bluuebunny/crossref_metadata_2025_split huggingface dataset:
A two-pronged approach for rapid and high-throughput SARS-CoV-2 nucleic acid testing
Authors: Gandotra Neeru , Tikhonova Irina , Cheemarla Nagarjuna R. , Knight James , Foxman Ellen , Giraldez Antonio , Shen Peidong , Bilguvar Kaya , Scharfe Curt 
Published: December 2020

AbstractImproved molecular screening and diagnostic tools are needed to substantially increase SARS-CoV-2 testing capacity and throughput while reducing the time to receive test results. Here we developed multiplex reverse transcriptase polymerase chain reaction (m-RT-PCR) for detection of SARS-CoV-2 using rapid DNA electrophoresis and alternatively using multiplex viral sequencing (mVseq). For RNA specimens extracted from nasopharyngeal (NP) swabs in viral transport media (VTM), our assays achieved a sensitivity for SARS-CoV-2 detection corresponding to cycle threshold (Ct) of 37.2 based on testing of these specimens using quantitative reverse transcription PCR (RT-qPCR). For NP swab-VTM specimens without prior RNA extraction, sensitivity was reduced to Ct of 31.6, which was due to lower concentration of SARS-CoV-2 genome copies in VTM compared to RNA-extracted samples. Assay turnaround time was 60 minutes using rapid gel electrophoresis, 90 minutes using Agilent Bioanalyzer, and 24-48 hours using Illumina sequencing, the latter of which required a second PCR to produce a sequence-ready library using m-RT-PCR products as the template. Our assays can be employed for high-throughput sequencing-based detection of SARS-CoV-2 directly from a clinical specimen without RNA isolation, while ease-of-use and low cost of the electrophoresis-based readout enables screening, particularly in resource-constrained settings.
Impact of intra-partum Azithromycin on carriage of group A streptococcus in The Gambia: a posthoc analysis of a double-blind randomized placebo-controlled trial
Authors: Jagne Isatou , Keeley Alexander J. , Bojang Abdoulie , Camara Bully , Jallow Edrissa , Senghore Elina , Oluwalana Claire , Bah Saikou Y. , Turner Claire E. , Sesay Abdul Karim , D’Alessandro Umberto , Bottomley Christian , de Silva Thushan I. , Roca Anna 
Published: December 2020

AbstractBackgroundGroup A Streptococcus (GAS) is a major human pathogen and an important cause of maternal and neonatal sepsis.MethodsWe performed a posthoc analysis of a double-blind, placebo-controlled randomized-trial (ratio 1:1) carried out in The Gambia to determine the impact of one oral dose (2g) of intra-partum azithromycin on maternal and neonatal GAS carriage. Breast milk, nasopharyngeal and vaginal swabs were collected at different time points during 4 weeks post-treatment. All samples were processed using conventional microbiology techniques. Whole genome sequencing (WGS) of GAS isolates was performed by Illumina MiSeq platform.ResultsWe randomized 829 mothers who delivered 843 babies. GAS carriage in mothers in the azithromycin arm was lower in breast milk (0.28% vs 2.48%, Prevalence Ratio (PR)=0.11, 95% CI 0.01-0.90) and the nasopharynx (0.28% vs 1.93%, PR=0.15, 95% CI 0.02-1.19), but not in the vaginal tract (1.99% vs 1.93%, PR=1.03, 95% CI 0.37-2.91). Among neonates, GAS carriage in the nasopharynx was slightly lower in the azithromycin arm (0.57% vs 1.91%, PR=0.30, 95% CI 0.06-1.42). Prevalence of azithromycin-resistant GAS was similar in both arms, except for a higher prevalence in the vaginal tract among women in the azithromycin arm (1.99% vs 0.28%, PR=7.24, 95% CI 0.87-56.92). WGS revealed ten of the 45 GAS isolates (22.2%) were Streptococcus dysgalactiae subspecies equisimilis expressing Lancefield group A carbohydrate (SDSE(A)). All SDSE(A) isolates were azithromycin-resistant, harbouring macrolide resistant genes msrD and mefA.ConclusionsOral intra-partum azithromycin reduced prevalence of GAS carriage among mothers and neonates. Azithromycin-resistant SDSE(A) carriage was observed among participants treated with azithromycin.Short SummaryGroup A streptococcus (GAS) is an important cause of sepsis. One oral dose (2g) of intra-partum azithromycin reduced maternal and neonatal GAS carriage. However, azithromycin-resistant Streptococcus dysgalactiae subspecies equisimilis expressing Lancefield group A carbohydrate was detected in women receiving azithromycin.
Lipid storm within the lungs of severe COVID-19 patients: Extensive levels of cyclooxygenase and lipoxygenase-derived inflammatory metabolites
Authors: Archambault Anne-Sophie , Zaid Younes , Rakotoarivelo Volatiana , Doré Étienne , Dubuc Isabelle , Martin Cyril , Amar Youssef , Cheikh Amine , Fares Hakima , El Hassani Amine , Tijani Youssef , Laviolette Michel , Boilard Éric , Flamand Louis , Flamand Nicolas 
Published: December 2020

