bluuebunny/crossref_metadata_2025_split huggingface dataset:
Text mining-based word representations for biomedical data analysis and machine learning tasks
Authors: Alachram Halima , Chereda Hryhorii , Beißbarth Tim , Wingender Edgar , Stegmaier Philip 
Published: December 2020

AbstractBiomedical and life science literature is an essential way to publish experimental results. With the rapid growth of the number of new publications, the amount of scientific knowledge represented in free text is increasing remarkably. There has been much interest in developing techniques that can extract this knowledge and make it accessible to aid scientists in discovering new relationships between biological entities and answering biological questions. Making use of theword2vecapproach, we generated word vector representations based on a corpus consisting of over 16 million PubMed abstracts. We developed a text mining pipeline to produce word2vec embeddings with different properties and performed validation experiments to assess their utility for biomedical analysis. An important pre-processing step consisted in the substitution of synonymous terms by their preferred terms in biomedical databases. Furthermore, we extracted gene-gene networks from two embedding versions and used them as prior knowledge to train Graph-Convolutional Neural Networks (CNNs) on breast cancer gene expression data to predict the occurrence of metastatic events. Performances of resulting models were compared to Graph-CNNs trained with protein-protein interaction (PPI) networks or with networks derived using other word embedding algorithms. We also assessed the effect of corpus size on the variability of word representations. Finally, we created a web service with a graphical and a RESTful interface to extract and explore relations between biomedical terms using annotated embeddings. Comparisons to biological databases showed that relations between entities such as known PPIs, signaling pathways and cellular functions, or narrower disease ontology groups correlated with higher cosine similarity. Graph-CNNs trained with word2vec-embedding-derived networks performed best for the metastatic event prediction task compared to other networks. Word representations as produced by text mining algorithms like word2vec, therefore capture biologically meaningful relations between entities.
Single cell transcriptomics of the developing zebrafish lens and identification of putative controllers of lens development
Authors: Farnsworth Dylan , Posner Mason , Miller Adam 
Published: December 2020

AbstractThe vertebrate lens is a valuable model system for investigating the gene expression changes that coordinate tissue differentiation due to its inclusion of two spatially separated cell types, the outer epithelial cells and the deeper denucleated fiber cells that they support. Zebrafish are a useful model system for studying lens development given the organ’s rapid development in the first several days of life in an accessible, transparent embryo. While we have strong foundational knowledge of the diverse lens crystallin proteins and the basic gene regulatory networks controlling lens development, no study has detailed gene expression in a vertebrate lens at single cell resolution. Here we report an atlas of lens gene expression in zebrafish embryos at single cell resolution through five days of development, identifying a number of novel regulators of lens development as potential targets for future functional studies. Our temporospatial expression data address open questions about the function of α-crystallins during lens development and provides the first detailed view of β- and γ-crystallin expression in and outside the lens. We describe subfunctionalization in transcription factor genes that occur as paralog pairs in the zebrafish. Finally, we examine the expression dynamics of cytoskeletal, RNA-binding, and transcription factors genes, identifying a number of novel patterns. Overall these data provide a foundation for identifying and characterizing lens developmental regulatory mechanisms and revealing targets for future functional studies with potential therapeutic impact.
Drug-coated balloons for dysfunctional hemodialysis venous access: A patient-level meta-analysis of randomized controlled trials
Authors: Yung Fong Khi , Zhao Joseph J , Tan Eelin , Syn Nicholas , Sultana Rehena , Zhuang Kun Da , Chua Jasmine , Ming Er , Patel Ankur , Irani Farah Gillan , Hiong Tay Kiang , Soo Tan Bien , Wei Too Chow 
Published: December 2020

