bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vivo single-particle tracking of the aquaporin AtPIP2;1 in stomata reveals cell type-specific dynamics
Authors: Cui Yaning , Zhao Yanxia , Lu Yuqing , Su Xiao , Chen Yingying , Shen Yingbai , Lin Jinxing , Li Xiaojuan 
Published: January 2021

Abstract
Aquaporins such as the plasma membrane intrinsic proteins (PIPs) allow water to move through cell membranes and are vital for stomatal movement in plants. Despite their importance, the dynamic changes in aquaporins during water efflux and influx have not been directly observed in real time in vivo. Here, to determine which factors regulate these changes during the bidirectional translocation of water, we examined aquaporin dynamics during the stomatal immune response to the bacterial flagellin-derived peptide flg22. The Arabidopsis (Arabidopsis thaliana) aquaporin mutant pip2;1 showed defects in the flg22-induced stomatal response. Variable-angle total internal reflection fluorescence microscopy revealed that the movement dynamics and dwell times of AQ6]GFP-AtPIP2;1 in guard cells and subsidiary cells exhibited cell type-specific dependencies on flg22. The cytoskeleton, rather than the cell wall, was the major factor regulating AtPIP2;1 dynamics, although both the cytoskeleton and cell wall might form bounded domains that restrict the diffusion of AtPIP2;1 in guard cells and subsidiary cells. Finally, our analysis revealed the different roles of cortical actin and microtubules in regulating AtPIP2;1 dynamics in guard cells, as well as subsidiary cells, under various conditions. Our observations shed light on the heterogeneous mechanisms that regulate membrane protein dynamics in plants in response to pathogens.
Multi-omic Evaluation of Metabolic Alterations in Multiple Sclerosis Identifies Shifts in Aromatic Amino Acid Metabolism
Authors: Fitzgerald Kathryn C. , Smith Matthew D. , Sotirchos Elias S. , Kornberg Michael D. , Douglas Morgan , Nourbakhsh Bardia , Graves Jennifer , Rattan Ramandeep , Poisson Laila , Cerghet Mirela , Mowry Ellen M. , Waubant Emmanuelle , Giri Shailendra , Calabresi Peter A. , Bhargava Pavan 
Published: January 2021

ABSTRACTThe circulating metabolome is a product of interactions between the genome, epigenome, exposome and microbiome. The metabolome may be altered in people with multiple sclerosis (MS); however, existing metabolomics studies were relatively small or characterized a limited number of metabolites. Herein, we performed a multi-site study profiling the circulating metabolome to obtain relative abundances for 269 metabolites in a large cohort of MS patients and healthy controls. After adjusting for batch effects and extensive quality control, we created an overall metabolic dysfunction score, defined apriori sets of metabolites using known metabolic pathways, and derived novel networks of correlated metabolites using a weighted correlation network analysis (WGCNA). We assessed whether metabolic dysfunction, individual metabolites, metabolic pathways or WGCNA-identified module scores differed between people with MS versus healthy controls (HC) after adjusting for age, sex and race using generalized estimating equations (participants could provide multiple samples). In a subset of patients, information on disability status was also available. Similar models assessed the association between metabolites and metabolite sets with measures of disability. In people with MS, we identified striking abnormalities in a WGCNA-defined module enriched in aromatic amino acid (AAA) metabolites (FDR-adjusted p-value=2.77E-18) that are also strongly associated with disability (FDR-adjusted p-value for AAA module=1.01E-4). Consistent results were obtained using apriori-defined metabolite sets or in analyses of individual metabolites. The identified abnormalities likely relate to imbalances in gut microbial metabolism of AAAs resulting in reduced production of immunomodulatory metabolites and increased production of metabotoxins (indole acetate, phenylacetylglutamine, p-cresol sulfate, p-cresol glucuronide). Single cell RNA sequencing data analysis demonstrated altered AAA metabolism in CSF and blood derived monocyte cell populations, while treatment of human peripheral blood mononuclear cells with AAA-derived metabotoxins resulted in increased production of tumor necrosis factor-α. We identify novel metabolic alterations in people with MS potentially contributing to disease pathophysiology.
The social experience of participation in a COVID-19 vaccine trial: Subjects’ motivations, others’ concerns, and insights for vaccine promotion
Authors: Wentzell Emily , Racila Ana-Monica 
Published: January 2021

