bluuebunny/crossref_metadata_2025_split huggingface dataset:
Compressed-sensing accelerated 4D flow MRI of cerebrospinal fluid dynamics
Authors: Jaeger Elena , Sonnabend Kristina , Schaarschmidt Frank , Maintz David , Weiss Kilian , Bunck Alexander C. 
Published: July 2020

Abstract
Background
4D flow magnetic resonance imaging (MRI) of CSF can make an important contribution to the understanding of hydrodynamic changes in various neurological diseases but remains limited in clinical application due to long acquisition times. The aim of this study was to evaluate the accuracy of compressed SENSE accelerated MRI measurements of the spinal CSF flow.

Methods
In 20 healthy subjects 4D flow MRI of the CSF in the cervical spine was acquired using compressed sensitivity encoding [CSE, a combination of compressed sensing and parallel imaging (SENSE) provided by the manufacturer] with acceleration factors between 4 and 10. A conventional scan using SENSE was used as reference. Extracted parameters were peak velocity, absolute net flow, forward flow and backward flow. Bland–Altman analysis was performed to determine the scan-rescan reproducibility and the agreement between SENSE and compressed SENSE. Additionally, a time accumulated flow error was calculated. In one additional subject flow of the spinal canal at the level of the entire spinal cord was assessed.

Results
Averaged acquisition times were 10:21 min (SENSE), 9:31 min (CSE4), 6:25 min (CSE6), 4:53 min (CSE8) and 3:51 min (CSE10). Acquisition of the CSF flow surrounding the entire spinal cord took 14:40 min. Bland–Altman analysis showed good agreement for peak velocity, but slight overestimations for absolute net flow, forward flow and backward flow (< 1 ml/min) in CSE4–8. Results of the accumulated flow error were similar for CSE4 to CSE8.

Conclusion
A quantitative analysis of acceleration factors CSE4–10 showed that CSE with an acceleration factor up to 6 is feasible. This allows a scan time reduction of 40% and enables the acquisition and analysis of the CSF flow dynamics surrounding the entire spinal cord within a clinically acceptable scan time.
FRET-based Tau seeding assay does not represent prion-like templated assembly of Tau filaments
Authors: Kaniyappan Senthilvelrajan , Tepper Katharina , Biernat Jacek , Chandupatla Ram Reddy , Hübschmann Sabrina , Irsen Stephan , Bicher Sandra , Klatt Christoph , Mandelkow Eva-Maria , Mandelkow Eckhard 
Published: July 2020

AbstractTau aggregation into amyloid fibers based on the cross-beta structure is a hallmark of several Tauopathies, including Alzheimer Disease (AD). Trans-cellular propagation of Tau with pathological conformation has been suggested as a key disease mechanism. This is thought to cause the spreading of Tau pathology in AD by templated conversion of naive Tau in recipient cells into a pathological state, followed by assembly of pathological Tau fibers, similar to the mechanism of nucleated polymerization proposed for prion pathogenesis. In cell cultures, the process is often monitored by a FRET assay where the recipient cell expresses the Tau repeat domain (TauRD) with a pro-aggregant mutation, fused to GFP-based FRET pairs. Since the size of the reporter GFP (barrel of ~ 3 nm × 4 nm) is ~ 7 times larger than the β-strand distance (0.47 nm), this points to a potential steric clash. Hence, we investigated the influence of the GFP tag on TauFL or TauRD aggregation. Using biophysical methods (light scattering, atomic force microscopy (AFM), and scanning-transmission electron microscopy (STEM)), we found that the assembly of TauRD-GFP was severely inhibited and incompatible with that of Alzheimer filaments. These observations argue against the hypothesis that the propagation of Tau pathology in AD is caused by the prion-like templated aggregation of Tau protein, transmitted via cell-to-cell spreading of Tau. Thus, even though the observed local increase of FRET in recipient cells may be a valid hallmark of a pathological reaction, our data argue that it is caused by a process distinct from assembly of TauRD filaments.
Long non-coding RNA CASC9 promotes tumor growth and metastasis via modulating FZD6/Wnt/β-catenin signaling pathway in bladder cancer
Authors: Zhan Yonghao , Zhang Lianghao , Yu Shuanbao , Wen Jianguo , Liu Yuchen , Zhang Xuepei 
Published: July 2020

Abstract
Background
Accumulating evidence have highlighted the importance of long noncoding RNAs (lncRNAs) in multiple cancers development and progression. Cancer susceptibility candidate 9 (CASC9) is a novel long non-coding RNA and plays important regulatory role in diverse biological processes of cancers. However, the clinical significance and molecular mechanism of CASC9 in bladder cancer is still unknown.

