bluuebunny/crossref_metadata_2025_split huggingface dataset:
How we teach children with asthma to use their inhaler: A scoping review protocol
Authors: McCrossan Patrick , Mallon Orla , Shields Michael , O'Donoghue Dara 
Published: July 2020

Abstract
Background One reason that asthma remains poorly controlled in children is poor inhaler technique. Current guidelines recommend checking inhaler technique at each clinical visit. However, they do not specify how best to train children to mastery of correct inhaler technique. Currently many children are simply shown how to use inhalers (brief intervention) which results in less than 50% with correct inhaler technique. The aim of this scoping review is to explore published literature on teaching methods used to train children to master correct inhaler technique.Methods This scoping review will follow the Arksey and O'Malley framework and the Joanna Briggs Institute guidelines. We will search (from inception onwards): MEDLINE, Embase, Scopus, Web of Science, CINAHL and the Cochrane library. We will include quantitative studies, (e.g. randomised controlled trials, cohort studies and case-control studies), published from the year 1956 to present, on teaching the skill of inhaler technique to children with asthma. Two reviewers will complete all screening and data abstraction independently. Data will be extracted onto a data charting table to create a descriptive summary of the results. Data will then be synthesised with descriptive statistics and visual mapping.Discussion This scoping review will provide a broad overview of currently used educational methods to improve inhaler technique in children with asthma. The analysis will allow us to refine future research in this area by focusing on the most effective methods and optimising them.
Development and application of perfect SSR markers in cotton
Authors: wu yuzhen , Huang Longyu , Zhou Dayun , Fu Xiaoqiong , Li Chao , Wei Shoujun , Peng Jun , Kuang Meng 
Published: July 2020

Abstract
Background: This study aimed to develop a set of perfect simple sequence repeat (SSR) markers with a single copy in the cotton genome, with the objective of constructing a DNA fingerprint database that is suitable for authenticating cotton cultivars. We optimized the polymerase chain reaction (PCR) system for multi-platform compatibility and improving detection efficiency. Based on the reference genome of upland cotton and 10× resequencing data of 48 basic cotton germplasm lines, single-copy polymorphic SSR sites were identified and developed as diploidization SSR markers. The SSR markers were detected by denaturing polyacrylamide gel electrophoresis (PAGE) for initial screening, then fluorescence capillary electrophoresis for secondary screening. The final perfect SSR markers were evaluated and verified using 210 lines from different sources among Chinese cotton regional trials. Results: Using bioinformatics techniques, 1 246 SSR markers were designed from 26 626 single-copy SSR loci. Adopting a stepwise (primary and secondary) screening strategy, a set of 60 perfect SSR markers was selected that showed high amplification efficiency and stability, easy interpretation of peak type, multiple allelic variations, high polymorphism information content (PIC) value, uniform chromosome distribution, and single-copy characteristics. A multiplex PCR system was established with ten SSR markers using capillary electrophoresis detection. Conclusions: A set of perfect SSR markers of cotton was developed and a high-throughput SSR marker detection system was established. This study lays a foundation for large-scale and standardized construction of a cotton DNA fingerprint database for authenticating cotton varieties.
Whole exome sequencing identifies a novel mutation in spermine synthase gene (SMS) associated with Snyder-Robinson Syndrome
Authors: Qazi Talal J. , Wu Qiao , Aierken Ailikemu , Lu Daru , Bukhari Ihtisham , Hussain Hafiz M. J. , Yang Jingming , Mir Asif , Qing Hong 
Published: July 2020

Abstract
Background: Loss of function mutations in the spermine synthase gene (SMS) have been reported to cause a rare X-linked intellectual disability known as Snyder-Robinson Syndrome (SRS). Besides intellectual disability, SRS is also characterized by reduced bone density, osteoporosis and facial dysmorphism. SRS phenotypes evolve with age from childhood to adulthood. Methods: Whole exome sequencing was performed to know the causative gene/pathogenic variant. Later we confirmed the pathogenic variant through Sanger sequencing. Furthermore, we also performed the mutational analysis through HOPE SERVER and SWISS-MODEL. Also, radiographs were also obtained for affected individual to confirm the disease features. Results: In this article, we report the first Pakistani family consisting of three patients with SRS and a novel missense pathogenic variant in the SMS gene (c.905 C>T p.(Ser302Leu)). In addition to the typical phenotypes, one patient presented with early-onset seizures. Clinical features, genetic and in-silico analysis linked the affected patients of the family with Snyder-Robinson and suggest that this novel mutation affects the spermine synthase activityConclusion: A novel missense variant in the SMS, c.905C >T p. (Ser302Leu), causing Snyder- Robinson Syndrome (SRS) is reported in three members of Pakistani Family.
Implementing oncology clinical trials in Nigeria: A model for Capacity building.
Authors: Ntekim Atara , Ibraheem Abiola , Sofoluwe Adenike , Adepoju Toyosi , Oluwasanu Mojisola , Aniagwu Toyin , Awolude Olutosin , Balogun Williams , Kotila Olayinka , Adejumo Prisca , Babalola Chinedum Peace , Arinola Ganiyu , Ojengbede Oladosu , Olopade Christopher O , Olopade Olufunmilayo I 
Published: July 2020

