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ISSN / EISSN : 19326203 / 19326203
Current Publisher: Public Library of Science (PLoS) (10.1371)
Total articles ≅ 231,144
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Midori Awazu, Mariko Hida
Published: 6 April 2020
PLOS ONE, Volume 15; doi:10.1371/journal.pone.0230289

Abstract:
We previously reported that maternal nutrient restriction (NR) inhibited ureteric branching, metanephric growth, and nephrogenesis in the rat. Here we examined whether folic acid, a methyl-group donor, rescues the inhibition of kidney development induced by NR and whether DNA methylation is involved in it. The offspring of dams given food ad libitum (CON) and those subjected to 50% food restriction (NR) were examined. NR significantly reduced ureteric tip number at embryonic day 14, which was attenuated by folic acid supplementation to nutrient restricted dams. At embryonic day 18, glomerular number, kidney weight, and global DNA methylation were reduced by NR, and maternal folic acid supplementation again alleviated them. Among DNA methyltransferases (DNMTs), DNMT1 was strongly expressed at embryonic day 15 in CON but was reduced in NR. In organ culture, an inhibitor of DNA methylation 5-aza-2 '-deoxycytidine as well as medium lacking methyl donors folic acid, choline, and methionine, significantly decreased ureteric tip number and kidney size mimicking the effect of NR. In conclusion, global DNA methylation is necessary for normal kidney development. Folic acid supplementation to nutrient restricted dams alleviated the impaired kidney development and DNA methylation in the offspring.
Akari Nakamura-Utsunomiya, Miyuki Tsumura, Satoshi Okada, Hiroshi Kawaguchi, Masao Kobayashi
Published: 6 April 2020
PLOS ONE, Volume 15; doi:10.1371/journal.pone.0230665

Abstract:
Phagocytes in patients with chronic granulomatous disease (CGD) do not generate reactive oxidative species (ROS), whereas nitric oxide (NO) production is increased in response to the calcium ionophore A23187 in CGD phagocytes compared with healthy phagocytes. Recently, patients with X-linked CGD (X-CGD) have been reported to show higher flow-mediated dilation, suggesting that endothelial cell function is affected by NO production from phagocytes. We studied NOS3 and EDN1 mRNA and protein expression in human umbilical vein endothelial cells (HUVECs) in a co-culture system with neutrophils from X-CGD patients. HUVECs were co-cultured for 30 minutes with human neutrophils from X-CGD or healthy participants in response to A23187 without cell-to-cell contact. The expression of NOS3 and EDN1 mRNA in HUVECs was quantified by real-time polymerase chain reaction. Moreover, we demonstrated the protein expression of eNOS, ET-1, and NFκB p65, including phosphorylation at Ser1177 of eNOS and Ser536 of NFκB p65. Neutrophils from X-CGD patients showed significantly higher NO and lower H2O2 production in response to A23187 than healthy neutrophils in vitro. Compared with healthy neutrophils, X-CGD neutrophils under A23187 stimulation exhibited significantly increased NO and decreased H2O2, and promoted downregulated NOS3 and EDN1 expression in HUVECs. The total expression and phosphorylation at Ser1177 of eNOS and ET-1 expression were significantly decreased in HUVECs co-cultures with stimulated X-CGD neutrophils. Also, phosphorylation at Ser536 of NFκB p65 were significantly decreased. In conclusions, eNOS and ET-1 significantly down-regulated in co-culture with stimulated X-CGD neutrophils through their excessive NO and the lack of ROS production. These findings suggest that ROS generated from neutrophils may mediate arterial tone affecting eNOS and ET-1 expression via their NO and ROS production.
Yuta Ibuki, Yukie Nishiyama, Yasuhiro Tsutani, Manabu Emi, Yoichi Hamai, Morihito Okada, Hidetoshi Tahara
Published: 6 April 2020
PLOS ONE, Volume 15; doi:10.1371/journal.pone.0231116

