bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and validation of functional markers from Dw1 and Dw2 loci to accurately predict apple rootstock dwarfing ability
Authors: Yang Feng , Shen Fei , Liu Zhi , He Mingli , Wang Yi , Wu Ting , Xu Xuefeng , Li Wei , Qiu Changpeng , Zhang Xinzhong , Han Zhenhai 
Published: February 2020

Abstract
Background: ‘M9’ is a widely used apple dwarfing rootstock due to the outstanding effects on both precocity and vigorous control. Two quantitative trait loci (QTLs), Dw1 and Dw2 , for the dwarfing effect were previously mapped on ‘M9’, but the genetic variations that underpin the dwarfing ability have not been elucidated to date. Result: By using ‘Red Fuji’ trees grafted on 1123 hybrids from ‘ M alus baccata ’ × ‘M9’, the intervals of Dw1 and Dw2 were narrowed down. MdLBD3 and MdARF6 were predicted as candidate genes from Dw1 , while MdG3OX3 was a candidate gene from Dw2 . An 11 bp deletion at -339 bp upstream of the transcription start site (TSS) of MdLBD3 generated a new cis-element binding site with MdWRKY2 and caused increased expression of MdLBD3 . Coincidently, a ten bp deletion at -278 bp upstream of the TSS of MdG3OX3 created an additional binding site of MdABI5 , leading to higher expression of MdG3OX3 . At -954 bp of the MdARF6 promoter, a 14 bp insertion destroyed the binding ability by MdABI5 and reduced MdARF6 expression. The genotype effects of these insertion and deletions as diagnostic markers on dwarfing traits (tree height, trunk diameter, and canopy width) were estimated in 108 F1 hybrids. The genomic predicted genetic values (GEGV) were calculated by adding up the genotype effects of the three markers and the population mean phenotype. The GEGV of the dwarfing traits exhibited high correlation coefficients of 0.93, 0.94, and 0.93 in terms of tree height, trunk diameter, and canopy width for the observed phenotype values, respectively. The predictability of GEGV was validated in 64 Malus accessions. Conclusion : The development of the three functional markers, Ld/Li, Ad/Ai, and Gd/Gi, ensures the accurate genomic assisted prediction of dwarfing ability in apple rootstock breeding. The data also suggested that ABA, auxin, GA, and zeatin signals may be involved in the regulation of apple rootstock dwarfing mechanism.
Transcutaneous electrical acupoint stimulation for high-normal blood pressure: study protocol for a randomized controlled pilot trial
Authors: Wang Yu , Shi Guang-Xia , Tian Zhong-Xue , Liu Jun-Hong , Qi You-Sheng , Tu Jian-Feng , Yang Jing-Wen , Wang Li-Qiong , Liu Cun-Zhi 
Published: February 2020

Abstract
Background: High-normal blood pressure (BP) is associated with increased all-cause, cardiovascular mortality and frequently progresses to hypertension. Transcutaneous electrical acupoint stimulation (TEAS) might be a non-pharmaceutical therapy option to control BP. This trial aims to determine the efficacy and safety of TEAS combined with lifestyle modification for high-normal BP. Methods/design: This prospective, randomized and parallel clinical trial will be conducted in a community service center in China. Sixty participants with high-normal BP will be randomly allocated to receive TEAS plus lifestyle modification (intervention group) or lifestyle modification alone (control group) in a 1:1 ratio. In addition to lifestyle modification, the intervention group will receive TEAS at four acupoints for 30 minutes, 4 times weekly for 12 weeks for a total of 48 sessions at home. The control group will receive same lifestyle modification but no TEAS. The primary outcome will be the change in mean systolic blood pressure at 12-week from the baseline measurement. Secondary outcomes include the change of mean diastolic blood pressure, proportion of subjects with progression to hypertension, quality of life, physical activity, body mass index and waist circumference. Adverse events during the trial will be monitored. Discussion: This trial will explore the feasibility and provide potential evidence for the efficacy and safety of TEAS plus lifestyle modification for high-normal BP. The results of this study will be published in a peer-reviewed journal. Trial registration: Chinese Clinical Trial Registry, ChiCTR1900024982. Registered on August 6, 2019.
Acupuncture for osteoporosis: study protocol for a randomized controlled trial
Authors: Huang M , Lai MX , Wang XY , Wang YF , Yang J , Yang ZG , Ren ZQ , Mei R , Li JY , Zhao R , Wang ZH 
Published: February 2020

