bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exosomes derived from platelet-rich plasma present a novel potential in alleviating knee osteoarthritis by promoting proliferation and inhibiting apoptosis of chondrocyte via Wnt/β-catenin signaling pathway
Authors: Liu Xuchang , Wang Lubo , Ma Chengshan , Wang Guozong , Zhang Yuanji , Sun Shui 
Published: December 2019

Abstract
Background
Platelet-rich plasma (PRP) provides a nonsurgical approach for treating osteoarthritis (OA). Exosomes that play vital roles in intercellular communication have been studied extensively. Here, we investigated the therapeutic potential and molecular mechanism of exosomes derived from PRP (PRP-Exos) in alleviating OA.

Methods
Exosomes derived from PRP(PRP-Exos) were isolated and purified using the exoEasy Maxi Kit and then identified and analyzed. Primary rabbit chondrocytes were isolated and treated with interleukin 1 beta (IL-1β) to establish the OA model in vitro. Proliferation, migration, and apoptosis assays were measured and compared between PRP-Exos and activated PRP (PRP-As) to evaluate the therapeutic effects on OA. The mechanism involving the Wnt/β-catenin signaling pathway was investigated by Western blot analysis. In vivo, we established animal knee OA model by surgery to compare the therapeutic effect of PRP-Exos and PRP-As.

Results
We successfully isolated and purified exosomes from PRP using the exoEasy Maxi Kit. We also isolated and identified chondrocytes from the New Zealand white rabbit and established the IL-1β-induced OA model; meanwhile, PRP-Exos and PRP-As both inhibited the release of tumor necrosis factor-α(TNF-α) and there was no statistically significant difference between the two. In proliferation, migration, scratch assay, the promoting effect of PRP-Exos was significantly more better than PRP-As. Furthermore, PRP-Exos could significantly decreased apoptotic rate of OA chondrocyte compared with PRP-As. In Western blot analysis, the expression of β-catenin, and RUNX2, Wnt5a were increased in IL-1β-treated chondrocytes, but PRP-Exos and PRP-As could both reverse these changes, and the reversal effect of the former was better than the latter. In vivo, we found that both PRP-Exos and PRP-As displayed the progression of OA, and the effect of PRP-Exos was obviously better than PRP-As by chondrocyte count and Osteoarthritis Research Society International (OARSI) scoring system.

Conclusion
The therapeutic effects of PRP-Exos on OA were similar or better compared with those of PRP-As in vitro or in vivo. PRP-Exos acting as carriers containing growth factors derived from PRP present a novel therapy for OA by activating the Wnt/β-catenin signaling pathway.
Utilizing network pharmacology to explore the underlying mechanism of Radix Salviae in diabetic retinopathy
Authors: Piao Chun-Li , Luo Jin-Li , Jin De , Tang Cheng , Wang Li , Lian Feng-Mei , Tong Xiao-Lin 
Published: December 2019

Abstract
Introduction
Radix Salviae (Dan-shen in pinyin), a classic Chinese herb, has been extensively used to treat diabetic retinopathy in clinical practice in China for many years. However, the pharmacological mechanisms of Radix Salviae remain vague. The aim of this study was to decrypt the underlying mechanisms of Radix Salviae in the treatment of diabetic retinopathy using a systems pharmacology approach.

Methods
A network pharmacology-based strategy was proposed to elucidate the underlying multi-component, multi-target, and multi-pathway mode of action of Radix Salviae against diabetic retinopathy. First, we collected putative targets of Radix Salviae based on the Traditional Chinese Medicine System Pharmacology database and a network of the interactions among the putative targets of Radix Salviae and known therapeutic targets of diabetic retinopathy was built. Then, two topological parameters, “degree” and “closeness certainty” were calculated to identify the major targets in the network. Furthermore, the major hubs were imported to the Database for Annotation, Visualization and Integrated Discovery to perform a pathway enrichment analysis.

