occlusion group (15.3±14.3%, p=0.0039). We used three types of embolic materials and ΔnTBV% did not differ between treatments with or without the use of each material: 42.8±42.4% vs 28.7±20.1% for microspheres (p=0.12), 36.1±20.6% vs 28.1±41.1% for n-butyl cyanoacrylate (p=0.33), and 32.3±37.3% vs 34.1±19.0% for bare platinum coils (p=0.77).

Conclusions: The flow reduction effect of intratumoral embolization was superior to that of proximal feeder occlusion in preoperative embolization for intracranial meningioma in an assessment using DSC-PWI.
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http://dx.doi.org/10.1136/neurintsurg-2020-017116DOI Listing
March 2021

Circulating miR-21, miR-29a, and miR-126 are associated with premature death risk due to cancer and cardiovascular disease: the JACC Study.

Sci Rep 2021 Mar 5;11(1):5298. Epub 2021 Mar 5.

Department of Public Health, Hokkaido University Graduate School of Medicine, Sapporo, Japan.

Primary prevention of premature death is a public health concern worldwide. Circulating microRNAs (miRNAs) have been described as potential diagnostic biomarkers for diseases as cancer and cardiovascular disease (CVD). This case-cohort study aimed to investigate the potential relationship between circulating miRNAs and the risk of premature death. A total of 39,242 subjects provided baseline serum samples in 1988-1990. Of these, 345 subjects who died of intrinsic disease (< 65 years old) and for which measurable samples were available were included in this study. We randomly selected a sub-cohort of 879 subjects. Circulatring miR-21, miR-29a, and miR-126 were determined using qRT-PCR. Conditional logistic regression models were used to analyse the data with respect to stratified miRNA levels. Multivariable logistic regression revealed that subjects with high circulating miR-21 and miR-29a individual levels had a significantly higher risk of total death, cancer death, and CVD death than those with medium miR-21 and miR-29a individual levels. Conversely, subjects with low circulating miR-126 levels had a significantly higher risk of total death than those with medium levels. This suggests that circulating miRNAs are associated with the risk of premature death from cancer and CVD, identifying them as potential biomarkers for early detection of high-risk individuals.
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http://dx.doi.org/10.1038/s41598-021-84707-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935984PMC
March 2021

A 10-year longitudinal study of deep white matter lesions on magnetic resonance imaging.

Neuroradiology 2021 Feb 18. Epub 2021 Feb 18.

Department of Neurology, Kyoto Prefectural University of Medicine, 465, Kajii-cho, Kamigyo-ku, Kyoto-shi, Kyoto-fu, 602-8566, Japan.

Purpose: Deep white matter lesions (DWMLs), T2 high-intensity areas in the subcortical white matter on magnetic resonance imaging (MRI), are a clinical phenotype of cerebral small vessel disease. Factors such as age and hypertension have been reported to significantly contribute to the presence and severity of DWMLs in cross-sectional studies. We herein report a 10-year longitudinal study on DWMLs in elderly Japanese subjects to reveal the clinical variables contributing to the progression of DWMLs.

Methods: A total of 469 Japanese subjects were invited to participate in the study. Of the participants at baseline, 259 subjects completed the revisit MRI study 10 years later. In those 259 subjects, we evaluated the correlation between the progression of DWMLs and clinical variables, such as the gender, age, and overt vascular risk factors. To clarify the role of hypertension, 200 subjects with grade 1 DWMLs at baseline were categorized into three groups according to their status of hypertension and its treatment.

Results: Of the 200 subjects with grade 1 DWMLs, 47 subjects (23.5%) showed progression of DWMLs (progression group). In the progression group, the percentage of subjects with hypertension and the systolic blood pressure values were higher than in the non-progression group. In addition, subjects ≥ 60 years old at baseline tended to show deterioration of DWMLs in the group with hypertension without antihypertensive treatment.

Conclusion: The results of this 10-year longitudinal study imply a positive correlation between long-standing hypertension and the progression of DWMLs.
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http://dx.doi.org/10.1007/s00234-020-02626-2DOI Listing
February 2021

Assessing the Relationship between and Chronic Kidney Disease.

Healthcare (Basel) 2021 Feb 3;9(2). Epub 2021 Feb 3.

Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto 602-8566, Japan.

The relationship between infection and/or gastric disorders and chronic kidney disease (CKD) has not been elucidated. We investigated the relationship between and/or atrophic gastritis (AG) and chronic kidney disease. In total, 3560 participants (1127 men and 2433 women) were eligible for this cross-sectional study. We divided participants into four study groups: with/without infection and with/without AG. The HP (+) AG (-) group demonstrated a significant association with CKD compared with the HP (-) AG (-) group (adjusted odds ratio, 1.443; 95% confidence interval, 1.047-1.989). In contrast, the HP (+) AG (+) group showed significantly lower adjusted odds of CKD than the HP (-) AG (-) group (adjusted odds ratio, 0.608; 95% confidence interval, 0.402-0.920). infection without AG might be associated with CKD in these participants. Conversely, the HP (+) AG (+) group had lower odds of CKD. Uncovering an association between gastric and renal conditions could lead to development of new treatment strategies.
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http://dx.doi.org/10.3390/healthcare9020162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7913305PMC
February 2021

Fat tissue as an embolic material changes the embolization time in a size-dependent manner: a basic investigation using rabbits.