Abstract
Background: There is both higher mortality and morbidity from cancer in low and medium income countries (LMICs) compared with high income countries (HICs). Clinical trial activities and development of more effective and less toxic therapies have led to significant improvements in morbidity and mortality from cancer in HICs. Unfortunately, clinical trials remain low in LMICs due to poor infrastructure and paucity of experienced personnel to execute clinical trials. There is an urgent need to build local capacity for evidence based treatment for cancer patients in LMICs. Methods: We conducted a survey at facilities in four Teaching Hospitals in South West Nigeria using a checklist of information on various aspects of clinical trial activities. The gaps identified were addressed using resources sourced in partnership with investigators at HIC institutions. Results: Deficits in infrastructure were in areas of patient care such as availability of oncology pharmacists, standard laboratories and diagnostic facilities, clinical equipment maintenance and regular calibrations, trained personnel for clinical trial activities, investigational products handling and disposals and lack of standard operating procedures for clinical activities. There were two GCP trained personnel, two study coordinators and one research pharmacist across the four sites. Interventions were instituted to address the observed deficits in all four sites which are now well positioned to undertake clinical trials in oncology. Training on all aspects of clinical trial was also provided.Conclusions: Partnerships with institutions in HICs can successfully identify, address, and improve deficits in infrastructure for clinical trial in LMICs. The HICs should lead in providing funds, mentorship and training for LMIC institutions to improve and expand clinical trials in LMIC countries.
Targeted alpha immunotherapy of CD20-positive B-cell lymphoma model: Dosimetry estimate of 225Ac-DOTA-rituximab using 64Cu-DOTA-rituximab
Authors: Lee Chul-Hee , Lim Ilhan , Woo Sang-Keun , Kim Wook , Kim Kwang Il , Lee Kyo Chul , Song Kanghyon , Lim Sang Moo 
Published: July 2020

Abstract
Background: To evaluate the radiation dosimetry of 225Ac-DOTA-rituximab using Monte Carlo simulation of 64Cu-DOTA-rituximab. Methods: CD20 expression was evaluated in lymphoma cell lines (Jurkat and Raji). DOTA-rituximab was conjugated and then chelated by 64Cu. Tumor xenograft models were established in BALB/c-nu mice. Animal PET/CT imaging was obtained after tail vein injection with and without a pre-dose of 2 mg of cold rituximab. Specific binding of tumors was evaluated by an organ distribution assay and autoradiography. CD20 expression in tumor tissues was evaluated by immunohistochemistry. The residence time was calculated using 64Cu-DOTA-rituximab PET/CT acquisition data using OLINDA/EXM software. 225Ac-DOTA-rituximab tumor dosimetry was performed using Monte Carlo simulation with 64Cu-DOTA-rituximab PET/CT images.Results: CD20 protein was highly expressed in Raji cells. Specific binding of Raji cells was 90 times that of Jurkat cells (p<0.0001). Immunoreactivity was more than 75%. PET/CT imaging with 64Cu-DOTA-rituximab was specifically observed in tumors. The radioactivity of the tumor was much higher than that of other organs, and tumor uptake was related to CD20 expression. The predicted human dose for the administration of 64Cu-DOTA-rituximab was measured as the effective dose (1.07E-02 mSv/MBq). In the tumor region, equivalent doses of 225Ac-DOTA-rituximab (14 SvRBE5/MBq) were much higher (74-fold) than those of 64Cu-DOTA-rituximab (0.19 SvRBE5/MBq) (p<0.01).Conclusion: Tumor dosimetry of 225Ac-DOTA-rituximab can be estimated via the Monte Carlo simulation of 64Cu-DOTA-rituximab. 225Ac-DOTA-rituximab can be employed for lymphoma as targeted alpha therapy.
Atorvastatin Promotes Bone Formation in Aged apoE–/– Mice through the Sirt1–Runx2 Axis
Authors: Hong Wei , Wei Zhanying , Qiu Zhaohui , Li Zheng , Fu Chensheng , Ye Zhibin , Xu Xiaoya 
Published: July 2020

