bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of a Video-based Evidence Synthesis Knowledge Translation Resource: Applying a User-Centred Approach
Authors: Deliv Cristian , Putnam El , Devane Declan , Healy Patricia , Hall Amanda , Rosenbaum Sarah , Toomey Elaine 
Published: March 2021

AbstractBackgroundPeople of all ages and walks of life are bombarded with health claims from an array of sources. An understanding of evidence synthesis is important for people to make truly informed healthcare decisions. There is an increasing focus on the use of knowledge translation resources within healthcare; however, the development of these resources has often been poorly described or studied.ObjectivesThis study employs a user-centred approach to develop a video animation resource to explain the purpose, use and importance of evidence synthesis to the general public regarding healthcare decision-making.MethodsWe employed a user-centred approach to developing a spoken animated video that could explain evidence synthesis to a public audience, conducting several cycles of idea generation, prototyping, user-testing, analysis and refinement. Six researchers with expertise in evidence synthesis and knowledge translation resource development gave input on the key messages of the video animation and informed the first draft of the storyboard and script. Seven members of the public provided feedback on this draft through Think-aloud interviews, which we used to develop a video animation prototype. Seven additional members of the public participated in Think-aloud interviews while watching the video prototype. In addition to interviews, participants completed a questionnaire that collected data on perceived usefulness, desirability, clarity and credibility. One experienced patient and public involvement (PPI) advocate also provided feedback on the script and prototype. At the end of each feedback cycle, we assimilated all data and made necessary changes, resulting in a final, rendered version of the animation video.ResultsResearchers identified the initial key messages for the SAV as 1) the importance of evidence synthesis, 2) what an evidence synthesis is and 3) how evidence synthesis can impact healthcare decision-making. Using guidance and feedback from members of the public, we produced a three-and-a-half-minute video animation that members of the public rated 9/10 for usefulness, 8/10 for desirability, 8/10 for clarity and 9/10 for credibility. The video was uploaded on YouTube (https://www.youtube.com/watch?v=nZR0xQmZVQg) and has been viewed over 5500 times to date.ConclusionsEmploying a user-centred approach, we developed a video animation knowledge translation resource to explain evidence synthesis to the general public that was assessed as useful, desirable and clear by its intended target audience. This study describes the structured and systematic development of this knowledge translation resource and how key stakeholders and end-users informed the final output.
Comparing the efficacy of anti□infectious drugs for the treatment of mild to severe COVID-19 patients: a protocol for a systematic review and network meta-analysis of randomized clinical trials
Authors: Debela Dejene Tolossa , Heraro Kidist Digamo 
Published: March 2021

ABSTRACTBackgroundCOVID-19 is a viral infection spreading at a great speed and has quickly caused an extensive burden to individuals, families, countries, and the world. No intervention has yet been proven highly effective for the treatment of COVID-19. Different drugs were being evaluated and reported through randomized clinical trials, and more are currently under trial. This review aimed to compare the efficacy of anti-infectious drugs with a comparator of the standard of care or placebo in patients with COVID-19.Methods and analysisTwo independent review authors will extract data and assess a risk of bias using RoB2. Randomized controlled trials (RCT) that evaluate single and/or combined antiviral drugs recommended by WHO latest guideline for the treatment of COVID-19 will be included. We will search for Pub Med, the Cochrane Center for Clinical Trial database (CENTRAL), clinicaltrials.gov, etc. databases for articles published in the English language between December 2019 to April 2021. We will follow the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) involving Network Meta-analysis guidelines for the design and reporting of the results. The primary endpoints will be time to clinical recovery and time to RNA negativity. The certainty of evidence will be evaluated using the GRADE extension of NMA. Data analysis will be performed using the frequentist NMA approach with netmeta package implemented in R.Ethics and disseminationThere are no ethical considerations associated with this study as we will use publicly available data from previously published studies. We plan to publish results in open access peer-reviewed journals.PROSPERO registration numberID=CRD42021230919.Strengths and limitations of this studyThis will be the first systematic review and network meta-analysis to assess the efficacy specific to anti-infectious drugs category for for mild to severe patients of COVID-19.Its compliance with the Preferred Reporting Items for Systematic Review and Meta-Analysis for Protocols (PRISMA-P) involving network meta-analysis(NMA) will ensure the quality of reporting.Doing both pairwise meta-analysis and network meta-analysis (NMA) can comprehensively analyse direct and indirect comparison results of different anti-infectious drugs for COVID 19 will give more reliable conclusions aswell as the rank of those drugs.There is risk of heterogeneity and inconsistency, given the different anti-infectious drugs that will be included; however, we try to control intransitivity by carefully identifying the eligibility criteria depending on PICOS strategy and assess inconsistency using local as well as global approaches.The limitation of this study is it will not explore the economic benefits of these drugs.
Within-country age-based prioritisation, global allocation, and public health impact of a vaccine against SARS-CoV-2: a mathematical modelling analysis
Authors: Hogan Alexandra B , Winskill Peter , Watson Oliver J , Walker Patrick G T , Whittaker Charles , Baguelin Marc , Brazeau Nicholas F , Charles Giovanni D , Gaythorpe Katy A M , Hamlet Arran , Knock Edward , Laydon Daniel J , Lees John A , Løchen Alessandra , Verity Robert , Whittles Lilith K , Muhib Farzana , Hauck Katharina , Ferguson Neil M , Ghani Azra C 
Published: March 2021