ABSTRACTPurposeTo perform an individual patient data-level meta-analysis of randomized controlled trials comparing drug-coated balloon angioplasty (DCB) against conventional percutaneous transluminal angioplasty (PTA) in the treatment of dysfunctional hemodialysis venous access.MethodsA search was conducted from inception till 13thNovember 2020. Kaplan-Meier curves comparing DCB to PTA by target lesion primary patency (TLPP) and access circuit primary patency (ACPP) were graphically reconstructed to retrieve patient-level data. One-stage meta-analyses with Cox-models with random-effects gramma-frailties were conducted to determine hazard ratios (HRs). Dynamic restricted mean survival times (RMST) were conducted in view of violation of the proportional hazards assumption. Conventional two-stage meta-analyses and network meta-analyses under random-effects Frequentist models were conducted to determine overall and comparative outcomes of paclitaxel concentrations utilised. Where outliers were consistently detected through outlier and influence analyses, sensitivity analyses excluding those studies were conducted.ResultsAmong 10 RCTs (1,207 patients), HRs across all models favoured DCB (one-stage shared-frailty HR=0.62, 95%-CI: 0.53–0.73, P<0.001; two-stage random-effects HR=0.60, 95%-CI: 0.42–0.86, P=0.018,I2=65%) for TLPP. Evidence of time-varying effects (P=0.005) was found. TLPP RMST was +3.47 months (25.0%) longer in DCB-treated patients compared to PTA (P=0.001) at 3-years. TLPP at 6-months, 1-year and 2-years was 75.3% vs 58.0%, 51.1% vs 37.1% and 31.3% vs 26.0% for DCB and PTA respectively. P-Scores within the Frequentist network meta-analysis suggest that higher concentrations of paclitaxel were associated with better TLPP and ACPP. Among 6 RCTs (854 patients), the one-stage model favoured DCB (shared-frailty HR=0.72, 95%-CI: 0.60–0.87, P<0.001) for ACPP. Conversely, the two-stage random-effects model demonstrated no significant difference (HR=0.76, 95%-CI: 0.35–1.67, P=0.414,I2=81%). Sensitivity analysis excluding outliers significantly favoured DCB (HR=0.61, 95%-CI: 0.41–0.91, P=0.027,I2=62%).ConclusionOverall evidence suggests that DCB is favoured over PTA in TLPP and ACPP. The increased efficacy of higher concentrations of paclitaxel may warrant further investigation.
Development And Performance Evaluation of A Rapid In-House ELISA for Retrospective Serosurveillance of SARS-CoV-2
Authors: Sil Bijon Kumar , Oishee Mumtarin Jannat , Haq Md. Ahsanul , Jahan Nowshin , Ali Tamanna , Khandker Shahad Saif , Kobatake Eiry , Mie Masayasu , Khondoker Mohib Ullah , Jamiruddin Mohd. Raeed , Adnan Nihad 
Published: December 2020

AbstractBackgroundIn the ongoing pandemic situation of COVID-19, serological tests can complement the molecular diagnostic methods, and can be one of the important tools of sero-surveillance and vaccine evaluation.AimTo develop and evaluate a rapid SARS-CoV-2 specific ELISA for detection of anti-SARS-CoV2 IgG from patient’s biological samples.MethodsIn order to develop the ELISA, three panels of samples (n=184) have been used: panel 1 (n=19) and panel 2 (n=60) were collected from RT-PCR positive patients within 14 and after 14 days of onset of clinical symptoms respectively, whereas panel 3 consisted of negative samples (n=105) collected either from healthy donors or pre-pandemic dengue patients. As a capturing agent full-length SARS-CoV2 specific recombinant nucleocapsid was immobilized. Commercial SARS-CoV2 IgG kit based on chemiluminescent assay was used for the selection of samples and optimization of the assay. The threshold cut-off point, inter-assay and intra-assay variations were determined. The total assay time for this in-house ELISA was set for 30 minutes.ResultsThe assay time was set at a total of 30 minutes with the sensitivity of 84% (95% confidence interval, CI, 60.4%, 96.6%) and 98% (95% CI, 91.1%, 100.0%), for panel 1 and 2 respectively, with over all 94.9% sensitivity (95% CI 87.5%, 98.6%). Moreover, the clinical specificity is 97.1% (95% CI, 91.9%, 99.4%) with no cross reaction with dengue sample. The overall positive and negative predictive values are 96.2% (95% CI 89.2%, 99.2%) and 96.2% (95% CI, 90.6% 99.0%) respectively. In-house ELISA demonstrated 100% positive and negative percent agreement with ROCHE (Elecsys; Anti-SARS-CoV-2), with a Cohen’s kappa value of 1.00 (very strong agreement), while comparing 13 positive and 17 negative confirmed cases.ConclusionThe assay is rapid and can be applied as one of the early and retrospective sero-monitoring tools in all over the affected areas.
Decreased DNA methylation at promoters and gene-specific neuronal hypermethylation in the prefrontal cortex of patients with bipolar disorder
Authors: Bundo Miki , Ueda Junko , Nakachi Yutaka , Kasai Kiyoto , Kato Tadafumi , Iwamoto Kazuya 
Published: December 2020