Methods
Comprehensive lncRNAs profiling analysis were conducted to identify lncRNAs profile alterations and uncover valuable lncRNA candidates for bladder cancer. The expression level of CASC9 was determined in a total of 106 patients with bladder cancer. Loss-of-function experiments were performed to identify the functions of CASC9 in tumor growth and metastasis of bladder cancer in vitro and in vivo. Bioinformatics analysis and further experiments were performed to explore the molecular mechanisms underlying the functions of CASC9.

Results
This study found that CASC9 expression was markedly upregulated in bladder cancer and related to histological grade, TNM stage and prognosis. Knockdown of CASC9 inhibited tumor growth and metastasis of bladder cancer in vitro and in vivo. Mechanistically, we found that CASC9 functions as a miRNA sponge to positively regulate FZD6 expression and subsequently activates Wnt/β-catenin signaling pathway, thus playing an oncogenic role in bladder cancer pathogenesis.

Conclusion
In summary, lncRNA CASC9 plays a critical regulatory role in bladder cancer. The CASC9/miR-497-5p/ FZD6 axis provides insights for regulatory mechanism of bladder cancer, and new strategies for clinical practice.
Safety and efficacy of belimumab after B cell depletion therapy in systemic LUPUS erythematosus (BEAT-LUPUS) trial: statistical analysis plan
Authors: Muller Patrick , Chowdhury Kashfia , Gordon Caroline , Ehrenstein Michael R. , Doré Caroline J. 
Published: July 2020

AbstractBackgroundThere is limited evidence that rituximab, a B cell depletion therapy, is an effective treatment for systemic lupus erythematosus (SLE). Data on the mechanisms of B cell depletion in SLE indicate that the combination of rituximab and belimumab may be more effective than rituximab alone. The safety and efficacy of belimumab after B cell depletion therapy in systemic LUPUS erythematosus (BEAT-LUPUS) trial aims to determine whether belimumab is superior to placebo, when given 4–8 weeks after treatment with rituximab. This article describes the statistical analysis plan for this trial as an update to the published protocol. It is written prior to the end of patient follow-up, while the outcome of the trial is still unknown.Design and methodsBEAT-LUPUS is a randomised, double-blind, phase II trial of 52 weeks of belimumab versus placebo, initiated 4–8 weeks after rituximab treatment. The primary outcome is anti-dsDNA antibodies at 52 weeks post randomisation. Secondary outcomes include lupus flares and damage, adverse events, doses of concomitant medications, quality of life, and clinical biomarkers. We describe the trial’s clinical context, outcome measures, sample size calculation, and statistical modelling strategy, and the supportive analyses planned to evaluate for mediation of the treatment effect through changes in concomitant medication doses and bias from missing data.DiscussionThe analysis will provide detailed information on the safety and effectiveness of belimumab. It will be implemented from July 2020 when patient follow-up and data collection is complete.Trial registrationISRCTN:47873003. Registered on 28 November 2016.EudracT:2015-005543-14. Registered on 19 November 2018.
eTest: a limited-interaction, longitudinal randomized controlled trial of a mobile health platform that enables real-time phone counseling after HIV self-testing among high-risk men who have sex with men
Authors: Wray Tyler B. , Chan Philip A. , Klausner Jeffrey D. , Mena Leandro A. , Brock James B. , Simpanen Erik M. , Ward Lori M. , Chrysovalantis Stafylis 
Published: July 2020

Abstract
Background
HIV disproportionately affects men who have sex with men (MSM) in the USA, and new infections continue to increase, particularly among African American (AA) and Hispanic/Latino (H/L) MSM. Rates of HIV testing are particularly low among AA and H/L MSM, and innovative approaches to encourage testing may help address high incidence in these men. HIV self-testing (HST) may be an important tool for increasing rates and frequency of testing. HST may be particularly well-suited for AA and H/L MSM, given that stigma and mistrust of medical care contribute to low testing rates. Despite its promise, however, many are concerned that HST does not sufficiently connect users with critical post-testing resources, such as confirmatory testing and care among those who test positive, and that these limitations may result in delayed linkage to care.

