bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of the SureX HPV genotyping test for the detection of high-risk HPV in cervical cancer screening
Authors: Wei Baojun , Mei Ping , Huang Shengkai , Yu Xueting , Zhi Tong , Wang Guojing , Xu Xiaotian , Xiao Lin , Dong Xin , Cui Wei 
Published: November 2020

Abstract

Background
The SureX HPV genotyping test (SureX HPV test), which targets the human papillomavirus (HPV) E6/E7 genes was compared with the Cobas 4800 and Venus HPV tests for detecting 14 high-risk HPV (HR-HPV) types in clinical referral and follow-up patients to evaluate its value for cervical cancer screening.

Methods
Two different populations were enrolled in the study. The first population comprised 185 cases and was used for comparing the SureX HPV test (Health, China) with the Cobas 4800 test (Roche, USA). The second population comprised 290 cases and was used for comparing the SureX HPV test (Health, China) with the Venus HPV test (Zhijiang, China). Polymerase chain reaction (PCR) sequencing was performed for further confirmation of discordant results.

Results
In the first population, the overall agreement rate was 95.6% for 14 high-risk HPV types. Eight discordant cases were confirmed by PCR sequencing, which showed that the agreement rates were 75.0% between the SureX HPV test and PCR sequencing and 25.0% between the Cobas 4800 test and PCR sequencing (P < 0.01). In the second population, the overall agreement rate was 95.5%. Thirteen discordant cases were confirmed by PCR sequencing, which showed that the agreement rates were 76.9% between the SureX HPV test and PCR sequencing and 23.1% between the Venus HPV test and PCR sequencing (P < 0.01). With cervical intraepithelial neoplasia grade 2+ (CIN2+) as the reference standard, the sensitivity values of the SureX HPV test and the Venus HPV test were 93.5% and 92.0%, (P > 0.05), while the specificity values were 43.3% and 46.7%, respectively (P > 0.05).

Conclusion
The SureX HPV test had good consistency with both the Cobas 4800 and Venus HPV tests for 14 HR-HPV types. In addition, it avoided some false negatives and false positives. Therefore, the SureX HPV test can be used for cervical cancer screening.
Tauopathy-associated tau modifications selectively impact neurodegeneration and mitophagy in a novel C. elegans single-copy transgenic model
Authors: Guha Sanjib , Fischer Sarah , Johnson Gail V. W. , Nehrke Keith 
Published: November 2020

AbstractBackgroundA defining pathological hallmark of the progressive neurodegenerative disorder Alzheimer’s disease (AD) is the accumulation of misfolded tau with abnormal post-translational modifications (PTMs). These include phosphorylation at Threonine 231 (T231) and acetylation at Lysine 274 (K274) and at Lysine 281 (K281). Although tau is recognized to play a central role in pathogenesis of AD, the precise mechanisms by which these abnormal PTMs contribute to the neural toxicity of tau is unclear.MethodsHuman 0N4R tau (wild type) was expressed in touch receptor neurons of the genetic model organismC. elegansthrough single-copy gene insertion. Defined mutations were then introduced into the single-copy tau transgene through CRISPR-Cas9 genome editing. These mutations included T231E, to mimic phosphorylation of a commonly observed pathological epitope, and K274/281Q, to mimic disease-associated lysine acetylation – collectively referred as “PTM-mimetics” – as well as a T231A phosphoablation mutant. Stereotypical touch response assays were used to assess behavioral defects in the transgenic strains as a function of age. Genetically-encoded fluorescent biosensors were expressed in touch neurons and used to measure neuronal morphology, mitochondrial morphology, mitophagy, and macro autophagy.ResultsUnlike existing tau overexpression models,C. eleganssingle-copy expression of tau did not elicit overt pathological phenotypes at baseline. However, strains expressing disease associated PTM-mimetics (T231E and K274/281Q) exhibited reduced touch sensation and neuronal morphological abnormalities that increased with age. In addition, the PTM-mimetic mutants lacked the ability to engage neuronal mitophagy in response to mitochondrial stress.ConclusionsLimiting the expression of tau results in a genetic model where modifications that mimic pathologic tauopathy-associated PTMs contribute to cryptic, stress-inducible phenotypes that evolve with age. These findings and their relationship to mitochondrial stress provides a new perspective into the pathogenic mechanisms underlying AD.
Pathway information extracted from 25 years of pathway figures
Authors: Hanspers Kristina , Riutta Anders , Summer-Kutmon Martina , Pico Alexander R. 
Published: November 2020

