bluuebunny/crossref_metadata_2025_split huggingface dataset:
Managing clustering effects and learning effects in the design and analysis of multicentre randomised trials: a survey to establish current practice
Authors: Conroy Elizabeth J. , Blazeby Jane M. , Burnside Girvan , Cook Jonathan A. , Gamble Carrol 
Published: May 2020

Abstract
Background
Patient outcomes can depend on the treating centre, or health professional, delivering the intervention. A health professional’s skill in delivery improves with experience, meaning that outcomes may be associated with learning. Considering differences in intervention delivery at trial design will ensure that any appropriate adjustments can be made during analysis. This work aimed to establish practice for the allowance of clustering and learning effects in the design and analysis of randomised multicentre trials.

Methods
A survey that drew upon quotes from existing guidelines, references to relevant publications and example trial scenarios was delivered. Registered UK Clinical Research Collaboration Registered Clinical Trials Units were invited to participate.

Results
Forty-four Units participated (N = 50). Clustering was managed through design by stratification, more commonly by centre than by treatment provider. Managing learning by design through defining a minimum expertise level for treatment provider was common (89%). One-third reported experience in expertise-based designs. The majority of Units had adjusted for clustering during analysis, although approaches varied. Analysis of learning was rarely performed for the main analysis (n = 1), although it was explored by other means. The insight behind the approaches used within and reasons for, or against, alternative approaches were provided.

Conclusions
Widespread awareness of challenges in designing and analysing multicentre trials is identified. Approaches used, and opinions on these, vary both across and within Units, indicating that approaches are dependent on the type of trial. Agreeing principles to guide trial design and analysis across a range of realistic clinical scenarios should be considered.
Glioma patients in outpatient care—optimization of psychosocial care in neuro-oncological patients (GLIOPT): Protocol for a cluster randomized controlled trial
Authors: Renovanz Mirjam , Hippler Melina , Voss Martin , Wehinger Jens , Keßler Almuth F. , Gempt Jens , Nadji-Ohl Minou , Weiß Lucas Carolin , Rapp Marion , Misch Martin , Coburger Jan , Mehlitz Marcus , Meixensberger Jürgen , Keric Naureen , Tabatabai Ghazaleh , Blettner Maria , Schranz Melanie , Singer Susanne 
Published: May 2020

Abstract
Background
Patients with high-grade gliomas (HGG) often suffer from high distress and require psychosocial support. However, due to neurological and neurocognitive deficits, adequate assessment of distress and support needs remains challenging in clinical practice. The objective of the present study is to investigate whether a systematic implementation of signaling questions into the routine outpatient consultation will be helpful to bridge this gap.

Methods/design
This is a multicenter cluster randomized study with two arms. Randomization is done on a cluster level with 13 hospitals providing regular neuro-oncological outpatient services conducted by neurologists and/or neurosurgeons. The intervention will include an assessment of psychosocial distress of patients in doctor–patient conversation compared to assessment of psychosocial distress via questionnaire (control, standard of care).
In total, 616 HGG patients will be enrolled. The outcome will be the number of HGG patients with increased psychosocial distress who receive professional support from psychosocial services.
Secondary endpoints are inter alia number of patients reporting psychosocial distress and unmet needs detected correctly by the respective method; quality of life; psychological well-being and burden of the patients before and after doctor–patient consultation; as well as the length of the doctor–patient consultation.

Discussion
Patients with HGG are confronted with an oncological diagnosis and at the same time with high symptom burden. This often leads to distress, which is not always adequately recognized and treated. So far, only a limited number of adequate instruments are available to assess HGG patient’s distress. Yet, an adequate care and support network might facilitate the course of the disease and tumor therapies for patients. Our hypothesis is that an assessment conducted directly by attending doctors and in which the doctors talk to patients with HGG will be more effective than an assessment via a questionnaire, leading to better identifying patients in need of support. This may lead to an improvement of health care in these patients. Further, this method might be implemented also in other brain tumor patients (e.g., patients with brain metastases).

