bluuebunny/crossref_metadata_2025_split huggingface dataset:
Localising occult prostate cancer metastasis with advanced imaging techniques (LOCATE trial): a prospective cohort, observational diagnostic accuracy trial investigating whole–body magnetic resonance imaging in radio-recurrent prostate cancer
Authors: Adeleke Sola , Latifoltojar Arash , Sidhu Harbir , Galazi Myria , Shah Taimur T. , Clemente Joey , Davda Reena , Payne Heather Ann , Chouhan Manil D. , Lioumi Maria , Chua Sue , Freeman Alex , Rodriguez-Justo Manuel , Coolen Anthony , Vadgama Sachin , Morris Steve , Cook Gary J. , Bomanji Jamshed , Arya Manit , Chowdhury Simon , Wan Simon , Haroon Athar , Ng Tony , Ahmed Hashim Uddin , Punwani Shonit 
Published: November 2019

Abstract
Background
Accurate whole-body staging following biochemical relapse in prostate cancer is vital in determining the optimum disease management. Current imaging guidelines recommend various imaging platforms such as computed tomography (CT), Technetium 99 m (99mTc) bone scan and 18F-choline and recently 68Ga-PSMA positron emission tomography (PET) for the evaluation of the extent of disease. Such approach requires multiple hospital attendances and can be time and resource intensive. Recently, whole-body magnetic resonance imaging (WB-MRI) has been used in a single visit scanning session for several malignancies, including prostate cancer, with promising results, providing similar accuracy compared to the combined conventional imaging techniques. The LOCATE trial aims to investigate the application of WB-MRI for re-staging of patients with biochemical relapse (BCR) following external beam radiotherapy and brachytherapy in patients with prostate cancer.

Methods/design
The LOCATE trial is a prospective cohort, multi-centre, non-randomised, diagnostic accuracy study comparing WB-MRI and conventional imaging. Eligible patients will undergo WB-MRI in addition to conventional imaging investigations at the time of BCR and will be asked to attend a second WB-MRI exam, 12-months following the initial scan. WB-MRI results will be compared to an enhanced reference standard comprising all the initial, follow-up imaging and non-imaging investigations. The diagnostic performance (sensitivity and specificity analysis) of WB-MRI for re-staging of BCR will be investigated against the enhanced reference standard on a per-patient basis. An economic analysis of WB-MRI compared to conventional imaging pathways will be performed to inform the cost-effectiveness of the WB-MRI imaging pathway. Additionally, an exploratory sub-study will be performed on blood samples and exosome-derived human epidermal growth factor receptor (HER) dimer measurements will be taken to investigate its significance in this cohort.

Discussion
The LOCATE trial will compare WB-MRI versus the conventional imaging pathway including its cost-effectiveness, therefore informing the most accurate and efficient imaging pathway.

Trial registration
LOCATE trial was registered on ClinicalTrial.gov on 18th of October 2016 with registration reference number NCT02935816.
Vitamin e-loaded membrane dialyzers reduce hemodialysis inflammaging
Authors: Sepe Vincenzo , Gregorini Marilena , Rampino Teresa , Esposito Pasquale , Coppo Rosanna , Galli Francesco , Libetta Carmelo 
Published: November 2019

