bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of recombinant nucleocapsid and spike proteins for serological diagnosis of novel coronavirus disease 2019 (COVID-19)
Authors: Zhang Pingping , Gao Qi , Wang Tang , Ke Yuehua , Mo Fei , Jia Ruizhong , Liu Wanbing , Liu Lei , Zheng Shangen , Liu Yuzhen , Li Luping , Wang Yao , Xu Lei , Hao Kun , Yang Ruifu , Li Shiyue , Lin Changqing , Zhao Yong 
Published: March 2020

AbstractBackgroundThe colloidal gold immunochromatography assay (GICA) is a rapid diagnostic tool for novel coronavirus disease 2019 (COVID-19) infections. However, with significant numbers of false negatives, improvements to GICA are needed.MethodsSix recombinant HCoV-19 nucleocapsid and spike proteins were prepared and evaluated. The optimal proteins were employed to develop a sandwich-format GICA strip to detect total antibodies (IgM and IgG) against HCoV-19. GICA’s performance was assessed with comparison of viral RNA detection.ResultsRecombinant HCoV-19 proteins were obtained, including three prokaryotically expressed rN, rN1, rN2 nucleocapsid proteins, and three eukaryotically expressed rS1, rS-RBD, rS-RBD-mFc spike proteins. The recombinant proteins with the highest ELISA titers (rS1 and rS-RBD-mFc) against coronavirus-specific IgM and IgG were chosen for GICA development. The GICA has a sensitivity and specificity of 86.89% (106/122) and 99.39% (656/660), respectively. Furthermore, 65.63% (21/32) of the clinically confirmed but RT-PCR negative samples were GICA positive.ConclusionsThe eukaryotically-expressed spike proteins (rS1and rS-RBD-mFc) are more suitable than the prokaryotically expressed nucleocapsid proteins for HCoV-19 serological diagnosis. The GICA sandwich used to detect total antibodies is a powerful complement to the current standard RNA-based tests.
Degree irregularity and rank probability bias in network meta-analysis
Authors: Davies Annabel L. , Galla Tobias 
Published: March 2020

AbstractNetwork meta-analysis (NMA) is a statistical technique for the comparison of treatment options. The nodes of the network are the competing treatments and edges represent comparisons of treatments in trials. Outcomes of Bayesian NMA include estimates of treatment effects, and the probabilities that each treatment is ranked best, second best and so on. How exactly network geometry affects the accuracy and precision of these outcomes is not fully understood. Here we carry out a simulation study and find that disparity in the number of trials involving different treatments leads to a systematic bias in estimated rank probabilities. This bias is associated with an increased variation in the precision of treatment effect estimates. Using ideas from the theory of complex networks, we define a measure of ‘degree irregularity’ to quantify asymmetry in the number of studies involving each treatment. Our simulations indicate that more regular networks have more precise treatment effect estimates and smaller bias of rank probabilities. We also find that degree regularity is a better indicator of NMA quality than both the total number of studies in a network and the disparity in the number of trials per comparison. These results have implications for planning future trials. We demonstrate that choosing trials which reduce the network’s irregularity can improve the precision and accuracy of NMA outcomes.
Challenges of false positive and negative results in cervical cancer screening
Authors: Grimes David Robert , Corry Edward M.A. , Malagón Talía , O’Riain Ciaran , Franco Eduardo L. , Brennan Donal J. 
Published: March 2020