AbstractThe worldwide endeavour to develop safe and effective COVID-19 vaccines has been extraordinary, and vaccination is now underway in many countries. However, the doses available in 2021 are likely to be limited. We extended a mathematical model of SARS-CoV-2 transmission across different country settings to evaluate the public health impact of potential vaccines using WHO-developed target product profiles. We identified optimal vaccine allocation strategies within- and between-countries to maximise averted deaths under constraints on dose supply. We found that the health impact of SARS-CoV-2 vaccination depends on the cumulative population-level infection incidence when vaccination begins, the duration of natural immunity, the trajectory of the epidemic prior to vaccination, and the level of healthcare available to effectively treat those with disease. Within a country we find that for a limited supply (doses for <20% of the population) the optimal strategy is to target the elderly. However, with a larger supply, if vaccination can occur while other interventions are maintained, the optimal strategy switches to targeting key transmitters to indirectly protect the vulnerable. As supply increases, vaccines that reduce or block infection have a greater impact than those that prevent disease alone due to the indirect protection provided to high-risk groups. Given a 2 billion global dose supply in 2021, we find that a strategy in which doses are allocated to countries proportional to population size is close to optimal in averting deaths and aligns with the ethical principles agreed in pandemic preparedness planning.HighlightsThe global dose supply of COVID-19 vaccines will be constrained in 2021Within a country, prioritising doses to protect those at highest mortality risk is efficientFor a 2 billion dose supply in 2021, allocating to countries according to population size is efficient and equitable
Novel blood test for early biomarkers of preeclampsia and Alzheimer’s disease
Authors: Cheng Shibin , Banerjee Sayani , Daiello Lori A. , Nakashima Akitoshi , Jash Sukanta , Huang Zheping , Drake Jonathan D. , Ernerudh Jan , Berg Goran , Padbury James , Saito Shigeru , Ott Brian R. , Sharma Surendra 
Published: March 2021

AbstractNon-invasive and sensitive blood test has long been a goal for early stage disease diagnosis and treatment for Alzheimer’s disease (AD) and other proteinopathy diseases. However, a blood test based on a mechanistic link to pathologic protein aggregate complexes has not been yet elucidated. We previously reported that preeclampsia (PE), a severe pregnancy complication, is another proteinopathy disorder with impaired autophagy. We hypothesized that induced autophagy deficiency would promote accumulation of pathologic protein aggregates. Here, we describe a novel, sensitive assay that detects serum protein aggregates from patients with PE as well as AD in both dementia and prodromal mild cognitive impairment (MCI) stages. The assay employs exposure of genetically engineered, autophagy-deficient human trophoblasts (ADTs) to serum from patients. The aggregated protein complexes and their individual components, including transthyretin, amyloid β-42, α-synuclein, and phosphorylated tau231, can be detected and quantified by co-staining with ProteoStat, a rotor dye with affinity to aggregated proteins, and respective antibodies. Autophagy-proficient human trophoblasts failed to accumulate serum protein aggregates under similar culture conditions. Detection of protein aggregates in ADTs was not dependent on transcriptional upregulation of these biomarkers. The ROC curve analysis validated the robustness of the assay for its specificity and sensitivity. In conclusion, we have developed a novel noninvasive diagnostic and predictive assay for AD, MCI and PE.
Effect of information about COVID-19 vaccine effectiveness and side effects on behavioural intentions: two online experiments
Authors: Kerr John R. , Freeman Alexandra L. J. , Marteau Theresa M. , van der Linden Sander 
Published: March 2021