Trial registration
German Clinical Trials Register, DRKS00018079. Registered on 3rd September 2019.
Urinary activated leukocyte cell adhesion molecule as a novel biomarker of lupus nephritis histology
Authors: Ding Huihua , Lin Cheng , Cai Jingyi , Guo Qiang , Dai Min , Mohan Chandra , Shen Nan 
Published: May 2020

Abstract
Background
Lupus nephritis (LN) is one of the most severe complications of SLE patients. We aim to validate urinary ALCAM as a biomarker in predicting renal disease histpathology in a Chinese lupus cohort.

Methods
In this cross-sectional study, a total of 256 patients and controls were recruited. Urinary levels of ALCAM were determined by ELISA. Renal histopathology was reviewed by an experienced renal pathologist.

Results
Urinary ALCAM levels were significantly increased in active LN patients when compared to active SLE patients without renal involvement (p < 0.001), inactive LN patients (p = 0.023), inactive SLE patients without renal involvement (p < 0.001), and healthy controls (p < 0.001). Correlation analysis revealed a positive correlation between urinary ALCAM and general disease activity—SLEDAI score (r = 0.487, p < 0.001), as well as renal disease activity—rSLEDAI (r = 0.552, p < 0.001) and SLICC RAS (r = 0.584, p < 0.001). Urinary ALCAM also correlated with lab parameters including 24-h urine protein, hemoglobin, and complement 3. Moreover, urinary ALCAM levels were significantly increased in class III and IV (proliferative) LN as compared to those in class V (membranous) LN. It outperformed conventional biomarkers (anti-dsDNA antibody, C3, C4, proteinuria) in discriminating the two groups of LN. On renal histopathology, urinary ALCAM levels correlated positively with activity index (r = 0.405, p < 0.001) but not chronicity index (r = 0.079, p = 0.448).

Conclusion
Urinary ALCAM is a potential biomarker for predicting renal pathology activity in LN and may serve as a valuable surrogate marker of renal histopathology.
Quantitative proteomic analysis of Rett iPSC-derived neuronal progenitors
Authors: Varderidou-Minasian Suzy , Hinz Lisa , Hagemans Dominique , Posthuma Danielle , Altelaar Maarten , Heine Vivi M. 
Published: May 2020

Abstract
Background
Rett syndrome (RTT) is a progressive neurodevelopmental disease that is characterized by abnormalities in cognitive, social, and motor skills. RTT is often caused by mutations in the X-linked gene encoding methyl-CpG binding protein 2 (MeCP2). The mechanism by which impaired MeCP2 induces the pathological abnormalities in the brain is not understood. Both patients and mouse models have shown abnormalities at molecular and cellular level before typical RTT-associated symptoms appear. This implies that underlying mechanisms are already affected during neurodevelopmental stages.

Methods
To understand the molecular mechanisms involved in disease onset, we used an RTT patient induced pluripotent stem cell (iPSC)-based model with isogenic controls and performed time-series of proteomic analysis using in-depth high-resolution quantitative mass spectrometry during early stages of neuronal development.

Results
We provide mass spectrometry-based quantitative proteomic data, depth of about 7000 proteins, at neuronal progenitor developmental stages of RTT patient cells and isogenic controls. Our data gives evidence of proteomic alteration at early neurodevelopmental stages, suggesting alterations long before the phase that symptoms of RTT syndrome become apparent. Significant changes are associated with the GO enrichment analysis in biological processes cell-cell adhesion, actin cytoskeleton organization, neuronal stem cell population maintenance, and pituitary gland development, next to protein changes previously associated with RTT, i.e., dendrite morphology and synaptic deficits. Differential expression increased from early to late neural stem cell phases, although proteins involved in immunity, metabolic processes, and calcium signaling were affected throughout all stages analyzed.

Limitations
The limitation of our study is the number of RTT patients analyzed. As the aim of our study was to investigate a large number of proteins, only one patient was considered, of which 3 different RTT iPSC clones and 3 isogenic control iPSC clones were included. Even though this approach allowed the study of mutation-induced alterations due to the usage of isogenic controls, results should be validated on different RTT patients to suggest common disease mechanisms.

