bluuebunny/crossref_metadata_2025_split huggingface dataset:
Online patient simulation training to improve clinical reasoning: a feasibility randomised controlled trial
Authors: Plackett Ruth , Kassianos Angelos P. , Kambouri Maria , Kay Natasha , Mylan Sophie , Hopwood Jenny , Schartau Patricia , Gray Shani , Timmis Jessica , Bennett Sarah , Valerio Chris , Rodrigues Veena , Player Emily , Hamilton Willie , Raine Rosalind , Duffy Stephen , Sheringham Jessica 
Published: July 2020

Abstract
Background
Online patient simulations (OPS) are a novel method for teaching clinical reasoning skills to students and could contribute to reducing diagnostic errors. However, little is known about how best to implement and evaluate OPS in medical curricula. The aim of this study was to assess the feasibility, acceptability and potential effects of eCREST — the electronic Clinical Reasoning Educational Simulation Tool.

Methods
A feasibility randomised controlled trial was conducted with final year undergraduate students from three UK medical schools in academic year 2016/2017 (cohort one) and 2017/2018 (cohort two). Student volunteers were recruited in cohort one via email and on teaching days, and in cohort two eCREST was also integrated into a relevant module in the curriculum. The intervention group received three patient cases and the control group received teaching as usual; allocation ratio was 1:1. Researchers were blind to allocation. Clinical reasoning skills were measured using a survey after 1 week and a patient case after 1 month.

Results
Across schools, 264 students participated (18.2% of all eligible). Cohort two had greater uptake (183/833, 22%) than cohort one (81/621, 13%). After 1 week, 99/137 (72%) of the intervention and 86/127 (68%) of the control group remained in the study. eCREST improved students’ ability to gather essential information from patients over controls (OR = 1.4; 95% CI 1.1–1.7, n = 148). Of the intervention group, most (80/98, 82%) agreed eCREST helped them to learn clinical reasoning skills.

Conclusions
eCREST was highly acceptable and improved data gathering skills that could reduce diagnostic errors. Uptake was low but improved when integrated into course delivery. A summative trial is needed to estimate effectiveness.
Public awareness of and attitudes towards research biobanks in Latvia
Authors: Mezinska S. , Kaleja J. , Mileiko I. , Santare D. , Rovite V. , Tzivian L. 
Published: July 2020

Abstract
Background
Public awareness and engagement are among the main prerequisites for protecting the rights of research participants and for successful and sustainable functioning of research biobanks. The aim of our study was to analyse public awareness and attitudes towards research biobanks in Latvia, and to compare these data with the results of the 2010 Eurobarometer study. We also analysed the influence of awareness and attitudes towards biobanks on willingness to participate in biobank studies and on preferred type of informed consent.

Methods
We developed a 12-question survey repeating seven questions about biobanks from the 2010 Eurobarometer questionnaire and adding five others. After describing the study variables, we performed a two-stage analysis of the results. In the first stage we analysed differences between the answers from 2010 and 2019 and conducted univariate analyses of relationships among particular variables, and between those variables and the socio-demographic characteristics of participants. In the second stage we investigated multivariable associations of willingness to participate and type of consent with awareness, trust and the socio-economic characteristics of participants.

Results
According to our study, the general public in Latvia is still not well informed about research biobanks. Fewer respondents have heard about research biobanks than in 2010. At the same time, the number of respondents who are willing to donate biological samples and personal data to a biobank has increased, e.g. the number of respondents who would definitely or probably be willing to provide information about themselves has increased from 25.8.% to 40.7 since 2010. Overall, concerns about the donation of different types of biological samples and data to a biobank have slightly decreased.

Conclusions
Public awareness about biobanks is important for their sustainability. It needs to be increased not only by traditional methods of informing the public, but also by more innovative and participatory approaches, e.g. by citizen science projects. There is a need to strengthen the public visibility and trustworthiness of ethics committees in Latvia in the field of biobanking.
Antibiotic fidaxomicin is an RdRp inhibitor as a potential new therapeutic agent against Zika virus
Authors: Yuan Jie , Yu Jianchen , Huang Yun , He Zhenjian , Luo Jia , Wu Yun , Zheng Yingchun , Wu Jueheng , Zhu Xun , Wang Haihe , Li Mengfeng 
Published: July 2020

Abstract
Background
Zika virus (ZIKV) infection is a global health problem, and its complications, including congenital Zika syndrome and Guillain-Barré syndrome, constitute a continued threat to humans. Unfortunately, effective therapeutics against ZIKV infection are not available thus far.