AbstractThe success of mass COVID-19 vaccination campaigns rests on widespread uptake. However, although vaccinations provide good protection, they do not offer full immunity and while they likely reduce transmission of the virus to others, the extent of this remains uncertain. This produces a dilemma for communicators who wish to be transparent about benefits and harms and encourage continued caution in vaccinated individuals but not undermine confidence in an important public health measure. In two large pre-registered experimental studies on quota-sampled UK public participants we investigate the effects of providing transparent communication—including uncertainty—about vaccination effectiveness on decision-making. In Study 1 (n= 2,097) we report that detailed information about COVID-19 vaccines, including results of clinical trials, does not have a significant impact on beliefs about the efficacy of such vaccines, concerns over side effects, or intentions to receive a vaccine. Study 2 (n= 2,217) addressed concerns that highlighting the need to maintain protective behaviours (e.g. social distancing) post-vaccination may lower perceptions of vaccine efficacy and willingness to receive a vaccine. We do not find evidence of this: transparent messages did not significantly reduce perceptions of vaccine efficacy, and in some cases increased perceptions of efficacy. We again report no main effect of messages on intentions to receive a vaccine. The results of both studies suggest that transparently informing people of the limitations of vaccinations does not reduce intentions to be vaccinated but neither does it increase intentions to engage in protective behaviours post-vaccination.
SARS-CoV-2 variants of concern are associated with lower RT-PCR amplification cycles between January and March 2021 in France
Authors: Roquebert Benedicte , Haim-Boukobza Stéphanie , Trombert-Paolantoni Sabine , Lecorche Emmanuel , Verdurme Laura , Foulongne Vincent , Burrel Sonia , Alizon Samuel , Sofonea Mircea T. 
Published: March 2021

AbstractSARS-CoV-2 variants raise concern regarding the mortality caused by COVID-19 epidemics. We analyse 88,375 cycle amplification (Ct) values from variant-specific RT-PCR tests performed between January 26 and March 13, 2021. We estimate that on March 12, nearly 85% of the infections were caused by the V1 variant and that its transmission advantage over wild type strains was between 38 and 44%. We also find that tests positive for V1 and V2/V3 variants exhibit significantly lower cycle threshold (Ct) values.
Collaborative Cohort of Cohorts for COVID-19 Research (C4R) Study: Study Design
Authors: Oelsner Elizabeth C , Allen Norrina Bai , Ali Tauqeer , Anugu Pramod , Andrews Howard , Asaro Alyssa , Balte Pallavi P , Barr R Graham , Bertoni Alain G , Bon Jessica , Boyle Rebekah , Chang Arunee A , Chen Grace , Cole Shelley A , Coresh Josef , Cornell Elaine , Correa Adolfo , Couper David , Cushman Mary , Demmer Ryan T , Elkind Mitchell S. V. , Folsom Aaron R , Fretts Amanda M , Gabriel Kelley Pettee , Gallo Linda , Gutierrez Jose , Han MeiLan K. , Henderson Joel M , Howard Virginia J , Isasi Carmen R , Jacobs David R , Judd Suzanne E , Mukaz Debora Kamin , Kanaya Alka M , Kandula Namratha R , Kaplan Robert , Krishnaswamy Akshaya , Kinney Gregory L , Kucharska-Newton Anna , Lee Joyce S. , Lewis Cora E , Levine Deborah A. , Levitan Emily B. , Levy Bruce , Make Barry , Malloy Kimberly , Manly Jennifer J , Meyer Katie A , Min Yuan-I , Moll Matthew , Moore Wendy C. , Mauger Dave , Ortega Victor E. , Palta Priya , Parker Monica M , Phipatanakul Wanda , Post Wendy , Psaty Bruce M , Regan Elizabeth A , Ring Kimberly , Roger Véronique L. , Rotter Jerome I , Rundek Tatjana , Sacco Ralph L. , Schembri Michael , Schwartz David A. , Seshadri Sudha , Shikany James M , Sims Mario , Hinckley Stukovsky Karen D , Talavera Gregory A , Tracy Russell P , Umans Jason G , Vasan Ramachandran S , Watson Karol , Wenzel Sally E. , Winters Karen , Woodruff Prescott G. , Xanthakis Vanessa , Zhang Ying , Zhang Yiyi ,   For the C4R Investigators
Published: March 2021