Conclusions
During early neuronal differentiation, there are consistent and time-point specific proteomic alterations in RTT patient cells carrying exons 3–4 deletion in MECP2. We found changes in proteins involved in pathway associated with RTT phenotypes, including dendrite morphology and synaptogenesis. Our results provide a valuable resource of proteins and pathways for follow-up studies, investigating common mechanisms involved during early disease stages of RTT syndrome.
Three-dimensional culture of MSCs produces exosomes with improved yield and enhanced therapeutic efficacy for cisplatin-induced acute kidney injury
Authors: Cao Jingyuan , Wang Bin , Tang Taotao , Lv Linli , Ding Zhaoying , Li Zuolin , Hu Ruoyu , Wei Qing , Shen Anran , Fu Yuqi , Liu Bicheng 
Published: May 2020

AbstractBackgroundExosomes derived from mesenchymal stem cells (MSC-exos) have been demonstrated with great potential in the treatment of multiple human diseases including acute kidney injury (AKI) by virtue of their intrinsic cargoes. However, there are major challenges of low yield and the lack of an established biomanufacturing platform to efficiently produce MSC-exos, thereby limiting their therapeutic application. Here, we aimed to establish a novel strategy to produce MSC-exos with a hollow fiber bioreactor-based three-dimensional (3D) culture system and evaluate the therapeutic efficacy of 3D-exosomes (3D-exos) on AKI.MethodsMesenchymal stem cells (MSCs) were isolated from fresh human umbilical cord and cultured in two-dimensional (2D) flasks. 2 × 108MSCs were inoculated into the hollow fiber bioreactor for 3D culture. The culture supernatants were collected every 1 or 2 days for isolating exosomes. Exosomes from 2D (2D-exos) and 3D cultures were characterized by transmission electron microscopy, nanoparticle tracking analysis, and western blotting analysis of exosome markers. The yield of exosomes from 2 × 108MSCs seeded in 2D and 3D culture system was compared, based on protein quantification. The therapeutic efficacy of 2D-exos and 3D-exos was investigated in a murine model of cisplatin-induced AKI in vivo and in vitro.Results3D culture did not significantly change the surface markers of MSCs, as well as the morphology, size, and exosomal markers of 3D-exos when compared to those of 2D-exos. Compared with conventional 2D culture, the 3D culture system increased total exosome production up to 19.4-fold. 3D-exos were more concentrated in the harvested supernatants (15.5-fold) than 2D-exos, which led to a higher exosome collection efficiency of 3D culture system. In vivo,both 2D-exos and 3D-exos significantly alleviated cisplatin-induced murine AKI evidenced by improved renal function, attenuated pathological changes of renal tubules, reduced inflammatory factors, and repressed T cell and macrophage infiltration. Impressively, 3D-exos were more effective than 2D-exos. Moreover, 3D-exos were taken up by tubular epithelial cells (TECs) with improved efficiency, thereby exhibiting superior anti-inflammatory effect and improved viability of TECs in vitro.ConclusionsIn summary, our findings demonstrate that the hollow fiber 3D culture system provides an efficient strategy for the continuous production of MSC-exos which has enhanced therapeutic potential for cisplatin-induced AKI.
The influence of fear effect to the Lotka–Volterra predator–prey system with predator has other food resource
Authors: Zhu Zhenliang , Wu Runxin , Lai Liyun , Yu Xiangqin 
Published: May 2020

AbstractA Lotka–Volterra predator–prey system incorporating fear effect of the prey and the predator has other food resource is proposed and studied in this paper. It is shown that the trivial equilibrium and the predator free equilibrium are both unstable, and depending on some inequalities, the system may have a globally asymptotically stable prey free equilibrium or positive equilibrium. Our study shows the fear effect is one of the most important factors that lead to the extinction of the prey species. Such a finding is quite different from the known result. Numeric simulations are carried out to show the feasibility of the main results.
A preconditioned fast collocation method for a linear bond-based peridynamic model
Authors: Zhang Xuhao , Li Xiao , Cheng Aijie , Wang Hong 
Published: May 2020

AbstractWe develop a fast collocation method for a static bond-based peridynamic model. Based on the analysis of the structure of the stiffness matrix, a fast matrix-vector multiplication technique was found, which can be used in the Krylov subspace iteration method. In this paper, we also present an effective preconditioner to accelerate the convergence of the Krylov subspace iteration method. Using the block-Toeplitz–Toeplitz-block (BTTB)-type structure of the stiffness matrix, we give a block-circulant-circulant-block (BCCB)-type preconditioner. The numerical experiments show the utility of the preconditioned fast collocation method.
Fractional operators for the Wright hypergeometric matrix functions
Authors: Abdalla M. 
Published: May 2020

