bluuebunny/crossref_metadata_2025_split huggingface dataset:
The influence of training load on hematological Athlete Biological Passport variables in elite cyclists
Authors: Tiffany Astolfi , von Roten Fabienne Crettaz , Bengt Kayser , Martial Saugy , Raphael Faiss 
Published: October 2020

AbstractThe hematological module of the Athlete Biological Passport (ABP) is used in elite sport for antidoping purposes. Its aim is to better target athletes for testing and to indirectly detect blood doping. The ABP allows to monitor hematological variations in athletes using selected primary blood biomarkers (hemoglobin concentration ([Hb] and reticulocyte percentage (Ret%)) with an adaptive Bayesian model to set individual upper and lower limits. If values fall without the individual limits, an athlete may be further targeted and ultimately sanctioned.Since [Hb] and Ret% vary with plasma volume (PV) fluctuations, possibly caused by training load changes, we investigated the putative influence of acute and chronic training load changes on the ABP variables.Monthly blood samples were collected over one year in 10 elite cyclists (25.6 ± 3.4 yrs, 181 ± 4 cm, 71.3 ± 4.9 kg, 6.7 ± 0.8 W.kg-1 5-min maximal power output) to calculate individual ABP profiles and monitor hematological variables. Total hemoglobin mass (Hbmass) and PV were additionally measured by carbon monoxide rebreathing. Acute and chronic training loads – respectively 5 and 42 days before sampling – were calculated considering duration and intensity (training stress score, TSS™).[Hb] averaged 14.2 ± 0.0 (mean ± SD) g.dL-1 (range: 13.3 to 15.5 g·dl-1) over the study with significant changes over time (P = 0.004). Hbmass was 1’030 ± 87 g (range: 842 to 1116 g) with no significant variations over time (P = 0.118), whereas PV was 4309 ± 350 mL (range: 3688 to 4751 mL) with a time-effect observed over the study time (P = 0.014). Higher acute – but not chronic – training loads were associated with significantly decreased [Hb] (P <0.001). Although individual hematological variations were observed, all ABP variables remained within the individually calculated limits.Our results support that acute training load variations significantly affect [Hb], likely due to short-term PV fluctuations, underlining the importance of considering training load when interpreting individual ABP variations for anti-doping purposes.
An ultra-sensitive, ultra-fast whole blood monocyte CD169 assay for COVID-19 screening
Authors: Michel Moïse , Malergue Fabrice , Belkacem Inès Ait , Bourgoin Pénélope , Morange Pierre-Emmanuel , Arnoux Isabelle , Miloud Tewfik , Million Matthieu , Tissot-Dupont Hervé , Mege Jean-Louis , Busnel Jean-Marc , Vitte Joana 
Published: October 2020

AbstractCoVID-19 is an unprecedented epidemic, globally challenging health systems, societies, and economy. Its diagnosis relies on molecular methods, with drawbacks revealed by current use as mass screening. Monocyte CD169 upregulation has been reported as a marker of viral infections, we evaluated a flow cytometry three-color rapid assay of whole blood monocyte CD169 for CoVID-19 screening.Outpatients (n=177) with confirmed CoVID-19 infection, comprising 80 early-stage (≤14 days after symptom onset), 71 late-stage (≥15 days), and 26 asymptomatic patients received whole blood CD169 testing in parallel with SARS-CoV-2 RT-PCR. Upregulation of monocyte CD169 without polymorphonuclear neutrophil CD64 changes was the primary endpoint. Sensitivity was 98% and 100% in early-stage and asymptomatic patients respectively, specificity was 50% and 84%. Rapid whole blood monocyte CD169 evaluation was highly sensitive when compared with RT-PCR, especially in early-stage, asymptomatic patients whose RT-PCR tests were not yet positive.Diagnostic accuracy, easy finger prick sampling and minimal time-to-result (15-30 minutes) rank whole blood monocyte CD169 upregulation as a potential screening and diagnostic support for CoVID-19. Secondary endpoints were neutrophil CD64 upregulation as a marker of bacterial infections and monocyte HLA-DR downregulation as a surrogate of immune fitness, both assisting with adequate and rapid management of non-CoVID cases.
Application of Full Genome Analysis to Diagnose Rare Monogenic Disorders
Authors: Shieh Joseph T. , Penon-Portmann Monica , Wong Karen H.Y. , Levy-Sakin Michal , Verghese Michelle , Slavotinek Anne , Gallagher Renata C. , Mendelsohn Bryce A. , Tenney Jessica , Beleford Daniah , Perry Hazel , Chow Stephen K. , Sharo Andrew G. , Brenner Steven E. , Qi Zhongxia , Yu Jingwei , Klein Ophir D. , Martin David , Kwok Pui-Yan , Boffelli Dario 
Published: October 2020