Methods
We screened the compounds collection consisting of 1789 FDA-approved drugs by a computational docking method to obtain anti-ZIKV candidate compounds targeting ZIKV RNA-dependent RNA polymerase (RdRp). SPR (BIAcore) assay was employed to demonstrate the candidate compounds’ direct binding to ZIKV RdRp, and polymerase activity assay was used to determine the inhibitory effect on ZIKV RdRp-catalyzed RNA synthesis. The antiviral effects on ZIKV in vitro and in vivo were detected in infected cultured cells and in Ifnar1−/− mice infected by ZIKV virus using plaque assay, western blotting, tissue immunofluorescence, and immunohistochemistry.

Results
Here, we report that a first-in-class macrocyclic antibiotic, which has been clinically used to treat Clostridium difficile infection, fidaxomicin, potently inhibits ZIKV replication in vitro and in vivo. Our data showed that fidaxomicin was effective against African and Asian lineage ZIKV in a wide variety of cell lines of various tissue origins, and prominently suppressed ZIKV infection and significantly improved survival of infected mice. In addition, fidaxomicin treatment reduced the virus load in the brains and testes, and alleviated ZIKV-associated pathological damages, such as paralysis, hunching, and neuronal necrosis in the cerebra. Furthermore, our mechanistic study showed that fidaxomicin directly bound ZIKV NS5 protein and inhibited the RNA synthesis-catalyzing activity of ZIKV RdRp.

Conclusions
Our data suggest that fidaxomicin may represent an effective anti-ZIKV agent. In the light that fidaxomicin is already a clinically used drug, there might be a promising prospect in the development of fidaxomicin to be an antiviral therapeutic.
A novel use for Levey-Jennings charts in prenatal molecular diagnosis
Authors: Weng Binghuan , Xu Ya-li , Ying Jun , Yang Hao-kun , Su Lan , Yang Yan-mei , Chen Min 
Published: July 2020

Abstract
Background
The goal of this study was to determine whether Levey-Jennings charts, which are widely used in clinical laboratories, can be used to create standardized internal quality controls (IQCs) for prenatal molecular diagnosis.

Methods
Aneuploid amniocyte lines with trisomy 13, 21, and 18, and 47,XXY were established by transfection with SV40LTag-pcDNA3.1(−)and combined at different ratios to generate aneuploidy chimeric quality-control cell mixtures A to H. These quality-control cells were then used to calculate the $$ \overline{\mathrm{X}} $$

X
¯

, $$ \overline{\mathrm{X}} $$

X
¯

±1 standard deviation (SD), $$ \overline{\mathrm{X}} $$

X
¯

±2 SD, and $$ \overline{\mathrm{X}} $$

X
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±3 SD values to develop standardized IQCs for methods used for the prenatal diagnosis of aneuploidies such as FISH.

Results
Methods for constructing aneuploid amniocyte lines were developed and a set of quality-control cells (A-H) were prepared. The $$ \overline{\mathrm{X}} $$

X
¯

±1 SD, $$ \overline{\mathrm{X}} $$

X
¯

±2 SD, and $$ \overline{\mathrm{X}} $$

X
¯

±3 SD values of these quality-control cells for trisomy 13 and 21 were 10.2 ± 1.7, 10.2 ± 3.4, and 10.2 ± 5.1, and 90.3 ± 2.3, 90.3 ± 4.6, and 90.3 ± 6.9, respectively. Based on the values and Levey-Jennings charts, a set of standardized IQCs for prenatal diagnosis such as FISH were established.