Abstract
Background: The rapid increase in the prevalence of osteoporosis and the rate of fractures after osteoporosis indicates that osteoporosis has become a serious global public health problem. A recent meta-analysis showed that oral alendronate and parenteral injection of zoledronate had no statistical significance in preventing postmenopausal hip fractures. Acupuncture and moxibustion are widely used in the treatment of osteoporosis due to their good analgesic effects. Early observation showed that integral adjustment of acupuncture and moxibustion therapy could improve the quality of life of patients with osteoporosis and prevent the occurrence of osteoporosis fractures. As the observation period of fracture is too long, it is necessary to carry out a large and strictly designed multi-center randomized trial covering the risk factors of fracture and fracture induction, so as to evaluate the effectiveness of acupuncture and moxibustion in the treatment of primary osteoporosis.Methods/Design: A multicenter randomized controlled trial will be performed in three hospitals. 312 participants patients within primary osteoporosis will be divided into an experimental group and a control group randomly. The experimental group is treated with acupuncture and western medicine while the control group is treated with Western medicine. All the patients will receive a 3-month treatment and 6-month,and one year follow-ups. The primary outcome is the bone mineral density (BMD), the secondary outcome is Bone-derived alkaline phosphatase(BALP), bone glaprotein(BGP), visual pain scale score(VAS),Traditional Chinese Medicine (TCM) syndrome scores, quality of daily life score(QOL) and adverse events. Outcome measures (including primary and secondary outcome measures) are collected at baseline,3 months of the intervention, Causes and number of falls are collected at 6 months and one year after the intervention.Discussion: This study will provide clinical evidence for the treatment of primary osteoporosis with holistic adjustment acupuncture. This study will evaluate the synergistic effect of acupuncture treatment for primary osteoporosis and provide evidence for clinical treatment.Trial registration: This trial was registed at Chinese Clinical Trial Registry, registration date: 5 August 2018.URL:http://www.chictr.org.cn,registration number:ChiCTR1800017581.
The β-catenin/TCF-4 pathway regulates the expression of OPN in human osteoarthritic chondrocytes
Authors: Tian Jian , Gao Shu-Guang , Li Yu-Sheng , Cheng Chao , Deng Zhen-Han , Luo Wei , Zhang Fang-Jie 
Published: February 2020

Abstract
Background Cartilage destruction is the main characteristic of osteoarthritis (OA), and osteopontin (OPN) is elevated in OA articular cartilage; however, the reason for the increased OPN level is not determined. In addition, Wnt/β-catenin signaling participates in the progression of OA. The aim of the present study was to evaluate whether canonical Wnt signaling could regulate the expression of OPN in human chondrocytes in vitro. Methods Human chondrocytes were cultured in vitro, and we first assayed the mRNA levels of OPN and β-catenin in chondrocytes. Next, we performed transient transfection of TCF 4 shRNA into chondrocytes to inhibit TCF 4 expression and explore changes in the OPN level. Then, the Wnt/β-catenin signaling inhibitor dinkkopf-1 (Dkk-1) was incubated with chondrocytes, and we assayed the changes in β-catenin and OPN. Results Our results showed that the expression of both β-catenin and OPN was increased in OA chondrocytes, but there were no correlations between β-catenin and OPN expression. TCF4 shRNA downregulated the expression of TCF 4 and OPN in chondrocytes, while after treatment with rDKK-1 at a concentration of 400 ng/ml for 24 h, the mRNA and protein expression of both β-catenin and OPN was significantly decreased in chondrocytes. Conclusions Elevated OPN expression might be regulated by the β-catenin/TCF-4 pathway, and the Wnt/β-catenin inhibitor DKK1 could inhibit the expression of β-catenin and OPN in OA chondrocytes.
Measuring spatial accessibility and disparity to county hospitals in western China: based on the web map navigation data
Authors: Shen Chi , Zhou Zhongliang , Lai Sha , Lu Li , Dong Wanyue , Su Min , Zhang Jian , Wang Xinyu , Deng Qiwei , Chen Yaru , Chen Xi 
Published: February 2020