AbstractCurrent genetic tests for rare diseases provide a diagnosis in only a modest proportion of cases. The Full Genome Analysis method, FGA, combines long-range assembly and whole-genome sequencing to detect small variants, structural variants with breakpoint resolution, and phasing. We built a variant prioritization pipeline and tested FGA’s utility for diagnosis of rare diseases in a clinical setting. FGA identified structural variants and small variants with an overall diagnostic yield of 40% (20 of 50 cases) and 35% in exome-negative cases (8 of 23 cases), 4 of these were structural variants. FGA detected and mapped structural variants that are missed by short reads, including non-coding duplication, and phased variants across long distances of more than 180kb. With the prioritization algorithm, longer DNA technologies could replace multiple tests for monogenic disorders and expand the range of variants detected. Our study suggests that genomes produced from technologies like FGA can improve variant detection and provide higher resolution genome maps for future application.
COVID-19 and Socioeconomic Factors: Cross-country Evidence
Authors: Jani Vishalkumar , Mavalankar Dileep 
Published: October 2020

AbstractBackgroundCOVID-19 pandemic has affected all countries across the globe in varying intensity resulting in varied numbers for total cases and deaths.ObjectivesThe paper aims to understand if different socioeconomic factors have a role to play in determining the intensity of COVID-19 impact.MethodsThe study uses a country-wise number of corona cases and deaths and analyse them in a cross-country multivariate regression framework. It uses gross domestic product per capita, average temperature, population density, and median age as independent variables. The study uses testing data as a control variable.ResultsIn absence of the testing variable, higher-income countries have experienced a higher number of COVID cases. The population density, median age, climate do not have significant impact. The countries with higher population density have lower deaths. Each region shows different patterns of correlation between socioeconomic factors and COVID intensity.ConclusionThe majority of the cross-country variation can be attributed to the number of tests done by a country. The countries with high population density would have applied strict lockdowns and proactive testing to curb the deaths. The study essentially refutes claims around corona being a high-income group disease, cold-climate disease, or a disease impacting old-age patients more.
THE IMPACT OF LOCKDOWN ON PUBLIC HEALTH DURING THE FIRST WAVE OF COVID-19 PANDEMIC: LESSONS LEARNED FOR DESIGNING EFFECTIVE CONTAINMENT MEASURES TO COPE WITH SECOND WAVE
Authors: Coccia Mario 
Published: October 2020

AbstractWhat is hardly known in the studies of the COVID-19 global pandemic crisis is the impact of general lockdown during the first wave of COVID-19 pandemic both public health and economic system. The main goal of this study is a comparative analysis of some European countries with a longer and shorter period of national lockdown during the first wave of COVID-19 from March to August 2020. Findings suggests that: a) countries with shorter period of lockdown have a variation of confirmed cases/population (%) higher than countries with longer period of lockdown; b) countries with shorter period of lockdown have average fatality rate (5.45%) lower than countries with longer period of lockdown (12.70%), whereas variation of fatality rate from August to March 2020 suggests a higher reduction in countries with longer period of lockdown (−1.9% vs 0.72%). However, Independent Samples Test and the Mann-Whitney test reveal that the effectiveness of longer period of lockdown versus shorter one on public health is not significant. In addition, the COVID-19 pandemic associated with longer period of lockdown has a higher negative impact on economic growth with consequential social issues in countries. Results of the impact of COVID-19 lockdowns on public health and economies of some leading countries in Europe, during the first wave of the COVID-19 pandemic, can provide vital information to design effective containment strategies in future waves of this pandemic to minimize the negative effects in society.
Longitudinal caries prevalence in a comprehensive, multi-component, school-based prevention program
Authors: Starr Jacqueline R. , Ruff Ryan R. , Palmisano Joseph , Goodson J. Max , Bukhari Omair M. , Niederman Richard 
Published: October 2020