AbstractThousands of pathway diagrams are published each year as static figures inaccessible to computational queries and analyses. Using a combination of machine learning, optical character recognition, and manual curation, we identified 64,643 pathway figures published between 1995 and 2019 and extracted 1,112,551 instances of human genes, comprising 13,464 unique NCBI genes, participating in a wide variety of biological processes. This collection represents an order of magnitude more genes than found in the text of the same papers, and thousands of genes missing from other pathway databases, thus presenting new opportunities for discovery and research.
Process evaluation within pragmatic randomised controlled trials: what is it, why is it done, and can we find it?—a systematic review
Authors: French Caroline , Pinnock Hilary , Forbes Gordon , Skene Imogen , Taylor Stephanie J. C. 
Published: November 2020

Abstract

Background
Process evaluations are increasingly conducted within pragmatic randomised controlled trials (RCTs) of health services interventions and provide vital information to enhance understanding of RCT findings. However, issues pertaining to process evaluation in this specific context have been little discussed. We aimed to describe the frequency, characteristics, labelling, value, practical conduct issues, and accessibility of published process evaluations within pragmatic RCTs in health services research.

Methods
We used a 2-phase systematic search process to (1) identify an index sample of journal articles reporting primary outcome results of pragmatic RCTs published in 2015 and then (2) identify all associated publications. We used an operational definition of process evaluation based on the Medical Research Council’s process evaluation framework to identify both process evaluations reported separately and process data reported in the trial results papers. We extracted and analysed quantitative and qualitative data to answer review objectives.

Results
From an index sample of 31 pragmatic RCTs, we identified 17 separate process evaluation studies. These had varied characteristics and only three were labelled ‘process evaluation’. Each of the 31 trial results papers also reported process data, with a median of five different process evaluation components per trial. Reported barriers and facilitators related to real-world collection of process data, recruitment of participants to process evaluations, and health services research regulations. We synthesised a wide range of reported benefits of process evaluations to interventions, trials, and wider knowledge. Visibility was often poor, with 13/17 process evaluations not mentioned in the trial results paper and 12/16 process evaluation journal articles not appearing in the trial registry.

Conclusions
In our sample of reviewed pragmatic RCTs, the meaning of the label ‘process evaluation’ appears uncertain, and the scope and significance of the term warrant further research and clarification. Although there were many ways in which the process evaluations added value, they often had poor visibility. Our findings suggest approaches that could enhance the planning and utility of process evaluations in the context of pragmatic RCTs.

Trial registration
Not applicable for PROSPERO registration
Genomics in the era of COVID-19: ethical implications for clinical practice and public health
Authors: Geller Gail , Duggal Priya , Thio Chloe L. , Mathews Debra , Kahn Jeffrey P. , Maragakis Lisa L. , Garibaldi Brian T. 
Published: November 2020

Abstract
Genomic studies of patients with COVID-19, or exposed to it, are underway to delineate host factors associated with variability in susceptibility, infectivity, and disease severity. Here, we highlight the ethical implications—both potential benefits and harms—of genomics for clinical practice and public health in the era of COVID-19.
Single-cell transcriptome conservation in a comparative analysis of fresh and cryopreserved human skin tissue: pilot in localized scleroderma
Authors: Mirizio Emily , Tabib Tracy , Wang Xinjun , Chen Wei , Liu Christopher , Lafyatis Robert , Jacobe Heidi , Torok Kathryn S. 
Published: November 2020

Abstract
Background
The purpose of this study was to assess variability in cell composition and cell-specific gene expression in the skin of patients with localized scleroderma (LS) utilizing CryoStor® CS10 in comparison to RPMI to produce adequate preservation of tissue samples and cell types of interest for use in large-scale multi-institutional collaborations studying localized scleroderma and other skin disorders.