AbstractThe Collaborative Cohort of Cohorts for COVID-19 Research (C4R) is a national prospective study of adults at risk for coronavirus disease 2019 (COVID-19) comprising 14 established United States (US) prospective cohort studies. For decades, C4R cohorts have collected extensive data on clinical and subclinical diseases and their risk factors, including behavior, cognition, biomarkers, and social determinants of health. C4R will link this pre-COVID phenotyping to information on SARS-CoV-2 infection and acute and post-acute COVID-related illness. C4R is largely population-based, has an age range of 18-108 years, and broadly reflects the racial, ethnic, socioeconomic, and geographic diversity of the US. C4R is ascertaining severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19 illness using standardized questionnaires, ascertainment of COVID-related hospitalizations and deaths, and a SARS-CoV-2 serosurvey via dried blood spots. Master protocols leverage existing robust retention rates for telephone and in-person examinations, and high-quality events surveillance. Extensive pre-pandemic data minimize referral, survival, and recall bias. Data are being harmonized with research-quality phenotyping unmatched by clinical and survey-based studies; these will be pooled and shared widely to expedite collaboration and scientific findings. This unique resource will allow evaluation of risk and resilience factors for COVID-19 severity and outcomes, including post-acute sequelae, and assessment of the social and behavioral impact of the pandemic on long-term trajectories of health and aging.
Validation of a NGS panel, with automated analysis, designed for detection of medically actionable tumor biomarkers for Latin America
Authors: Salvo Mauricio , González-Feliú Evelin , Toro Jessica , Gallegos Iván , Maureira Ignacio , González Nicolás Miranda , Barajas Olga , Bustamante Eva , Ahumada Mónica , Colombo Alicia , Armisén Ricardo , Villamán Camilo , Ibañez Carolina , Loreto Bravo María , Sanhueza Verónica , Spencer Loreto , Toro Gonzalo de , Morales Erik , Bizama Carolina , García Patricia , María Carrasco Ana , Gutiérrez Lorena , Lorenzo-Bermejo Justo , Verdugo Ricardo A. , Marcelain Katherine 
Published: March 2021

AbstractThe genomic characterization of solid tumors and a rapidly growing repertoire of target drugs are revolutionizing cancer treatment. Next-generation sequencing (NGS) panels are progressively used in clinical practice for target therapy in high-income countries. In contrast, limited access to tumor sequencing, among other barriers, precludes precision cancer treatment in low- and middle-income countries. To build towards the implementation of precision oncology in Chile and Latin America, we designed a 25-gene panel that contains predictive biomarkers for currently or near-future available therapies in Latin America. Library preparation was optimized to account for DNA integrity variability in Formalin-Fixed Paraffin-Embedded (FFPE) tissue. The bioinformatic pipeline removes FFPE-induced artifacts and known germline variants; while identifying possible discrepancies in somatic mutations due to Latin Americans’ underrepresentation in the reference genome databases. Analytic sensitivity and accuracy were assessed using commercial standard controls for FFPE DNA and for germline BRCA1 and BRCA2 mutations, which are biomarkers for PARP inhibitors. Our panel detects small insertions and deletions and single nucleotide variants (SNVs) with 100% sensitivity and specificity down to allelic frequencies of 0.05, and with 100% between-run and within-run reproducibility for non-synonymous variants. The workflow was validated in 265 clinical samples, including breast, colorectal, gastric, ovarian, and gallbladder tumors and blood, leading to identifying 131 actionable variants. Therefore, this NGS panel constitutes an accurate and sensitive method for routine tumor biopsies that could replace multiple non-NGS assays and costly large NGS panels in the Latin American clinical context. The proposed streamlined assay and automated analysis are expected to facilitate the implementation of precision medicine in Latin America.
Heterogeneous immunological recovery trajectories revealed in post-acute COVID-19
Authors: Su Yapeng , Yuan Dan , Chen Daniel G. , Wang Kai , Choi Jongchan , Dai Chengzhen L. , Hong Sunga , Zhang Rongyu , Xie Jingyi , Li Sarah , Scherler Kelsey , Pavlovitch-Bedzyk Ana Jimena , Dong Shen , Lausted Christopher , Ng Rachel H. , Lee Inyoul , Fallen Shannon , Kornilov Sergey A. , Baloni Priyanka , Duvvuri Venkata R. , Anderson Kristin G. , Li Jing , Yang Fan , Rostomily Clifford , Troisch Pamela , Smith Brett , Zhou Jing , Mackay Sean , Murray Kim , Edmark Rick , Jones Lesley , Zhou Yong , Rowen Lee , Liu Rachel , Chour William , Berrington William R. , Wallick Julie A , Algren Heather A ,   the ISB-Swedish COVID19 Biobanking Unit, Wrin Terri , Petropoulos Christos J. , Wei Wei , Price Nathan D. , Subramanian Naeha , Hadlock Jennifer , Magis Andrew T. , Ribas Antoni , Lanier Lewis L. , Boyd Scott D. , Bluestone Jeffrey A. , Hood Leroy , Gottardo Raphael , Greenberg Philip D. , Davis Mark M. , Goldman Jason D. , Heath James R. 
Published: March 2021