Jpn J Radiol 2021 May 29;39(5):503-510. Epub 2021 Jan 29.

Department of Radiology, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga, 520-2192, Japan.

Purpose: To evaluate the usefulness of fat tissue as an embolic material and determine whether the embolization time depends on the size of the fat tissue.

Materials And Methods: Inguinal fat tissues from 16 rabbits were processed as follows: (1) fat tissues were cut into 2-mm squares, and (2) fat tissue squares were dissociated 20 × through a syringe without a needle (1-139 μm in diameter). The distal main trunk of the right or left renal artery was completely embolized using one of the two types of fat tissue. After 1 or 7 days, renal angiography was performed.

Results: On day 1 after embolization of the renal artery with 2-mm fat tissue squares (Group 1-1) and on day 7 (Group 1-2), the reperfusion rates were 4.0 ± 5.5% and 29.9 ± 6.9%, respectively. On day 1 after embolization of the renal artery with fat tissues dissociated using a 20 × pumping cycle (Group 2-1) and on day 7 (Group 2-2), the reperfusion rates were 59.9 ± 9.9% and 74.3 ± 26.0%, respectively. The reperfusion rates were significantly different between the two types of fat tissue.

Conclusions: Fat tissue serves as an embolic material that changes the embolization time in a size-dependent manner.
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http://dx.doi.org/10.1007/s11604-020-01083-4DOI Listing
May 2021

Relationship of Four Blood Pressure Indexes to Subclinical Cerebrovascular Diseases Assessed by Brain MRI in General Japanese Men.

J Atheroscler Thromb 2021 Jan 22. Epub 2021 Jan 22.

Department of Public Health, Shiga University of Medical Science.

Aim: The relationship of blood pressure (BP) indexes (systolic blood pressure [SBP], diastolic blood pressure [DBP], pulse pressure [PP], mean arterial pressure [MAP]) to subclinical cerebrovascular diseases (SCVDs) remains unclear. This study aimed to elucidate the relationship of four BP indexes measured at two visits on SCVDs assessed by magnetic resonance imaging (MRI) in general Japanese men.

Methods: In general Japanese men aged 40-79 years (N=616), office BP indexes were measured at two visits (Visits 1 [2006-2008] and 2 [2010-2014]). MRI images obtained on the third visit (2012-2015) were examined for prevalent SCVDs: lacunar infarction, periventricular hyperintensity (PVH), deep subcortical white matter hyperintensity (DSWMH), microbleeds, and intracranial artery stenosis (ICAS). Using a multivariable logistic regression analysis, we computed and estimated the odds ratio of each prevalent SCVD for one standard deviation higher BP indexes. The same analyses were performed using home BP.

Results: All four office BP indexes at both visits associated with lacunar infarction. Visit 1 and 2 DBP and Visit 1 MAP associated with PVH and DSWMH, and Visit 1 SBP associated with DSWMH. All Visit 2 BP indexes appear to show stronger association with microbleeds than Visit 1 indexes, and Visit 1 and 2 SBP, PP, and MAP showed similar associations with ICAS. Additional analyses using home BP indexes revealed similar relationships; however, the significance of some relationships decreased.

Conclusion: In general Japanese men, BP indexes were associated with most of SCVDs, and BP indexes measured at different periods associated with different SCVDs assessed by MRI.
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http://dx.doi.org/10.5551/jat.58537DOI Listing
January 2021

Increased F-FDG accumulation in less-affected lung area in patients with non-small cell lung cancer and postoperative acute exacerbation of interstitial lung disease.

Eur J Radiol 2021 Feb 11;135:109477. Epub 2020 Dec 11.

Division of Respiratory Medicine, Department of Internal Medicine, Shiga University of Medical Science, Otsu, Shiga, 520-2192, Japan.

Purpose: To investigate whether or not F-FDG accumulation in normal or less-affected lung fields increased in non-small cell lung cancer (NSCLC) patients with postoperative acute exacerbation (PAE) of interstitial lung disease (ILD) MATERIAL AND METHODS: Thirty-six NSCLC patients with ILD and 50 patients without ILD (non-ILD patients) underwent pre-operative F-FDG-PET/CT at 2 institutions. Volume-of-interest (VOI) was placed to measure the mean standardized uptake value (SUV) in normal or less-affected lung fields at pre-defined 12 areas on ventral and dorsal locations of both lungs. SUV was defined as corrected SUV by using TF and mean computed tomography density on PET/CT. Harmonized SUV (hSUV) and SUV (hSUV) were calculated based on results of phantom study, which was performed to optimize the measured SUV difference among 2 institutions. Both the h-SUV and the h-SUV were compared between 8 patients with PAE of ILD (PAE group) or remaining 28 patients without PAE of ILD (non-PAE group) and non-ILD patients in each of the 12 areas.

Results: The hSUV in PAE group was higher in 9 out of 12 locations as compared with non-ILD patients, whereas the hSUV was mostly similar between non-PAE group and non-ILD patients. In contrast, the hSUV in non-PAE group was similar to that in PAE group, and higher than in non-ILD patients in most locations.