Abstract
Background The Chinese government proposed the initiative of "XIAO BING BU CHU CUN, DA BING BU CHU XIAN” in 2016, which means the rate of health care service provided by county hospitals should reach 90%. The prerequisite for achieving this goal is that residents can access to county hospitals’ services conveniently and impartially. However, little research reported the level of spatial accessibility of county hospitals in western China. Therefore, we aim to measure the spatial accessibility to county hospitals of county residents and identify regional disparities in Shaanxi Province in western China. Methods We implemented a novel method – navigation data of the AutoNavi map (knows as Gaode map in Chinese) – to assess time and distance from villages and neighborhoods to county hospitals. The navigation data was collected by requesting an application-programming-interface using a web crawler in Python. The minimum driving time and distance were extracted from the navigation data. The travel impedance to the nearest provider was used to measure spatial accessibility. Results The results show that county residents in northwestern China's Shaanxi Province have poor spatial accessibility to county hospitals. Only 68.8% of villages and neighborhoods can reach the county hospitals within 60 minutes, while 13.4% of them are reachable beyond 90 minutes. Moreover, a significant within-province disparity exists, with residents in the central area most accessible to county hospitals, while the north and south areas still need improvement. Conclusions Health resource planning is required to improve spatial accessibility and eliminate the regional disparity. Further studies are called for to integrate navigation data of web map with GIS methods to measure spatial accessibility of health facilities in more complex contexts.
Setting Health Care Services Tariffs in Iran: Half a Century Quest for a Window of Opportunity
Authors: Doshmangir Leila , Rashidian Arash , Kouhi Farhad , Gordeev Vladimir S 
Published: February 2020

Abstract
Background Pricing health services remains to be a contentious issue in Iran. The Universal Health Services Insurance Law of 1994 aimed at introducing structural and legal bases for pricing health services to enhance efficiency and to equate demand and supply, while referring to equity objectives. Until now, the implementation of this law has failed to meet its original objectives. This paper explores the experience of setting health care services tariffs in the Iranian health care system over the last five decades. Methods We analyzed data collected through documentary and literature reviews of the official documents developed at the various levels of the Iranian health using inductive and deductive content analysis. 22 face-to-face semi-structured interviews supplemented the analysis. Policy triangle policy analysis model was used to guide data analysis. Results Our comprehensive overview of changes in the medical pricing system provides valuable lessons for major stakeholders. Most changes were implemented in a sporadic, inadequate, and a non-evidence-based manner. Disparities in prices between public and private sectors make tariffs setting a contentious issue in Iran. Lack of clarity in pricing health care services makes negotiations between various stakeholders difficult and can potentially become a source of a corrupt income. Such clarity can be achieved by using adequate and technically sound pricing. Technical aspects of pricing health services should be separated from the political negotiations over the overall payment to the medical professionals. Transparency regarding a conflict of interest and establishing punitive measures against those violating the rules could help improving trust in the doctor-patient relationship. Conclusion Evidence-based changes in medical pricing policies can help striking the right balance in the health care services provision process. A sensitive application of policy models can offer significant insights into the nature of medical price policy setting and highlight existing constraints and opportunities.
First cured patient with 2019 novel coronavirus in Changsha, China, a case report
Authors: Zhou Jian , Jiang Di-xuan , Cao Zi-qin , Wang Wanchun , Huang Kang , Zheng Fang , Xie Yuan-lin , Zhou Zhi-guo 
Published: February 2020