AbstractBackgroundVaccine hesitancy could undermine the effectiveness of COVID-19 vaccination programs. Knowledge about people’s lived experiences regarding COVID-19 vaccination can enhance vaccine promotion and increase uptake.AimTo use COVID-19 vaccine trial participants’ experiences to identify key themes in the lived experience of vaccination early in the vaccine approval and distribution process.MethodsWe interviewed 31 participants in the Iowa City, Iowa US site of the Pfizer/BioNTech COVID-19 vaccine phase 3 clinical trial. While trial participation differs from clinical receipt of an approved vaccine in key ways, it offers the first view of people’s lived experiences of potentially receiving a COVID-19 vaccine. The trial context is also useful since decision-making about vaccination and medical research participation often involve similar hopes and concerns, and because the public appears to view even approved COVID-19 vaccines as experimental given their novelty. Semi-structured interviews addressed subjects’ experiences, including decision-making and telling others about their trial participation. We analyzed verbatim transcripts of these interviews thematically and identified common themes relevant for vaccination decision-making.ResultsParticipants across demographic groups, including age, sex/gender, race/ethnicity, and political affiliation, described largely similar experiences. Key motivations for participation included ending the pandemic/restoring normalcy, protecting oneself and others, doing one’s duty, promoting/modeling vaccination, and expressing aspects of identity like being a helper, career-related motivations, and support of science/vaccines. Participants often felt uniquely qualified to help via trial participation due to personal attributes like health, sex/gender or race/ethnicity. They reported hearing concerns about side effects and the speed and politicization of vaccine development. Participants responded by normalizing and contextualizing side effects, de-politicizing vaccine development, and explaining how the rapid development process was nevertheless safe.ConclusionThese findings regarding participants’ reported motivations for trial participation and interactions with concerned others can be incorporated into COVID-19 vaccine promotion messaging aimed at similar populations.
Prediction of confirmed and death cases of Covid-19 in Chile through time series techniques: A comparative study
Authors: Barría-Sandoval Claudia , Ferreira Guillermo , Benz-Parra Katherine , López-Flores Pablo 
Published: January 2021

Abstract(1)BackgroundChile has become one of the countries most affected by Covid-19, a pandemic that has generated a large number of cases worldwide, which if not detected and treated in time can cause multi-organic failure and even death. The social determinants of health such as education, work, social security, housing, environment, support networks and social cohesion are important aspects to consider for the control and intervention of this pathology. Therefore, it is essential to have information about the progress of the infections at the national level and thus apply effective public health interventions. In this paper, we compare different time series methodologies to predict the number of confirmed cases and deaths from Covid-19 in Chile and thus support the decisions of health agencies;(2)MethodsWe modeled the confirmed cases and deaths from Covid-19 in Chile by using ARIMA models, exponential smoothing techniques, Poisson models for time-dependent counting data. In addition, we evaluated the accuracy of the predictions by using a training set and test set;(3)ResultsThe database used in this paper allows us to say that for the confirmed Covid-19 cases the best model corresponds to a well-known Autoregressive Integrated Moving Average (ARIMA) time-series model, whereas for deaths from Covid-19 in Chile the best model resulted in damped trend method;(4)ConclusionARIMA models are an alternative to model the behavior of the spread of Covid19, however, and depending on the characteristics of the data set, other methodologies can better capture the behavior of these records, for example, Holt-winter’s method and time-dependent counting models.
Ascertaining the initiation of epidemic resurgences: an application to the COVID-19 second surges in Europe and the Northeast United States
Authors: Vilar Jose M. G. , Saiz Leonor 
Published: January 2021