Methods
We developed a mobile health platform (eTest) that monitors when HST users open their tests in real time, allowing us to provide timely, “active” follow-up counseling and referral over the phone. In this study, 900 high-risk MSM (with targets of 40% AA, 35% H/L) who have not tested in the last year will be recruited from social media and other gay-oriented websites in several major cities. Over 12 months, participants will be randomly assigned to receive (1) HST with post-test phone counseling and referral (eTest condition), (2) HST without active follow-up (standard condition), or (3) reminders to get tested for HIV at a local clinic (control) every 3 months. Primary outcomes include rates of HIV testing, receipt of additional HIV prevention services, and PrEP initiation verified by clinical medical records.

Discussion
This study tests whether providing more active counseling and referral after HST encourages more regular HIV testing and engagement with other prevention services among MSM, compared to more passive approaches or clinic-based testing alone. It will also explore the cost-effectiveness and emotional/behavioral effects of these two strategies.

Trial registration
ClinicalTrials.gov identifier NCT03654690. Registered on 31 August 2018.
Predictors of poor adherence to antidiabetic therapy in patients with type 2 diabetes: a cross-sectional study insight from Ethiopia
Authors: Demoz Gebre Teklemariam , Wahdey Shishay , Bahrey Degena , Kahsay Halefom , Woldu Gebremariam , Niriayo Yirga Legesse , Collier Andrew 
Published: July 2020

Abstract
Background
Poor adherence to the medical regimen is a major clinical problem in the management of patients with diabetes. This study sought to investigate the level of medication adherence to antidiabetic therapy and to identify possible predictors of poor adherence.

Methods
A hospital based cross-sectional study was conducted from July 2018 to June 2019 among randomly selected follow-up T2D patients at a hospital diabetes clinic. Data were collected through patient interviews, followed by medical chart review. Adherence to antidiabetic therapy that we assessed patients’ responses using validated Brief Medication Questionnaire (BMQ). To identify predictors of poor medication adherence, binary logistic regression analyses were performed using SPSS version 25. Statistical significance was set at p value ≤ 0.05.

Results
Of the total 357 study participants, 25% were non-adherent to their antidiabetic therapy. Predictors statistically associated with poor adherence were; being female gender (AOR = 1.71, 95% CI 1.01–2.76), and presence of at least one diabetic complication (AOR = 2.02, 95% CI 1.02–3.22). Participants with having at least primary level of education were more likely to adhere to anti-diabetes medication (AOR = 0.42, 95% CI 0.18–0.96). The most common self-reported reasons for non-adherence were forgetfulness, unavailability of medication plus the unaffordability of anti-diabetes medications.

Conclusions
The proportion of participants’ adherent to anti-diabetes therapies was suboptimal. Being female, the presence of chronic diabetic complications and having no formal education were the main predictors of poor adherence. Strategies that aimed at improving adherence to antidiabetic medications deemed to be compulsory.
Coronavirus infection (SARS-CoV-2) in obesity and diabetes comorbidities: is heat shock response determinant for the disease complications?
Authors: Krause Mauricio , Gerchman Fernando , Friedman Rogério 
Published: July 2020

AbstractChronic inflammation is involved in the pathogenesis of several metabolic diseases, such as obesity and type 2 diabetes mellitus (T2DM). With the recent worldwide outbreak of coronavirus disease (SARS-CoV-2), it has been observed that individuals with these metabolic diseases are more likely to develop complications, increasing the severity of the disease and a poorer outcome. Coronavirus infection leads to the activation of adaptive and innate immune responses, resulting in massive inflammation (to so called cytokine storm), which in turn can lead to damage to various tissues, septic shock and multiple organ failure. Recent evidence suggests that the common link between metabolic diseases and SARS-CoV-2 is the inflammatory response (chronic/low-grade for metabolic diseases and acute/intense in coronavirus infection). However, the ability of the infected individuals to resolve the inflammation has not yet been explored. The heat shock response (HSR), an important anti-inflammatory pathway, is reduced in patients with metabolic diseases and, consequently, may impair inflammation resolution and control in patients with SARS-CoV-2, thus enabling its amplification and propagation through all tissues. Herein, we present a new hypothesis that aims to explain the increased severity of SARS-CoV-2 infection in people with metabolic diseases, and the possible benefits of HSR-inducing therapies to improve the inflammatory profile in these patients.
Cardiovascular risk factors indirectly affect acute post-stroke cognition through stroke severity and prior cognitive impairment: a moderated mediation analysis
Authors: Drozdowska Bogna A. , Elliott Emma , Taylor-Rowan Martin , Shaw Robert C. , Cuthbertson Gillian , Langhorne Peter , Quinn Terence J. 
Published: July 2020

