bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrin α2 gene polymorphism is a risk factor of coronary artery lesions in Chinese children with Kawasaki disease
Authors: Yuan Jia , Jiang Zhiyong , Li Meiai , Li Wei , Gu Xueping , Wang Zhouping , Pi Lei , Xu Yufen , Zhou Huazhong , Zhang Baidu , Deng Qiulian , Wang Yanfei , Huang Ping , Zhang Li , Gu Xiaoqiong 
Published: February 2021

AbstractBackgroundKawasaki disease (KD) is a systemic vasculitis, and the formation of coronary artery lesions(CAL) is its most common sequela. Both genetic and environmental factors are considered to be important factors of in KD. Integrin α2 (ITGA2) is a transmembrane receptor that is associated with susceptibility to several diseases, but its relevance to KD with CAL is unclear.MethodsWe genotyped ITGA2 rs1126643 in 785 KD patients with the CAL and no-CAL(NCAL) (300 patients with CAL, and 485 age- and sex-matched patients with NCAL). OR (95% CI) and adjusted OR (95% CI) were used to evaluate the intensity of the association.ResultsWe found a significantly increased risk of KD with CAL associated with ITGA2 rs1126643 genotypes (CT vs CC: adjusted OR = 1.57, 95% CI = 1.16–2.12,P = 0.0032; CT/TT vs CC: adjusted OR = 1.49, 95% CI = 1.12–2.00,P = 0.0068; T vs C: adjusted OR = 1.66, 95% CI = 1.16–2.51,P = 0.0165). Moreover, we found that carriers of the CT/TT genotype had a significant risk of KD with coronary artery lesion susceptibility for children ≤60 months of age, and the CT/TT genotype was significantly associated with an increased risk of SCAL formation and MCAL formation when compared with the CC genotype.ConclusionITGA2 rs1126643 was associated with increased susceptibility and severity of CAL in KD.
Clinical utility of the over-ground bodyweight-supporting walking system Andago in children and youths with gait impairments
Authors: van Hedel Hubertus J. A. , Rosselli Irene , Baumgartner-Ricklin Sandra 
Published: February 2021

Abstract
Background
The Andago is a rehabilitation robot that allows training walking over-ground while providing bodyweight unloading (BWU). We investigated the practicability, acceptability, and appropriateness of the device in children with gait impairments undergoing neurorehabilitation. Concerning appropriateness, we investigated whether (i) stride-to-stride variability of the stride time and inter-joint coordination was higher when walking over-ground in Andago versus treadmill walking, and (ii) activation of antigravity leg muscles decreased with higher levels of BWU.

Methods
Eighteen children and adolescents with gait impairments participated in three sessions. Practicability was assessed by determining the time needed to get a patient in and out of Andago, the accuracy of the BWU system, and other aspects. Acceptability was assessed by patients responding to questions, while six therapists filled out the System Usability Scale. To determine appropriateness, the participants were equipped with surface electromyography (sEMG) electrodes, electrogoniometers and accelerometers. Various parameters were compared between walking over-ground and on a treadmill, and between walking with three different levels of BWU (median: 20%, 35% and 50% of the bodyweight) over-ground.

Results
Practicability: the average time needed to get in and out of Andago amounted to 60 s and 16 s, respectively. The BWU system seemed accurate, especially at higher levels. We experienced no technical difficulties and Andago prevented 12 falls. However, participants had difficulties walking through a door without bumping into it. Acceptability: after the second session, nine participants felt safer walking in Andago compared to normal walking, 15 preferred walking in Andago compared to treadmill walking, and all wanted to train again with Andago. Therapists rated the usability of the Andago as excellent. Appropriateness: stride-to-stride variability of stride duration and inter-joint coordination was higher in Andago compared to treadmill walking. sEMG activity was not largely influenced by the levels of BWU investigated in this study, except for a reduced M. Gluteus Medius activity at the highest level of BWU tested.

Conclusions
The Andago is a practical and well-accepted device to train walking over-ground with BWU in children and adolescents with gait impairments safely. The system allows individual stride-to-stride variability of temporospatial gait parameters without affecting antigravity muscle activity strongly.
Trial registration: ClinicalTrials.gov Identifier: NCT03787199.
Validation of IMU-based gait event detection during curved walking and turning in older adults and Parkinson’s Disease patients
Authors: Romijnders Robbin , Warmerdam Elke , Hansen Clint , Welzel Julius , Schmidt Gerhard , Maetzler Walter 
Published: February 2021

Abstract
Background
Identification of individual gait events is essential for clinical gait analysis, because it can be used for diagnostic purposes or tracking disease progression in neurological diseases such as Parkinson’s disease. Previous research has shown that gait events can be detected from a shank-mounted inertial measurement unit (IMU), however detection performance was often evaluated only from straight-line walking. For use in daily life, the detection performance needs to be evaluated in curved walking and turning as well as in single-task and dual-task conditions.