AbstractBackgroundInflammaging is a persistent, low−grade, sterile, nonresolving inflammatory state, associated with the senescence of the immune system. Such condition downregulates both innate and adaptive immune responses during chronic disorders as type II diabetes, cancer and hemodialysis, accounting for their susceptibility to infections, malignancy and resistance to vaccination.Aim of this study was to investigate hemodialysis inflammaging, by evaluating changes of several hemodialysis treatments on indoleamine 2,3-dioxygenase-1 activity and nitric oxide formation.MethodsWe conducted a randomized controlled observational crossover trial. Eighteen hemodialysis patients were treated with 3 different hemodialysis procedures respectively: 1) Low−flux bicarbonate hemodialysis, 2) Low−flux bicarbonate hemodialysis with vitamin E − loaded dialyzers, and 3) Hemodialfitration. The control group consisted of 14 hospital staff healthy volunteers. Blood samples were collected from all 18 hemodialysis patients just after the long interdialytic interval, at the end of each hemodialysis treatment period.ResultsHemodialysis kynurenine and kynurenine/L − tryptophan blood ratio levels were significantly higher, when compared to the control group, indicating an increased indoleamine 2,3-dioxygenase-1 activity in hemodialysis patients. At the end of the low−flux bicarbonate hemodialysis with vitamin E − loaded dialyzers period, L − tryptophan serum levels remained unchanged vs both low−flux bicarbonate hemodialysis and hemodialfitration. Kynurenine levels instead decreased, resulting in a significant reduction of kynurenine/L − tryptophan blood ratio and indoleamine 2,3-dioxygenase-1 activity, when matched to both low−flux bicarbonate hemodialysis and HDF respectively. Serum nitric oxide control group levels, were significantly lower when compared to all hemodialysis patient groups. Interestingly, low−flux bicarbonate hemodialysis with vitamin E − loaded dialyzers nitric oxide serum levels from venous line blood samples taken 60 min after starting the hemodialysis session were significantly lower vs serum taken simultaneously from the arterial blood line.ConclusionsThe treatment with more biocompatible hemodialysis procedure as low−flux bicarbonate hemodialysis with vitamin E − loaded dialyzers, reduced indoleamine 2,3-dioxygenase-1 activity and nitric oxide formation when compared to both low−flux bicarbonate hemodialysis and hemodialfitration. These data suggest that low−flux bicarbonate hemodialysis with vitamin E − loaded dialyzers lowering hemodialysis inflammaging, could be associated to changes of proinflammatory signalling a regulated molecular level.Trial registrationNCT Number:NCT02981992; Other Study ID Numbers: 20100014090. First submitted: November 26, 2016. First posted: December 5, 2016. Last Update Posted: December 5, 2016.
Analysis of cardiac monitoring and safety data in patients initiating fingolimod treatment in the home or in clinic
Authors: Brown Brandon , Weiss Jamie L. , Kolodny Scott , Meng Xiangyi , Williams Ian M. , Osborne John A. 
Published: November 2019

AbstractBackgroundFingolimod (Gilenya®) is approved for relapsing forms of multiple sclerosis in the USA. Owing to transient heart-rate effects when initiating fingolimod, eligible patients undergo precautionary baseline assessment and first-dose observation (FDO) for ≥6 h. Prior to 2014, FDO was undertaken only in clinics. As the FDO period is short, and fingolimod has accumulated evidence of a positive benefit:risk ratio, an in-home treatment-initiation program, Gilenya@Home, was developed to offer a convenient alternative.MethodsCardiac parameters and adverse events (AEs) were recorded by healthcare professionals performing fingolimod FDOs in the US Gilenya@Home program or in US Gilenya Assessment Network clinics. Anonymized data were collated retrospectively from the first 34 months in the home setting and from 78 months in clinics; data are reported descriptively. Satisfaction with Gilenya@Home was rated by patients using a 7-item questionnaire that considered aspects such as ease of scheduling, courtesy, and competency.ResultsData were captured as part of standard care from 5573 patients initiating fingolimod in-home (October 2014 to July 2017) and from 15,025 patients initiating in-clinic (July 2010 to December 2016). In the Gilenya@Home questionnaire, 91.7% of 1848 respondents rated their overall satisfaction as “very good,” and 7.6% rated their satisfaction as “good.” AEs were reported for 30.7 and 32.6% of in-home and in-clinic patients, respectively. In total, 557 in-home (10.0%) and 398 in-clinic (2.6%) patients were monitored for > 6 h; 15 (0.3%) in-home and 129 (0.9%) in-clinic patients were transferred to an emergency room for overnight monitoring. The mean (standard deviation) heart rate (HR; bpm) pre-FDO was 74.8 (12.2) in-home and 74.2 (11.3) in-clinic; reduction in HR at 6 h postdose was 10.6 (12.0) and 6.3 (9.6), respectively. New-onset first-degree atrioventricular block was experienced by 132 (2.4%) in-home and 74 (0.5%) in-clinic patients, and Wenckebach (Mobitz type I) second-degree atrioventricular block by four (0.07%) and nine (0.1%) patients, with no cases of third-degree atrioventricular block.ConclusionsA substantial number of patients have initiated fingolimod at home, reporting very high levels of satisfaction. Gilenya@Home was as rigorous as the clinic setting in detecting cardiovascular events. Overall, FDO safety outcomes were similar with Gilenya@Home and in-clinic.
Countering the poor oral health of people with intellectual and developmental disability: a scoping literature review
Authors: Wilson Nathan J. , Lin Zhen , Villarosa Amy , Lewis Peter , Philip Philcy , Sumar Bashir , George Ajesh 
Published: November 2019

