bluuebunny/crossref_metadata_2025_split huggingface dataset:
An observational analysis of patient recruitment in clinical trials in France using real-word database PMSI
Authors: Seanehia Joy , Lampuré Aurélie , Gordejuela Raimundo , Amdouni Basma , Manzione Pedro , Mammas Konstantinos 
Published: April 2022

AbstractBackgroundFrance has significant clinical research and development potential, however, struggles in comparison to neighbouring countries. A significant reason is the difficulty to recruit patients, thus causing delays in the availability of new therapies to market. IQVIA uses Health Insurance Claims Data among other data assets, to better locate patients for trials based on the potential of hospitals.ObjectiveThe aim of the study was to monitor whether an increased number of patients enrolled in clinical trials in France was observed when PMSI data supported patient recruitment, as well as describing clinical trial landscape worldwide and in Europe.MethodsWe used data from ClinicalTrials.gov and Citeline to describe the clinical trial landscape in Europe between 2010 and 2019. We also looked at the IQVIA internal clinical trial tracker, Clinical Trial Management System (CTMS) to describe IQVIA-run trials and their performance after matching trials supported with PMSI data in France. We compared the average number of enrolled patients per site in PMSI and non-PMSI supported trials according to the study phase, using a Student t-test.ResultsResults suggest that the support of PMSI on the average number of enrolled patients per site, when comparing at similar trial phase level, shows a positive trend especially for phase 4 studies (11.0 with PMSI vs 9.3 without PMSI, p=0.67), and for phases 3b, 3 and 1, when compared to non-PMSI supported studies.ConclusionsThe findings of this study suggest that PMSI use has the potential to increase patient recruitment into clinical trials run in France, rendering France more attractive in its exploitation of the clinical research potential. Optimising patient recruitment has a direct impact on the availability and timeliness of innovative therapies to market for French patients.
Self-Reported Mask Use among Persons with or without SARS CoV-2 Vaccination —United States, December 2020–August 2021
Authors: Calamari Lydia E. , Tjaden Ashley H. , Edelstein Sharon L. , Weintraub William S. , Santos Roberto , Gibbs Michael , Ward Johnathan , Santacatterina Michele , Bertoni Alain G. , Ward Lori M. , Saydah Sharon , Plumb Ian D. , Runyon Michael S. ,   COVID-19 Community Research Partnership Study Group
Published: April 2022

AbstractWearing a facemask can help to decrease the transmission of COVID-19. We investigated self-reported mask use among subjects aged 18 years and older participating in the COVID-19 Community Research Partnership (CRP), a prospective longitudinal COVID-19 surveillance study in the mid-Atlantic and southeastern United States. We included those participants who completed ≥5 daily surveys each month from December 1, 2020 through August 31, 2021. Mask use was defined as self-reported use of a face mask or face covering on every interaction with others outside the household within a distance of less than 6 feet. Participants were considered vaccinated if they reported receiving ≥1 COVID-19 vaccine dose. Participants (n=17,522) were 91% non-Hispanic White, 68% female, median age 57 years, 26% healthcare workers, with 95% self-reported receiving ≥1 COVID-19 vaccine dose through August; mean daily survey response was 85%. Mask use was higher among vaccinated than unvaccinated participants across the study period, regardless of the month of the first dose. Mask use remained relatively stable from December 2020 through April (range 71–80% unvaccinated; 86–93% vaccinated) and declined in both groups beginning in mid-May 2021 to 34% and 42% respectively in June 2021; mask use has increased again since July 2021. Mask use by all was lower during weekends and on Christmas and Easter, regardless of vaccination status. Independent predictors of higher mask use were vaccination, age ≥65 years, female sex, racial or ethnic minority group, and healthcare worker occupation, whereas a history of self-reported prior COVID-19 illness was associated with lower use.
Effectiveness of 2 and 3 mRNA COVID-19 Vaccines Doses against Omicron and Delta-Related Outpatient Illness among Adults, October 2021 – February 2022
Authors: Kim Sara S. , Chung Jessie R. , Talbot H. Keipp , Grijalva Carlos G. , Wernli Karen J. , Kiniry Erika , Martin Emily T. , Monto Arnold S. , Belongia Edward A. , McLean Huong Q. , Gaglani Manjusha , Mamawala Mufaddal , Nowalk Mary Patricia , Geffel Krissy Moehling , Tartof Sara Y. , Florea Ana , Lee Justin S. , Tenforde Mark W. , Patel Manish M. , Flannery Brendan ,   Strain Surveillance and Emerging Variants Team
Published: April 2022