AbstractIn this paper, we contribute to the results of Bakhet et al. (Integral Transforms Spec. Funct. 30:138–156, 2019) by applying fractional operators to the Wright hypergeometric matrix functions. We give matrix recurrence relations and integral formulas for the Wright hypergeometric matrix functions. We also clarify particular cases of the main results.
Interactions between abiotic factors and the bioactivity of biodynamic horn manure on the growth of garden cress (Lepidium sativum L.) in a bioassay
Authors: Morau Alain , Piepho Hans-Peter 
Published: May 2020

AbstractBackgroundThe use of biostimulants like humic substances is a promising innovative approach in agriculture to activate and sustain physiological plant processes. The development of specific bioassays is required to study their bioactivity in laboratory conditions. In previous investigations, a soil-less bioassay with cress seedlings (Lepidium sativumL.) was developed for a biostimulant used in the biodynamic agriculture, the horn-manure preparation (HMP), a fermented cow manure sprayed at low concentrations onto fields. Objectives of the present study were to refine the bioassay by investigating the interactions between the HMP bioactivity and the test factors (i) water volume, (ii) gravistimulation, and (iii) exposure to fluorescent light.ResultsThe interactions between the test factors and the HMP treatment were significant in all series (p < 0.05, WaldF-test). Water overdose and gravitropic stress reduced root growth (down to − 24.2% and − 19.9%, respectively,p < 0.0001, Tukey–Kramer test). The HMP treatment partly compensated these effects by enhancing root growth by (i) water overdose (up to + 4.3%,p = 0.048,n = 4), and (ii) gravitropic stress (up to + 9.5%,p = 0.0004,n = 8). (iii) Furthermore, under the combined stress factors, fluorescent light exposure enhanced the HMP enhancing effect (up to + 12.3%,p = 0.007,n = 6).ConclusionsThe HMP bioactivity appeared to consist of a compensatory mode of action regarding the stress factors water overdose and gravistimulation, and a synergetic interaction with fluorescent light exposure. The HMP seems to interact with the plant sensory systems, likely stimulating the plant’s adaptability to its environment by increasing self-regulating processes. The bioassay sensitivity was successfully increased by integrating these interactions in the experimental set-up and adjusting the growth environment. This approach can be used to adjust the bioassay to other biostimulants.
A cultural comparison of Persian and English short stories regarding the use of emotive words: implications for teaching English to Iranian young learners
Authors: Namaziandost Ehsan , Nasri Mehdi , Rahimi Esfahani Fariba , Neisi Leila , Ahmadpour KarimAbadi Farahnaz 
Published: May 2020

AbstractUsing a contrastive analysis approach, this study aimed to study emotive words (EWs) in Persian and English short stories for children. It actually tries to find the similarities and differences between the two languages in terms of using emotive words based on different types and tokens of emotions introduced by Wierzbicka (Emotions across cultures: Diversity and universality, 1999) and Devon (The origin of emotions, 2006). Additionally, it sought to investigate the impact of teaching emotive narratives on the learners’ practical knowledge of controlling emotions. To fulfill this objective, 20 short stories with similar length and level of difficulty were randomly selected, 10 in English and l0 in Persian, and 35 lines of each story were investigated to identify and classify their EWs based on the two models employed for classification. To examine the extent of similarities and differences between the frequency of EWs used in English and Persian short stories, a Chi-square test was run. The results revealed that there was not a significant difference between the two groups of stories in terms of emotion tokens; however, a significant difference was found between the frequency of EWs used in English and Persian short stories concerning different types of emotion. In the second phase of the study, emotive short stories were explicitly taught to a sample of 25 EFL learners; a DCT was utilized as the pre-test and post-test to find if learners’ practical knowledge would improve in the wake of this intervention. The findings revealed a significant improvement in the practical understanding of the participants after being exposed to the instruction of emotive narratives. The results also demonstrated that literature-based activities containing emotional cues could improve young learners’ practical knowledge required for controlling their emotions.
Simulcast: a case study in the establishment of a virtual community of simulation practice
Authors: Symon Benjamin , Spurr Jesse , Brazil Victoria 
Published: May 2020