AbstractBackgroundPeople with intellectual and developmental disability (IDD) have poor oral health and need support to maintain optimal oral health outcomes. Little is known about how, when and where to intervene for this population. Thus the aim of this review was to summarise the existing evidence surrounding improving oral health outcomes for people with IDD.MethodsA scoping literature review was conducted focusing on ‘oral health’ and ‘intellectual disability’. Systematic searches of five electronic databases were conducted in line with the study aims and two authors independently examined all records for relevance, with consensus achieved by a third author.ResultsA small number of approaches and interventions were identified to support people with IDD to independently maintain optimal oral hygiene. Identified studies highlighted that caregivers play a vital role in the provision of oral health support, emphasising the effectiveness of educational interventions for caregivers. However, there was uncertainty regarding the efficacy of specific tooth brushing interventions for people with IDD. In cases of more severe IDD and/or dental-related behavioural problems, dental treatment under general anaesthesia was often both a necessary and effective method of oral health care provision. The findings also identified outreach and exclusive oral health services as successful strategies for increasing the limited access of people with IDD to oral care services.ConclusionsA uniform approach to supporting oral health for people with IDD is unlikely to succeed. A system-based approach is needed to address the diverse needs of the population of people with IDD, their caregivers and service context. Further high quality evidence is required to confirm these findings.
Psychological morbidity in Nepali cross-border migrants in India: a community based cross-sectional study
Authors: Dhungana Raja Ram , Aryal Nirmal , Adhikary Pratik , KC Radheshyam Krishna , Regmi Pramod Raj , Devkota Bikash , Sharma Guna Nidhi , Wickramage Kolitha , van Teijlingen Edwin , Simkhada Padam 
Published: November 2019

Abstract
Background
Since Nepali cross-border migrants can freely enter, work and stay in India, they are largely undocumented. The majority is involved in semi-skilled or unskilled jobs with limited labour rights and social security, a fact which predisposes them to psychological distress. We aimed to assess the prevalence of and factors associated with psychological morbidity among Nepali migrants upon their return from India.

Methods
A community based cross-sectional study was conducted in six districts of Nepal between September 2017 and February 2018. A total of 751 participants who had worked at least six months in India and returned to Nepal were interviewed from 24 randomly selected clusters. The General Health Questionnaire (GHQ)-12 was used to measure the psychological morbidity. Data were analysed using Poisson regression analysis.

Results
The majority was younger than 35 years (64.1%), male (96.7%), married (81.8%), had at least a primary education (66.6%), and belonged to Dalit, Janajati and religious minorities (53.7%). The prevalence of psychological morbidity was 13.5% (CI: 11.2–16.1%). Participants aged 45 years and above (adjusted prevalence ratio (aPR) = 2.74), from the Terai (aPR = 3.29), a religious minority (aPR = 3.64), who received no sick leave (aPR = 2.4), with existing health problems (aPR = 2.0) and having difficulty in accessing health care (aPR = 1.88) were more likely than others to exhibit a psychological morbidity.