Results
A total of 130 nodes, including 18 putative targets of Radix Salviae, were observed to be major hubs in terms of topological importance. The results of pathway enrichment analysis indicated that putative targets of Radix Salviae mostly participated in various pathways associated with angiogenesis, protein metabolism, inflammatory response, apoptosis, and cell proliferation. The putative targets of Radix Salviae (vascular endothelial growth factor, matrix metalloproteinases, plasminogen, insulin-like growth factor-1, and cyclooxygenase-2) were recognized as active factors involved in the main biological functions of treatment, which implied that these were involved in the underlying mechanisms of Radix Salviae on diabetic retinopathy.

Conclusions
Radix Salviae could alleviate diabetic retinopathy via the molecular mechanisms predicted by network pharmacology. This research demonstrates that the network pharmacology approach can be an effective tool to reveal the mechanisms of traditional Chinese medicine from a holistic perspective.
The evolving therapeutic landscape of genetic skeletal disorders
Authors: Sabir Ataf Hussain , Cole Trevor 
Published: December 2019

Abstract
Background
Rare bone diseases account for 5% of all birth defects yet very few have personalised treatments. Developments in genetic diagnosis, molecular techniques and treatment technologies however, are leading to unparalleled therapeutic advance. This review explores the evolving therapeutic landscape of genetic skeletal disorders (GSDs); the key conditions and there key differentials.

Methods
A retrospective literature based review was conducted in December 2018 using a systematic search strategy for relevant articles and trials in Pubmed and clinicaltrials.gov respectively. Over 140 articles and 80 trials were generated for review.

Results
Over 20 personalised therapies are discussed in addition to several novel disease modifying treatments in over 25 GSDs. Treatments discussed are at different stages from preclinical studies to clinical trials and approved drugs, including; Burosumab for X-linked hypophosphatemia, Palovarotene for Hereditary Multiple Exostoses, Carbamazepine for Metaphyseal Chondrodysplasia (Schmid type), Lithium carbonate and anti-sclerostin therapy for Osteoporosis Pseudoglioma syndrome and novel therapies for Osteopetrosis. We also discuss therapeutic advances in Achondroplasia, Osteogenesis Imperfecta (OI), Hypophosphotasia (HPP), Fibrodysplasia Ossificans Progressiva, and RNA silencing therapies in preclinical studies for OI and HPP.

Discussion
It is an exciting time for GSD therapies despite the challenges of drug development in rare diseases. In discussing emerging therapies, we explore novel approaches to drug development from drug repurposing to in-utero stem cell transplants. We highlight the improved understanding of bone pathophysiology, genetic pathways and challenges of developing gene therapies for GSDs.
Violent conflict and breastfeeding: the case of Iraq
Authors: Diwakar Vidya , Malcolm Michael , Naufal George 
Published: December 2019

Abstract
Background
This study explores the relationship between armed conflict and breastfeeding practices of Iraqi mothers. To date, the relationship between violent conflict and breastfeeding is surprisingly understudied. Especially in the Middle East, which is conflict-prone and has a young population, research on war and household behavior is critical for promoting recovery and sustainable development.

Methods
This study employs a unique pairing of the Iraq Body Count Database and the 2006 and 2011 Multiple Indicator Cluster Surveys for Iraq. We use probit models to explore the association between armed conflict and several breastfeeding outcomes – whether a child was ever breastfed, whether a child was breastfed within 1 h after birth, whether a child is currently breastfed, and whether an infant under 6 months of age is exclusively breastfed. Our proxies for conflict intensity are the average rate of conflict-related casualties across the 3 years prior to survey administration and the rate of casualties averaged across the 2 years prior to the birth of the child, in the governorate in which the family resides. We employ a number of other independent variables important for breastfeeding status, including health controls and characteristics of the household, child and mother. We also use a Cox proportional hazards model to study the association between conflict and breastfeeding duration. We complement this analysis with various robustness checks, including disaggregation by year, controls for household wealth and an analysis of breastmilk substitutes and their potential for an interaction with household wealth.