Conclusion: F-FDG-PET/CT demonstrated increased SUV along with elevated SUV in normal or less-affected lung fields for NSCLC patients with PAE of ILD, which may reflect regional invisible fibrosis and inflammatory change.
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http://dx.doi.org/10.1016/j.ejrad.2020.109477DOI Listing
February 2021

Preoperative assessment of localized pleural adhesion: Utility of software-assisted analysis on dynamic-ventilation computed tomography.

Eur J Radiol 2020 Dec 22;133:109347. Epub 2020 Oct 22.

Department of Radiology, Shiga University of Medical Science, Otsu, Shiga, 520-2192, Japan.

Purpose: To assess the usefulness of software analysis using dynamic-ventilation CT for localized pleural adhesion (LPA).

Materials And Methods: Fifty-one patients scheduled to undergo surgery underwent both dynamic-ventilation CT and static chest CT as preoperative assessments. Five observers independently evaluated the presence and severity of LPA on a three-point scale (non, mild, and severe LPA) for 9 pleural regions (upper, middle, and lower pleural aspects on ventral, lateral, and dorsal areas) on the chest CT by three different methods by observing images from: static high-resolution CT (static image); dynamic-ventilation CT (movie image), and dynamic-ventilation CT while referring to the adhesion map (movie image with color map), which was created using research software to visualize movement differences between the lung surface and chest wall. The presence and severity of LPA was confirmed by intraoperative thoracoscopic findings. Parameters of diagnostic accuracy for LPA presence and severity were assessed among the three methods using Wilcoxon signed rank test in total and for each of the three pleural aspects.

Results: Mild and severe LPA were confirmed in 14 and 8 patients. Movie image with color map had higher sensitivity (56.9 ± 10.7 %) and negative predictive value (NPV) (91.4 ± 1.7 %) in LPA detection than both movie image and static image. Additionally, for severe LPA, detection sensitivity was the highest with movie image with color map (82.5 ± 6.1 %), followed by movie image (58.8 ± 17.0 %) and static image (38.8 ± 13.9 %). For LPA severity, movie image with color map was similar to movie image and superior to static image in accuracy as well as underestimation and overestimation, with a mean value of 80.2 %.

Conclusion: Software-assisted dynamic-ventilation CT may be a useful novel imaging approach to improve the detection performance of LPA.
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http://dx.doi.org/10.1016/j.ejrad.2020.109347DOI Listing
December 2020

Relationship Between Step Counts and Cerebral Small Vessel Disease in Japanese Men.

Stroke 2020 12 5;51(12):3584-3591. Epub 2020 Nov 5.

Center for Epidemiologic Research in Asia (M.M., A.K., H.S., H.U., K.M.), Shiga University of Medical Science, Otsu, Japan.

Background And Purpose: Cerebral small vessel disease (CSVD) is a common subclinical feature of the aging brain. Steps per day may contribute to its prevention. We herein investigated the association between step counts and CSVD in a healthy Japanese male population.

Methods: We analyzed data from 680 men who were free of stroke and participated in this observational study. Seven-day step counts were assessed at baseline (2006-2008) using a pedometer. CSVD was assessed at follow-ups (2012-2015) based on deep and subcortical white matter hyperintensities (WMHs), periventricular hyperintensities, lacunar infarcts, and cerebral microbleeds on magnetic resonance imaging. Using a logistic regression analysis, we computed the adjusted odds ratios, with 95% CIs, of prevalent CSVD according to quartiles of step counts (reference: Q1). We also investigated the association between step counts and WMH volumes using a quantile regression.

Results: Steps per day were significantly associated with lower odds ratios, with the lowest at Q3 (8175-10 614 steps/day), of higher (versus low or no burden) deep and subcortical WMHs (odds ratio, 0.52 [95% CI, 0.30-0.89]), periventricular hyperintensities (0.50 [95% CI, 0.29-0.86]), and lacunar infarcts (0.52 [95% CI, 0.30-0.91]) compared with Q1 (≤6060 steps/day) but not cerebral microbleeds. An inverse linear association was observed between step counts and WMH volumes. These associations were independent of age and smoking and drinking status and remained consistent when adjusted for vascular risk factors.

Conclusions: We found a J-shaped relationship between step counts and prevalent CSVD in healthy Japanese men, with the lowest risk being observed among participants with ≈8000 to 10 000 steps/day. Higher steps were also associated with lower WMH volumes.
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http://dx.doi.org/10.1161/STROKEAHA.120.030141DOI Listing
December 2020

Relationship between white matter microstructure and work hours.

Neurosci Lett 2021 01 18;740:135428. Epub 2020 Oct 18.