AbstractBipolar disorder (BD) is a severe mental disorder characterized by repeated mood swings. Although genetic factors are collectively associated with the etiology of BD, the underlying molecular mechanisms, particularly how environmental factors affect the brain, remain largely unknown. We performed promoter-wide DNA methylation analysis of neuronal and nonneuronal nuclei in the prefrontal cortex of patients with BD (N=34) and controls (N=35). We found decreased DNA methylation at promoters in both cell types in the BD patients compared to the controls. Gene Ontology (GO) analysis of differentially methylated region (DMR)-associated genes revealed enrichment of molecular motor-related genes in neurons, chemokines in both cell types, and ion channel- and transporter-related genes in nonneurons. Detailed analysis further revealed that growth cone- and dendrite-related genes, including NTRK2 and GRIN1, were hypermethylated in neurons of BD patients. To assess the effect of medication, neuroblastoma cells were cultured under therapeutic concentrations of three different mood stabilizers (lithium, valproate, and carbamazepine). We observed that up to 37.9% of DMRs detected in BD overlapped with mood stabilizer-induced DMRs. Interestingly, mood stabilizer-induced DMRs showed the opposite direction of changes in DMRs in BD, suggesting the therapeutic effects of mood stabilizers on DNA methylation. Among the DMRs, 12 overlapped with loci identified by a previous genome-wide association study of BD. Finally, we performed qPCR analysis of 10 DNA methylation-related genes and found that DNMT3B was overexpressed in BD. The cell type-specific DMRs identified in this study will be useful for understanding the pathophysiology of BD.
Effect of the COVID-19 pandemic in stroke code activations in the region of Madrid: a retrospective cohort study
Authors: Riera-López Nicolás , Fuentes-Gimeno Blanca , de Donlebun Jorge Rodriguez-Pardo 
Published: December 2020

ABSTRACTAcute Stroke (AS) is the most common time-dependent disease attended in the Emergency Medicine Service (EMS) of Madrid (SUMMA 112). Community of Madrid has been one of the most affected regions in Spain by the coronavirus disease 2019 (COVID19) pandemic. A significant reduction in AS hospital admissions has been reported during the COVID-19 pandemic compared to the same period one year before. As international clinical practice guidelines support those patients with suspected acute stroke should be accessed via EMS, it is important to know whether the pandemic has jeopardized urgent pre-hospital stroke care, the first medical contact for most patients. We aimed to examine the impact of the COVID-19 in stroke codes (SC) in our EMS among three periods of time: the COVID-19 period, the same period the year before, and the 2019-2020 seasonal influenza period. Methods: We compared the SC frequency among the periods with high cumulative infection rate (above the median of the series) of the first wave of COVID-19, seasonal influenza, and also with the same period of the year before. Results: 1,130 SC were attended during the three periods. No significant reduction in SC was found during the COVID-19 pandemic. The reduction of hospital admissions might be attributable to patients attending the hospital by their means. The maximum SC workload seen during seasonal influenza has not been reached during the pandemic. We detected a non-significant deviation from the SC protocol, with a slight increase in hospitals’ transfers to hospitals without stroke units.
Inferring perturbation profiles of cancer samples
Authors: Pirkl Martin , Beerenwinkel Niko 
Published: December 2020