ABSTRACTBACKGROUNDSevere Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) is the infectious agent responsible for Coronavirus disease 2019 (COVID-19). While SARS-CoV-2 infections are often benign, there are also severe COVID-19 cases, characterized by severe bilobar pneumonia that can decompensate to an acute respiratory distress syndrome, notably characterized by increased inflammation and a cytokine storm. While there is no cure against severe COVID-19 cases, some treatments significantly decrease the severity of the disease, notably aspirin and dexamethasone, which both directly or indirectly target the biosynthesis (and effects) of numerous bioactive lipids.OBJECTIVEOur working hypothesis was that severe COVID-19 cases necessitating mechanical ventilation were characterized by increased bioactive lipid levels modulating lung inflammation. We thus quantitated several lung bioactive lipids using liquid chromatography combined to tandem mass spectrometry.RESULTSWe performed an exhaustive assessment of the lipid content of bronchoalveolar lavages from 25 healthy controls and 33 COVID-19 patients necessitating mechanical ventilation. Severe COVID-19 patients were characterized by increased fatty acid levels as well as an accompanying inflammatory lipid storm. As such, most quantified bioactive lipids were heavily increased. There was a predominance of cyclooxygenase metabolites, notably TXB2>> PGE2∼ 12-HHTrE > PGD2. Leukotrienes were also increased, notably LTB4, 20-COOH-LTB4, LTE4, and eoxin E4. 15-lipoxygenase metabolites derived from linoleic, arachidonic, eicosapentaenoic and docosahexaenoic acids were also increased. Finally, yet importantly, specialized pro-resolving mediators, notably lipoxin A4and the D-series resolvins, were also found at important levels, underscoring that the lipid storm occurring in severe SARS-CoV-2 infections involves pro- and anti-inflammatory lipids.CONCLUSIONSOur data unmask the important lipid storm occurring in the lungs of patients afflicted with severe COVID-19. We discuss which clinically available drugs could be helpful at modulating the lipidome we observed in the hope of minimizing the deleterious effects of pro-inflammatory lipids and enhancing the effects of anti-inflammatory and/or pro-resolving lipids.
Evidence forGRNas part of a neuroinflammatory mechanism connecting common neurodegenerative diseases
Authors: Nalls Mike A. , Blauwendraat Cornelis , Sargent Lana , Vitale Dan , Leonard Hampton , Iwaki Hirotaka , Song Yeajin , Bandres-Ciga Sara , Menden Kevin , Faghri Faraz , Heutink Peter , Cookson Mark R. , Singleton Andrew B. 
Published: December 2020