Methods
Participants (older adults, people with Parkinson’s disease, or people who had suffered from a stroke) performed three different walking trials: (1) straight-line walking, (2) slalom walking, (3) Stroop-and-walk trial. An optical motion capture system was used a reference system. Markers were attached to the heel and toe regions of the shoe, and participants wore IMUs on the lateral sides of both shanks. The angular velocity of the shank IMUs was used to detect instances of initial foot contact (IC) and final foot contact (FC), which were compared to reference values obtained from the marker trajectories.

Results
The detection method showed high recall, precision and F1 scores in different populations for both initial contacts and final contacts during straight-line walking (IC: recall $$=$$
=
100%, precision $$=$$
=
100%, F1 score $$=$$
=
100%; FC: recall $$=$$
=
100%, precision $$=$$
=
100%, F1 score $$=$$
=
100%), slalom walking (IC: recall $$=$$
=
100%, precision $$\ge$$
≥
99%, F1 score $$=$$
=
100%; FC: recall $$=$$
=
100%, precision $$\ge$$
≥
99%, F1 score $$=$$
=
100%), and turning (IC: recall $$\ge$$
≥
85%, precision $$\ge$$
≥
95%, F1 score $$\ge$$
≥
91%; FC: recall $$\ge$$
≥
84%, precision $$\ge$$
≥
95%, F1 score $$\ge$$
≥
89%).

Conclusions
Shank-mounted IMUs can be used to detect gait events during straight-line walking, slalom walking and turning. However, more false events were observed during turning and more events were missed during turning. For use in daily life we recommend identifying turning before extracting temporal gait parameters from identified gait events.
A hybrid model based on general regression neural network and fruit fly optimization algorithm for forecasting and optimizing paclitaxel biosynthesis in Corylus avellana cell culture
Authors: Salehi Mina , Farhadi Siamak , Moieni Ahmad , Safaie Naser , Hesami Mohsen 
Published: February 2021

Abstract
Background
Paclitaxel is a well-known chemotherapeutic agent widely applied as a therapy for various types of cancers. In vitro culture of Corylus avellana has been named as a promising and low-cost strategy for paclitaxel production. Fungal elicitors have been reported as an impressive strategy for improving paclitaxel biosynthesis in cell suspension culture (CSC) of C. avellana. The objectives of this research were to forecast and optimize growth and paclitaxel biosynthesis based on four input variables including cell extract (CE) and culture filtrate (CF) concentration levels, elicitor adding day and CSC harvesting time in C. avellana cell culture, as a case study, using general regression neural network-fruit fly optimization algorithm (GRNN-FOA) via data mining approach for the first time.

Results
GRNN-FOA models (0.88–0.97) showed the superior prediction performances as compared to regression models (0.57–0.86). Comparative analysis of multilayer perceptron-genetic algorithm (MLP-GA) and GRNN-FOA showed very slight difference between two models for dry weight (DW), intracellular and extracellular paclitaxel in testing subset, the unseen data. However, MLP-GA was slightly more accurate as compared to GRNN-FOA for total paclitaxel and extracellular paclitaxel portion in testing subset. The slight difference was observed in maximum growth and paclitaxel biosynthesis optimized by FOA and GA. The optimization analysis using FOA on developed GRNN-FOA models showed that optimal CE [4.29% (v/v)] and CF [5.38% (v/v)] concentration levels, elicitor adding day (17) and harvesting time (88 h and 19 min) can lead to highest paclitaxel biosynthesis (372.89 µg l−1).