Abstract
Background: In December, 2019, the novel coronavirus (2019-nCoV) firstly occurred in Wuhan, Hubei Province, China. It spreads rapidly and many cases are identified in multiple countries, which pose a great threat to people's health. Here we report the first cured patient with 2019-nCoV infection in Changsha, China, and the symptoms, diagnosis, treatment and management of this patient are all described in the present study.
Case presentation: A 57 year old woman developed cough and fever after returning from Wuhan to Changsha on January 9, 2020. She was tested positive for 2019-nCoV infection, which was supported by Chest CT. Lopinavir and ritonavir tablets and interferon alfa-2b injection were used for treatment. A small dose of glucocorticoids were used in a short period to control the immune response in bilateral lung and this patient avoided the occurrence of cytokine storms. The clinical condition of this patient improved and negative result was obtained for 2019-nCoV assay on January 25, 2020. This patient was recovered and discharged on January 30, 2020.
Conclusions: At present, many reports about 2019-nCoV infection focused on the epidemiological and clinical characteristics of this disease. This case described the symptoms, diagnosis, treatment and management of a cured patient with 2019-nCoV infection, which may provide information for the treatment of 2019-nCoV infection.
Development, Validation and Regulatory Acceptance of Improved Purification and Simplified Quality Control of [13N] Ammonia
Authors: Yokell Daniel L , Rice Peter A , Neelamegam Ramesh , Fakhri Georges N El 
Published: February 2020

Abstract
Background: [ 13 N]Ammonia is a widely used cyclotron produced myocardial perfusion imaging agent. With the development of high-yielding [ 13 N]Ammonia cyclotron targets using a solution of 5mM ethanol in water, there was a need to develop and validate an automated purification and formulation system for [ 13 N]Ammonia to be in a physiological compatible formulation of 0.9% sodium chloride since there is no widely available commercial system at this time. Due to its short half-life of 10 minutes, FDA and USP regulations allow [ 13 N]Ammonia to be tested in quality control (QC) sub-batches with limited quality control testing performed on the sub-batches for patient use. The current EP and the original USP method for the determination of the radiochemical purity and identity of [ 13 N]Ammonia depended on an HPLC method using a conductivity detector and a solvent free of other salts. This HPLC method created issues in a modern cGMP high volume PET manufacturing facility where the HPLC is used with salt containing mobile phase buffers for quality control analysis of other PET radiopharmaceuticals. Flushing of the HPLC system of residual salt buffers which may interfere with the [ 13 N]Ammonia assay can take several hours of instrument time. Since there are no mass limits on [ 13 N]Ammonia, a simplified TLC assay to determine radiochemical identity and purity could be developed to simplify and streamline QC. Results: We have developed and validated a streamlined automated synthesis for [ 13 N]Ammonia which provides the drug product in 8mL of 0.9% sodium chloride for injection. A novel radio-TLC method was developed and validated to demonstrate feasibility to quantitate [ 13 N]Ammonia and separate it from all known radiochemical impurities. Conclusions: The process for automated synthesis of [ 13 N]Ammonia simplifies and automates the purification and formulation of [ 13 N]Ammonia in a cGMP compliant manner needed for high-throughput manufacture of [ 13 N]Ammonia. The novel radio-TLC method has simplified [ 13 N]Ammonia quality control (QC) and now enables it to be tested using the same QC equipment as F-18 Fludeoxyglucose. Both the streamlined automated synthesis of [ 13 N]Ammonia and the novel radio-TLC method have been accepted and approved by the US Food and Drug Administration (FDA) for the cGMP manufacture of [ 13 N]Ammonia.
Effect of hyaluronic acid on osteoblast function in vivo and on fracture healing in an experimental rabbit model
Authors: Li Xiang , Xie Ruimin , Wang Xiong , LI Bohua , Wang Yongping 
Published: February 2020

Abstract
Background Fracture healing is regulated by endocrine hormones and biochemical and biophysical factors, including hyaluronic acid (HA), which is a component of the extracellular matrix. The prerequisites for biological responses that promote fracture healing, such as biomechanical conditions, and molecular factors, can be investigated in bone cell cultures. Methods In cell experiments, CCK-8 was used to detect the effect of different concentrations of HA on MC3T3-E1 cells after cell intervention. After 10% of HA interfered with MC3T3-E1 cells, they were cultured in induction medium and observed for their mineralization Impact. Total protein was extracted from cells to observe Runx2 and OCN protein expression. After successful modeling in animal experiments, X-rays of the fracture site were taken to determine bone density at the fracture end. After the fracture site was taken, histological examination was performed and the callus was analyzed quantitatively and qualitatively. Results In this study, HA promoted the formation of calcium nodules and the expression of runt-related transcription factor (Runx)2 and osteocalcin (OCN) proteins in MC3T3-E1 cells; In a rabbit tibial fracture model, HA promoted formation of larger calluses than those in control or sham-treated animals at 2, 4, 6, and 8 weeks ( P < 0.05). Osteophytes were larger in HA-treated than in control animals at 4 and 6 weeks ( P < 0.05). Bone mineral density was greater in HA-treated than in control animals at 4, 6, and 8 weeks ( P < 0.05). Conclusions The results showed that HA promoted the formation of calcified nodules in bone cell cultures and healing of rabbit tibial fractures.
Mutation analysis and prenatal diagnosis of 419 cases of Spinal Muscular Atrophy in China
Authors: Sun YingJie , Kong Xiangdong , Zhao Xuechao , Zhao Zhenhua 
Published: February 2020