Conclusion
This study demonstrated that psychological morbidity was prevalent in the study participants and varied significantly with individual characteristics, work conditions and health. Multifaceted approaches including psychological counselling for returnees and protection of labour and health rights in the workplace are recommended to help reduce psychological morbidity.
Three-dimensional finite element analysis of silk protein rod implantation after core decompression for osteonecrosis of the femoral head
Authors: Huang Liangta , Chen Feiyan , Wang Siqun , Wei Yibing , Huang Gangyong , Chen Jie , Shi Jingsheng , Naidu Rajeev K. , Xia Jun , Tao Tiger H. 
Published: November 2019

AbstractBackgroundSeveral methods are available for the treatment of early-stage osteonecrosis of the femoral head. Core decompression with implantation is a widely-used treatment. However, no single implant is recognized as the most effective way to prevent disease progression. Silk has high strength and resiliency. This study explored the possibility of a strong and resilient silk protein biomaterial as a new alternative implant.MethodsWe investigated the biomechanical properties of the silk protein material by regular compression, torsion, and three-point bending tests. We established three-dimensional finite element models of different degrees of femoral head osteonecrosis following simple core decompression, fibula implantation, porous tantalum rod implantation, and silk protein rod implantation. Finally, we compared the differences in displacement and surface stress under load at the femoral head weight-bearing areas between these models.ResultsThe elastic modulus and shear modulus of the silk protein material was 0.49GPa and 0.66GPa, respectively. Three-dimensional finite element analyses demonstrated less displacement and surface stress at the femoral head weight-bearing areas following silk protein rod implantation compared to simple core decompression (p < 0.05), regardless of the extent of osteonecrosis. No differences were noted in the surface deformation or surface stress of the femoral head weight-bearing areas following silk protein rod, fibula or tantalum rod implantation (p > 0.05).ConclusionsWhen compared with simple core decompression, silk protein rod implantation demonstrated less displacement and surface stress at the femoral head weight-bearing area, but more than fibula or tantalum rod implantation. Similar effects on the surface stress of the femoral head between the silk rod, fibula and tantalum rod implantations, combined with additional modifiable properties support the use of silk protein as a suitable biomaterial in osteonecrosis surgery.
Coix lacryma-jobi var. ma-yuen Stapf sprout extract induces cell cycle arrest and apoptosis in human cervical carcinoma cells
Authors: Son Eun Suk , Kim Se-Hee , Kim Young Ock , Lee Young Eun , Kyung Sun Young , Jeong Sung Hwan , Kim Yu Jin , Park Jeong-Woong 
Published: November 2019

Abstract
Background
Cervical cancer is the second-leading cause of cancer-related mortality in females. Coix lacryma-jobi L. var. ma-yuen (Rom.Caill.) Stapf ex Hook. f. is the most widely recognized medicinal herb for its remedial effects against inflammation, endocrine system dysfunctions, warts, chapped skin, rheumatism, and neuralgia and is also a nourishing food.

Methods
To investigate the activity of Coix lacryma-jobi sprout extract (CLSE) on cell proliferation in human cervical cancer HeLa cells, we conducted a Cell Counting Kit-8 (CCK-8) assay. Flow-cytometric analysis and western blot analysis were performed to verify the effect of CLSE on the regulation of the cell cycle and apoptosis in HeLa cells.

Results
We observed that CLSE significantly inhibited cell proliferation. Furthermore, CLSE dose-dependently promoted cell cycle arrest at the sub-G1/ S phase in HeLa cells, as detected by bromodeoxyuridine (BrdU) staining. The cell-cycle-arrest effects of CLSE in HeLa cells were associated with downregulation of cyclin D1 and cyclin-dependent kinases (CDKs) 2, 4, and 6. Moreover, CLSE induced apoptosis, as determined by flow-cytometric analysis and nuclear DNA fragmentation with Annexin V/propidium iodide (PI) and 4′6′-diamidino-2-phenylindole (DAPI) staining. Induction of apoptosis by CLSE was involved in inhibition of the antiapoptotic protein B-cell lymphoma 2 (Bcl-2) and upregulation of the apoptotic proteins p53, cleaved poly (ADP-ribose) polymerase (PARP), cleaved caspase-3, and cleaved caspase-8. Finally, we observed that CLSE inactivated the phosphoinositide 3-kinase (PI3K) and protein kinase B (AKT) pathways.