AbstractMotivationCancer is one of the most prevalent diseases in the world. Tumors arise due to important genes changing their activity, e.g., when inhibited or over-expressed. But these gene perturbations are difficult to observe directly. Molecular profiles of tumors can provide indirect evidence of gene perturbations. However, inferring perturbation profiles from molecular alterations is challenging due to error-prone molecular measurements and incomplete coverage of all possible molecular causes of gene perturbations.ResultsWe have developed a novel mathematical method to analyze cancer driver genes and their patient-specific perturbation profiles. We combine genetic aberrations with gene expression data in a causal network derived across patients to infer unobserved perturbations. We show that our method can predict perturbations in simulations, CRISPR perturbation screens, and breast cancer samples from The Cancer Genome Atlas.AvailabilityThe method is available as the R-package nempi athttps://github.com/cbg-ethz/nempi.Contactmartin.pirkl@bsse.ethz.ch,niko.beerenwinkel@bsse.ethz.ch
Identification of glutamine synthetase as a novel contryphan-Bt binding protein by his-tag pull down
Authors: Han Penggang , Cao Ying , Dai Xiandong , Liu Shangyi , Fan Chongxu , Wu Wenjian , Chen Jisheng 
Published: December 2020

Abstract(1)BackgroundContryphan-Bt is a D-tryptophan-containing disulfide-constrained decapeptide recently isolated from the venom ofConus betulinus. The molecular targets of contryphans are controversial, and the identification of its interacting proteins may be of great importance.(2)MethodsHis-tag pull down assays were performed to investigate binding proteins of contryphan-Bt from rat brain lysate. Bt-Acp-[His]6, a contryphan-Bt derivative containing hexahistidine tag, was synthesized and used as the bait. As a control, Acp-[His]6was used to exclude nonspecific bindings.(3)ResultsGlutamine synthetase was identified as a potential contryphan-Bt binding protein by pull down assays and subsequent LC-MS/MS. The binding of contryphan-B to glutamine synthetase was confirmed and determined using microscale thermophoresis, with a Kd of 74.02 ± 2.8 μM. The binding did not affect glutamine synthetase activity, suggesting that the interaction site was distinct from the catalytic center.(4)ConclusionsGlutamine synthetase was identified as a novel contryphan-Bt binding protein. This is the first report that the conopeptide binds to an intracellular protein, therefore offering a new concept and methodology for developing peptide toxins.Key ContributionThis is the first report that the conopeptide binds to an intracellular protein, therefore offering a new concept and methodology for developing peptide toxins.
An emergency system for monitoring pulse oximetry, peak expiratory flow and body temperature of patients with COVID-19 at home: Development and preliminary application
Authors: Motta Leonardo Pereira , da Silva Pedro Paulo Ferreira , Borguezan Bruno Max , do Amaral Jorge Luis Machado , Gonçalves Milagres Lucimar , Bóia Márcio Neves , Ferraz Marcos Rochedo , Mogami Roberto , Acatauassú Nunes Rodolfo , de Melo Pedro Lopes 
Published: December 2020

AbstractBackgroundCOVID-19 is characterized by a rapid change in the patient’s condition, with major changes occurring over a few days. Our aim was to develop and evaluate an emergency system for monitoring patients with COVID-19, which may be useful in hospitals where more severe patients stay in their homes.Methodology/Principal findingsThe system consists of the home-based patient unit, which is set up around the patient and the hospital unit, which enables the medical staff to telemonitor the patient’s condition and help to send medical recommendations. The home unit allows the data transmission from the patient to the hospital, which is performed using a cell phone application. The hospital unit includes a virtual instrument developed in LabVIEW® environment that is able to provide a real-time monitoring of the oxygen saturation (SpO2), beats per minute (BPM), body temperature (BT) and peak expiratory flow (PEF). Abnormal events may be fast and automatically identified. After the design details are described, the system is validated by a 30-day home monitoring study in 12 controls and 12 patients with COVID-19 presenting asymptomatic to mild disease. Patients presented reduced SpO2 (p<0.0001) and increased BPM values (p<0.0001). Three patients (25%) presented PEF values between 50 and 80% of the predicted. Three of the 12 monitored patients presented events of desaturation (SpO2<92%). The experimental results were in close agreement with the involved pathophysiology, providing clear evidences that the proposed system can be a useful tool for the remote monitoring of patients with COVID-19.ConclusionsAn emergency system for home monitoring of patients with COVID-19 was developed in the current study. The proposed system allowed us to quickly respond to early abnormalities in these patients. This system may contribute to conserve hospital resources for those most in need, while simultaneously enabling early recognition of patients under acute deterioration, requiring urgent assessment.
Design tactics for enhancing the adaptability of primary and middle schools to the new needs of postpandemic reuse
Authors: Güzelci Orkan Zeynel , Şen Bayram Asena Kumsal , Alaçam Sema , Güzelci Handan , Akkuyu Elif Işık , Şencan İnanç 
Published: December 2020