Abstract
Background Statins are the most widely used drugs in elderly patients, the most common clinical application of statins is in aged hyperlipemia patients. There are few studies on the effects and mechanisms of statins on bone in elderly mice with hyperlipemia. The study is to examine the effects of atorvastatin on bone phenotypes and metabolism in aged apolipoprotein E-deficient (apoE –/– ) mice, and the possible mechanisms involved in these changes. Methods Twenty-four 60-week-old apoE –/– mice were randomly allocated to two groups. Twelve mice were orally gavaged with atorvastatin (10 mg/kg body weight/day) for 12 weeks; the others served as the control group. Bone mass and skeletal microarchitecture were determined using micro-CT. Bone metabolism was assessed by serum analyses, qRT-PCR, and Western blot. Bone marrow-derived mesenchymal stem cells (BMSCs) from apoE –/– mice were differentiated into osteoblasts and treated with atorvastatin and Sirt1 inhibitor EX-527. Results The results showed that long-term administration of atorvastatin increases bone mass and improves bone microarchitecture in trabecular bone but not in cortical bone. Furthermore, the serum bone formation marker osteocalcin (OCN) was ameliorated by atorvastatin, whereas the bone resorption marker tartrate-resistant acid phosphatase 5b (Trap5b) did not appear to be impacted by atorvastatin treatment. The mRNA expression of Sirt1, runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP) and OCN in bone tissue were increased after atorvastatin administration. Western blot showed same trend in Sirt1 and Runx2. The in vitro study showed that when BMSCs from apoE –/– mice were pretreated with EX527, the higher expression of Runx2, ALP and OCN activated by atorvastatin decreased significantly or showed no difference compared with the control. The protein expression of Runx2 showed same trend. Conclusions Accordingly, the current study validates the hypothesis that atorvastatin can increase bone mass and promote osteogenesis in aged apoE −/− mice by regulating the Sirt1–Runx2 axis.
High expression of Fibroblast activation protein (FAP) predicts poor outcome in high-grade serous ovarian cancer
Authors: Li Min , Cheng Xue , Rong Rong , Tang Xiuwu , Chen Youguo 
Published: July 2020

Abstract
Background: High-grade serous ovarian cancer (HSOC) is a fatal form of ovarian cancer. Previous studies indicated some potential biomarkers for clinical evaluation of HSOC prognosis. However, there is a lack of systematic analysis of different expression genes (DEGs) to screen and detect significant biomarkers of HSOC. Method and materials: TCGA database was conducted to analyze relevant genes expression in HSOC. Outcomes of candidate genes expression, including overall survival (OS) and progression-free survival (PFS), were calculated by Cox regression analysis for hazard rates (HR). Histopathological investigation of the identified genes was carried out in 151 Chinese HSOC patients to validate gene expression in different stages of HSOC. Results: Of all 57,331 genes that were analyzed, FAP was identified as the only novel gene that significantly contributed to both OS and PFS of HSOC. In addition, FAP had a consistent expression profile between carcinoma-paracarcinoma and early-advanced stages of HSOC. Immunological tests in paraffin section also confirmed that up-regulation of FAP was present in advanced stage HSOC patients. Prediction of FAP network association suggested that FN1 could be a potential downstream gene which further influenced HSOC survival. Conclusions: High-level expression of FAP was associated with poor prognosis of HSOC via FN1 pathway.
Association of organizational and patient behaviors with nurse well-being in China: a cross-sectional study
Authors: Wang Xiaoyu , Ye Beizhu , Gao Xiao , Liang Yuan 
Published: July 2020