ABSTRACTAssessing a potential resurgence of an epidemic outbreak with certainty is as important as challenging. The low number of infectious individuals after a long regression, and the randomness associated with it, makes it difficult to ascertain whether the infectious population is growing or just fluctuating. We have developed an approach to compute confidence intervals for the switching time from decay to growth and to compute the corresponding supra-location aggregated quantities to increase the precision of the determination. We estimated the aggregate prevalence over time for Europe and the Northeast United States to characterize the COVID-19 second surge in these regions during year 2020. We find a starting date as early as July 3 (95% Confidence Interval (CI): July 1– July 6) for Europe and August 19 (95% CI: August 16 – August 23) for the Northeast; subsequent infectious populations that, as of December 31 have always increased or remained stagnant; and the resurgences being the collective effect of each overall region with no location dominating the regional dynamics by itself.
Pharmacokinetic modelling to estimate intracellular favipiravir ribofuranosyl-5’-triphosphate exposure to support posology for SARS-CoV-2
Authors: Pertinez Henry , Rajoli Rajith KR , Khoo Saye H , Owen Andrew 
Published: January 2021

AbstractBackgroundThe role of favipiravir as a treatment for COVID-19 is unclear, with discrepant activity against SARS-CoV-2in vitro, concerns about teratogenicity and pill burden, and an unknown optimal dose. In Vero-E6 cells, high concentrations are needed to inhibit SARS-CoV-2 replication. The purpose of this analysis was to use available data to simulate intracellular pharmacokinetics of favipiravir ribofuranosyl-5⍰-triphosphate (FAVI-RTP) to better understand the putative applicability as a COVID-19 intervention.MethodsPreviously publishedin vitrodata for the intracellular production and elimination of FAVI- RTP in MDCK cells incubated with parent favipiravir was fitted with a mathematical model to describe the time course of intracellular FAVI-RTP concentrations as a function of incubation concentration of parent favipiravir. Parameter estimates from this model fitting were then combined with a previously published population PK model for the plasma exposure of parent favipiravir in Chinese patients with severe influenza (the modelled free plasma concentration of favipiravir substituting forin vitroincubation concentration) to predict the human intracellular FAVI-RTP pharmacokinetics.ResultsIn vitroFAVI-RTP data was adequately described as a function ofin vitroincubation media concentrations of parent favipiravir with an empirical model, noting that the model simplifies and consolidates various processes and is used under various assumptions and within certain limits. Parameter estimates from the fittings toin vitrodata predict a flatter dynamic range of peak to trough for intracellular FAVI-RTP when driven by a predicted free plasma concentration profile.ConclusionThis modelling approach has several important limitations that are discussed in the main text of the manuscript. However, the simulations indicate that despite rapid clearance of the parent drug from plasma, sufficient intracellular FAVI-RTP may be maintained across the dosing interval because of its long intracellular half-life. Population average intracellular FAVI-RTP concentrations are estimated to maintain the Km for the SARS-CoV-2 polymerase for 3 days following 800 mg BID dosing and 9 days following 1200 mg BID dosing after a 1600 mg BID loading dose on day 1. Further evaluation of favipiravir as part of antiviral combinations for SARS-CoV-2 is warranted.
Genomic epidemiology of the SARS-CoV-2 epidemic in Zimbabwe: Role of international travel and regional migration in spread
Authors: Mashe Tapfumanei , Takawira Faustinos Tatenda , Martins Leonardo de Oliveira , Gudza-Mugabe Muchaneta , Chirenda Joconiah , Munyanyi Manes , Chaibva Blessmore V , Tarupiwa Andrew , Gumbo Hlanai , Juru Agnes , Nyagupe Charles , Phiri Isaac , Manangazira Portia , Goredema Alexander , Danda Sydney , Chabata Israel , Jonga Janet , Munharira Rutendo , Masunda Kudzai , Mukeredzi Innocent , Mangwanya Douglas ,   The COVID-19 Genomics UK (COG-UK) Consortium,   SARS-CoV-2 Research Group, Trotter Alex , Viet Thanh Le , Kay Gemma , Baker David , Thilliez Gaetan , Gutierrez Ana-Victoria , O’Grady Justin , Hove Maxwell , Mutapuri-Zinyowera Sekesai , Page Andrew J. , Kingsley Robert A. , Mhlanga Gibson 
Published: January 2021