PurposeThe aim of this study is to present design tactics (DTs) for supporting the adaptability of existing primary and middle school buildings into the emerging needs of coronavirus disease 2019 (COVID-19). The study introduces a novel algorithmic model for postoccupancy evaluation of the existing school buildings and provides solutions to enhance the adaptability of these buildings.Design/methodology/approachThis study employs the DTs defined by the authors, integration of DTs to the algorithmic model and tests the usability of the proposed model in the selected sample set. The sample set consists of four primary and middle school buildings with different architectural qualities. The degrees of flexibility of the existing sample set are evaluated depending on the outcomes of the implementation.FindingsThe degrees of flexibility are achieved as a result of execution of the algorithmic model for each selected school building. Initial results of the case studies show that the flexibility of a school building is highly related to affordances and design decisions of the plan layout which were considered in the initial phases of the design process. Architectural qualities such as open plan and having sufficient voids in the interior and exterior space become prominent factors for ensuring flexibility.Originality/valueDeveloping a systematic approach to the adaptation problem of primary and middle school buildings to postpandemic reuse is a novel research topic. Apart from this contextual originality, the proposed taxonomy for postpandemic reuse in terms of three levels of adaptation is a new conceptual framework. Moreover, the proposed algorithmic model itself can be considered as an original contribution, as well as a merge of qualitative values such as adaptation and flexibility with an algorithmic model.
Conditions for collaboration between higher education and healthcare providers organising clinical placements
Authors: Bivall Ann-Charlotte , Gustavsson Maria , Lindh Falk Annika 
Published: December 2020

PurposeClinical placement is an important formalised student activity for linking healthcare education and healthcare practices. The purpose of this study is to investigate the organising of clinical placements by examining conditions for collaboration between higher education and healthcare organisations.Design/methodology/approachThe study is based on interviews with central actors at a university and two healthcare organisations with official duties of organising clinical placements.FindingsThe findings indicate that collaboration in the organising of clinical placements is a complex matter of interconnected actors in different organisational positions, at both strategic and operative levels. The university and the healthcare organisations approached the clinical placement with a shared commitment.Practical implicationsThe findings provide important guidance for improving collaboration in the organising of clinical placements. This may have an impact on how contextual conditions of the educational framing and daily healthcare practices are viewed and how the interdependency between the long-term strategic issues and the short-term needs of healthcare organisations is approached.Originality/valueThis research emphasises the need for careful consideration of the collaborative practices on an organisational level between higher education and healthcare organisations as different needs, motives and logics have to be considered.
Will what is measured be used? An analysis of performance management systems in Pakistani state organizations
Authors: Zahra Abiha , Bouckaert Geert 
Published: December 2020

PurposeWith performance as a core theme of public sector reforms, this article explores performance management systems in inter-organizational settings while testing the effect of performance measurement on its use for accountability and control. Using economic neo-institutional perspective in a hierarchical context with turbulent political history, the article investigates the variations in the use of performance information in inter-institutional settings across different legal categories of state organizations.Design/methodology/approachThe performance management framework of Van Dooren et al. (2010) is employed as the basis for this research that explains the link between performance measurement and use. To explore the management of performance in Pakistan, the survey data was collected in 2018; after two democratic governments completed their tenures.FindingsThe research indicated a lower extent of performance measurement and use by the parent ministries in the democratic regimes. This finding adds to the implications of economic institutional theory in a politically turbulent context, where political actors place less emphasis on performance and more emphasis on procedures. It was confirmed that the ministries use the measured performance information for accountability and control on the results, but the moderating role of legal categories in the performance framework did not get confirmation.Originality/valueThe article empirically tests the performance management framework from a Western context in a developing country that has not been discussed frequently in the performance management systems literature.