Department of Pathology of Mental Diseases, National Institute of Mental Health, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi, Kodaira, Tokyo 187-8553, Japan; Osaka University, 1-1 Yamadaoka, Suita, Osaka 565-0871, Japan. Electronic address:

Human social activities are realized by a synergy of neuronal activity over various regions of the brain, which is supported by their connectivity. In the present study, we examined associations between social activities, represented by work hours, and brain connectivity as quantified using diffusion tensor imaging (DTI). In 483 healthy participants, DTI analysis was performed using 3 T magnetic resonance imaging, and work hours were calculated, considering hours of paid employment (the "Work for Pay" category), hours of housework (the "Work at Home" category), and hours of school-related study (the "Student" category). The correlations between each class of work time and DTI indices were analyzed. The mean diffusivity (MD) values of the anterior limb of the internal capsule (ALIC) and the superior fronto-occipital fasciculus (SFO) were negatively correlated with total work hours (ALIC: r = -0.192, p =  2.3 × 10; SFO: r = -0.161, p =  3.8 × 10). We also found that the MD values of the ALIC and the SFO were correlated with work hours in the Work for Pay category (ALIC: r = -0.211, p =  3.2 × 10; SFO: r = -0.163, p =  3.4 × 10) but not with those in the Work at Home category or the Student category. These results suggest that social activity is associated with the white matter microstructure of the ALIC and the SFO. The main difference between "Work for Pay" and the other two social activities appears to be the type of motivation-for example, external versus internal. Therefore, the white matter microstructure of the ALIC and SFO may be related to externally motivated social activities.
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http://dx.doi.org/10.1016/j.neulet.2020.135428DOI Listing
January 2021

Evaluation of myostatin as a possible regulator and marker of skeletal muscle-cortical bone interaction in adults.

J Bone Miner Metab 2021 May 12;39(3):404-415. Epub 2020 Oct 12.

Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine, 465 Kajiicho, Kawaramachi-hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan.

Introduction: Bone mass was recently reported to be related to skeletal muscle mass in humans, and a decrease in cortical bone is a risk factor for osteoporosis. Because circulating myostatin is a factor that primarily controls muscle metabolism, this study examined the role of myostatin in bone mass-skeletal muscle mass interactions.

Methods: The subjects were 375 middle-aged community residents with no history of osteoporosis or sarcopenia who participated in a health check-up. Cortical bone thickness and cancellous bone density were measured by ultrasonic bone densitometry in a health check-up survey. The subjects were divided into those with low cortical bone thickness (LCT) or low cancellous bone density (LBD) and those with normal values (NCT/NBD). Bone metabolism markers (TRACP-5b, etc.), skeletal muscle mass, serum myostatin levels, and lifestyle were then compared between the groups.

Results: The percentage of diabetic participants, TRACP-5b, and myostatin levels were significantly higher, and the frequency of physical activity, skeletal muscle mass, grip strength, and leg strength were significantly lower in the LCT group than in the NCT group. The odds ratio (OR) of high myostatin levels in the LCT group compared with the NCT group was significant (OR 2.17) even after adjusting for related factors. Between the low cancellous bone density (LBD) and normal cancellous bone density (NBD) groups, significant differences were observed in the same items as between the LCT and NCT groups, but no significant differences were observed in skeletal muscle mass and blood myostatin levels. The myostatin level was significantly negatively correlated with cortical bone thickness and skeletal muscle mass.

Conclusions: A decrease in cortical bone thickness was associated with a decrease in skeletal muscle mass accompanied by an increase in the blood myostatin level. Blood myostatin may regulate the bone-skeletal muscle relationship and serve as a surrogate marker of bone metabolism, potentially linking muscle mass to bone structure.
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http://dx.doi.org/10.1007/s00774-020-01160-8DOI Listing
May 2021

Geometry of Sleeve Gastrectomy Measured by 3D CT Versus Weight Loss: Preliminary Analysis.

World J Surg 2021 Jan 9;45(1):235-242. Epub 2020 Oct 9.

Department of Surgery, Shiga University of Medical Science, Tsukinowa-cho, Seta, Otsu, Shiga, 520-2192, Japan.

Background: The size of the remnant stomach with respect to weight loss failure after laparoscopic sleeve gastrectomy (LSG) remains controversial. This study aimed to evaluate the impact of the actual size and volume of the remnant stomach, as measured by three-dimensional computed tomography (3D-CT) volumetry, on weight loss after LSG.

Methods: The clinical outcomes of 52 patients who underwent LSG between October 2008 and February 2019 were assessed. Weight metrics were recorded at 1, 3, and 6 months and 1 year postoperatively. 3D-CT volumetry was performed 1 year postoperatively, and the total remnant stomach volume (TSV), proximal stomach volume (PSV), antral stomach volume (ASV), and the distance between the pylorus and the distal edge of staple line (DPS) were measured. The relationship between the weight metrics and aforementioned factors was analyzed.

Results: Of the 52 patients who underwent LSG, 40 patients participated in this study. The average body mass index preoperatively was 38.3 ± 5.1 kg/m, and the average percentage of total weight loss (%TWL) 1 year after LSG was 26.6 ± 9.3%. The average TSV, PSV, ASV, and DPS were 123.2 ± 60.3 ml, 73.4 ± 37.2 ml, 49.8 ± 30.3 ml, and 59.9 ± 18.5 mm, respectively. The DPS (r = - 0.394, p = 0.012) and ASV (r = - 0.356, p = 0.024) were correlated with %TWL 1 year postoperatively.

Conclusions: The actual DPS and ASV measured by 3D-CT affected weight loss after LSG. 3D-CT may be useful for the immediate identification of factors affecting insufficient weight loss in patients; this may, in turn, aid in the implementation of early intervention treatments.
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http://dx.doi.org/10.1007/s00268-020-05807-5DOI Listing
January 2021

Non-Invasive Early Molecular Detection of Gastric Cancers.

Cancers (Basel) 2020 Oct 7;12(10). Epub 2020 Oct 7.

Division of Gastroenterology and Hepatology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki 216-8511, Japan.