Methods
We performed single-cell RNA sequencing on paired skin biopsy specimens from 3 patients with LS. Each patient with one sample cryopreserved in CryoStor® CS10 and one fresh in RPMI media using 10× Genomics sequencing.

Results
Levels of cell viability and yield were comparable between CryoStor® CS10 (frozen) and RPMI (fresh) preserved cells. Furthermore, gene expression between preservation methods was collectively significantly correlated and conserved across all 18 identified cell cluster populations.

Conclusion
Comparable cell population and transcript expression yields between CryoStor® CS10 and RPMI preserved cells support the utilization of cryopreserved skin tissue in single-cell analysis. This suggests that employing standardized cryopreservation protocols for the skin tissue will help facilitate multi-site collaborations looking to identify mechanisms of disease in disorders characterized by cutaneous pathology.
Mycophenolic acid, the active form of mycophenolate mofetil, interferes with IRF7 nuclear translocation and type I IFN production by plasmacytoid dendritic cells
Authors: Shigesaka Minoru , Ito Tomoki , Inaba Muneo , Imai Kai , Yamanaka Hideki , Azuma Yoshiko , Tanaka Akihiro , Amuro Hideki , Nishizawa Tohru , Son Yonsu , Satake Atsushi , Ozaki Yoshio , Nomura Shosaku 
Published: November 2020

AbstractBackgroundBoth humoral and cellular immune mechanisms are involved in the onset and progression of autoimmune responses in systemic lupus erythematosus (SLE). Plasmacytoid dendritic cells (pDCs) play a central role in the pathogenesis of SLE via the dysregulation of type I interferon (IFN) production; these cells act together with activated myeloid DCs (mDCs) to amplify the vicious pathogenic spiral of autoimmune disorders. Therefore, control of aberrant DC activation in SLE may provide an alternative treatment strategy against this disease. Mycophenolate mofetil (MMF), which has been used to treat lupus nephritis, specifically blocks the proliferation of B and T lymphocytes via inhibition of inosine-5-monophosphate dehydrogenase. Here, we focus on the effects of MMF in targeting DC functions, especially the IFN response of pDCs.MethodsWe isolated human blood pDCs and mDCs by flow cytometry and examined the effect of mycophenolic acid (MPA), which is a metabolic product of MMF, on the toll-like receptor (TLR) ligand response of DC subsets. Additionally, we cultured pDCs with serum from SLE patients in the presence or absence of MPA and then examined the inhibitory function of MPA on SLE serum-induced IFN-α production.ResultsWe found that treatment with 1−10 μM of MPA (covering the clinical trough plasma concentration range) dose-dependently downregulated the expression of CD80 and CD86 on mDCs (but not pDCs) without inducing apoptosis, in response to R848 or CpG-ODN, respectively. Notably, in pDCs, MPA significantly suppressed IFN-α production with IRF7 nuclear translocation and repressed the AKT activity. In addition, MPA inhibited IL-12 production with STAT4 expression in mDCs. We further identified that MPA had an inhibitory effect on SLE serum-induced IFN-α production by pDCs.ConclusionsOur data suggest that MPA can interrupt the vicious pathogenic spiral of autoimmune disorders by regulating the function of DC subsets. This work unveiled a novel mechanism for the therapeutic ability of MMF against SLE.
Autism-linked mutations of CTTNBP2 reduce social interaction and impair dendritic spine formation via diverse mechanisms
Authors: Shih Pu-Yun , Hsieh Bing-Yuan , Tsai Ching-Yen , Lo Chiu-An , Chen Brian E. , Hsueh Yi-Ping 
Published: November 2020