ABSTRACTObjectiveTo quantify the impact and accuracy of different screening approaches for cervical cancer, including liquid based cytology (LBC), molecular testing for human papillomavirus (HPV) infection, and their combinations via parallel co-testing and sequential triage. The secondary goal was to predict the effect of differing coverage rates of HPV vaccination on the performance of screening tests and in the interpretation of their results.DesignModelling study.Main outcomes measuredDifferent screening modalities were compared in terms of number of cases of Cervical intra-epithelial neoplasia (CIN) grade 2 and 3 detected and missed, as well as the number of false positives leading to excess colposcopy, and number of tests required to achieve a given level of accuracy. The positive predictive value (PPV) and negative predictive value (NPV) of different modalities were simulated under varying levels of HPV vaccination.ResultsThe model predicted that in a typical population, primary LBC screening misses 4.9 (95% Confidence Interval (CI) 3.5-CIN 2 / 3 cases per 1000 women, and results in 95 (95% CI: 93-97%) false positives leading to excess colposcopy. For primary HPV testing, 2.0 (95% CI: 1.9-2.1) cases were missed per 1000 women, with 99 (95% CI: 98-101) excess colposcopies undertaken. Co-testing markedly reduced missed cases to 0.5 (95% CI: 0.3-0.7) per 1000 women, but at the cost of dramatically increasing excess colposcopy referral to 184 per 1000 women (95% CI: 182-188). Conversely, triage testing with reflex screening substantially reduced excess colposcopy to 9.6 cases per 1000 women (95% CI: 9.3 - 10) but at the cost of missing more cases (6.4 per 1000 women, 95% CI: 5.1 - 8.0). Over a life-time of screening, women who always attend annual and 3-year co-testing were predicted to have a virtually 100% chance of falsely detecting a CIN 2 / 3 case, while 5 year co-testing has a 93.8% chance of a false positive over screening life-time. For annual, 3 year, and 5 year triage testing (either LBC with HPV reflex or vice versa), lifetime risk of a false positive is 35.1%, 13.4%, and 8.3% respectively. HPV vaccination rates adversely impact the PPV, while increasing the NPV of various screening modalities. Results of this work indicate that as HPV vaccination rates increase, HPV based screening approaches result in fewer unnecessary colposcopies than LBC approaches.ConclusionThe clinical relevance of cervical cancer screening is crucially dependent upon the prevalence of cervical dysplasia and/or HPV infection or vaccination in a given population, as well as the sensitivity and specificity of various modalities. Although screening is life-saving, false negatives and positives will occur, and over-testing may cause significant harm, including potential over-treatment.
Double-Quencher Probes Improved the Detection Sensitivity of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) by One-Step RT-PCR
Authors: Hirotsu Yosuke , Mochizuki Hitoshi , Omata Masao 
Published: March 2020

AbstractBackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerges in Wuhan City, Hubei Province, spreads worldwide, and threats the human life. The detection of SARS-CoV-2 is important for the prevention of the outbreak and management of patients. Real-time reverse-transcription polymerase chain reaction (RT-PCR) assay detected the virus in clinical laboratory.MethodsThis study utilized primers and single-quencher probes in accordance with the Centers for Disease Control and Prevention (CDC) in the USA and the National Institute of Infectious Diseases (NIID) in Japan. Moreover, we designed the double-quencher probes (YCH assay) according to the oligonucleotide sequence established by NIID. Using these assays, we conducted a one-step real-time RT-PCR with serial DNA positive control to assess the detection sensitivity.ResultsThe threshold cycle (Ct) value of RT-PCR was relatively low in CDC and YCH assays compared to NIID assay. Serial dilution assay showed that both CDC and YCH assays could detect a low-copy number of DNA positive control. The background fluorescent signal at the baseline was lower in YCH than that of NIID.ConclusionDouble-quencher probes decreased background fluorescent signal and improved detection sensitivity of SARS-CoV-2.
Integrated Micropillar Polydimethylsiloxane Accurate CRISPR Detection (IMPACT) System for Rapid Viral DNA Sensing
Authors: Hass Kenneth N. , Bao Mengdi , He Qian , Park Myeongkee , Qin Peiwu , Du Ke 
Published: March 2020