Gastric cancer (GC) is a significant source of global cancer death with a high mortality rate, because the majority of patients with GC are diagnosed at a late stage, with limited therapeutic choices and poor outcomes. Therefore, development of minimally invasive or noninvasive biomarkers which are specific to GC is crucially needed. The latest advancements in the understanding of GC molecular landscapes and molecular biological methods have accelerated attempts to diagnose GC at an early stage. Body fluids, including peripheral blood, saliva, gastric juice/wash, urine, and others, can be a source of biomarkers, offering new methods for the early detection of GC. Liquid biopsy-based methods using circulating sources of cancer nucleic acids could also be considered as alternative strategies. Moreover, investigating gastric juices/washes could represent an alternative for the detection of GC via invasive biopsy. This review summarizes recently reported biomarkers based on DNA methylation, microRNA, long noncoding RNA, circular RNA, or extracellular vesicles (exosomes) for the detection of GC. Although the majority of studies have been conducted to detect these alterations in advanced-stage GC and only a few in population studies or early-stage GC, some biomarkers are potentially valuable for the development of novel approaches for an early noninvasive detection of GC.
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http://dx.doi.org/10.3390/cancers12102880DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7600616PMC
October 2020

Noncontrast MRI of acute abdominal pain caused by gastrointestinal lesions: indications, protocol, and image interpretation.

Jpn J Radiol 2021 Mar 9;39(3):209-224. Epub 2020 Oct 9.

Department of Radiology, Shiga University of Medical Science, Seta, Tsukinowa-cho, Otsu, Shiga, 520-2192, Japan.

Gastrointestinal tract lesions are major causes of acute abdominal pain. A rapid, accurate, and reliable diagnosis is required to manage patients. Magnetic resonance imaging (MRI) is a nonionizing modality that is beneficial for pregnant women, children, and young adults who are sensitive to ionizing radiation. For patients with renal impairment who are not accurately diagnosed with noncontrast computed tomography, noncontrast MRI can serve as an alternative diagnostic modality. MRI protocols used for acute abdominal pain are supposed to be optimized and prioritized to shorten scanning times. Single-shot T2-weighted and fat-suppressed T2-weighted imaging are important pulse sequences that are used to reveal pathology and inflammation in the gastrointestinal tract. Diffusion-weighted imaging clearly depicts inflammation and abscesses as hyperintense lesions. Most acute gastrointestinal tract lesions, including inflammation, ischemia, obstruction, and perforation, demonstrate bowel wall thickening. Bowel obstruction and adynamic ileus present bowel dilatation, and perforation and penetration show bowel wall defects. MRI can be used to reveal these pathological findings with some characteristics depending on their underlying pathophysiology. This review article discusses imaging modalities for acute abdominal pain, describes a noncontrast MRI protocol for acute abdominal pain caused by gastrointestinal tract lesions, and reviews MRI findings of acute gastrointestinal tract lesions.
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http://dx.doi.org/10.1007/s11604-020-01053-wDOI Listing
March 2021

Improvement of the diagnostic accuracy for intracranial haemorrhage using deep learning-based computer-assisted detection.

Neuroradiology 2021 May 6;63(5):713-720. Epub 2020 Oct 6.

Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.

Purpose: To elucidate the effect of deep learning-based computer-assisted detection (CAD) on the performance of different-level physicians in detecting intracranial haemorrhage using CT.

Methods: A total of 40 head CT datasets (normal, 16; haemorrhagic, 24) were evaluated by 15 physicians (5 board-certificated radiologists, 5 radiology residents, and 5 medical interns). The physicians attended 2 reading sessions without and with CAD. All physicians annotated the haemorrhagic regions with a degree of confidence, and the reading time was recorded in each case. Our CAD system was developed using 433 patients' head CT images (normal, 203; haemorrhagic, 230), and haemorrhage rates were displayed as corresponding probability heat maps using U-Net and a machine learning-based false-positive removal method. Sensitivity, specificity, accuracy, and figure of merit (FOM) were calculated based on the annotations and confidence levels.

Results: In patient-based evaluation, the mean accuracy of all physicians significantly increased from 83.7 to 89.7% (p < 0.001) after using CAD. Additionally, accuracies of board-certificated radiologists, radiology residents, and interns were 92.5, 82.5, and 76.0% without CAD and 97.5, 90.5, and 81.0% with CAD, respectively. The mean FOM of all physicians increased from 0.78 to 0.82 (p = 0.004) after using CAD. The reading time was significantly lower when CAD (43 s) was used than when it was not (68 s, p < 0.001) for all physicians.

Conclusion: The CAD system developed using deep learning significantly improved the diagnostic performance and reduced the reading time among all physicians in detecting intracranial haemorrhage.
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http://dx.doi.org/10.1007/s00234-020-02566-xDOI Listing
May 2021

Survey of the current status of subclinical coronavirus disease 2019 (COVID-19).

J Infect Chemother 2020 Dec 6;26(12):1294-1300. Epub 2020 Sep 6.

Kanagawa Physicians Association, Japan.

Objectives: We investigated relationships between subclinical COVID-19 (coronavirus disease 2019) and background factors.