Abstract
Background: Nurse play a primary care role, although existing research about improving nurse well-being mainly focus on the workplace environment, there is controversy regarding the underlying factors. The purpose of this study was to investigate the relationship between organizational and patient behaviors with nurse well-being.Methods: A cross-sectional quantitative study was carried out in 77 hospitals in China between July 2014 and April 2015.Results: Of the 4885 respondents, 58.78% nurses reported being satisfied with their life; however, only 36.14% nurses were satisfied with their work, and 79.85% nurses reported they would not choose nursing again if given the opportunity. Within the organizational behaviors, nurses reporting very poor pay justice tended to report a higher turnover intention (OR = 2.03, 95% CI:1.29-3.21) and lower life happiness (OR = 0.67, 95% CI:0.45-0.98). Similarly, very poor attention to staff interests (OR = 1.79, 95% CI:1.15–2.77) and opinions (OR = 2.41, 95% CI: 1.55–3.73) were strongly associated with higher turnover intention. Within the patient behaviors, a low level of patient trust was more strongly and negatively associated with job satisfaction (OR = 0.44, 95% CI: 0.32–0.61) and life happiness (OR = 0.53, 95% CI: 0.37–0.75) compared with unreasonable demands by patients, and more positively associated with turnover intention (OR = 5.61, 95% CI: 3.66–8.60).Conclusion: Given the widespread distress among nurses, these findings suggest that interventions targeting improved nurse well-being should be expanded from individual nurses to hospital organization and patients, reflected the internal and external hospital environment, respectively.
Decreased Cerebrovascular Reserve is the Initial Cause of White Matter Hyperintensity Related Cognitive Decline
Authors: Yang Dan , Chu Lan , Xu Hengheng , Ni Ling , Qin Ruomeng , Ma Junyi , Shao Pengfei , Huang Lili , Luo Caimei , Li Mengchun , Yao Zhelv , Sheng Xiaoning , Zhang Bing , Zhang Meijuan , Xu Yun 
Published: July 2020

Abstract
Background: Increasing evidences have demonstrated the progressions of white matter hyperintensity (WMH) are associated with cerebrovascular reserve(CVR) and cognitive decline.The present study hypothesized that impaired CVR is associated with WMH progression and may lead to cognitive decline through WMH.Methods:A total of 244 WMH subjects were recruited and were categorized into WMH-I (n=112), WMH-II (n=76)and WMH-III(n=56) groups according to Fazekas rating scale.The individual CVR was measured using blood-oxygenation level-dependent (BOLD) signal fluctuations obtained from resting-state functional MRI(rs-fMRI). We compared maps of the CVR and clinical features among the three groups. Multiple linear regression analysis was performed to investigate the correlations of WMH volume with impaired CVR and cognitive functions indifferent domains controlling for age, sex, years of education, vascular risk factors, numbers of lacunas and cerebral microbleeds in all WMH individuals.Results: Compared with the WMH-I group, both WMH-II and WMH-III groups showed CVR decline in the left frontal and occipital areas. Multiple linear regression analysis showed WMH volumewas negatively associated with CVR impairments in left frontal/occipital areas and cognitive functions including global cognitive function (GCF), executive function (EF), information processing speed (IPS), memory and visuospatial processing function (VPF)(all P<0.05). Additionally, mediation analysis revealed CVR impairments in left frontal and occipital areas didn’t directly lead to cognitive decline, but indirectly caused cognitive decline in multiple domains through increasing WMH burdens (all 95% confidence intervals didn’t contain zero). Conclusion:The CVR decline initially resulted in WMH progression, which is responsible for the following development of cognitive decline. This study shed lights on exploring the pathogenesis of WMH progression and underlying mechanisms of WMH-related cognitive decline.
Effectiveness of Intravitreal Chemotherapy-Assisted Endoresection in Monocular Patients with Group D Retinoblastoma
Authors: Yu Xiling , Li Xueke , Xing Yue , Lu Siduo , Tanumiharjo Silvia , Ma Jin 
Published: July 2020

Abstract
Background: To determine the efficacy and complications of intravitreal chemotherapy-assisted endoresection for refractory group D retinoblastoma in monocular patients.Methods: In this retrospective case series, intravitreal chemotherapy-assisted endoresection by pars plana vitrectomy was performed in 11 eyes with refractory ICRB group D retinoblastoma unresponsive to standard therapies in monocular patients.Results: Across a mean follow-up period of 42.7 months, globe salvage was attained in all 11 eyes (100%). There was no case of extra-ocular tumor seeding or remote metastasis. In 9 eyes (81.8%), tumor control was achieved with one-time pars plana vitrectomy, whereas in 2 cases (18.2%), repeated treatment such as laser, intravitreal chemotherapy or second pars plana vitrectomy were needed. Retinal reattachment was achieved in all 4 eyes (100%) with previous retinal detachment. 4 eyes (36.4%) required subsequent cataract surgery due to secondary cataract. 10 eyes (90.9%) had improvement in best-corrected visual acuity at the last follow-up.Conclusion: Intravitreal chemotherapy-assisted endoresection appears to be a safe and effective globe-salvaging method for refractory group D retinoblastoma. It is a promising alternative to enucleation and a supplementary therapeutic strategy for those unresponsive to standard therapies, especially for the monocular retinoblastoma patients.
Neurexin and Neuroligins Jointly Regulate Synaptic Degeneration at the Drosophila Neuromuscular Junction based on TEM Studies
Authors: Gan Guangming , Chenchen Zhang , Xiang Gao , Keze Lu , Wei Xie , Junhua Geng 
Published: July 2020