ABSTRACTA fully Integrated Micropillar Polydimethylsiloxane Accurate CRISPR Detection (IMPACT) system is developed for viral DNA detection. This powerful system is patterned with high-aspect ratio micropillars to enhance reporter probe binding. After surface modification and probe immobilization, CRISPR Cas12a/crRNA complex is injected into the fully enclosed system. With the presence of double-stranded DNA target, the CRISPR enzyme is activated and non-specifically cleaves the ssDNA reporters initially immobilized on the micropillars. This collateral cleavage releases fluorescence dyes into the assay, and the intensity is linearly proportional to the target DNA concentration ranging from 0.1 to 10 nM. Importantly, this system does not rely on traditional dye-quencher labeled probe thus eliminating the fluorescence background presented in the assay. Furthermore, our one-step detection protocol is performed at isothermal conditions (37°C) without using complicated and time-consuming off-chip probe hybridization and denaturation. This miniaturized and fully packed IMPACT chip demonstrates rapid, sensitive, and simple nucleic acid detection and is an ideal candidate for the next generation molecular diagnostic platform for point-of-care (POC) applications, responding to emerging and deadly pathogen outbreaks.
SARS-CoV-2 specific antibody responses in COVID-19 patients
Authors: Okba Nisreen M.A. , Müller Marcel A. , Li Wentao , Wang Chunyan , GeurtsvanKessel Corine H. , Corman Victor M. , Lamers Mart M. , Sikkema Reina S. , de Bruin Erwin , Chandler Felicity D. , Yazdanpanah Yazdan , Le Hingrat Quentin , Descamps Diane , Houhou-Fidouh Nadhira , Reusken Chantal B. E. M. , Bosch Berend-Jan , Drosten Christian , Koopmans Marion P.G. , Haagmans Bart L. 
Published: March 2020

AbstractA new coronavirus, SARS-CoV-2, has recently emerged to cause a human pandemic. Whereas molecular diagnostic tests were rapidly developed, serologic assays are still lacking, yet urgently needed. Validated serologic assays are important for contact tracing, identifying the viral reservoir and epidemiological studies. Here, we developed serological assays for the detection of SARS-CoV-2 neutralizing, spike- and nucleocapsid-specific antibodies. Using serum samples from patients with PCR-confirmed infections of SARS-CoV-2, other coronaviruses, or other respiratory pathogenic infections, we validated and tested various antigens in different in-house and commercial ELISAs. We demonstrate that most PCR-confirmed SARS-CoV-2 infected individuals seroconverted, as revealed by sensitive and specific in-house ELISAs. We found that commercial S1 IgG or IgA ELISAs were of lower specificity while sensitivity varied between the two, with IgA showing higher sensitivity. Overall, the validated assays described here can be instrumental for the detection of SARS-CoV-2-specific antibodies for diagnostic, seroepidemiological and vaccine evaluation studies.
Incidence of Microbial Infections in English UK Biobank Participants: Comparison with the General Population
Authors: Hilton Bridget , Wilson Daniel , O’Connell Anne-Marie , Ironmonger Dean , Rudkin Justine K , Allen Naomi , Oliver Isabel , Wyllie David 
Published: March 2020

AbstractUnderstanding the genetic and environmental risk factors for serious bacterial infections in ageing populations remains incomplete. Utilising the UK Biobank (UKB), a prospective cohort study of 500,000 adults aged 40-69 years at recruitment (2006-2010), could help address this.We assess the feasibility of linking an England-wide dataset of microbiological isolations to UKB participants, to enable characterisation of microbial infections within the UKB Cohort. Microbiological infections occurring in patients in England, as recorded in the Public Health England Second Generation Surveillance System (SGSS), were linked to UKB participants using pseudonymised identifiers. By January 2015, ascertainment of laboratory reports from UKB participants by SGSS was estimated at 98%. 4.5% of English UKB participants had a positive microbiological isolate in 2015. Half of UKB isolates came from 12 laboratories, and 70% from 21 laboratories. Incidence rate ratios for microbial isolation, which is indicative of serious infection, from the UKB cohort relative to the comparably aged general population ranged from 0.6 to 1, compatible with the previously described healthy participant bias in UKB.Data on microbial isolations can be linked to UKB participants from January 2015 onwards. This linked data would offer new opportunities for research into infectious disease in older individuals.
Buprenorphine treatment of opioid dependence: analysis of individual patient data
Authors: Bergen Andrew W , Baurley James W , Ervin Carolyn M , McMahan Christopher S , Bible Joe , Stafford Randall S , Mudumbai Seshadri C , Saxon Andrew J 
Published: March 2020