Methods: We determined SARS-CoV-2 antibody (IgG) prevalence in 1603 patients, doctors, and nurses in 65 medical institutions in Kanagawa Prefecture, Japan and investigated their background factors. Antibodies (IgG) against SARS-CoV-2 were analyzed by Immunochromatographic test.

Results: The 39 subjects (2.4%) were found to be IgG antibody-positive: 29 in the patient group (2.9%), 10 in the doctor/nurse group (2.0%), and 0 in the control group. After adjustment for age, sex, and the antibody prevalence in the control group, antibody prevalence was 2.7% in the patient group and 2.1% in the doctor/nurse group. There was no significant difference between the antibody-positive subjects and the antibody-negative subjects in any background factors investigated including overseas travel, contact with overseas travelers, presence/absence of infected individuals in the living area, use of trains 5 times a week or more, BCG vaccination, and use of ACE inhibitor and ARB.

Conclusions: Antibody prevalence in the present survey at medical institution is higher than that in Tokyo and in Osaka measured by the government suggesting that subclinical infections are occurring more frequently than expected. No background factor that influenced antibody-positive status due to subclinical infection was identified.
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http://dx.doi.org/10.1016/j.jiac.2020.09.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7474902PMC
December 2020

Left hemispheric α band cerebral oscillatory changes correlate with verbal memory.

Sci Rep 2020 09 14;10(1):14993. Epub 2020 Sep 14.

Department of Neurological Diagnosis and Restoration, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.

Event-related synchronisation (ERS) and event-related desynchronisation (ERD) have been observed via magnetoencephalography (MEG) in the language-dominant hemisphere. However, the relationship between ERS/ERD and clinical language indices is unclear. Therefore, the present study evaluated brain activity utilising MEG during a verb generation task in 36 subjects and determined ERS/ERD power values in θ, α, β, low γ and high γ frequency bands. To measure clinical language indices, we adopted Wechsler Memory Scale-revised. We observed ERD in the α band from the bilateral occipital to the left central brain region, in the β band from the bilateral occipital to the left frontal region and in the low γ band a high-power signal in the left frontal region. We also observed ERS in the θ band in bilateral frontal region and in the high γ band in bilateral occipital region. Furthermore, we found a significant negative correlation between α-band ERD power at the left postcentral gyrus and medial superior frontal gyrus and verbal memory score (correlation coefficients =  - 0.574 and - 0.597, respectively). These results suggest that individuals with lower linguistic memory have less desynchronised α-band ERD power and α-band ERD power in the left hemisphere may be a neurophysiological biomarker for verbal memory.
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http://dx.doi.org/10.1038/s41598-020-72087-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7490359PMC
September 2020

Association between the superior longitudinal fasciculus and perceptual organization and working memory: A diffusion tensor imaging study.

Neurosci Lett 2020 11 2;738:135349. Epub 2020 Sep 2.

Department of Psychiatry, Osaka University Graduate School of Medicine, Osaka, Japan; Department of Pathology of Mental Diseases, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo, Japan; Molecular Research Center for Children's Mental Development, United Graduate School of Child Development, Osaka University, Osaka, Japan.

The superior longitudinal fasciculus (SLF) is a white matter structure that has long bidirectional projections among the prefrontal, temporal, occipital, and parietal cortices and extends over a wide area in a human brain. Recently, anatomical details of the SLF have been clarified using a diffusion tensor imaging (DTI) template of subjects from the Human Connectome Project. However, the neurobehavioral functions of the SLF have not been fully elucidated. It is speculated that the SLF contributes to a broad cognitive domain including visuospatial nonverbal cognitive ability and verbal memory ability because of its anatomical location; however, previous findings in imaging studies are inconsistent. Showing the contribution of the SLF to cognitive function may be important for improving our understanding of the functional role of white matter structures in the human brain. This study aimed to identify the relationship between DTI indices of the SLF and the Verbal Comprehension, Perceptual Organization, Working Memory and Processing Speed Indices of the Wechsler Adult Intelligence Scale-Third Edition using regression analysis, accounting for the effects of age, sex and scanner type in 583 healthy volunteers. We showed significant correlations between the fractional anisotropy of the left SLF and the Perceptual Organization Index (β = 0.21, p =  4.5×10) and Working Memory Index (β = 0.19, p =  4.0×10). These findings may have implications for the rehabilitation of cognitive function in patients with neurological disorders.
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http://dx.doi.org/10.1016/j.neulet.2020.135349DOI Listing
November 2020

Cancer-related genetic variants of Helicobacter pylori strains determined using gastric wash-based whole-genome analysis with single-molecule real-time technology.

Int J Cancer 2021 01 11;148(1):178-192. Epub 2020 Sep 11.

Division of Gastroenterology and Hepatology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan.