Abstract
Background: The Drosophila larval neuromuscular junction (NMJ) is a well-known model system and is often used to study synapse development and signal transmission in neurology. Here, we show the synaptic degeneration at NMJ boutons, primarily based on transmission electron microscopy (TEM) studies.Methods: To this aim, we extensively acquire the ultrastructure of diffuse NMJ boutons using continuous sectioning and transmission electron microscope in the wide type and the dneurexin (dnrx) and dneuroligins (dngs) mutant.Results: When degeneration starts, the subsynaptic reticulum (SSR) swells, retracts and folds inward, and then, the residual SSR degenerates into a disordered, thin or linear membrane with a shrinking postsynaptic area (PSA) and axon terminal. The axon terminal begins to degenerate from the central region, and the T-bar structure detaches from the presynaptic membrane with clustered synaptic vesicles to accelerate large-scale degeneration, accompanied by retraction of synaptic vesicles and mitochondria. There are two degeneration modes for clear synaptic vesicles. In the first mode, synaptic vesicles without actin filaments degenerate on the membrane with ultrafine spots and collapse and disperse to form an irregular profile with dark ultrafine particles. In the second mode, clear synaptic vesicles with actin filaments degenerate into dense synaptic vesicles, form irregular dark clumps without a membrane, and collapse and disperse to form an irregular profile with dark ultrafine particles. Last, all residual membranes in NMJ boutons, including presynaptic and postsynaptic membranes, become very thin, most of the SSR degenerates into a linear shape, and all the residual elements in axon terminals, such as synaptic vesicles, mitochondria, the cytoskeleton, and the T-bar, degenerate in situ and eventually form a cluster of dark ultrafine particles. Axon terminals and elements within axon terminals degenerate with the postsynaptic SSR, and swelling and retraction of the SSR occurs prior to axon terminal degradation, which degenerates faster and with more intensity than the SSR. NMJ bouton degeneration occurs under normal physiological conditions, but degeneration in dnrx and dnlgs mutant is accelerated. Furthermore, there is a synergistic effect in dnrx;dnlgs double mutants and dnlg2;dnlg3 double mutants that promotes degeneration of NMJ boutons.Conclusions: NMJ bouton degeneration occurs under normal physiological conditions but is accelerated in dnrx and dnlgs mutants. Furthermore, there is a synergistic effect in dnrx;dnlgs double mutants and dnlg2;dnlg3 double mutants that promotes degeneration of NMJ boutons, which suggests that both neurexin and neuroligins play a vital role in preventing synaptic degeneration. This study proposes the model of NMJ bouton degeneration patterns, which is very conducive to in-depth study of neurodegeneration.
Influence of Cyst Size on Ovarian Reserve After Unilateral Laparoscopic Ovarian Cystectomy for Endometrioma and Ovarian Mature Teratoma.
Authors: Chae Heesuk 
Published: July 2020

Abstract
Background:The present study is aimed to investigate the influence of ovarian cyst size on serum anti-Müllerian hormone levels after laparoscopic ovarian cystectomy in women with endometrioma and ovarian mature teratomaMethods: From March 2017 to December 2018, we retrospectively studied eighty-one patients who underwent unilateral laparoscopic cystectomy for endometrioma (n = 41, endometrioma group) and ovarian mature cystic teratoma (n = 40, teratoma group). Serum anti-Müllerian hormone (AMH) levels were measured preoperatively and 1 month after surgery.Results: The rate of decrease in serum AMH levels after laparoscopic cystectomy was significantly higher in the endometrioma group than in the teratoma group (0.35 ± 0.04% vs. 0.19 ± 0.04%, p = 0.013). In patients with mature cystic teratoma, a statistically significant correlation between the rate of decrease in serum AMH levels and cyst size was observed (r = 0.391, p = 0.013); the rate of decrease in serum AMH levels after surgery was significantly higher in the > 5.13 cm subgroup than in the ≤ 5.13 cm subgroup (p = 0.006). Conclusions: Laparoscopic cystectomy for endometriomas may result in a more significant damage to the ovarian reserve compared with that for ovarian mature cystic teratomas. Cyst diameter and reduced ovarian reserve after surgery were not correlated in patients with endometriomas, whereas a significant correlation was observed in patients with ovarian mature teratomas. The decrease in AMH levels was more evident in patients with a mature teratoma > 5.13 cm.