AbstractVirtual Communities of Practice (vCoP) is a nascent approach to professional development for simulation educators (Thoma et al., Simul Healthc. 2018;13(2):124-30). vCoPs overcome geographic barriers to accessing expertise and professional networks and may promote ‘democratisation’ of voices in the simulation community. However, the optimal process for creating, nurturing and joining vCoPs in healthcare simulation is not well understood.We report on the establishment of our healthcare simulation hybrid podcast/blog—Simulcast (www.simulationpodcast.com)—utilising the conceptual framework of Wenger’s three dimensions of Communities of Practice. In exploring these dimensions—joint enterprise, mutual engagement and shared repertoire—we hope to contextualise vCoP within professional development approaches for simulation faculty and invite readers to engage with our existing community.
The effect of nocturnal epileptic seizures on cognitive functions in children with idiopathic epilepsy
Authors: Al-Malt Ayman M. , Abo Hammar Shereen A. , Rashed Khaled H. , Ragab Osama A. 
Published: May 2020

Abstract
Background
Cognitive impairment is a common finding epileptic children. Studies have linked nocturnal epileptic discharges to delayed cognitive abilities in children.

Objective
The study aims to evaluate the effect of nocturnal epileptic seizures on cognitive functions in children with idiopathic epilepsy.

Patients and methods
The study was conducted on 70 children with idiopathic generalized or benign focal epilepsy. Based on seizures semiology, they were classified into cases either with nocturnal epileptic seizures (NES) (n = 40) or with diurnal epileptic seizures (DES) (n = 30). Patients receiving antiepileptic drugs (AEDs) that affect cognitive function, patients with intelligence quotient (IQ) below 70, and those having other neurological or psychiatric disorders' were excluded. All patients were subjected to neurological examination, brain magnetic resonance imaging (MRI), and electroencephalography. Cognition was assessed using Wechsler Intelligence scale for children (WISC) to measure IQ, Wisconsin card sorting test (WCST) (computerized version), Trail Making Test, and Digit spans test.

Results
There was no significant difference between both groups regarding age, sex, age of epilepsy onset, or seizure frequency. There was a significant difference in almost all cognitive variables including digit forward, digit backward, processing speed, verbal IQ, WCST perseverative responses, WCST failure to maintain set, Trail Making Test A (error), Trail Making Test B (Time), and Trail Making Test B (error). There was no significant difference regarding the associated sleep disturbances between the studied groups.

Conclusion
Children with idiopathic epilepsy suffering from predominant nocturnal seizure have overt and subtle cognitive functions impairments compared to children with predominant diurnal seizure.
Pharmacist-Driven Oral Oncolytic Medication Education and Consent
Authors: Bowles Harmony , Tawfik Bernard , Abernathy Janet , Lauer Richard , Hashemi Neda , Dayao Zoneddy 
Published: May 2020

PURPOSE: The numbers and types of oral oncolytics in oncology are expanding rapidly. Oral oncolytics have serious adverse effects, and pharmacist-driven patient education has the potential to reduce adverse events. The University of New Mexico Comprehensive Cancer Center (UNM CCC) initiated a patient education and consent process for oral oncolytics in our minority, rural, and economically disadvantaged population. PATIENTS AND METHODS: The UNM CCC initiated a pharmacist-driven education and consent process from August 2016 to October 2018. The process metric measured via statistical process control charts was the percentage of patients receiving oral oncolytic therapy who were educated and consented. The balancing metric was time for benefit investigation. The intervention was pharmacy team members providing standardized education for and obtaining consent from each patient, supported by electronic medical record orders, physician education, pharmacy notifications, and hospital discharge planning. RESULTS: The initial monthly education and consent rate was 17.9%, followed by 45.5% the subsequent month. This quickly grew to an average of 87.0% (95% CI, 81.5% to 92.4%) for the subsequent 15 months in which control was achieved. Additional changes increased the education rate to 95.7% (95% CI, 93.4% to 98.1%). These 2 periods were statistically different ( P = .0025). There was no change in time for benefit investigation (5.60 v 5.52 days; P = .75). CONCLUSION: A pharmacist-driven program for education and consent upon initiation of oral oncolytics is possible and can successfully educate a majority of patients. Future directions will include ensuring patient adherence and educating patients who fill oral oncolytic prescriptions outside UNM CCC.