SUMMARYBackgroundPrevious research using genome wide association studies (GWAS) has identified variants that may contribute to lifetime risk of multiple neurodegenerative diseases. However, whether there are common mechanisms that link neurodegenerative diseases is uncertain. Here, we focus on one gene,GRN, encoding progranulin, and the potential mechanistic interplay between genetic risk, gene expression in the brain and inflammation across multiple common neurodegenerative diseases.MethodsWe utilized GWAS, expression quantitative trait locus (eQTL) mapping and Bayesian colocalization analyses to evaluate potential causal and mechanistic inferences. We integrate various molecular data types from public resources to infer disease connectivity and shared mechanisms using a data driven process.FindingseQTL analyses combined with GWAS identified significant functional associations between increasing genetic risk in theGRNregion and decreased expression of the gene in Parkinson’s, Alzheimer’s and amyotrophic lateral sclerosis. Additionally, colocalization analyses show a connection between blood based inflammatory biomarkers relating to platelets andGRNexpression in the frontal cortex.InterpretationGRNexpression mediates neuroinflammation function related to general neurodegeneration. This analysis suggests shared mechanisms for Parkinson’s, Alzheimer’s and amyotrophic lateral sclerosis.FundingNational Institute on Aging, National Institute of Neurological Disorders and Stroke, and the Michael J. Fox Foundation.
Diet, physical activity and behavioural disinhibition in middle-aged and older adults: a UK Biobank study
Authors: Schweren Lizanne JS , van Rooij Daan , Shi Huiqing , Arias-Vasquez Alejandro , Li Lin , Larsson Henrik , Kvalvik Liv Grimstvedt , Haavik Jan , Buitelaar Jan , Hartman Catharina A 
Published: December 2020

AbstractBackground and aimsBehavioural disinhibition is a prominent feature of multiple psychiatric disorders, and has been associated with poor long-term somatic health outcomes. Modifiable lifestyle factors including diet and moderate-to-vigorous physical activity (MVPA) may be associated with behavioural disinhibition, but their shared and unique contributions have not previously been quantified.MethodsN=157,354 UK Biobank participants who completed the online mental health assessment were included (age 40-69, 2006-2010). Using principal component analyses, we extracted a single disinhibition score and four dietary component scores (prudent diet, elimination of wheat/dairy/eggs, meat consumption, full-cream dairy consumption). In addition, latent profile analysis assigned participants to one of five empirical dietary groups: moderate-healthy, unhealthy, restricted, meat-avoiding, low-fat dairy. Participants self-reported MVPA in minutes/week. Disinhibition was regressed on the four dietary components, the dietary grouping variable and MVPA.Resultsin men and women, behavioural disinhibition was negatively associated with prudent diet scores, and positively associated with wheat/dairy/eggs elimination. In men only, disinhibition was associated with consumption of meat and full-cream dairy products. Comparing groups, disinhibition was lower in the moderate-and-prudent diet (reference) group compared to all other groups. Absolute βs ranged from 0.02-0.13 indicating very weak effects. Disinhibition was not associated with MVPA.ConclusionsAmong middle-aged and older adults, behavioural disinhibition is associated with multiple features of diet. While the observational nature of UK Biobank does not allow causal inference, our findings foster specific hypotheses (e.g. early malnutrition, elevated immune-response, dietary restraint) to be tested in alternative study designs.
How to predict relapse in leukemia using time series data: A comparative in silico study
Authors: Hoffmann Helene , Baldow Christoph , Zerjatke Thomas , Gottschalk Andrea , Wagner Sebastian , Karg Elena , Niehaus Sebastian , Roeder Ingo , Glauche Ingmar , Scherf Nico 
Published: December 2020

AbstractRisk stratification and treatment decisions for leukemia patients are regularly based on clinical markers determined at diagnosis, while measurements on system dynamics are often neglected. However, there is increasing evidence that linking quantitative time-course information to disease outcomes can improve the predictions for patient-specific treatment responses.We designed a synthetic experiment to compare different computational methods with respect to their ability to accurately predict relapse for chronic and acute myeloid leukemia treatment. Technically, we used clinical reference data to first fit a model and then generate de novo model simulations of individual patients’ time courses for which we can systematically tune data quality (i.e. measurement error) and quantity (i.e. number of measurements). Based hereon, we compared the prediction accuracy of three different computational methods, namely mechanistic models, generalized linear models, and deep neural networks that have been fitted to the reference data.Our results show that data quality has a higher impact on prediction accuracy than the specific choice of the particular method. We further show that adapted treatment and measurement schemes can considerably improve the prediction accuracy.Our proof-of-principle study highlights how computational methods and optimized data acquisition strategies can improve risk assessment and treatment of leukemia patients.
Use of Public Data to Describe COVID-19 Contact Tracing in China during January 20–February 29, 2020
Authors: Dirlikov Emilio , Zhou Suizan , Han Lifeng , Li Zhijun , Hao Ling , Millman Alexander J. , Marston Barbara 
Published: December 2020