Abstract
Background Spinal muscular atrophy (SMA) is a common and lethal autosomal recessive neurodegenerative disease, which is caused by mutations of the survival motor neuron 1 (SMN1) gene. At present, the gene therapy medicine for SMA, i.e. , Spinraza (Nusinersen), has been approved by the FDA, bringing hope to SMA patients and families. In this study, we analyzed the deletion of SMN gene in patients suspected of SMA, and performed prenatal genetic diagnosis of SMA. Methods In this study, we collected the peripheral blood of 419 probands and their parents who were treated in the genetic counseling clinic at our hospital from January 2010 to September 2019, and extracted DNA from the blood samples for analysis. Patients who were diagnosed with SMA were first tested by MLPA. The patients with negative MLPA results were further analysed with long-range PCR combined with nest PCR and validated by Sanger sequencing to look for point mutations. In 293 families, pregnant women were subjected to chorionic villus or amniotic fluid sampling for prenatal genetic diagnosis depending on gestational weeks. In addition to the above methods used for genetic diagnosis, we also used QF-PCR in all prenatal diagnoses, which can help detect the presence of trisomy of chromosome while eliminating maternal contamination. Results 1. Homozygous deletion of SMN1 exon 7 was detected in 96.40% (404/419) of patients. Homozygous deletion of SMN1 exon 7 alone was detected in 15 patients (3.60%). 2. In total, 10 point mutations were detected in the 15 pedigrees. Five of these variants have not been previously reported in the literature. 3. Among the 293 pedigrees that underwent one prenatal diagnosis, 118 foetuses were normal, 149 foetuses were carriers of heterozygous variants, and the remaining 72 foetuses harboured compound heterozygous variants or homozygous variants. 4. In all prenatal diagnoses, we found one 21-trisomy fetus by QF-PCR. Couples whose foetuses were normal or carriers continued the pregnancy, whereas couples whose foetuses harboured compound heterozygous variants or homozygous variants decided to terminate the pregnancy. The follow-up results were consistent with the prenatal diagnosis.
Validation of the arabic version of the low anterior resection syndrome score
Authors: Essangri Hajar , Majbar Mohammed Anass , Benkabbou Amine , Amrani Laila , Mohsine Raouf , Amine Souadka 
Published: February 2020

Abstract
Purpose: Sphincter sparing surgery is oftentimes associated with bowel dysfunction complaints, namely the low anterior resection syndrome (LARS). The LARS questionnaire is widely used to assess this syndrome. The aim of this study is to translate this tool into arabic and test its psychometric properties in rectal cancer patients, in order to ease its use in clinical practice and future research. Methods: The LARS questionnaire was translated to arabic and administered to a total of 143 patients. A subgroup of 42 patients took the test twice for test-retest reliability. Internal consistency was examined through cronbach’s alpha. The score results were correlated to the EORTC QLQ-C30 questionnaire for convergent validity assessment while discriminant validity was established through the ability of the LARS score to differentiate patients with different clinical and pathological criteria. Results: The arabic version of the LARS score was completed by 143 patients. The internal consistency was demonstrated through a cronbach alpha score of 0.66. The agreement between the test and retest was established by a Bland Altman plot with 95% limits of agreement. 85.6% of patients remained in the same LARS category. The LARS score showed negative correlation with all five of the QLQ-C30 functional scales as well as positive correlation to the diarrhea symptom scale. The questionnaire score differed between patients according to their tumor location, Chemoradiotherapy, type of mesorectal excision and anastomosis. Conclusion: The Arabic version of the LARS score shows good psychometric properties and can be used for bowel dysfunction assessment in clinical and research settings.