Abstract:
MicroRNA (miR)s are promising diagnostic biomarkers of cancer. Recent next generation sequencer (NGS) studies have found that isoforms of micro RNA (isomiR) circulate in the bloodstream similarly to mature micro RNA (miR). We hypothesized that combination of circulating miR and isomiRs detected by NGS are potentially powerful cancer biomarker. The present study aimed to investigate their application in esophageal cancer. Serum samples from patients with esophageal squamous cell carcinoma (ESCC) and age and sex matched healthy control (HC) individuals were investigated for the expression of miR/isomiRs using NGS. Candidate miR/isomiRs which met the criteria in the 1st group (ESCC = 18 and HC = 12) were validated in the 2nd group (ESCC = 30 and HC = 30). A diagnostic panel was generated using miR/isomiRs that were consistently confirmed in the 1st and 2nd groups. Accuracy of the panel was tested then in the 3rd group (ESCC = 18 and HC = 18). Their use was also investigated in 22 paired samples obtained pre- and post-treatment, and in patients with esophageal adenocarcinoma (EAD) and high‐grade dysplasia (HGD). Twenty-four miR/isomiRs met the criteria for diagnostic biomarker in the 1st and 2nd group. A multiple regression model selected one mature miR (miR-30a-5p) and two isomiRs (isoform of miR-574-3p and miR-205-5p). The index calculated from the diagnostic panel was significantly higher in ESCC patients than in the HCs (13.3±8.9 vs. 3.1±1.3, p<0.001). The area under the receiver operating characteristics (ROC) curves of the panel index was 0.95. Sensitivity and specificity were 93.8%, and 81% in the 1st and 2nd groups, and 88.9% and 72.3% in the 3rd group, respectively. The panel index was significantly lower in patients with EAD (6.2±4.5) and HGD (4.2±1.7) than in those with ESCC and was significantly decreased at post-treatment compared with pre-treatment (6.2±5.6 vs 11.6±11.5, p = 0.03). Our diagnostic panel had high accuracy in the diagnosis of ESCC. MiR/isomiRs detected by NGS could serve as novel biomarkers of ESCC.
Xieling Chen, Juan Chen, Gary Cheng, Tao Gong
Published: 6 April 2020
PLOS ONE, Volume 15; doi:10.1371/journal.pone.0231192

Abstract:
Artificial intelligence (AI) assisted human brain research is a dynamic interdisciplinary field with great interest, rich literature, and huge diversity. The diversity in research topics and technologies keeps increasing along with the tremendous growth in application scope of AI-assisted human brain research. A comprehensive understanding of this field is necessary to assess research efficacy, (re)allocate research resources, and conduct collaborations. This paper combines the structural topic modeling (STM) with the bibliometric analysis to automatically identify prominent research topics from the large-scale, unstructured text of AI-assisted human brain research publications in the past decade. Analyses on topical trends, correlations, and clusters reveal distinct developmental trends of these topics, promising research orientations, and diverse topical distributions in influential countries/regions and research institutes. These findings help better understand scientific and technological AI-assisted human brain research, provide insightful guidance for resource (re)allocation, and promote effective international collaborations.
Haruka Seki, Akito Miura, Nahoko Sato, Jun Yuda, Toshiko Shimauchi
Published: 6 April 2020
PLOS ONE, Volume 15; doi:10.1371/journal.pone.0231015

Abstract:
Hallux valgus is a serious medical concern for classical ballet dancers. Although it is well-known that progression of hallux valgus is related to inappropriate movement techniques in classical ballet, the kinematic relationship between the degree of hallux valgus and ballet techniques has not been substantiated. To develop proper training methods that prevent progression of hallux valgus, this study aimed to investigate the relationship between the degree of hallux valgus and movement techniques in classical ballet. Seventeen female classical ballet dancers at the advanced college-level participated in this study. Kinematic analysis of standing and plié in the first position was conducted via video capture technique. The Pearson product-moment correlation analysis was performed to examine the degree of hallux valgus and the following three kinematic variables: (1) the extent to which turnout is forced by other joints in the lower extremity than the hip joint, (2) the direction difference between the knee and toe in the transverse plane, and (3) the pelvis obliquity angle. Among these kinematic variables, we found a significant correlation between the hallux valgus angle and the pelvis obliquity angle during plié (P = .045). The greater the hallux valgus angle, the greater the retroversion of the pelvis, a result which was contrary to our prediction. We present the first evidence that the degree of hallux valgus correlates with kinematics in a very basic technique of classical ballet.
Tohru Irie, Alejandro A. Espinoza Orías, Tomoyo Y. Irie, Shane J. Nho, Daisuke Takahashi, Norimasa Iwasaki, Nozomu Inoue
Published: 6 April 2020
PLOS ONE, Volume 15; doi:10.1371/journal.pone.0231001