Conclusions
This method resolves the problems of a shortage of quality-control materials and a lack of quality-control charts in prenatal molecular diagnosis such as NIPT, NGS, aCGH/SNP, PCR, and FISH. Levey-Jennings chart-based IQCs for prenatal diagnosis such as FISH can be used to easily monitor whether IQC results are within acceptable limits, and then infer whether the diagnostic results for clinical samples are reliable. We expect that this standardized IQC will be useful for a wide range of molecular diagnostic laboratories.
Engineering marine fungi for conversion of d-galacturonic acid to mucic acid
Authors: Vidgren Virve , Halinen Satu , Tamminen Anu , Olenius Susanna , Wiebe Marilyn G. 
Published: July 2020

Abstract
Background
Two marine fungi, a Trichoderma sp. and a Coniochaeta sp., which can grow on d-galacturonic acid and pectin, were selected as hosts to engineer for mucic acid production, assessing the suitability of marine fungi for production of platform chemicals. The pathway for biotechnologcial production of mucic (galactaric) acid from d-galacturonic acid is simple and requires minimal modification of the genome, optimally one deletion and one insertion. d-Galacturonic acid, the main component of pectin, is a potential substrate for bioconversion, since pectin-rich waste is abundant.

Results
Trichoderma sp. LF328 and Coniochaeta sp. MF729 were engineered using CRISPR-Cas9 to oxidize d-galacturonic acid to mucic acid, disrupting the endogenous pathway for d-galacturonic acid catabolism when inserting a gene encoding bacterial uronate dehydrogenase. The uronate dehydrogenase was expressed under control of a synthetic expression system, which fucntioned in both marine strains. The marine Trichoderma transformants produced 25 g L−1 mucic acid from d-galacturonic acid in equimolar amounts: the yield was 1.0 to 1.1 g mucic acid [g d-galacturonic acid utilized]−1. d-Xylose and lactose were the preferred co-substrates. The engineered marine Trichoderma sp. was more productive than the best Trichoderma reesei strain (D-161646) described in the literature to date, that had been engineered to produce mucic acid. With marine Coniochaeta transformants, d-glucose was the preferred co-substrate, but the highest yield was 0.82 g g−1: a portion of d-galacturonic acid was still metabolized. Coniochaeta sp. transformants produced adequate pectinases to produce mucic acid from pectin, but Trichoderma sp. transformants did not.

Conclusions
Both marine species were successfully engineered using CRISPR-Cas9 and the synthetic expression system was functional in both species. Although Coniochaeta sp. transformants produced mucic acid directly from pectin, the metabolism of d-galacturonic acid was not completely disrupted and mucic acid amounts were low. The d-galacturonic pathway was completely disrupted in the transformants of the marine Trichoderma sp., which produced more mucic acid than a previously constructed T. reesei mucic acid producing strain, when grown under similar conditions. This demonstrated that marine fungi may be useful as production organisms, not only for native enzymes or bioactive compounds, but also for other compounds.
Assessment of nonnegative matrix factorization algorithms for electroencephalography spectral analysis
Authors: Hu Guoqiang , Zhou Tianyi , Luo Siwen , Mahini Reza , Xu Jing , Chang Yi , Cong Fengyu 
Published: July 2020

AbstractBackgroundNonnegative matrix factorization (NMF) has been successfully used for electroencephalography (EEG) spectral analysis. Since NMF was proposed in the 1990s, many adaptive algorithms have been developed. However, the performance of their use in EEG data analysis has not been fully compared. Here, we provide a comparison of four NMF algorithms in terms of accuracy of estimation, stability (repeatability of the results) and time complexity of algorithms with simulated data. In the practical application of NMF algorithms, stability plays an important role, which was an emphasis in the comparison. A Hierarchical clustering algorithm was implemented to evaluate the stability of NMF algorithms.ResultsIn simulation-based comprehensive analysis of fit, stability, accuracy of estimation and time complexity, hierarchical alternating least squares (HALS) low-rank NMF algorithm (lraNMF_HALS) outperformed the other three NMF algorithms. In the application of lraNMF_HALS for real resting-state EEG data analysis, stable and interpretable features were extracted.ConclusionBased on the results of assessment, our recommendation is to use lraNMF_HALS, providing the most accurate and robust estimation.
Recent advances in Surface Guided Radiation Therapy
Authors: Freislederer P. , Kügele M. , Öllers M. , Swinnen A. , Sauer T.-O. , Bert C. , Giantsoudi D. , Corradini S. , Batista V. 
Published: July 2020