AbstractBackgroundThe efficacy and safety of buprenorphine alone and in combination with naloxone for treatment of opioid dependence were evaluated in Federally-sponsored randomized clinical trials. Meta-analysis of pooled individual participant data provides an opportunity to identify multiple predictors of buprenorphine treatment outcome.MethodsWe selected six buprenorphine efficacy and safety trials from NIDA’s Data Share database for analysis. Treatment, sociodemographic, and drug use history variable domains were systematically harmonized and included in analysis. After exclusions, 3,022 participants randomized or enrolled in buprenorphine treatment for opioid dependence (mean (SD) age 36.1 (9.8) years, 33% female, 66% White, 16% Hispanic, 14% Black), were analyzed using a generalized linear mixed model with time-weighted treatment variables and participant covariates. We defined positive urinalysis or self-reported lapse as the primary outcome.ResultsFour treatment variables were significantly associated (p < 0.001) with lapse. Time-weighted dose and time-weighted adaptive dose had greater estimated effects than time-in-trial and time-weighted clinic visit. All treatment variables were novel predictors of lapse.ConclusionsIn a large cohort of trial participants treated with buprenorphine and behavioral counseling for opioid dependence, we identified and ranked four novel treatment factors reflecting components of buprenorphine dose, clinical provider engagement and patient engagement. Additional research to explore the effects of pharmacologic and non- pharmacologic treatment factors, and to explore relations with provider and patient factors will help our understanding of buprenorphine treatment outcomes. Continued analyses of publicly available data will extend discovery and support development of personalized opioid use disorder treatments.Highlights (3 to 5 bullet point max 85 characters each including spaces)Treatment and participant variables were harmonized in six buprenorphine trialsTime-weighted treatment variables were used in a random effects mixed model of lapseBuprenorphine dose and three clinical interactions were protective against lapseSupport of protective treatment factors may improve buprenorphine treatment success
Dynamic profile of severe or critical COVID-19 cases
Authors: Xu Yang 
Published: March 2020

AbstractIn December 2019, a cluster of acute respiratory illness, now known as SARS-CoV-2 pneumonia, occurred in Wuhan, China. World Health Organization (WHO) declared the rapidly spreading coronavirus outbreak a pandemic on March 11, 2020, acknowledging what has seemed clear for some time — the virus will likely spread to all countries on the globe. As of February 11, 2020, the Chinese Center for Disease Control and Prevention (China CDC) has officially reported that there are 2.0% (889) asymptomatic cases, 2.3% (1,023) death cases, and 80.9% mild cases among 44,672 confirmed cases. 51.4% (22,981) were male and 48.6% (21,691) were female. Lymphopenia, in particular T lymphopenia, was common among patients with SARS-COV-2 in the observation. A notable drop in CD4 and CD8 lymphocyte counts occurred early in the course of the syndrome and was associated with adverse outcomes. The appearing a phenomenon of lymphocyte depletion (PLD) suggested severe adverse outcomes. The outcome observed: 60% had discharged and 20% had die.
Facing small and biased data dilemma in drug discovery with federated learning
Authors: Xiong Zhaoping , Cheng Ziqiang , Xu Chi , Lin Xinyuan , Liu Xiaohong , Wang Dingyan , Luo Xiaomin , Zhang Yong , Qiao Nan , Zheng Mingyue , Jiang Hualiang 
Published: March 2020

AbstractArtificial intelligence (AI) models usually require large amounts of high-quality training data, which is in striking contrast to the situation of small and biased data faced by current drug discovery pipelines. The concept of federated learning has been proposed to utilize distributed data from different sources without leaking sensitive information of these data. This emerging decentralized machine learning paradigm is expected to dramatically improve the success of AI-powered drug discovery. We here simulate the federated learning process with 7 aqueous solubility datasets from different sources, among which there are overlapping molecules with high or low biases in the recorded values. Beyond the benefit of gaining more data, we also demonstrate federated training has a regularization effect making it superior than centralized training on the pooled datasets with high biases. Further, two more cases are studied to test the usability of federated learning in drug discovery. Our work demonstrates the application of federated learning in predicting drug related properties, but also highlights its promising role in addressing the small data and biased data dilemma in drug discovery.
Fidgetin-like 2 is a novel negative regulator of axonal growth and can be targeted to promote functional nerve regeneration after injury
Authors: Baker Lisa , Tar Moses , Villegas Guillermo , Charafeddine Rabab , Kramer Adam , Vafaeva Olga , Nacharaju Parimala , Friedman Joel , Davies Kelvin P. , Sharp David J. 
Published: March 2020