Abstract:
Whether borderline hip dysplasia is pathologic remains unclear. In order to evaluate the three-dimensional joint congruity, this study sought to answer the question: are borderline dysplastic hip curvature mismatch and eccentricity between the acetabulum and the femoral head different from dysplastic or control hips three-dimensionally? The 113 hips, categorized as: dysplastic (LCEA ≤ 20°), 47 hips; borderline (20° ≤ LCEA < 25°), 32 hips; and control (25° ≤ LCEA < 35°), 34 hips; were evaluated. Three-dimensional (3D) femoral and coxal bone models were reconstructed from CT images. Using a custom-written Visual C++ routine, the femoral head and acetabular radii of curvature, and the femoral head and the acetabular curvature center were calculated. Then the ratio of the acetabular radius to the femoral head radius (3D curvature mismatch ratio), and the distance between the acetabular curvature center and the femoral head center (3D center discrepancy distance) were calculated. These indices were compared statistically among the three groups using Tukey’s post hoc test. The mean 3D curvature mismatch ratio in the borderline (1.13 ± 0.05) was smaller than in the dysplasia (1.23 ± 0.08, p < 0.001), and larger than in the control (1.07 ± 0.02, p < 0.001). The mean 3D center discrepancy distance in the borderline (3.2 ± 1.4 mm) was smaller than in the dysplasia (4.8 ± 2.3, p < 0.001) and larger than in the control (1.6 ± 0.7, p < 0.001). These results demonstrated that three-dimensional congruity of the borderline dysplastic hip is impaired, but its incongruity is not as severe as in dysplastic hips. The 3D curvature mismatch ratio and the 3D center discrepancy distance can be valuable signs of joint congruity in patients with borderline dysplasia. However, future studies are necessary to clarify any associations between curvature mismatch and pathogenesis of osteoarthritis in borderline dysplasia.
Charlotte Bernhard Madsen, Katrine Lindholm Bøgh
Published: 6 April 2020
PLOS ONE, Volume 15; doi:10.1371/journal.pone.0231139

Abstract:
There are several reports describing allergy to hydrolyzed wheat products. After a large outbreak in Japan it was established that sensitization was caused by skin contact with acid hydrolyzed gluten in soap. It is still not clear if other forms of hydrolyzed gluten may sensitize, and if the skin is the only relevant route of sensitization in humans and to what extent oral tolerance to wheat play a role. The aim of the present study was to examine if wheat-tolerant rats may be sensitized via the oral or i.p. route when exposed to gluten, enzymatic or acid hydrolyzed gluten. Brown Norway rats, tolerant to wheat, were dosed by three i.p. injections without adjuvant or by oral gavage daily for 35 days with the three gluten products, respectively. Sera were analyzed by ELISA for specific IgG1 and IgE. In addition inhibition and avidity ELISAs were performed. Results were compared to a similar study in rats naïve to wheat. More than half the animals had measurable IgG1 at the start of the dosing period. I.p. immunization resulted in significant specific IgG1 and IgE to the antigen used for immunization but significantly lower than in naïve rats. The results of inhibition and avidity ELISA’s indicate that the underlying tolerance to epitopes common to the three products influences the immune response. Oral dosing did not induce significant changes in response to either gluten or the hydrolyzed gluten product used for dosing. The study shows that i.p. immunization with the three products can break the underlying tolerance to wheat. Exposure by the oral route to enzymatic or acid hydrolyzed gluten is very unlikely to break an already established tolerance to gluten and induce sensitization.
Krisztian Buza, Ladislav Peška, Júlia Koller
Published: 6 April 2020
PLOS ONE, Volume 15; doi:10.1371/journal.pone.0230726