AbstractThe growing acceptance and recognition of Surface Guided Radiation Therapy (SGRT) as a promising imaging technique has supported its recent spread in a large number of radiation oncology facilities. Although this technology is not new, many aspects of it have only recently been exploited. This review focuses on the latest SGRT developments, both in the field of general clinical applications and special techniques.SGRT has a wide range of applications, including patient positioning with real-time feedback, patient monitoring throughout the treatment fraction, and motion management (as beam-gating in free-breathing or deep-inspiration breath-hold). Special radiotherapy modalities such as accelerated partial breast irradiation, particle radiotherapy, and pediatrics are the most recent SGRT developments.The fact that SGRT is nowadays used at various body sites has resulted in the need to adapt SGRT workflows to each body site. Current SGRT applications range from traditional breast irradiation, to thoracic, abdominal, or pelvic tumor sites, and include intracranial localizations.Following the latest SGRT applications and their specifications/requirements, a stricter quality assurance program needs to be ensured. Recent publications highlight the need to adapt quality assurance to the radiotherapy equipment type, SGRT technology, anatomic treatment sites, and clinical workflows, which results in a complex and extensive set of tests.Moreover, this review gives an outlook on the leading research trends. In particular, the potential to use deformable surfaces as motion surrogates, to use SGRT to detect anatomical variations along the treatment course, and to help in the establishment of personalized patient treatment (optimized margins and motion management strategies) are increasingly important research topics. SGRT is also emerging in the field of patient safety and integrates measures to reduce common radiotherapeutic risk events (e.g. facial and treatment accessories recognition).This review covers the latest clinical practices of SGRT and provides an outlook on potential applications of this imaging technique. It is intended to provide guidance for new users during the implementation, while triggering experienced users to further explore SGRT applications.
Comparisons of the surface micromotions of cementless femoral prosthesis in the horizontal and vertical levels: a network analysis of biomechanical studies
Authors: Wang Bomin , Li Qinghu , Dong Jinlei , Zhou Dongsheng , Liu Fanxiao 
Published: July 2020

AbstractBackgroundNumerous quantitatively biomechanical studies measuring the fixation stability of femoral stem using micromotions at the bone-implant interfaces in different directions and levels remain inconclusive. This network meta-analysis performed systematically aims to explore the rank probability of micromotions at the bone-implant interfaces based on biomechanical data from studies published.MethodsTwo electronic databases, PubMed/MEDLINE and Embase, were utilized to retrieve biomechanical studies providing the data of micromotions at the bone-stem interfaces. After screening and diluting out, the studies that met inclusion criteria will be utilized for statistical analysis. In order to contrast the stability of commonness and differences of the different parts of the femoral stem, the horizontal and vertical comparison of micromotions at the bone-implant interfaces were conducted using the pooled evaluation indexes including the mean difference (MD) and the surface under the cumulative ranking (SUCRA) curve, while inconsistency analysis, sensitivity analysis, subgroup analyses, and publication bias were performed for the stability evaluation of outcomes.ResultsScreening determined that 20 studies involving a total of 249 samples were deemed viable for inclusion in the network meta-analysis. Tip point registered the highest micromotions of 13 measurement points. In the horizontal level, the arrangements of 4 measurement points at the proximal (P1–P4), middle (P5–P8) and distal part of the stem (P9–P12) were P1 = P2 = P3 = P4, P7 > P8 > P6 = P5 and P10 ≥ P12 = P9 = P11, respectively. In the vertical level, the arrangements of 3 measurement points at the anterior, posterior, medial, and lateral directions was P9 > P5 = P1, P10 > P6 > P2, P11 > P7 > P3, and P12 > P8 > P4, respectively.ConclusionThe network meta-analysis seems to reveal that the distal part of the femoral stem is easier to register higher micromotion, and tip point of femoral stem registers the highest micromotions.
Zymosan promotes proliferation, Candida albicans adhesion and IL-1β production of oral squamous cell carcinoma in vitro
Authors: Chen Xu , Luo Qingqiong , Ding Jieying , Yang Meng , Zhang Ruiyang , Chen Fuxiang 
Published: July 2020