AbstractBackgroundGlobally, children’s caries prevalence exceeds 30% and has not markedly changed in 30 years. School-based caries prevention programs may be an effective method to reduce caries prevalence, obviate traditional barriers to care, and use aerosol-free interventions. The objective of this study was to explore the clinical effectiveness of a comprehensive school-based, aerosol-free, caries prevention program.MethodsWe conducted a 6-year prospective open cohort study in 33 U.S. public elementary schools, providing care to 6,927 children in communities with and without water fluoridation. Following a dental examination, dental hygienists provided twice-yearly prophylaxis, glass ionomer sealants, glass ionomer interim therapeutic restorations, fluoride varnish, toothbrushes, fluoride toothpaste, oral hygiene instruction, and referral to community dentists as needed. We used generalized estimating equations to estimate the change in the prevalence of untreated caries over time.ResultsThe prevalence of untreated caries decreased by greater than 50%: from 39% to 18% in phase 1, and from 28% to 10% in phase 2. The per-visit adjusted odds ratio of untreated decay was 0.79 (95% CI: 0.73, 0.85).Conclusions and Practical ImplicationsWe show that a school-based comprehensive caries prevention program was associated with substantial reductions in children’s caries, supporting the concept of expanding traditional practices to include office- and community-based aerosol-free care.
Multimodal profiling of lung granulomas reveals cellular correlates of tuberculosis control
Authors: Gideon Hannah P. , Hughes Travis K. , Tzouanas Constantine N. , Wadsworth Marc H. , Tu Ang Andy , Gierahn Todd M. , Peters Joshua M. , Hopkins Forrest F. , Wei Jun-Rong , Kummerlowe Conner , Grant Nicole L. , Nargan Kievershen , Phuah Jia Yao , Borish H. Jacob , Maiello Pauline , White Alexander G. , Winchell Caylin G. , Nyquist Sarah K. , Ganchua Sharie Keanne C. , Myers Amy , Patel Kush V , Ameel Cassaundra L. , Cochran Catherine T. , Ibrahim Samira , Tomko Jaime A , Frye Lonnie James , Rosenberg Jacob M. , Shih Angela , Chao Michael , Scanga Charles A. , Ordovas-Montanes Jose , Berger Bonnie , Mattila Joshua T. , Madansein Rajhmun , Love J. Christopher , Lin Philana Ling , Leslie Alasdair , Behar Samuel M. , Bryson Bryan , Flynn JoAnne L , Fortune Sarah M. , Shalek Alex K. 
Published: October 2020

AbstractMycobacterium tuberculosislung infection results in a complex multicellular structure, the granuloma. In some granulomas, immune activity promotes bacterial clearance; in others, bacteria persist and grow. We identified correlates of bacterial control in cynomolgus macaque lung granulomas by co-registering longitudinal PET-CT imaging, single-cell RNA-sequencing, and measures of bacterial clearance. We find that bacterial persistence occurs in granulomas enriched for mast, endothelial, fibroblast and plasma cells, signaling amongst themselves via Type II immunity and wound healing pathways. In contrast, these interactions are largely absent in granulomas that drive bacterial control, which are often those that form later in the course of infection; these restrictive lesions are characterized by cellular ecosystems enriched for Type1-Type17, stem-like, and cytotoxic T cells engaged in pro-inflammatory signaling networks that involve diverse myeloid and non-immune cell populations. There is also a temporal aspect to bacterial control, in that granulomas that arise later in infection (in the context of an established immune response) share the functional characteristics of restrictive granulomas and are more capable of killing Mtb. Taken together, our results define the complex multicellular ecosystems underlying (lack of) granuloma resolution and highlight host immune targets that can be leveraged to develop new vaccine and therapeutic strategies for TB.One-Sentence SummaryBacterial control in TB lung granulomas correlates with distinct cellular immune microenvironments and time of formation after infection.
1Cross Sectional Study of Middle East Respiratory Syndrome (Mers-Cov Infection) in Camels at Selected Sites of Amibara District, Afar Region, Ethiopia
Authors: Sibhatu Demeke , Mamo Gezahagne , Aklillu Fasil , Zewde Demeke , Walelign Elias , Muluneh Ayelech , Aliey Abdi , Mirkena Tadele , Tewolde Nega , Gari Getachew , van ‘t Klooster Gijs , Elmasry Ihab , VonDobschuetz Sophie , Peiris Malik , Chu Daniel , Perera Ranawaka APM , Jobire Yilma 
Published: October 2020