Abstract
Abnormal synaptic formation and signaling is one of the key molecular features of autism spectrum disorders (ASD). Cortactin binding protein 2 (CTTNBP2), an ASD-linked gene, is known to regulate the subcellular distribution of synaptic proteins, such as cortactin, thereby controlling dendritic spine formation and maintenance. However, it remains unclear how ASD-linked mutations of CTTNBP2 influence its function. Here, using cultured hippocampal neurons and knockin mouse models, we screen seven ASD-linked mutations in the short form of the Cttnbp2 gene and identify that M120I, R533* and D570Y mutations impair CTTNBP2 protein–protein interactions via divergent mechanisms to reduce dendritic spine density in neurons. R533* mutation impairs CTTNBP2 interaction with cortactin due to lack of the C-terminal proline-rich domain. Through an N–C terminal interaction, M120I mutation at the N-terminal region of CTTNBP2 also negatively influences cortactin interaction. D570Y mutation increases the association of CTTNBP2 with microtubule, resulting in a dendritic localization of CTTNBP2, consequently reducing the distribution of CTTNBP2 in dendritic spines and impairing the synaptic function of CTTNBP2. Finally, we generated heterozygous M120I knockin mice to mimic the genetic variation of patients and found they exhibit reduced social interaction. Our study elucidates that different ASD-linked mutations of CTTNBP2 result in diverse molecular deficits, but all have the similar consequence of synaptic impairment.
Spinal muscular atrophy type III complicated by spinal superficial siderosis: a case report with molecular and neuropathological findings
Authors: Pringle Catherine Elizabeth , Nelson Robert , Miller Willie , Kothary Rashmi , Michaud Jean 
Published: November 2020

Abstract
Spinal muscular atrophy (SMA) is largely linked to deletion or mutation of the Survival motor neuron 1 (SMN1) gene located on chromosome 5q13. Type III (Kugelberg–Welander disease) is the mildest childhood form and patients may become ambulatory and have a normal life expectancy. We report the clinical history and morphological findings of a 55-year-old woman who began to experience motor problems at the age of two. She was never fully ambulatory, and her severe scoliosis required the insertion of surgical rod at age 19. Unexpectedly, around 35 years of age, she began to experience sensory symptoms best characterized as a myelo-radiculo-neuropathy with pain as the dominant symptom. Investigations never clarified the etiology of these symptoms. Molecular confirmation of SMA type III was done post-mortem. Neuropathological examination showed classic changes of lower motor neuron neurodegeneration, in line with those reported in the single molecularly confirmed case published so far, and with findings in rare cases reported prior to the discovery of the gene defect. A key autopsy finding was the presence of a severe superficial siderosis of the lower half of the spinal cord. In recent years, the concept of duropathy was put forward, associating superficial siderosis of the spinal cord with various spinal abnormalities, some of which were present in our patient.
The presence of significant hemosiderin deposits in the spinal cord and sensory nerve roots with associated tissue and axonal damage provide a plausible explanation for the unexpected sensory symptomatology in this mild lower motor neurodegeneration.
Planar free-standing metal layer fabrication: implementing sub-structures in micromirror arrays for light steering applications
Authors: Worapattrakul Natalie , Tatzel Andreas , Viereck Volker , Hillmer Hartmut 
Published: November 2020

Abstract
We present a method to fabricate planar metal layers to be used as micromachined mirrors. Released mirrors of pure metal involve severe stress and reveal specific challenges to obtain planar mirror structures. Introducing sub-structures generating corrugated patterns, the metal mirror layers can be mechanically stabilized and undesired mirror bending can be reduced. For our investigations we used different arrangements of line structures on our metal mirrors, such as a group of straight or curved lines oriented differently. Comparing all the implemented different designs, planar micromirrors were achieved via sub-structures with a combination of straight lines arranged orthogonally to a single line. These planar micromirrors allow steering of the incident light by reflection and adjustment of the window transmittance. The presented low-cost method is suitable for large area fabrication of micromirror arrays, but also can be customized for other applications, where planar free-standing metal layers are required.
Sclerotherapy and prolotherapy for chronic patellar tendinopathies - a promising therapy with limited available evidence, a systematic review
Authors: Morath Oliver , Beck Manuel , Taeymans Jan , Hirschmüller Anja 
Published: November 2020