AbstractThe microtubule (MT) cytoskeleton plays a critical role in axon growth and guidance. Here, we identify the MT severing enzyme fidgetin-like 2 (FL2) as a negative regulator of axonal regeneration and a potential therapeutic target for promoting neural regeneration after injury. Genetic knockout of FL2 in cultured adult dorsal root ganglion (DRG) neurons resulted in longer axons and attenuated growth cone retraction in response to inhibitory molecules. Given the axonal growth-promoting effects of FL2 depletionin vitro, we tested whether the enzyme could be targeted to promote regeneration in a rodent model of peripheral nerve injury. In the model used in our experiments, the cavernous nerves (CN) are either crushed or transected, mimicking nerve injury caused by radical prostatectomy (RP). As with patients, CN injury results in erectile dysfunction, for which there are presently poor treatment options. At the time of injury, FL2-siRNA or control-siRNA was applied to the site using nanoparticles or chondroitin sulfate microgels as delivery agents. Treatment significantly enhanced functional nerve recovery, as determined by cavernosometry (measurements of corporal blood pressure in response to electrostimulation of the nerve). Remarkably, following complete bilateral nerve transection, visible and functional nerve regeneration was observed in 7 out of 8 animals treated with FL2-siRNA. In contrast, no control-siRNA treated animals showed regeneration. These observations suggest a novel therapeutic approach to treat peripheral nerve injury, particularly injuries resulting from surgical procedures such as RP, where treatments depleting FL2 could be applied locally at the time of injury.
Development of Project Risk Management framework based on Industry 4.0 technologies
Authors: Rane Santosh B. , Potdar Prathamesh Ramkrishana , Rane Suraj 
Published: March 2020

Purpose
The purpose of this paper is to identify the risks involved in the construction project based on a literature survey (LS), to develop a project risk management (PRM) framework based on Industry 4.0 technologies and to demonstrate the developed framework using Internet of Things (IoT) technology.

Design/methodology/approach
A comprehensive LS was carried out to know the different risks involved in the construction project and developed a PRM framework based on Industry 4.0 technologies to increase the effectiveness and efficiency of PRM. Heavy equipment and parameters were identified to demonstrate the developed framework based on IoT technology of Industry 4.0.

Findings
This paper demonstrates Industry 4.0 in the various stages of PRM. LS has identified 21 risks for a construction project. The demonstration of the PRM framework has identified the sudden breakdown of equipment and uncertainty of equipment as one of the critical risks associated with heavy equipment of construction project.

Research limitations/implications
The project complexity and features may add a few more risks in PRM.

Practical implications
The PRM framework based on Industry 4.0 technologies will increase the success rate of the project. It will enhance the efficiency and effectiveness of PRM.

Originality/value
The developed framework is helpful for the effective PRM of construction projects. The demonstration of PRM framework using IoT technology provides a logical way to manage risk involved in heavy equipment used in a construction project.
A closer look at determinants of organizational capability to innovate (OCI)
Authors: Montreuil Véra-Line , Lauzier Martin , Gagnon Stéphane 
Published: March 2020

PurposeThe purpose of this paper is to provide a portrait of the main managerial and organizational determinants of organizational capability to innovate (OCI). Despite its importance, research on the subject seems limited, and little attempt has been made, over the years, to offer an in-depth and simultaneous analysis of these particular determinants, as well as an exploration of the underlying and complex mechanisms explaining their relationships to OCI.Design/methodology/approachA systematic review of articles published between 1991 and 2018 was conducted in ProQuest (ABI/INFORM Collection) and Scopus databases. A total of 64 articles were selected and analysed through the use of a coding grid.FindingsResults highlight five key OCI determinants, namely: leadership, support, communication, culture, and learning. By using the dynamic capabilities theory (DCT) as a framework, this research suggests ways to better understand the dynamic action of these determinants as well as their contributions to OCI. Findings also suggest that OCI should be defined at the confluence of three perspectives (human, procedural and environmental aspects) to embrace the multiple facets of this complex construct. Proposals for future research are provided on how OCI can be better examined.Originality/valueThis research helps to understand the five core determinants through an integrated and holistic view and represents the first attempt to systematically analyse the scientific literature on OCI through the DCT lens.