Helicobacter pylori (H. pylori) are a primary factor in the pathogenesis of gastric cancer (GC); GC ranks third among cancer-related mortality. A clear understanding of the H. pylori genome factors underlying GC is necessary to develop more effective methods to prevent GC. A single-molecule real-time DNA sequencing-based H. pylori genome-wide association study analysis was performed using the H. pylori genome present in five early-stage GC (EGC) and five non-GC clinical DNA samples recovered from gastric washes. A total of 275 genes with 702 nucleotide variants (NVs) were found to be common to three or more patients with EGC but no non-GC patients (single-NV: 654/702, 93.2%; multi-NV: 40/702, 5.7%; deletion: 3/702, 0.4%; insertion: 3/702, 0.7%). Gene ontology analysis of H. pylori revealed that genes involved in the mitochondrial electron transport system, glycolytic processes and the TCA cycle were highly enriched. Cancer-related NVs were most frequently found in a member of the Helicobacter outer membrane protein family, hopL. In particular, one of the NVs in hopL was a novel six-nucleotide insertion (1159095̂1159096, TACTTC); this mutant was detected more frequently in a validation set of 50 additional EGC samples (22/50, 44.0%) than in 18 non-GC samples (3/18, 16.7%, P = .04). These results suggest that the hopL variant is associated with the development of GC and may serve as a genetic biomarker of H. pylori virulence and GC risk. Our assay can serve as a potent tool to expand our understanding of bacteria-associated tumorigenesis.
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http://dx.doi.org/10.1002/ijc.33257DOI Listing
January 2021

Foreign-body granulomas and abscesses caused by dropped gallstones after cholecystectomy: Four cases diagnosed with multimodality imaging.

Radiol Case Rep 2020 Sep 3;15(9):1480-1484. Epub 2020 Jul 3.

Department of Radiology, Shiga University of Medical Science, Seta, Tsukinowa-cho, Otsu-city, Shiga, 520-2192, Japan.

Four cases (age range, 60-78 years, male:female = 1:3) who had undergone cholecystectomy presented with fever (n = 1), right abdominal pain with fever (n = 1), appetite loss with fever (n = 1), and absence of symptoms (n = 1). Computed tomography (CT) showed an irregular-shaped invasive mass or fluid collection in the right Morrison's pouch, right paracolic gutter, gallbladder fossa, subphrenic space, or abdominal wall. CT and ultrasound revealed gallstones in the granuloma in 3 cases and an abscess in one case. The inflammatory process induced by dropped gallstones may mimic peritoneal malignancies. Awareness of cholecystectomy and the detection of gallstones in the lesion are essential for the diagnosis of dropped gallstones.
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http://dx.doi.org/10.1016/j.radcr.2020.05.073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7339004PMC
September 2020

Microsatellite instability in cancer: a novel landscape for diagnostic and therapeutic approach.

Arch Toxicol 2020 10 6;94(10):3349-3357. Epub 2020 Jul 6.

Division of Gastroenterology and Hepatology, Department of Internal Medicine, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, 216-8511, Japan.

Defective DNA mismatch repair creates a strong mutator phenotype, recognized as microsatellite instability (MSI). Various next-generation sequencing-based methods for evaluating cancer MSI status have been established, and NGS-based studies have thoroughly described MSI-driven tumorigenesis. Accordingly, high-frequency MSI (MSI-H) has been detected in 81 tumor types, including those in which MSI was previously underrated. The findings have increased the use of immunotherapy, which is assumed to be efficient in tumors having a high mutation burden and/or neoantigen load. In MSI tumorigenesis, positively and negatively selected driver gene mutations have been characterized in colorectal cancers. Recent advancements in genome-wide studies of MSI-H cancers have developed novel diagnostic and therapeutic approaches, including CXCR2 inhibitor, a synthetic lethal therapy targeting the Werner gene and inhibition of nonsense-mediated mRNA decay. MSI is a predictive marker for chemotherapy as well as immunotherapy. Thus, analyses of MSI status and MSI-related alterations in cancers are clinically relevant. We present an update on MSI-driven tumorigenesis, focusing on a novel landscape of diagnostic and therapeutic approaches.
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http://dx.doi.org/10.1007/s00204-020-02833-zDOI Listing
October 2020

Usability of the lateral decubitus position on four-dimensional ultra-low-dose computed tomography for the detection of localized pleural adhesion in the pulmonary apical region.

Acta Radiol 2021 Apr 1;62(4):462-473. Epub 2020 Jul 1.

Department of Radiology, Shiga University of Medical Science, Otsu, Shiga, Japan.

Background: Localized pleural adhesion (LPA) evaluation in the apical region is difficult even with four-dimensional ultra-low-dose computed tomography (4D-ULDCT) in the supine position due to smaller pleural movements.

Purpose: To assess usability of 4D-ULDCT in the lateral decubitus (LD) position for LPA detection in the apical region.

Material And Methods: Forty-seven patients underwent 4D-ULDCT of a single respiration cycle with 16-cm coverage of body axis in supine and LD positions with the affected lung uppermost. Intraoperative thoracoscopic findings confirmed LPA presence. A pleural point and a corresponding point on costal outer edge were placed in identical axial planes at end-inspiration. Pleuro-chest wall distance between two points (PCD) was calculated at each respiratory phase. In the affected lung, average change in amount of PCD (PCD) was compared between patients with and without LPA in total and two sub-groups (non-COPD and COPD, non-emphysematous and emphysematous patients) in supine and non-dependent (ND) LD positions. Receiver operating characteristic (ROC) curve analysis was performed to determine optimal thresholds in PCD for differentiating patients with LPA from those without.

Results: In COPD/emphysematous patients and total population, PCD with LPA was smaller than in those without in the supine and NDLD positions for overall, lateral, and dorsal regions. For the lateral region in COPD patients, area under ROC curve (AUC) increased from supine (0.64) to NDLD position (0.81). For the dorsal region in emphysematous patients, AUC increased from supine (0.76) to NDLD position (0.96).