AbstractObjectiveAlthough contact tracing is generally not used to control influenza pandemics, China and several countries in the Western Pacific Region employed contact tracing as part of COVID-19 response activities. To improve understanding on the use of contact tracing for COVID-19 emergency public health response activities, we describe reported COVID-19 contacts traced and quarantined in China and a proxy for number of reported contacts traced per reported case.MethodsWe abstracted publicly available online aggregate data reported from China’s National Health Commission and provincial health commissions’ COVID-19 daily situational reports for January 20–February 29, 2020. The number of new contacts traced by report date was computed as the difference between total contacts traced on consecutive reports. A proxy for the number of contacts traced per case was computed as the number of new contacts traced divided by the number of new cases.ResultsDuring January 20–February 29, 2020, China reported 80,968 new COVID-19 cases (Hubei Province = 67,608 [83%]), and 659,899 contacts traced (Hubei Province = 265,617 [40%]). Non-Hubei provinces reported more contacts traced per case than Hubei Province; this difference increased over time.DiscussionAlong with other NPI used in China, contact tracing likely contributed to reducing SARS-CoV-2 transmission by quarantining a large number of potentially infected contacts. Despite reporting only 15% of total cases, non-Hubei provinces had 1.5 times more reported contacts traced compared to Hubei Province. Contract tracing may have been more complete in areas and periods with lower case counts.
Multifaceted strategies for the control of COVID-19 outbreaks in long-term care facilities in Ontario, Canada
Authors: Vilches Thomas N. , Nourbakhsh Shokoofeh , Zhang Kevin , Juden-Kelly Lyndon , Cipriano Lauren E. , Langley Joanne M. , Sah Pratha , Galvani Alison P. , Moghadas Seyed M. 
Published: December 2020

AbstractThe novel coronavirus disease 2019 (COVID-19) has caused severe outbreaks in Canadian long-term care facilities (LTCFs). In Canada, over 80% of COVID-19 deaths during the first pandemic wave occurred in LTCFs. We sought to evaluate the effect of mitigation measures in LTCFs including frequent testing of staff, and vaccination of staff and residents. We developed an agent-based transmission model and parameterized it with disease-specific estimates, temporal sensitivity of nasopharyngeal and saliva testing, results of vaccine efficacy trials, and data from initial COVID-19 outbreaks in LTCFs in Ontario, Canada. Characteristics of staff and residents, including contact patterns, were integrated into the model with age-dependent risk of hospitalization and death. Estimates of infection and outcomes were obtained and 95% credible intervals were generated using a bias-corrected and accelerated bootstrap method. Weekly routine testing of staff with 2-day turnaround time reduced infections among residents by at least 25.9% (95% CrI: 23.3% - 28.3%), compared to baseline measures of mask-wearing, symptom screening, and staff cohorting alone. A similar reduction of hospitalizations and deaths was achieved in residents. Vaccination averted 2-4 times more infections in both staff and residents as compared to routine testing, and markedly reduced hospitalizations and deaths among residents by 95.9% (95% CrI: 95.4% - 96.3%) and 95.8% (95% CrI: 95.5% - 96.1%), respectively, over 200 days from the start of vaccination. Vaccination could have a substantial impact on mitigating disease burden among residents, but may not eliminate the need for other measures before population-level control of COVID-19 is achieved.
Active Neural Networks to Detect Mentions of Changes to Medication Treatment in Social Media
Authors: Weissenbacher Davy , Ge Suyu , Klein Ari , O’Connor Karen , Gross Robert , Hennessy Sean , Gonzalez-Hernandez Graciela 
Published: December 2020