Conclusions
Great accordance between the predicted and observed values of DW, intracellular, extracellular and total yield of paclitaxel, and also extracellular paclitaxel portion support excellent performance of developed GRNN-FOA models. Overall, GRNN-FOA as new mathematical tool may pave the way for forecasting and optimizing secondary metabolite production in plant in vitro culture.
Feasibility of a mini-pig model of radiation-induced brain injury to one cerebral hemisphere
Authors: Athanasiadi Ilektra , Perez Whitney D. , Plantenga Jeannie M. , Jones-Hall Yava , Perez-Torres Carlos J. 
Published: February 2021

Abstract
Background
Radiation-induced brain injury is a common concern for survivors of adult and pediatric brain cancer. Pre-clinically, rodent models are the standard approach to evaluate mechanisms of injury and test new therapeutics for this condition. However, these rodent models fail to recapitulate the radiological and histological characteristics of the clinical disease.

Methods
Here we describe a hemispheric mini-pig model of radiation-induced brain injury generated with a clinical 6 MV photon irradiator and evaluated with a clinical 3T MRI. Two pairs of Yucatan mini-pigs each received either 15 Gy or 25 Gy to the left brain hemisphere. Quality of intensity modulated radiation therapy treatment plans was evaluated retrospectively with parameters reported according to ICRU guidelines. The pigs were observed weekly to check for any outright signs of neurological impairment. The pigs underwent anatomical MRI examination before irradiation and up to 6 months post-irradiation. Immediately after the last imaging time point, the pigs were euthanized and their brains were collected for histopathological assessment.

Results
Analysis of the dose volume histograms showed that 93% of the prescribed dose was delivered to at least 93% of the target volume in the left hemisphere. Organs at risk excluded from the target volume received doses below clinical safety thresholds. For the pigs that received a 25 Gy dose, progressive neurological impairment was observed starting at 2 months post-irradiation leading to the need for euthanasia by 3–4 months. On MRI, these two animals presented with diffuse white matter pathology consistent with the human disease that progressed to outright radiation necrosis and severe brain swelling. Histology was consistent with the final MRI evaluation. The pigs that received a 15 Gy dose appeared normal all the way to 6 months post-irradiation with no obvious neurological impairment or lesions on MRI or histopathology.

Conclusion
Based on our results, a mini-pig model of radiation-induced brain injury is feasible though some optimization is still needed. The mini-pig model produced lesions on MRI that are consistent with the human disease and which are not seen in rodent models. Our data shows that the ideal radiation dose for this model likely lies between 15 and 25 Gy.
Clinical characteristics of 93 cases of isolated macrodactyly of the foot in children
Authors: Chen Wei , Tian Xiaofei , Chen Lu , Huang Wei 
Published: February 2021

Abstract
Background
The purpose of this study was to describe the clinical characteristics of macrodactyly of the foot through a large cohort of cases to further understand this rare entity.

Methods
Medical records, clinical photographs, plain radiographs, pathological findings, and intraoperative photographs of 95 feet of 93 patients were reviewed. Data including age; sex; laterality; ethnicity; birthplace; family history; and history of gestation, environment, whether smoking, or drinking during pregnancy were collected and analyzed.

Results
Female patients (60%), left foot (56%), and static overgrowth (63%) were more prominent in the study cohort. Southern provinces (74%) and Han Chinese ethnicity (95%) predominated in terms of geographical region and demographic distribution, respectively. Multiple-toe involvement was 2.01-times more frequent than single-toe involvement. All five toes were involved with midline toes being most frequently affected overall and a medial distribution being more common than a lateral one. The forefoot was affected in 90 feet. The affected areas (toes and forefeet) were mostly located in the innervation of the affected medial plantar nerve (91%). The nerves showed enlargement in 49 feet, fatty infiltration in 25, a tortuous course in one, and were normal in 10 feet. Only six feet involved the musculature. Enlargement of phalanges and metatarsals were observed in 92 and 57 feet, respectively, and advanced bone maturation was seen in 63 feet. Twenty-two cases had syndactyly.

Conclusions
Macrodactyly of the foot is a rare congenital malformation with diverse clinical manifestations and multiple elements’ involvement.
It also presents the characteristics of nerve-mediated overgrowth and “nerve territory-oriented” deformity similar to that of macrodactyly of the hand.
Mesenchymal stem cell-originated exosomal lncRNA HAND2-AS1 impairs rheumatoid arthritis fibroblast-like synoviocyte activation through miR-143-3p/TNFAIP3/NF-κB pathway
Authors: Su Yuhua , Liu Yajing , Ma Chao , Guan Chunxiao , Ma Xiufen , Meng Shan 
Published: February 2021