AbstractThe immunological picture of how different patients recover from COVID-19, and how those recovery trajectories are influenced by infection severity, remain unclear. We investigated 140 COVID-19 patients from diagnosis to convalescence using clinical data, viral load assessments, and multi-omic analyses of blood plasma and circulating immune cells. Immune-phenotype dynamics resolved four recovery trajectories. One trajectory signals a return to pre-infection healthy baseline, while the other three are characterized by differing fractions of persistent cytotoxic and proliferative T cells, distinct B cell maturation processes, and memory-like innate immunity. We resolve a small panel of plasma proteins that, when measured at diagnosis, can predict patient survival and recovery-trajectory commitment. Our study offers novel insights into post-acute immunological outcomes of COVID-19 that likely influence long-term adverse sequelae.
Combined computational and cellular screening identifies synergistic inhibition of SARS-CoV-2 by lenvatinib and remdesivir
Authors: Pohl Marie O. , Busnadiego Idoia , Marrafino Francesco , Wiedmer Lars , Hunziker Annika , Fernbach Sonja , Glas Irina , Moroz-Omori Elena V. , Hale Benjamin G. , Caflisch Amedeo , Stertz Silke 
Published: March 2021

ABSTRACTRapid repurposing of existing drugs as new therapeutics for COVID-19 has been an important strategy in the management of disease severity during the ongoing SARS-CoV-2 pandemic. Here, we used high-throughput docking to screen 6000 compounds within the DrugBank library for their potential to bind and inhibit the SARS-CoV-2 3CL main protease, a chymotrypsin-like enzyme that is essential for viral replication. For 19 candidate hits, parallelin vitrofluorescence-based protease-inhibition assays and Vero-CCL81 cell-based SARS-CoV-2 replication-inhibition assays were performed. One hit, diclazuril (an investigational anti-protozoal compound), was validated as a SARS-CoV-2 3CL main protease inhibitorin vitro(IC50 value of 29 µM) and modestly inhibited SARS-CoV-2 replication in Vero-CCL81 cells. Another hit, lenvatinib (approved for use in humans as an anti-cancer treatment), could not be validated as a SARS-CoV-2 3CL main protease inhibitorin vitro, but serendipitously exhibited a striking functional synergy with the approved nucleoside analogue remdesivir to inhibit SARS-CoV-2 replication, albeit this was specific to Vero-CCL81 cells. Lenvatinib is a broadly-acting host receptor tyrosine kinase (RTK) inhibitor, but the synergistic effect with remdesivir was not observed with other approved RTK inhibitors (such as pazopanib or sunitinib), suggesting that the mechanism-of-action is independent of host RTKs. Furthermore, time-of-addition studies revealed that lenvatinib/remdesivir synergy probably targets SARS-CoV-2 replication subsequent to host-cell entry. Our work shows that combining computational and cellular screening is a means to identify existing drugs with repurposing potential as antiviral compounds. Future studies could be aimed at understanding and optimizing the lenvatinib/remdesivir synergistic mechanism as a therapeutic option.