AbstractZimbabwe reported its first case of SARS-Cov-2 infection in March 2020, and case numbers increased to more than 8,099 to 16th October 2020. An understanding of the SARS-Cov-2 outbreak in Zimbabwe will assist in the implementation of effective public health interventions to control transmission. Nasopharyngeal samples from 92,299 suspected and confirmed COVID-19 cases reported in Zimbabwe between 20 March and 16 October 2020 were obtained. Available demographic data associated with those cases identified as positive (8,099) were analysed to describe the national breakdown of positive cases over time in more detail (geographical location, sex, age and travel history). The whole genome sequence (WGS) of one hundred SARS-CoV-2-positive samples from the first 120 days of the epidemic in Zimbabwe was determined to identify their relationship to one another and WGS from global samples. Overall, a greater proportion of infections were in males (55.5%) than females (44.85%), although in older age groups more females were affected than males. Most COVID-19 cases (57 %) were in the 20-40 age group. Eight lineages, from at least 25 separate introductions into the region were found using comparative genomics. Of these, 95% had the D614G mutation on the spike protein which was associated with higher transmissibility than the ancestral strain. Early introductions and spread of SARS-CoV-2 were predominantly associated with genomes common in Europe and the United States of America (USA), and few common in Asia at this time. As the pandemic evolved, travel-associated cases from South Africa and other neighbouring countries were also recorded. Transmission within quarantine centres occurred when travelling nationals returning to Zimbabwe. International and regional migration followed by local transmission were identified as accounting for the development of the SARS-CoV-2 epidemic in Zimbabwe. Based on this, rapid implementation of public health interventions are critical to reduce local transmission of SARS-CoV-2. Impact of the predominant G614 strain on severity of symptoms in COVID-19 cases needs further investigation.
Reverse Transcriptase Loop Mediated Isothermal Amplification (RT-LAMP) for COVID-19 Diagnosis: A Systematic Review and Meta-Analysis
Authors: Subali Anita Dominique , Wiyono Lowilius 
Published: January 2021

ABSTRACTBackgroundCoronavirus Disease 2019 (COVID-19) has caused a severe outbreak and become a global public health priority. Rapid increment of infection number along with significant deaths have placed the virus as a serious threat to human health. Rapid, reliable, and simple diagnostic methods are critically essential for disease control. While Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) is the current diagnostic gold standard, Reverse Transcriptase Loop-Mediated Isothermal Amplification (RT-LAMP) appears as a compelling alternative diagnostic test due to its more simplicity, shorter time to result, and lower cost. This study examined RT-LAMP application for rapid identification of SARS-CoV-2 infection compared to RT-PCR assay.MethodsA systematic review and meta-analysis (2020) was conducted in 6 scientific databases following the PRISMA Guideline. Original published studies on human clinical samples in English were included. Articles evaluated sensitivity and specificity of RT-LAMP relative to RT-PCR were considered eligible. Quality assessment of bias and applicability was examined based on QUADAS-2.ResultsA total of 351 studies were found based on the keywords and search queries. 14 eligible case control studies fitted the respective criteria. Quality assessment using QUADAS-2 indicated low risk bias in all included studies. All case studies, comprises 2,112 samples, had the cumulative sensitivity of 95.5% (CI 97.5%=90.8-97.9%) and cumulative specificity of 99.5% (CI 97.5%=97.7-99.9%).ConclusionRT-LAMP assay could be suggested as a reliable alternative COVID-19 diagnostic method with reduced cost and time compared to RT-PCR. RT-LAMP could potentially be utilized during the high-throughput and high-demand critical situations.
Socioeconomic and gender disparities in tobacco smoking among Jamaican adults from a national health survey
Authors: Bennett Nadia R , Ferguson Trevor S , Younger-Coleman Novie O , Francis Damian K , Anderson Simon G , Harris E. Nigel , MacLeish Marlene Y , Wilks Rainford J ,   U.S. Caribbean Alliance for Health Disparities Research Group (USCAHDR):
Published: January 2021