AbstractBackgroundLong non-coding RNA heart and neural crest derivatives expressed 2-antisense RNA 1 (HAND2-AS1) was found to be elevated in rheumatoid arthritis (RA) fibroblast-like synoviocytes (RA-FLSs). However, whether HAND2-AS1 functions as an exosomal lncRNA related to mesenchymal stem cells (MSCs) in RA progression is unknown.MethodsThe expression of HAND2-AS1, microRNA (miR)-143-3p, and tumor necrosis factor alpha-inducible protein 3 (TNFAIP3) was detected using quantitative real-time polymerase chain reaction and Western blot. Cell proliferation, apoptosis, migration, and invasion were detected using cell counting kit-8, flow cytometry, and wound healing and transwell assays. The levels of tumor necrosis factor-α (TNF-α) and interleukins (IL)-6 were analyzed using enzyme-linked immunosorbent assay. The level of phosphorylated-p65 was examined by Western blot. The binding interaction between miR-143-3p and HAND2-AS1 or TNFAIP3 was confirmed by the dual-luciferase reporter and RIP assays. Exosomes were isolated by ultracentrifugation and qualified by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blot.ResultsHAND2-AS1 was lowly expressed in RA synovial tissues, and HAND2-AS1 re-expression suppressed the proliferation, motility, and inflammation and triggered the apoptosis in RA-FLSs via the inactivation of NF-κB pathway. Mechanistically, HAND2-AS1 directly sponged miR-143-3p and positively regulated TNFAIP3 expression, the target of miR-143-3p. Moreover, the effects of HAND2-AS1 on RA-FLSs were partially attenuated by miR-143-3p upregulation or TNFAIP3 knockdown. HAND2-AS1 could be packaged into hMSC-derived exosomes and absorbed by RA-FLSs, and human MSC-derived exosomal HAND2-AS1 also repressed above malignant biological behavior of RA-FLSs.ConclusionMSC-derived exosomes participated in the intercellular transfer of HAND2-AS1 and suppressed the activation of RA-FLSs via miR-143-3p/TNFAIP3/NF-κB pathway, which provided a novel insight into the pathogenesis and treatment of RA.
Changes in the bony alignment of the foot after tendo-Achilles lengthening in patients with planovalgus deformity
Authors: Kim Nak Tscheol , Lee Young Tae , Park Moon Seok , Lee Kyoung Min , Kwon Oh Sang , Sung Ki Hyuk 
Published: February 2021

Abstract
Background
This study was performed to investigate the change in the bony alignment of the foot after tendo-Achilles lengthening (TAL) and the factors that affect these changes in patients with planovalgus foot deformity.

Methods
Consecutive 97 patients (150 feet; mean age 10 years; range 5.1–35.7) with Achilles tendon contracture (ATC) and planovalgus foot deformity who underwent TAL were included. All patients underwent preoperative and postoperative weight-bearing anteroposterior (AP) or lateral (LAT) foot radiographics. Changes in AP talo-1st metatarsal angle, AP talo-2nd metatarsal angle, LAT talo-1st metatarsal angle, and calcaneal pitch angle and the factors affecting such changes after TAL were analyzed using lineal mixed model.

Results
There were no significant change in AP talo-1st metatarsal angle and AP talo-2nd metatarsal angle after TAL in patients with cerebral palsy (CP) (p = 0.236 and 0.212). However, LAT talo-1st metatarsal angle and calcaneal pitch angle were significantly improved after TAL (13.0°, p < 0.001 and 4.5°, p < 0.001). Age was significantly associated with the change in LAT talo-1st metatarsal angle after TAL (p = 0.028). The changes in AP talo-1st metatarsal angle, AP talo-2nd metatarsal angle, and calcaneal pitch angle after TAL were not significantly associated with the diagnosis (p = 0.879, 0.903, and 0.056). However, patients with CP showed more improvement in LAT talo-1st metatarsal angle (− 5.0°, p = 0.034) than those with idiopathic cause.

Conclusion
This study showed that TAL can improve the bony alignment of the foot in patients with planovalgus and ATC. We recommend that physicians should consider this study’s findings when planning operative treatment for such patients.
Neuroprotective effects of Shende’an tablet in the Parkinson’s disease model
Authors: Sheng Xiaoyan , Yang Shuiyuan , Wen Xiaomin , Zhang Xin , Ye Yongfeng , Zhao Peng , Zang Limin , Peng Kang , Du Enming , Li Sai 
Published: February 2021

Abstract
Background
Shende’an tablet (SDA) is a newly capsuled Chinese herbal formula derived from the Chinese traditional medicine Zhengan Xifeng Decoction which is approved for the treatment of neurasthenia and insomnia in China. This study aimed to investigate the neuroprotective effects of SDA against Parkinson’s disease (PD) in vitro and in vivo.