AbstractBackgroundA Cross sectional study of Middle East Respiratory Syndrome Corona virus (MERS-CoV) in Camel was conducted between February 2018 to April 2019 in three selected sites of Amibara district of Afar region, Northeast Ethiopia. The study was aimed to observe the current sero-prevalence status of MERS-CoV, assess the presence of active cases through detection RNA Viral particle and investigate possible risk factors of MERS-CoV in camels. A total of 589 sera were collected and tested with indirect Enzyme linked ImmunoSorbent Assay (iELISA).ResultThe overall seroprevalance of MERS-CoV was 87.3% (n=514/589, 95% CI: 84.5-89.9). Association of different risk factors with seroprevalance revealed that origin (X2=13.39,P=0.001), sex (X2=4.5 P=0.034), age ((X2=185.7, P=0.001) season (X2=41.7, P=0.000) and reproduction status (X2=96.1, P=0.001) displayed a statistical significant difference among the groups (P<0.05) while herd size did not show a Significant difference among groups (p>0.05). In multivariable logistic regression analysis, age (OR=7.39, 95% CI:3.43-15.91), season (OR=4.83, 95% CI:-2.14-10.90), and in adult female camel reproduction status (OR=7.39,95% C I:3.43-15.91) showed statistically significant difference among the groups for MERS CoV antibody detection while risk factors of origin, animal sex and herd size difference were statistically insignificant. A total of 857 nasal swab samples were collected for the detection of MERS-CoV RNA particle. However, all swab samples tested by Real-time reverse transcription polymerase chain reaction (RT-PCR) technique were Negative for the virus.ConclusionIn conclusion, the present study revealed a high seroprevalance of MERS CoV in adult camels. However, in spite of high seroprevalance the lack of any RNA viral particle in the study suggests the need for further in depth longitudinal study to detect the circulating virus focusing on juveniles and young camels whereby seroprevalance of antibody is low when compared with adult camel in order to get the active virus before the camel develop antibody. Moreover, the zoonotic significance and potential transmission routes of MERS CoV to pastoral communities should also be investigated and design strategy for the preparedness in control of the diseases in Ethiopia.
BioSamplr: An open source, low cost automated sampling system for bioreactors
Authors: Efromson John P. , Li Shuai , Lynch Michael D. 
Published: October 2020

AbstractAutosampling from bioreactors reduces error, increases reproducibility and offers improved aseptic handling when compared to manual sampling. Additionally, autosampling greatly decreases the hands-on time required for a bioreactor experiment and enables sampling 24 hrs a day. We have designed, built and tested a low cost, open source, automated bioreactor sampling system, the BioSamplr. The BioSamplr can take up to ten samples from a bioreactor at a desired sample interval and cools them to a desired temperature. The device, assembled from low cost and 3D printed components, is controlled wirelessly by a Raspberry Pi, and records all sampling data to a log file. The cost and accessibility of the BioSamplr make it useful for laboratories without access to more expensive and complex autosampling systems.
Drug self-administration in head-restrained mice for simultaneous multiphoton imaging
Authors: Vollmer Kelsey M. , Doncheck Elizabeth M. , Grant Roger I. , Winston Kion T. , Romanova Elizaveta V. , Bowen Christopher W. , Siegler Preston N. , Bobadilla Ana-Clara , Trujillo-Pisanty Ivan , Kalivas Peter W. , Otis James M. 
Published: October 2020

ABSTRACTMultiphoton microscopy is one of several new technologies providing unprecedented insight into the activity dynamics and function of neural circuits. Unfortunately, many of these technologies require experimentation in head-restrained animals, greatly limiting the behavioral repertoire that can be studied with each approach. This issue is especially evident in drug addiction research, as no laboratories have coupled multiphoton microscopy with simultaneous intravenous drug self-administration, the gold standard of behavioral paradigms for investigating the neural mechanisms of drug addiction. Such experiments would be transformative for addiction research as one could measure or perturb an array of behavior and drug-related adaptations in precisely defined neural circuit elements over time, including but not limited to dendritic spine plasticity, neurotransmitter release, and neuronal activity. Here, we describe a new experimental assay wherein mice self-administer drugs of abuse while head-restrained, allowing for simultaneous multiphoton imaging. We demonstrate that this approach enables longitudinal tracking of activity in single neurons from the onset of drug use to relapse. The assay can be easily replicated by interested labs for relatively little cost with readily available materials and can provide unprecedented insight into the neural underpinnings of substance use disorder.
The RNA Structurome in the Asexual Blood Stages of Malaria PathogenPlasmodium falciparum
Authors: Alvarez Diana Renteria , Ospina Alejandra , Barwell Tiffany , Zheng Bo , Dey Abhishek , Li Chong , Basu Shrabani , Shi Xinghua , Kadri Sabah , Chakrabarti Kausik 
Published: October 2020