AbstractBackgroundCognitive impairment is an important consequence of stroke and transient ischaemic attack, but its determinants are not fully understood. Simple univariable or multivariable models have not shown clinical utility for predicting cognitive impairment. Cardiovascular risk factors may influence cognition through multiple, direct, and indirect pathways, including effects on prior cognition and stroke severity. Understanding these complex relationships may help clinical teams plan intervention and follow-up strategies.MethodsWe analysed clinical and demographic data from consecutive patients admitted to an acute stroke ward. Cognitive assessment comprised Abbreviated Mental Test and mini-Montreal Cognitive Assessment. We constructed bias-corrected confidence intervals to test indirect effects of cardiovascular risk factors (hypertension, vascular disease, atrial fibrillation, diabetes mellitus, previous stroke) on cognitive function, mediated through stroke severity and history of dementia, and we assessed moderation effects due to comorbidity.ResultsFrom 594 eligible patients, we included 587 in the final analysis (age range 26–100; 45% female). Our model explainedR2 = 62.10% of variance in cognitive test scores. We found evidence for an indirect effect of previous stroke that was associated with increased risk of prevalent dementia and in turn predicted poorer cognitive score (estimate = − 0.39; 95% bias-corrected CI, − 0.75 to − 0.13;p = 0.02). Atrial fibrillation was associated with greater stroke severity and in turn with a poorer cognitive score (estimate = − 0.27; 95% bias-corrected CI, − 0.49 to − 0.05;p = 0.02). Conversely, previous TIA predicted decreased stroke severity and, through that, lesser cognitive impairment (estimate = 0.38; 95% bias-corrected CI, 0.08 to 0.75;p = 0.02). Through an association with reduced stroke severity, vascular disease was associated with lesser cognitive impairment, conditional on presence of hypertension and absence of diabetes mellitus (estimate = 0.36; 95% bias-corrected CI, 0.03 to 0.68;p = 0.02), although the modelled interaction effects did not reach statistical significance.ConclusionsWe have shown that relationships between cardiovascular risk factors and cognition are complex and simple multivariable models may be overly reductionist. Including direct and indirect effects of risk factors, we constructed a model that explained a substantial proportion of variation in cognitive test scores. Models that include multiple paths of influence and interactions could be used to create dementia prognostic tools for use in other healthcare settings.
EtMIC3 and its receptors BAG1 and ENDOUL are essential for site-specific invasion of Eimeria tenella in chickens
Authors: Li Wenyu , Wang Mingyue , Chen Yufeng , Chen Chen , Liu Xiaoqian , Sun Xiaoting , Jing Chuanxu , Xu Lixin , Yan Ruofeng , Li Xiangrui , Song Xiaokai 
Published: July 2020

AbstractAvian coccidian parasites exhibit a high degree of site specificity in different Eimeria species. Although the underlying mechanism is unclear, an increasing body of evidence suggests that site specificity is due to the interaction between microneme proteins (MICs) and their receptors on the surface of target host cells. In this study, the binding ability of E. tenella MICs (EtMICs) to different intestinal tissue was observed by immunofluorescence to identify the key surface molecule on the parasite responsible for the site specificity. Subsequently, we identified the corresponding host-cell receptors by yeast two-hybrid screening and glutathione-S-transferase pull-down experiments and the distribution of these receptors was observed by immunofluorescence in chicken intestinal tissues. Finally, we evaluated the efficacy of receptor antiserum against the infection of E. tenella in chickens. The results showed that EtMIC3 could only bind to the caecum while EtMIC1, EtMIC2, and EtAMA1 did not bind to any other intestinal tissues. Anti-serum to EtMIC3 was able to block the invasion of sporozoites with a blocking rate of 66.3%. The receptors for EtMIC3 were BCL2-associated athanogene 1 (BAG1) and Endonuclease polyU-specific-like (ENDOUL), which were mainly distributed in the caecum. BAG1 and ENDOUL receptor antiserum reduced weight loss and oocyst output following E. tenella infection, showing partial inhibition of E. tenella infection. These data elucidate the mechanism of site specificity for Eimeria infection and reveal a potential therapeutic avenue.
Intercellular transmission of Seneca Valley virus mediated by exosomes
Authors: Xu Guowei , Xu Shouxing , Shi Xijuan , Shen Chaochao , Hao Junhong , Yan Minhao , Zhang Dajun , Zhu Zixiang , Zhang Keshan , Zheng Haixue , Liu Xiangtao 
Published: July 2020