Methods
In the present work, the neuroprotective effects and mechanism of SDA were evaluated in the cellular PD model. Male C57BL/6J mice were subject to a partial MPTP lesion alongside treatment with SDA. Behavioural test and tyrosine-hydroxylase immunohistochemistry were used to evaluate nigrostriatal tract integrity. HPLC analysis and Western blotting were used to assess the effect of SDA on dopamine metabolism and the expression of HO-1, PGC-1α and Nrf2, respectively.

Results
Our results demonstrated that SDA had neuroprotective effect in dopaminergic PC12 cells with 6-OHDA lesion. It had also displayed efficient dopaminergic neuronal protection and motor behavior alleviation properties in MPTP-induced PD mice. In the PC12 cells and MPTP-induced Parkinson’s disease animal models, SDA was highly efficacious in α-synuclein clearance associated with the activation of PGC-1α/Nrf2 signal pathway.

Conclusions
SDA demonstrated potential as a future therapeutic modality in PD through protecting dopamine neurons and alleviating the motor symptoms, mediated by the activation of PGC-1α/Nrf2 signal pathway.
No evidence for a pathogen associated with pulmonary MALT lymphoma: a metagenomics investigation
Authors: Borie Raphaël , Caro Valérie , Nunes Hilario , Kambouchner Marianne , Cazes Aurélie , Antoine Martine , Crestani Bruno , Leroy Karen , Copie-Bergman Christiane , Kwasiborski Aurelia , Hennequin Christophe , Vandenbogaert Mathias , Hourdel Véronique , Cadranel Jacques 
Published: February 2021

AbstractMucosa-associated lymphoid tissue (MALT) lymphoma is generally associated with chronic antigen stimulation: auto-antigens or of microbial origin. Only one study suggested association between Achromobacter xylosoxidans and pulmonary MALT lymphoma. We aimed to investigate the presence of virus or any infectious agents in pulmonary MALT lymphoma by using metagenomic next-generation sequencing (mNGS).All lung samples were centrally reviewed. The t(11;18) (q21;q21) was evaluated by FISH analysis. The snap frozen large lung biopsies were analyzed by mNGS. After lung biopsies homogenization total nucleic acids (RNA and DNA) were extracted, amplified and classified according to their taxonomic assignment, after exclusion of host DNA.We included 13 samples from pulmonary MALT lymphoma (mean age: 60.3 years, 7 women, 3 with auto-immune background) and 10 controls. The diagnosis of MALT lymphoma was confirmed for the 13 samples, 3 showed API2-MALT1 translocation (23%). No evidence of the presence of a specific pathogen was clearly identified in the group of patients with pulmonary MALT lymphoma. We identifiedA. xylosoxidans sequence in 4/13 patients and in 4/10 controls.This study did not find evidence for a DNA or RNA virus, a fungi, a parasite or a bacteria associated with pulmonary MALT lymphoma either in the stroma or in tumor cells.
What is the prospect of indoleamine 2,3-dioxygenase 1 inhibition in cancer? Extrapolation from the past
Authors: Yao Yu , Liang Heng , Fang Xin , Zhang Shengnan , Xing Zikang , Shi Lei , Kuang Chunxiang , Seliger Barbara , Yang Qing 
Published: February 2021

AbstractIndoleamine 2,3-dioxygenase 1 (IDO1), a monomeric heme-containing enzyme, catalyzes the first and rate-limiting step in the kynurenine pathway of tryptophan metabolism, which plays an important role in immunity and neuronal function. Its implication in different pathophysiologic processes including cancer and neurodegenerative diseases has inspired the development of IDO1 inhibitors in the past decades. However, the negative results of the phase III clinical trial of the would-be first-in-class IDO1 inhibitor (epacadostat) in combination with an anti-PD1 antibody (pembrolizumab) in patients with advanced malignant melanoma call for a better understanding of the role of IDO1 inhibition. In this review, the current status of the clinical development of IDO1 inhibitors will be introduced and the key pre-clinical and clinical data of epacadostat will be summarized. Moreover, based on the cautionary notes obtained from the clinical readout of epacadostat, strategies for the identification of reliable predictive biomarkers and pharmacodynamic markers as well as for the selection of the tumor types to be treated with IDO1inhibitors will be discussed.