Conclusions
CLSE causes cell cycle arrest and apoptotic cell death through inactivation of the PI3K/AKT pathway in HeLa cells, suggesting it is a viable therapeutic agent for cervical cancer owing to its anticancer effects.
Quality analysis of smart phone sleep apps in China: can apps be used to conveniently screen for obstructive sleep apnea at home?
Authors: Xu Zhao-feng , Luo Xin , Shi Jianbo , Lai Yinyan 
Published: November 2019

Abstract
Background
Obstructive sleep apnea (OSA) is a sleep disorder with a high prevalence in China. Standard diagnosis of OSA requires polysomnography (PSG). Currently, smart phone applications (apps) are widely used as an important source of health guidance. However, the quality of the information provided by these apps has not been carefully assessed.

Methods
We searched for sleep apps available in China. We designed an evaluation scale that included scientific, functionality and usability, and accountability domains. The Scientific domain included an index of 16 items to evaluate the scientific quality of the apps for their level of adherence to PSG. The functionality and usability domain included 10 items to evaluate the functions of apps and 1 item to define whether the apps needed to connect with other devices. The accountability domain included 9 items that came from the Silberg Scale to evaluate whether the information provided by apps were trustable or not. We then calculated the sum of all domains. We also evaluated the popularity of each app.

Results
A total of 2379 apps were found, and 127 met the inclusion criteria. The mean total score of the apps was 14.23 ± 3.93. The mean scores of scientific basis, functionality and usability, and accountability were 5.51 ± 2.58, 2.90 ± 1.84, and 2.90 ± 1.84. The scientific scores of apps that could connect to other devices were higher than those of apps that worked alone (mean score: 5.26 vs. 4.17, P < 0.001). The functionality and usability score was correlated with the accountability score, and the coefficient of correlation was 0.304 (P = 0.001).

Conclusions
Apps that could connect to other devices were more scientific and powerful than those that worked alone. Multifunctional apps were more popular and reliable. Because of the low quality of sleep apps in China, more work is necessary to create an ideal app.
NG2 glia regulate brain innate immunity via TGF-β2/TGFBR2 axis
Authors: Zhang Shu-zhen , Wang Qin-qin , Yang Qiao-qiao , Gu Huan-yu , Yin Yan-qing , Li Yan-dong , Hou Jin-can , Chen Rong , Sun Qing-qing , Sun Ying-feng , Hu Gang , Zhou Jia-wei 
Published: November 2019

AbstractBackgroundBrain innate immunity is vital for maintaining normal brain functions. Immune homeostatic imbalances play pivotal roles in the pathogenesis of neurological diseases including Parkinson’s disease (PD). However, the molecular and cellular mechanisms underlying the regulation of brain innate immunity and their significance in PD pathogenesis are still largely unknown.MethodsCre-inducible diphtheria toxin receptor (iDTR) and diphtheria toxin-mediated cell ablation was performed to investigate the impact of neuron-glial antigen 2 (NG2) glia on the brain innate immunity. RNA sequencing analysis was carried out to identify differentially expressed genes in mouse brain with ablated NG2 glia and lipopolysaccharide (LPS) challenge. Neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice were used to evaluate neuroinflammatory response in the presence or absence of NG2 glia. The survival of dopaminergic neurons or glial cell activation was evaluated by immunohistochemistry. Co-cultures of NG2 glia and microglia were used to examine the influence of NG2 glia to microglial activation.ResultsWe show that NG2 glia are required for the maintenance of immune homeostasis in the brain via transforming growth factor-β2 (TGF-β2)-TGF-β type II receptor (TGFBR2)-CX3C chemokine receptor 1 (CX3CR1) signaling, which suppresses the activation of microglia. We demonstrate that mice with ablated NG2 glia display a profound downregulation of the expression of microglia-specific signature genes and remarkable inflammatory response in the brain following exposure to endotoxin lipopolysaccharides. Gain- or loss-of-function studies show that NG2 glia-derived TGF-β2 and its receptor TGFBR2 in microglia are key regulators of the CX3CR1-modulated immune response. Furthermore, deficiency of NG2 glia contributes to neuroinflammation and nigral dopaminergic neuron loss in MPTP-induced mouse PD model.ConclusionsThese findings suggest that NG2 glia play a critical role in modulation of neuroinflammation and provide a compelling rationale for the development of new therapeutics for neurological disorders.