AbstractOral squamous cell carcinoma (OSCC) is the most common type of head and neck squamous cell carcinoma (HNSCC), and the effect of zymosan (ZYM), a component of the yeast cell wall, on oral cancer remains unclear. The CCK-8 proliferation assay was performed to evaluate the effect of ZYM on the proliferation of the OSCC cell lines WSU-HN4, WSU-HN6 and CAL27, and the potential mechanism was explored by quantitative real-time PCR, immunofluorescence assay and western blot. A cell adhesion assay was conducted to determine the adhesion of Candida albicans to OSCC cells, and the expression of related genes, including TLR2, MyD88, NLRP3, ASC, Caspase-1 and IL-1β, and proteins, including TLR2, MyD88, NF-κB p65, p-NF-κB p65 and E-cadherin was determined. Additionally, the pro-inflammatory cytokines including IL-6, IL-8, TNF-α and IL-1β produced by OSCC cells were detected using a chemiluminescence immunoassay (CLIA). In the current study, the CCK-8 assay showed that ZYM promoted the proliferation of WSU-HN4, WSU-HN6 and CAL27 cells via the TLR2/MyD88 pathway. The cell adhesion assay showed that the number of C. albicans cells per field significantly increased in ZYM-treated OSCC cells compared to controls. When treated with ZYM, OSCC cells secreted significantly more pro-inflammatory cytokine IL-1β, which could enhance inflammation in oral cancer microenvironment. In conclusion, ZYM from the fungal cell wall promotes the proliferation, C. albicans adhesion and IL-1β production in OSCC, as demonstrated by in vitro experiments.
Alleviating toxic α-Synuclein accumulation by membrane depolarization: evidence from an in vitro model of Parkinson’s disease
Authors: Ross Alysia , Xing Viktoria , Wang Ting Ting , Bureau Samantha C. , Link Giovana A. , Fortin Teresa , Zhang Hui , Hayley Shawn , Sun Hongyu 
Published: July 2020

AbstractParkinson’s disease (PD) is characterized by the formation of toxic, fibrillar form alpha-synuclein (α-Syn) protein aggregates in dopaminergic neurons. Accumulating evidence has shown a multifactorial interplay between the intracellular calcium elevation and α-Syn dynamics. However, whether membrane depolarization regulates toxic α-Syn aggregates remains unclear. To understand this better, we used an in vitro α-Syn preformed fibrils (PFF) model of PD in human neural cells. We demonstrated functional membrane depolarization in differentiated SH-SY5Y cells induced by two independent treatments: high extracellular K+ and the GABAA receptor blocker picrotoxin. We then observed that these treatments significantly alleviated toxic α-Syn aggregation in PFF-treated SH-SY5Y cells. Moreover, clinically relevant direct current stimulation (DCS) also remarkably decreased toxic α-Syn aggregation in PFF-treated SH-SY5Y cells. Taken together, our findings suggest that membrane depolarization plays an important role in alleviating PFF-induced toxic α-Syn aggregates, and that it may represent a novel therapeutic mechanism for PD.
Myositis ossificans mimicking sarcoma: a not so rare bioptic diagnostic pitfall
Authors: Cortellazzo Wiel Luisa , Trevisan Matteo , Murru Flora Maria , Rabusin Marco , Barbi Egidio 
Published: July 2020

Abstract
Background
Myositis ossificans (MO) is a heterotopic bone formation in soft tissues, usually caused by traumas or neuropathies. Although the aetiology remains unclear, MO is supposed to be an osteoblast metaplasia with a benign and self-limiting course. Remarkably, at onset MO can be clinically, radiologically and histologically indistinguishable to soft tissue malignancies, especially in cases lacking a history of trauma, leading to misdiagnoses and improper treatments.

Case presentation
A 13-year-old male was referred to the Oncology Department because of a previous diagnosis of osteogenic sarcoma of his left thigh. The diagnosis was made upon a history of isolated thigh pain in the absence of traumas, the evidence of a contrast-enhanced soft tissue mass on magnetic resonance imaging and the histological findings of atypical nuclei and mitotic figures. The lesion was eventually radiologically unchanged after five cycles of chemotherapy; thus, the child was referred for radical surgery. At admission, endorsing the child well-appearance, together with the evidence of a reduced calcified lesion on a further magnetic resonance, a clinical suspicion of myositis ossificans was raised. Hence, the excisional biopsy confirmed the pathognomonic zonal pattern of myositis ossificans.

Conclusions
This case highlights some frequent diagnostic pitfalls facing myositis ossificans. A lacking history of traumas, along with a too early radiological and histological evaluation can lead to a misdiagnosis of soft tissue malignancies. Even in the absence of a clear history of trauma, a painful soft tissue swelling with a benign clinical course should raise the suspicion of myositis ossificans.