Conclusion: 4D-ULDCT in LD position may be useful for LPA detection in apical regions for COPD and/or emphysematous patients.
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http://dx.doi.org/10.1177/0284185120930611DOI Listing
April 2021

Evaluation of intrathoracic tracheal narrowing in patients with obstructive ventilatory impairment using dynamic chest radiography: A preliminary study.

Eur J Radiol 2020 Aug 19;129:109141. Epub 2020 Jun 19.

Department of Radiology, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga, 520-2192, Japan. Electronic address:

Purpose: Dynamic chest radiography (DCR) can observe the dynamic structure of the chest using continuous pulse fluoroscopy irradiation. However, its usefulness remains largely undetermined. The purpose of this study was to examine the relationship between changes in tracheal diameter during deep breathing and obstructive ventilation disorders using DCR.

Method: Twelve participants with obstructive ventilatory impairment and 28 with normal pulmonary function underwent DCR during one cycle of deep inspiration and expiration. Three evaluators blinded to pulmonary function test results independently measured lateral diameters of the trachea in DCR images to determine whether there was a difference in the amount of change in tracheal diameter depending on the presence or absence of pulmonary dysfunction. Tracheal narrowing was defined as a decrease in the lateral tracheal diameter of more than 30 %. Participants were divided into a narrowing group and a non-narrowing group, and it was examined whether each group correlated with values of pulmonary function tests.

Results: Tracheal diameter was significantly narrowed in subjects with obstructive ventilatory impairment compared to normal subjects (P <  0.01). When subjects were divided into narrowing (tracheal narrowing rate [TNr] = 41.5 ± 7.7 %, n = 9) and non-narrowing groups (TNr = 9.1 ± 7.0 %, n = 31, p < 0.01), FEV1%-G, and %V25 were significantly smaller in the narrowing group than in the non-narrowing group (p < 0.01).

Conclusions: Changes in tracheal diameter during deep breathing were easily evaluated using DCR. DCR may, therefore, be useful for evaluating obstructive ventilation disorders.
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http://dx.doi.org/10.1016/j.ejrad.2020.109141DOI Listing
August 2020

Genome-wide association meta-analysis identifies GP2 gene risk variants for pancreatic cancer.

Nat Commun 2020 06 24;11(1):3175. Epub 2020 Jun 24.

Department of Gastroenterological Surgery, Aichi Cancer Center Hospital, Nagoya, 464-8681, Japan.

Pancreatic cancer is the fourth leading cause of cancer-related deaths in Japan. To identify risk loci, we perform a meta-analysis of three genome-wide association studies comprising 2,039 pancreatic cancer patients and 32,592 controls in the Japanese population. Here, we identify 3 (13q12.2, 13q22.1, and 16p12.3) genome-wide significant loci (P < 5.0 × 10), of which 16p12.3 has not been reported in the Western population. The lead single nucleotide polymorphism (SNP) at 16p12.3 is rs78193826 (odds ratio = 1.46, 95% confidence interval = 1.29-1.66, P = 4.28 × 10), an Asian-specific, nonsynonymous glycoprotein 2 (GP2) gene variant. Associations between selected GP2 gene variants and pancreatic cancer are replicated in 10,822 additional cases and controls of East Asian origin. Functional analyses using cell lines provide supporting evidence of the effect of rs78193826 on KRAS activity. These findings suggest that GP2 gene variants are probably associated with pancreatic cancer susceptibility in populations of East Asian ancestry.
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http://dx.doi.org/10.1038/s41467-020-16711-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7314803PMC
June 2020

Multiscale modeling of human cerebrovasculature: A hybrid approach using image-based geometry and a mathematical algorithm.

PLoS Comput Biol 2020 06 22;16(6):e1007943. Epub 2020 Jun 22.

Graduate School of Engineering Science, Osaka University, Toyonaka, Osaka, Japan.

The cerebral vasculature has a complex and hierarchical network, ranging from vessels of a few millimeters to superficial cortical vessels with diameters of a few hundred micrometers, and to the microvasculature (arteriole/venule) and capillary beds in the cortex. In standard imaging techniques, it is difficult to segment all vessels in the network, especially in the case of the human brain. This study proposes a hybrid modeling approach that determines these networks by explicitly segmenting the large vessels from medical images and employing a novel vascular generation algorithm. The framework enables vasculatures to be generated at coarse and fine scales for individual arteries and veins with vascular subregions, following the personalized anatomy of the brain and macroscale vasculatures. In this study, the vascular structures of superficial cortical (pial) vessels before they penetrate the cortex are modeled as a mesoscale vasculature. The validity of the present approach is demonstrated through comparisons with partially observed data from existing measurements of the vessel distributions on the brain surface, pathway fractal features, and vascular territories of the major cerebral arteries. Additionally, this validation provides some biological insights: (i) vascular pathways may form to ensure a reasonable supply of blood to the local surface area; (ii) fractal features of vascular pathways are not sensitive to overall and local brain geometries; and (iii) whole pathways connecting the upstream and downstream entire-scale cerebral circulation are highly dependent on the local curvature of the cerebral sulci.
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http://dx.doi.org/10.1371/journal.pcbi.1007943DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7332106PMC
June 2020