AbstractObjectiveWe address a first step towards using social media data to supplement current efforts in monitoring population-level medication non-adherence: detecting changes to medication treatment. Medication treatment changes, like changes to dosage or to frequency of intake, that are not overseen by a physician are, by that, non-adherence to medication. Despite the consequences, including worsening health conditions or death, 50% of patients are estimated to not take medications as indicated. Current methods to identify non-adherence have major limitations. Direct observation may be intrusive or expensive, and indirect observation through patient surveys relies heavily on patients’ memory and candor. Using social media data in these studies may address these limitations.MethodsWe annotated 9,835 tweets mentioning medications and trained a convolutional neural network (CNN) to find mentions of medication treatment changes, regardless of whether the change was recommended by a physician. We used active and transfer learning from 12,972 reviews we annotated from WebMD to address the class imbalance of our Twitter corpus. To validate our CNN and explore future directions, we annotated 1,956 positive tweets as to whether they reflect non-adherence and categorized the reasons given.ResultsOur CNN achieved state-of-the-art performance with 0.50 F1-score. The manual analysis of positive tweets revealed that non-adherence is evident in a subset with nine categories of reasons for non-adherence.ConclusionWe showed that social media users publicly discuss medication treatment changes and may explain their reasons including when it constitutes non-adherence. This approach may be useful to supplement current efforts in adherence monitoring.
MeFSAT: A curated natural product database specific to secondary metabolites of medicinal fungi
Authors: Vivek-Ananth R.P. , Sahoo Ajaya Kumar , Kumaravel Kavyaa , Mohanraj Karthikeyan , Samal Areejit 
Published: December 2020

AbstractFungi are a rich source of secondary metabolites which constitutes a valuable and diverse chemical space of natural products. Medicinal fungi have been used in traditional medicine to treat human ailments for centuries. To date, there is no devoted resource on secondary metabolites and therapeutic uses of medicinal fungi. Such a dedicated resource compiling dispersed information on medicinal fungi across published literature will facilitate ongoing efforts towards natural product based drug discovery. Here, we present the first comprehensive manually curated database onMedicinalFungiSecondary metabolitesAndTherapeutics (MeFSAT) that compiles information on 184 medicinal fungi, 1830 secondary metabolites and 149 therapeutics uses. Importantly, MeFSAT contains a non-redundantin siliconatural product library of 1830 secondary metabolites along with information on their chemical structures, computed physicochemical properties, drug-likeness properties, predicted ADMET properties, molecular descriptors and predicted human target proteins. By comparing the physicochemical properties of secondary metabolites in MeFSAT with other small molecules collections, we find that fungal secondary metabolites have high stereochemical complexity and shape complexity similar to other natural product libraries. Based on multiple scoring schemes, we have filtered a subset of 228 drug-like secondary metabolites in MeFSAT database. By constructing and analyzing chemical similarity networks, we show that the chemical space of secondary metabolites in MeFSAT is highly diverse. The compiled information in MeFSAT database is openly accessible at:https://cb.imsc.res.in/mefsat/.
Selectively caring for the most severe COVID-19 patients delays ICU bed shortages more than increasing hospital capacity
Authors: Roberts Miles , Seymour Helena Duplechin ,   Faculty Advisor, Dimitrov Alexander 
Published: December 2020

1AbstractSARS-CoV-2, the virus responsible for COVID-19, has killed hundreds of thousands of Americans. Although physical distancing measures played a key role in slowing COVID-19 spread in early 2020, infection rates are now peaking at record levels across the country. Hospitals in several states are threatened with overwhelming numbers of patients, compounding the death toll of COVID-19. Implementing strategies to minimize COVID-19 hospitalizations will be key to controlling the toll of the disease, but non-physical distancing strategies receive relatively little attention. We present a novel system of differential equations designed to predict the relative effects of hospitalizing fewer COVID-19 patients vs increasing ICU bed availability on delaying ICU bed shortages. This model, which we call SEAHIRD, was calibrated to mortality data on two US states with different peak infection times from mid-March – mid-May 2020. It found that hospitalizing fewer COVID-19 patients generally delays ICU bed shortage more than a comparable increase in ICU bed availability. This trend was consistent across both states and across wide ranges of initial conditions and parameter values. We argue that being able to predict which patients will develop severe COVID-19 symptoms, and thus require hospitalization, should be a key objective of future COVID-19 research, as it will allow limited hospital resources to be allocated to individuals that need them most and prevent hospitals from being overwhelmed by COVID-19 cases.