AbstractChronic Patellar tendinopathy (CPT) is a frequent overuse disorder in athletes and active people. Sclerotherapy (ST) and prolotherapy (PT) are, among a wide range of conservative treatment options, two promising therapies and have shown positive results in other tendinopathies. Since the treatments’ efficacy and safety are still not defined, this review sought to answer questions on recommendations for use in clinical utility, safety, and how to perform the injection in the most effective way. An electronic database search was conducted following the PRISMA guidelines. Inclusion criteria were set up according to the PICOS-scheme. Included were athletes and non-athletes of all ages with diagnosed painful CPT. Studies including patients suffering from patellar tendinopathy which can be originated to any systemic condition affecting the musculoskeletal system (e.g. disorders associated with rheumatism) and animal studies were excluded. Methodological quality (modified Coleman Methodology Score) and risk of bias (Cochrane Risk of Bias Assessment Tool 2.0) were assessed by two independent reviewers, with disagreements resolved with a third reviewer. The search yielded a total of 416 entries. After screening titles, abstracts, and full texts, ten articles were found for qualitative analysis. The mean Coleman Score was 64.57. Three randomized-controlled trials showed positive results with an increase in VISA-P score or a decrease in VAS or NPPS, respectively. The non-randomized studies confirmed the positive results as well. Among all ten studies no serious adverse events were reported. Based on this limited set of studies, there seems to be some evidence that ST and PT may be effective treatment options to treat pain and to improve function in patients with CPT. To strengthen this recommendation, more research is needed with larger volume studies and randomized controlled studies with long term follow up.Level of evidenceIV
Optimising recruitment to the HAND-1 RCT feasibility study: integration of the QuinteT Recruitment Intervention (QRI)
Authors: Husbands Samantha , Elliott Daisy , Davis Tim R. C. , Blazeby Jane M. , Harrison Eleanor F. , Montgomery Alan A. , Sprange Kirsty , Duley Lelia , Karantana Alexia , Hollingworth William , Mills Nicola 
Published: November 2020

Abstract

Background
Recruitment to randomised controlled trials (RCTs) can be challenging, with most trials not reaching recruitment targets. Randomised feasibility studies can be set up prior to a main trial to identify and overcome recruitment obstacles. This paper reports on an intervention—the QuinteT Recruitment Intervention (QRI)—to optimise recruitment within a randomised feasibility study of surgical treatments for patients with Dupuytren’s contracture (the HAND-1 study).

Methods
The QRI was introduced in 2-phases: phase 1 sought to understand the recruitment challenges by interviewing trial staff, scrutinising screening logs and analysing audio-recorded patient consultations; in phase 2 a tailored plan of action consisting of recruiter feedback and training was delivered to address the identified challenges.

Results
Two key recruitment obstacles emerged: (1) issues with the recruitment pathway, in particular methods to identify potentially eligible patients and (2) equipoise of recruiters and patients. These were addressed by liaising with centres to share good practice and refine their pathway and by providing bespoke feedback and training on consent discussions to individual recruiters and centres whilst recruitment was ongoing. The HAND-1 study subsequently achieved its recruitment target.

Conclusions
Transferable lessons learnt from the QRI in the feasibility study will be implemented in the definitive RCT, enabling a “head start” in the tackling of wider issues around screening methods and consent discussions in the set up/early recruitment study phases, with ongoing QRI addressing specific issues with new centres and recruiters. Findings from this study are likely to be relevant to other surgical and similar trials that are anticipated to encounter issues around patient and recruiter equipoise of treatments and variation in recruitment pathways across centres. The study also highlights the value of feasibility studies in fine-tuning design and conduct issues for definitive RCTs. Embedding a QRI in an RCT, at feasibility or main stage, offers an opportunity for a detailed and nuanced understanding of key recruitment challenges and the chance to address them in “real-time” as recruitment proceeds.