Results
We find in our main results that increases in conflict-related casualties are associated with a significant decline in the probability that a child was ever breastfed and a decline in the probability that a child is currently breastfeeding. There is no significant association with exclusive breastfeeding or with initiation of breastfeeding within 1 h after birth. This result is robust to alternative measures of conflict, although some coefficients from estimation based on the 2006 subsample are positive and not significant, and reverse causation is a potential source of bias in interpreting cross-sectional feeding patterns. Results on breastfeeding duration are mixed. Our results also suggest an increase in the use of breastfeeding substitutes like formula concurrent to higher levels of conflict among wealthier households.

Conclusion
The results are informative in the context of designing policy aimed at stabilizing the long-term health and productivity of populations in conflict areas. Infant formula provided with the objective of offering temporary relief creates risks, including reducing the probability and duration of breastfeeding. Attention to the supply of health care and to support systems for women, especially skilled breastfeeding support and targeted support to infants dependent on formula, are matters of the utmost urgency during and after conflict periods.
CircNFIX promotes progression of glioma through regulating miR-378e/RPN2 axis
Authors: Ding Chenyu , Wu Zanyi , You Honghai , Ge Hongliang , Zheng Shufa , Lin Yuanxiang , Wu Xiyue , Lin Zhangya , Kang Dezhi 
Published: December 2019

Abstract
Background
Circular RNA nuclear factor I X (circNFIX) has been reported to play an important role in glioma progression. However, the mechanism by which circNFIX participates in glioma progression remains poorly understood.

Methods
GERIA online were used to analyze the abnormally expressed genes in glioma tissues. The expression levels of circNFIX, microRNA (miR)-378e and Ribophorin-II (RPN2) were measured by quantitative real-time polymerase chain reaction or western blot. Cell cycle distribution, apoptosis, glycolysis, migration and invasion were determined by flow cytometry, special kit and trans-well assays, respectively. The target association between miR-378e and circNFIX or RPN2 was confirmed by luciferase reporter assay, RNA immunoprecipitation and pull-down. Xenograft model was established to investigate the role of circNFIX in vivo.

Results
The expression of circNFIX was enhanced in glioma tissues and cells compared with matched controls and high expression of circNFIX indicated poor outcomes of patients. Knockdown of circNFIX led to arrest of cell cycle, inhibition of glycolysis, migration and invasion and promotion of apoptosis in glioma cells. circNFIX was a sponge of miR-378e. miR-378e overexpression suppressed cell cycle process, glycolysis, migration and invasion but promoted apoptosis. miR-378e silence abated the suppressive role of circNFIX knockdown in glioma progression. RPN2 as a target of miR-378e was positively regulated via circNFIX by competitively sponging miR-378e. Silencing circNFIX decreased glioma xenograft tumor growth by regulating miR-378e/RPN2 axis.

Conclusion
Knockdown of circNFIX inhibits progression of glioma in vitro and in vivo by increasing miR-378e and decreasing RPN2, providing a novel mechanism for understanding the pathogenesis of glioma.
Efficacy of Bimin decoction for patients with perennial allergic rhinitis: an open-label non-inferiority randomized controlled trial
Authors: Zhao Jingyi , Yan Xinyu , Gai Jianqing , Han Jinshuai , Zhang Hong , Luo Hui , Huang Shaoting , Wang Junge 
Published: December 2019

Abstract
Background
Allergic rhinitis (AR) is a common allergic disease. It affects people worldwide and traditional Chinese medicine is becoming popular among AR patients because it has a definite clinical effect and there are few adverse reactions. Lung qi deficiency and cold syndrome (LQDCS) is a frequent type of AR, and the Chinese herbal medicine bimin decoction (BMD) is prescribed for it. This study compared the clinical efficacy of BMD for AR patients with LQDCS to the conventional medicine loratadine and fluticasone nasal spray.

Methods
The study was an open-label non-inferiority randomized controlled trial. A total of 108 AR patients with LQDCS aged 19 to 60 were randomly allocated in a 1:1 ratio to the BMD group or the control group by the central computer system in Beijing Hospital of Traditional Chinese Medicine from January 2017 to April 2018. In total, 98 participants completed the study (BMD group n = 51 and control group n = 47). Patients in the BMD group received BMD while those in the control group received fluticasone nasal spray and loratadine tablets for 4 weeks. The primary outcome was the change in the Total Nasal Symptom Score (TNSS) between the baseline and the end of treatment. Changes in the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), nasal resistance, and acoustic rhinometry parameters were secondary outcomes. All side effects due to the treatments were recorded.