AbstractSeneca Valley virus (SVV) is a non-encapsulated single-stranded positive-strand RNA virus whose transmission routes have not yet been fully elucidated. Exosomes have been implicated in the intercellular transport of a variety of materials, such as proteins, RNA, and liposomes. However, whether exosomes can mediate SVV intercellular transmission remains unknown. In this study, we extracted exosomes from SVV-infected IBRS-2 cells to investigate intercellular transmission. Our results suggest that the intercellular transmission of SVV is mediated by exosomes. The results of co-localization and RT-qPCR studies showed that exosomes harbor SVV and enable the virus to proliferate in both susceptible and non-susceptible cells. Furthermore, the replication of SVV was inhibited when IBRS-2 cells were treated with interfering RNA Rab27a and exosome inhibitor GW4869. Finally, neutralization experiments were performed to further verify whether the virus was encapsulated by the exosomes that mediated transmission between cells. It was found that exosome-mediated intercellular transmission was not blocked by SVV-specific neutralizing antibodies. This study reveals a new transmission route of SVV and provides clear evidence regarding the pathogenesis of SVV, information which can also be useful for identifying therapeutic interventions.
A novel FPGA-based test-bench framework for SDI stream verification
Authors: Conti Giuseppe , Kyrkou Christos , Theocharides Theocharis , Hernández-Peñaloza Gustavo , Jiménez David 
Published: July 2020

AbstractThis paper presents a framework for complete simulation and verification of Serial Digital Interface (SDI) video using a verilog test-bench and geared toward FPGAs. This framework permits simulating the entire process: from test video signal generation to protocol verification in the FPGA which implements the Device Under Test (DUT). The novelty in the design is the combination of a customized test video signal generator with an implementation clone of DUT transceiver for in-depth protocol debugging. Identical input test patterns of the video protocol under test are generated and fed to DUT for verification. Thus, the model not only permits to evaluate the SDI transport layer but also validates the implementation at ultra low pixel level of the video format. This approach provides two advantages: cost saving in terms of additional lab test equipment and delivering all-in-one test solution to verify design and implementation. A practical implementation using a test example of a macroblock processing chain using SDI video interface shows the viability of the proposed framework for video protocol testing.
Certain results on a hybrid class of the Boas–Buck polynomials
Authors: Yasmin Ghazala , Islahi Hibah , Muhyi Abdulghani 
Published: July 2020

AbstractThis article aims to introduce a hybrid family of 2-variable Boas–Buck-general polynomials by taking Boas–Buck polynomials as a base with the 2-variable general polynomials. These polynomials are framed within the context of the monomiality principle, and their properties are established. Further, we investigate some members belonging to this family. A general method to express connection coefficients explicitly for the Boas–Buck general polynomial sets is presented. Carlitz theorem for mixed generating functions is also extended to these polynomials. The shapes are shown and zeros are computed for these polynomials using Mathematica software.
On a coupled system of fractional sum-difference equations with p-Laplacian operator
Authors: Siricharuanun Pimchana , Chasreechai Saowaluck , Sitthiwirattham Thanin 
Published: July 2020

AbstractIn this paper, we propose a nonlocal fractional sum-difference boundary value problem for a coupled system of fractional sum-difference equations with p-Laplacian operator. The problem contains both Riemann–Liouville and Caputo fractional difference with five fractional differences and four fractional sums. The existence and uniqueness result of the problem is studied by using the Banach fixed point theorem.