Abstract:
State-of-the-art approaches for the prediction of drug–target interactions (DTI) are based on various techniques, such as matrix factorisation, restricted Boltzmann machines, network-based inference and bipartite local models (BLM). In this paper, we propose the framework of Asymmetric Loss Models (ALM) which is more consistent with the underlying chemical reality compared with conventional regression techniques. Furthermore, we propose to use an asymmetric loss model with BLM to predict drug–target interactions accurately. We evaluate our approach on publicly available real-world drug–target interaction datasets. The results show that our approach outperforms state-of-the-art DTI techniques, including recent versions of BLM.
Hiroki Masuda, Masahiro Mori, Akiyuki Uzawa, Tomohiko Uchida, Ryohei Ohtani, Satoshi Kuwabara
Published: 6 April 2020
PLOS ONE, Volume 15; doi:10.1371/journal.pone.0224419

Abstract:
To investigate the difference of fatigue and pain in patients with neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS). Data from the Modified Fatigue Impact Scale (MFIS) and Pain Effects Scale (PES) were compared between 51 NMOSD and 85 MS patients. Each score was compared in each disease group with or without clinical abnormalities. Since almost no MS patients are without brain magnetic resonance imaging abnormalities, volumetry analysis by the Lesion Segmentation Tool and statistical parametric mapping 12 were added to obtain total lesion volume and intracranial volume in MS patients, and the correlations between total lesion volume/intracranial volume and each score were investigated. Compared to the MS group, the NMOSD group showed a higher PES score (median, 15.0 vs. 7.0, P = 0.045), no difference in MFIS, and an increased percentage of patients with extended spinal cord lesions (58.8% vs. 8.2%, P < 0.001). Moreover, NMOSD and MS patients with extended spinal cord lesions tended to demonstrate higher PES scores than those without. A positive correlation between MFIS and PES were found in patients with NMOSD and MS. On the other hand, MS patients showed a higher percentage of brain abnormalities (80.4% vs. 97.6%, P = 0.001) and a positive correlation between total lesion volume/intracranial volume and MFIS (Spearman’s ρ = 0.50, P = 0.033). The origin of fatigue may be associated with spinal cord lesions causing pain in NMOSD patients, but with brain lesions in MS patients.
Konstantin D. Bergmeister, Luisa Große-Hartlage, Simeon C. Daeschler, Patrick Rhodius, Arne Böcker, Marius Beyersdorff, Axel Olaf Kern, Ulrich Kneser, Leila Harhaus
Published: 6 April 2020
PLOS ONE, Volume 15; doi:10.1371/journal.pone.0229530

Abstract:
Peripheral nerve injury in the upper extremity is linked to high socioeconomic burden, yet cost-analyses are rare and from small cohorts. The objective of this study was to determine the costs and long-term socioeconomic effects of peripheral nerve injuries in the upper extremity in Germany. We analyzed data of 250 patients with 268 work-related upper extremity nerve injuries from acute treatment to long-term follow-up on rehabilitation, sick-leave and disability-pension. Patients were on average 39.9±14.2 years old, male (85%) and mean inpatient treatment was 7±6 days. Location of nerve was 8% (N = 19) proximal to the wrist, 26% (N = 65) at the wrist and metacarpus, and 66% (N = 166) at phalangeal level. Acute in-patient treatment for (single) median nerve injury accounted for 66% with hospital reimbursement of 3.570€, ulnar nerve injury for 24% and 2.650€ and radial nerve injury for 10% and 3.166€, all including finger nerve injuries. The remaining were combined nerve injuries, with significantly higher costs, especially if combined with tendon 5.086€ or vascular injury 4.886€. Based on location, nerve injuries proximal to the wrist averaged 5.360±6.429€, at the wrist and metacarpus 3.534±2.710€ and at the phalangeal level 3.418±3.330€. 16% required rehabilitation with average costs of 5.842€ and stay of 41±21 days. Sick leave was between 11–1109 days with an average of 147 days with socioeconomic costs of 197€/day, equaling on average 17.640€. 30% received a mean yearly disability pension of 3.187€, that would account to 102.167€ per lifetime. This large German patient sample indicates that nerve injury has a major impact on function and employment, resulting in significant health care costs. Both proximal and distal nerve injuries led to long-term disability, subsequent sick-leave and in 30% to permanent disability pension. These data are determined to support future studies and health economical work on prevention, treatment and rehabilitation of these often small injuries with great consequences.