Results
After the 4-week treatment, the total TNSS was significantly reduced in both groups compared to the baseline (P <  0.05). No significant between-groups differences were observed for changes in TNSS scores [− 0.298 (95% confidence interval −0.640 to 0.140)], which was within the defined non-inferiority margin. RQLQ in both groups decreased significantly (P <  0.001) from baseline, though a more obvious reduction was observed for the BMD group (P <  0.001). There were no significant differences in nasal resistance, nasal volume, or nasal minimum cross-sectional area between groups after treatment (P > 0.05).

Conclusions
These findings indicate that BMD helps relieve the symptoms of perennial AR and improves rhinitis-related quality of life. Our study indicates that BMD is non-inferior to loratadine tablets and fluticasone nasal spray for AR patients with LQDCS.

Trial registration
Chinese Clinical Trial Registry, ChiCTR-INR-16010063. Registered on 2 December 2016.
Results and lessons learnt from a randomized controlled trial: prophylactic treatment of vestibular migraine with metoprolol (PROVEMIG)
Authors:   PROVEMIG investigators, Bayer Otmar , Adrion Christine , Al Tawil Amani , Mansmann Ulrich , Strupp Michael 
Published: December 2019

Abstract
Background
Vestibular migraine (VM) is the most frequent cause of recurrent spontaneous attacks of vertigo causally related to migraine. The objective of the Prophylactic treatment of vestibular migraine with metoprolol (PROVEMIG) trial was to demonstrate that metoprolol succinate is superior to placebo in the prevention of episodic vertigo- and migraine-related symptoms in patients with VM.

Methods
This phase III, two-arm, parallel-group, double-blind, randomized placebo-controlled trial was designed to be conducted at tertiary referral centres at neurology and ear, nose and throat departments of eight German university hospitals. The planned sample size was a total of 266 patients to be allocated. Adults aged 18 years or above diagnosed with probable or definitive VM according to the Neuhauser criteria 2001 were randomly assigned 1:1 to 6 months blinded metoprolol (maintenance dosage of 95 mg daily) or placebo. The primary efficacy outcome was the self-reported number of vertiginous attacks per 30 days documented by means of a paper-based daily symptom diary. The pre-specified time period of primary interest was defined as months 4 to 6. Secondary outcomes included the patient-reported number of migraine days and vertigo days, the Dizziness Handicap Inventory, and clinical assessments. Adverse events were reported throughout the whole 9-month study period.

Results
At the time of trial termination, no evidence for a difference in the incidence of vertiginous attacks between groups was detected. For the full analysis set, the incidence rate ratio was 0.983 (95% confidence interval (CI) 0.902–1.071) for metoprolol versus placebo. In both groups, there was a significant decline over time in the overall monthly vertigo attacks by a factor of 0.830 (95% CI 0.776–0.887). Results were consistent for all subjective and objective key measures of efficacy. The treatment was well tolerated with no unexpected safety findings.

Conclusions
After randomizing 130 patients PROVEMIG had to be discontinued because of poor participant accrual not related to the tolerability of the study medication or safety concerns; no treatment benefit of metoprolol over placebo could be established. Additional preparatory work is much needed in the development, psychometric evaluation and interpretation of clinically meaningful end points in trials on episodic syndromes like VM taking into consideration the complexity of this disease entity comprising two domains (vertigo- and headache-related disability).

Trial registration
EudraCT, 2009-013701-34. Prospectively registered on 8 April 2011.
Motor intervention with and without Nintendo® Wii for children with developmental coordination disorder: protocol for a randomized clinical trial
Authors: Cavalcante Neto Jorge Lopes , Steenbergen Bert , Tudella Eloisa 
Published: December 2019

Abstract
Background
Despite the benefits highlighted by motor interventions based on virtual reality for children with Developmental Coordination Disorder (DCD), there are still doubts as to whether these are greater than those obtained with conventional interventions due to the absence of systematized protocols, and lack of evidence. Here, we present a protocol to systematically compare the effects of two motor-training programs (one Nintendo® Wii-based and the other no-Wii motor activities) on the motor learning in children with DCD.