AbstractRNA as an effector of biological functions often adopts secondary and tertiary structural folds.Plasmodium falciparumis a deadly human pathogen responsible for the devastating disease called malaria. In this study, we measured the differential accumulation of RNA secondary structures in coding and noncoding transcripts from the asexual developmental cycle inP. falciparumin human red blood cells. Our comprehensive analysis, combining high-throughput nuclease mapping of RNA structures by duplex RNA-seq, immunoaffinity purification and RNA analysis, collectively measured differentially base-paired RNA regions during the parasite development. Our mapping data not only aligned to a diverse pool of RNAs with known structures but also enabled us to identify new structural RNA regions in the malaria genome. On average, ~71% of the genes with secondary structures are found to be protein coding mRNAs. Mapping pattern of these base-paired RNAs corresponded to all parts of protein-coding mRNAs, including 5’ UTR, CDS and 3’ UTR. In addition to histone family genes which are known to form secondary structures in their mRNAs, transcripts from genes which are important for transcriptional and post-transcriptional control, such as unique plant-like transcription factor family,ApiAP2, DNA/RNA binding protein family,Alba, ribosomal proteins and eukaryotic initiation factors involved in translational control and the ones important for RBC invasion and cytoadherence also show strong accumulation of duplex RNA reads in various asexual stages. Intriguingly, our study determined a positive relationship between mRNA structural contents and translation efficiency inP. falciparumasexual blood stages, suggesting an essential role of RNA structural changes in malaria gene expression programs.
ALS monocyte-derived microglia reveal cytoplasmic TDP-43 accumulation, DNA damage, and cell-specific impairment of phagocytosis associated with disease progression
Authors: Quek Hazel , Cuní-López Carla , Stewart Romal , Colletti Tiziana , Notaro Antonietta , Sun Yifan , Guo Christine C. , Lupton Michelle K. , Nguyen Tam Hong , Oikari Lotta E. , Roberts Tara L. , Lim Yi Chieh , La Bella Vincenzo , White Anthony R. 
Published: October 2020

AbstractAimsAmyotrophic lateral sclerosis (ALS) is a multifactorial neurodegenerative disease characterised by the loss of upper and lower motor neurons. Neuroinflammation mediated by microglial activation is evident in post-mortem brain tissues, and in brain imaging of patients with ALS. However, the exact role of microglia in ALS remains to be elucidated partly due to the lack of an accurate microglial model system that is able to recapitulate the clinical pathology of ALS. Moreover, direct sampling of microglia from patients with ALS is not feasible, further limiting the study of microglial function in ALS. To address this shortcoming, we describe an approach that generates monocyte-derived microglia (MDMi) that are capable of expressing molecular markers, and functional characteristics similar to resident human brain microglia. Importantly, MDMi can be routinely and reproducibly generated from ALS patient blood, and reveal patient heterogeneity associated with age, sex and disease subgroup.MethodsMDMi were successfully established from all 30 ALS patients, including 15 patients with slow disease progression, 6 with intermediate progression, and 9 with rapid progression, together with 20 non-affected heathy controls (HC).ResultsOur ALS MDMi model recapitulated canonical pathological features of ALS including non-phosphorylated and phosphorylated-TDP-43-positive pathological inclusions. We further observed significantly impaired phagocytosis, altered cytokine expression and microglial morphology, as well as elevated DNA damage in ALS compared to HC MDMi. Abnormal phagocytosis was observed in all ALS cases, and was correlated to the progression of disease. Moreover, in-depth analysis of individual microglia revealed cell-specific variation in phagocytic function that was significantly altered, and exacerbated in rapid disease progression.ConclusionsOur approach enabled us to generate ALS patient microglia from peripheral blood samples using a rapid, robust, cost-effective, and reproducible protocol. We have shown that ALS monocyte-derived microglia have significantly altered functional behaviour compared to age-matched HCs, with a major deficit in phagocytic activity. This is also the first demonstration of abnormal TDP-43 localisation in microglia grown from ALS patients. Overall, this approach is highly applicable to monitor disease progression and can be applied as a functional readout in clinical trials for anti-neuroinflammatory agents. Additionally, this model system can be used as a basis for personalised therapeutic treatment for ALS, as well as other neurodegenerative diseases.