AbstractObjectivesLittle is known of socioeconomic and gender disparities in tobacco use in the Caribbean. We evaluated education and occupation disparities in tobacco smoking prevalence in Jamaica.MethodsData on tobacco smoking, education attainment and usual occupation in adults 25-74 years in a national survey collected between 2007 and 2008 was analyzed. Using post stratification survey weights, Poisson regression models estimated sex-specific, age-adjusted prevalence estimates, prevalence differences and prevalence ratios.ResultsAnalyses included 2299 participants (696 men, 1603 women), mean age 43 years. Current smoking prevalence was 26% in men and 8% in women (p<0.001). Among men, age adjusted prevalence of current smoking was highest in primary education (36.5%) and lowest in the post-secondary education groups (10.2%), (p= 0.003). Among women, prevalence was highest in junior secondary education (10.2%) and lowest in primary education groups (4.7%), (p = 0.014). Among men, for education, age-adjusted prevalence ratios for current smoking ranged from 2.6 to 3.6 using post-secondary education as the reference category (p<0.05). For occupation, age-adjusted prevalence ratios ranged from 1.7 to 4.1 using professionals and managers as the reference category. Among women, using the same reference categories age-adjusted prevalence ratios for education ranged from 1.4 to 2.2 and for occupation 0.6 to 2.2, neither were statistically significant.ConclusionIn Jamaica, there are socioeconomic disparities in current tobacco smoking among men, where it is inversely associated with education attainment and occupation but in women is less clear. These findings suggest interventions to reduce smoking should consider these disparities.
Triglyceride Glucose Index Predicts Risk of Adverse Cardio-metabolic and Mortality Outcomes Among Chinese Adults: A Territory-Wide Longitudinal Study
Authors: Zhou Jiandong , Lee Sharen , Hui Jeremy , Wong Wing Tak , Leung Keith SK , Wai Abraham KC , Liu Tong , Yung Cheung Bernard Man , Tse Gary , Zhang Qingpeng 
Published: January 2021

AbstractBackgroundThe triglyceride glucose (TyG) index has been proposed to be a surrogate of insulin resistance. In the study, we aimed to examine the relationship between TyG index and the risk of new onset DM and secondary outcomes included atrial fibrillation (AF), heart failure (HF), acute myocardial infarction (AMI), ventricular tachycardia/fibrillation (VTF), cardiovascular mortality (CAD) and all-cause mortality.MethodsThe retrospective observational study analyzed patients recruited from 1st January 2000 to 31st December 2003 and followed up until 31st December 2019. Demographics, past comorbidities, medications and laboratory tests were extracted. At baseline and follow-up, DM was defined as 1) any occasion Hb1Ac ≥14 g/dL, 2) fasting glucose≥7 mmol/L on two occasions, or 3) with DM diagnosis. We excluded 1) patients with prior DM or with the use of antidiabetic medications; 2) patients with prior AMI/HF/AF or with the use of diuretic/beta blockers for HF were excluded. Univariate analysis and multivariate Cox analysis with adjustments on demographics, past comorbidities and medications were conducted to identify the significant risk predictors of primary and secondary outcomes. Optimal cutoffs of TyG index for the primary and secondary outcomes were found with maximally selected rank statistics approach.ResultLager TyG index is significantly associated with new onset DM (HR: 1.51, 95% CI: [1.47, 1.55], P vlaue<0.0001), new onset HF (HR: 1.27, 95% CI: [1.2, 1.34], P vlaue<0.0001), new onset AF (HR: 2.36, 95% CI: [2.26, 2.46], P vlaue<0.0001), new onset AMI (HR: 1.51, 95% CI: [1.42, 1.6], P vlaue<0.0001), new onset VTF (HR: 1.22, 95% CI: [1.13, 1.31], P vlaue<0.0001), new onset CAD (HR: 1.56, 95% CI: [1.45, 1.69], P value<0.0001) and all-cause mortality (HR: 1.21, 95% CI: [1.18, 1.25], P vlaue<0.0001). TyG index and its 3rd tertile remained significant after being adjusted with significant demographics, past comorbidities and medicactions in multivariate cox models (HR>1, P value<0.05). Optimal cut-off values of baseline TyG index and adjusted multivariate restricted cubic spline models further uncovered detailed associations of larger baseline TyG index with the primary and secondary outcome.ConclusionHigher TyG index remained significantly associated with the elevated risk of new onset DM, AF, HF, AMI, VTF, CAD and all-cause mortality after adjustments on demographics, past comorbidities, and medications.