Methods/design
Two intervention protocols (one based on Nintendo® Wii and the other no-Wii motor activities) will be carried out, with interventions occurring twice a week in 60-min sessions, with a minimum of 12 and a maximum of 16 sessions per child.
The protocols were developed based on the domains of the Movement Assessment Battery for Children – Second Edition (MABC-2) (Manual Dexterity, Aiming and Catching, Balance), with two activities for each of the MABC − two domains. The study will include children aged 7 to 10 years with a total MABC-2 score ≤ 16, and a Developmental Coordination Disorder Questionnaire (DCDQ) score < 46 (age of 7 years), score < 55 (age group of 8 to 9 years and 11 months), or score < 57 (age of 10 years) as scored by the parents. Children will be randomly allocated by draw in one of the two intervention protocols. MABC-2 and DCDQ will be applied before and after intervention to evaluate the effects of the interventions on motor performance and parents’ perception, respectively. Motor learning will be assessed by means of the scores obtained in the games. Evaluators and therapists will be trained and evaluators will be blind regarding the data of the children in the study.

Discussion
Owing to its motivating aspects, training with Nintendo® Wii may be particularly beneficial for children with DCD. The results of this study protocol should help researchers and therapists to better understand the benefits of Nintendo® Wii-based motor intervention over those obtained with no-Wii interventions in children with DCD. It should also create references about more systematized protocols for replication in clinical practice, seeking the improvement of the motor components of these children.

Trial registration
RBR-89ydgj
Comparison of 22G standard and Franseen needles in endoscopic ultrasound-guided fine-needle aspiration for diagnosing pancreatic mass lesions: Study protocol for a controlled trial
Authors: Itonaga Masahiro , Yasukawa Satoru , Shimokawa Toshio , Takenaka Mamoru , Fukutake Nobuyasu , Ogura Takeshi , Sakagami Junichi , Shiomi Hideyuki , Okura Yasushi , Inatomi Osamu , Matsumoto Hisakazu , Kurita Akira , Suzuki Azumi , Tanaka Kiyohito , Kitano Masayuki 
Published: December 2019

Abstract
Background
Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) was developed with the aim of further improving the diagnostic performance of endoscopic ultrasound. Although novel puncture needles have been specifically designed for collecting sufficient tissue specimens, clinical studies have indicated no clear difference in diagnostic performance between these novel needles and conventional puncture needles. Recently, a needle with Franseen geometry was developed specifically for EUS-FNA biopsy. Due to the characteristic shape of its tip, the Franseen needle is expected to be effective for scraping tissues, thus potentially increasing the diagnostic accuracy of EUS-FNA biopsy. We plan to carry out a prospective, multicenter, open-labeled, controlled trial to compare conventional and Franseen needles in terms of the diagnostic accuracy of EUS-FNA for evaluating the malignancy of pancreatic mass lesions.

Methods/design
The study will enroll 520 patients with pancreatic mass managed at any of 21 participating endoscopic centers. Lesion samples obtained using 22G conventional and Franseen needles will be assessed to compare the efficacy and safety of these two types of needles in EUS-FNA for evaluating the malignancy of mass lesions in the pancreas. Tissue samples will be fixed in formalin and processed for histologic evaluation. For the purpose of this study, only samples obtained with the first needle pass will be used for comparing the: (i) accuracy of the malignancy diagnosis, (ii) sensitivity and specificity for the malignancy diagnosis, (iii) procedure completion rate, (iv) sample cellularity, and (v) incidence of complications. Patient enrollment begins on July 17, 2018.

Discussion
The outcomes of this study may provide insight into the optimal needle choice for evaluating the malignancy of pancreatic solid lesions, thus aiding in the development of practice guidelines for pancreatic diseases.

Trial registration
University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR), UMIN000030634. Registered on 29 December 2017.
http://www.umin.ac.jp/
Version number: 01.2017.12.28.