AbstractBackgroundWe estimated SARS-CoV-2 Delta and Omicron-specific effectiveness of 2 and 3 mRNA COVID-19 vaccine doses in adults against symptomatic illness in US outpatient settings.MethodsBetween October 1, 2021, and February 12, 2022, research staff consented and enrolled eligible participants who had fever, cough, or loss of taste or smell and sought outpatient medical care or clinical SARS-CoV-2 testing within 10 days of illness onset. Using the test-negative design, we compared the odds of receiving 2 or 3 mRNA COVID-19 vaccine doses among SARS-CoV-2 cases versus controls using logistic regression. Regression models were adjusted for study site, age, onset week, and prior SARS-CoV-2 infection. Vaccine effectiveness (VE) was calculated as (1 – adjusted odds ratio) x 100%.ResultsAmong 3847 participants included for analysis, 574 (32%) of 1775 tested positive for SARS-CoV-2 during the Delta predominant period and 1006 (56%) of 1794 participants tested positive during the Omicron predominant period. When Delta predominated, VE against symptomatic illness in outpatient settings was 63% (95% CI: 51% to 72%) among mRNA 2-dose recipients and 96% (95% CI: 93% to 98%) for 3-dose recipients. When Omicron predominated, VE was 21% (95% CI: -6% to 41%) among 2-dose recipients and 62% (95% CI: 48% to 72%) among 3-dose recipients.ConclusionsIn this adult population, 3 mRNA COVID-19 vaccine doses provided substantial protection against symptomatic illness in outpatient settings when the Omicron variant became the predominant cause of COVID-19 in the U.S. These findings support the recommendation for a 3rdmRNA COVID-19 vaccine dose.
Age-based variability in the association between restraint use and injury type and severity
Authors: Benedetti Marco H. , Humphries Kayleigh D. , Codden Rachel , Sagar Shraddha , Kufera Joseph A. , Cook Lawrence J. , Norris Jesse , Stamatiadis Nikiforos , Vesselinov Roumen , Zhu Motao 
Published: April 2022

ABSTRACTPurposePrevious studies have shown elderly individuals receive less relatively less protection from seat belts against fatal injuries, however it is less clear how seat belt protection against severe and torso injury changes with age. We estimated age-based variability in seat belt protection against fatal injuries, injuries with maximum abbreviated injury scale greater than 2 (MAIS3+), and torso injuries.MethodsWe leveraged the Crash Outcome Data Evaluation System (CODES) to analyze binary indicators of fatal, MAIS3+, and torso injuries. Using a matched cohort design and conditional Poisson regression, we estimated age-based relative risks (RR) of the outcomes associated with seat belt use.ResultsSeat belts were highly protective against fatal injuries for all ages. For ages 16-30, seat belt use was associated with 66% lower risk of MAIS3+ injury (RR 0.34, 95% CI 0.30, 0.38), whereas for ages 75 and older, seat belt use was associated with 38% lower risk of MAIS3+ injury (RR 0.62; 95% CI 0.45, 0.86). The association between restraint use and torso injury also appeared to attenuate with age.ConclusionsSeat belt protection against MAIS3+ and torso injury attenuated with age. We encourage that injury prevention continues to be tailored to vulnerable populations like the elderly.
Learning-related contraction of grey matter in rodent sensorimotor cortex is associated with adaptive myelination
Authors: Mediavilla Tomás , Özalay Özgün , Estévez-Silva Héctor M. , Frias Bárbara , Orädd Greger , Sultan Fahad R. , Brozzoli Claudio , Garzón Benjamín , Lövdén Martin , Marcellino Daniel J. 
Published: April 2022

AbstractFrom observations in rodents, it has been suggested that the cellular basis of learning-dependent changes, detected using structural magnetic resonance imaging (MRI), may be increased dendritic spine density, alterations in astrocyte volume, and adaptations within intracortical myelin. Myelin plasticity is crucial for neurological function and active myelination is required for learning and memory. However, the dynamics of myelin plasticity and how it relates to morphometric-based measurements of structural plasticity remains unknown. We used a motor skill learning paradigm to evaluate experience-dependent brain plasticity by voxel-based morphometry (VBM) in longitudinal MRI, combined with a cross-sectional immunohistochemical investigation. Whole brain VBM revealed non-linear decreases in grey matter (GM) juxtaposed to non-linear increases in white matter (WM) that were best modelled by an asymptotic time course. Using an atlas-based cortical mask, we found non-linear changes with learning in primary and secondary motor areas and in somatosensory cortex. Analysis of cross-sectional myelin immunoreactivity in forelimb somatosensory cortex confirmed an increase in myelin immunoreactivity followed by a return towards baseline levels. The absence of significant histological changes in cortical thickness further suggests that non-linear morphometric changes are likely due to changes in intracortical myelin for which morphometric WM volume (WMV) data significantly correlated with myelin immunoreactivity. Together, these observations indicate a non-linear increase of intracortical myelin during learning and support the hypothesis that myelin is a component of structural changes observed by VBM during learning.
Spatial heterogeneity alters the trade-off between growth and dispersal during a range expansion
Authors: Zamberletti Patrizia , Roques Lionel , Lavigne Florian , Papaïx Julien 
Published: April 2022

AbstractIndividuals who invest more in the development of their dispersal-related traits often reduce their investment in reproduction. Thus, there are two possible eco-evolutionary strategies: grow faster or disperse faster (R—Darbitrage). Here we explore, through a reaction-diffusion model, how spatial heterogeneity can shape theR—Dtrade-off by studying the spreading dynamics of a consumer species exploiting a resource in a spatially fragmented environment. Based on numerical simulations and analytical solutions derived from simpler models, we show that the classical mathematical symmetry between the effects of growth and dispersal on the spatial spreading speed is broken in the presence of competition between phenotypes. At the back of the forefront, the dynamics is almost always driven by theRspecialists. On the forefront, R-strategies are favored in spatially homogeneous environments, but the introduction of heterogeneity leads to a shift towards D-strategies. This effect is even stronger when spatial heterogeneity affects the diffusion term and when spatial fragmentation is lower. Introducing mutations between phenotypes produces an advantage towards the R-strategy and homogenizes the distribution of phenotypes, also leading to more polymorphism on the forefront.
Assessing TMS-evoked cognitive network responses depending on neurocognitive and oscillatory brain state: A simultaneous TMS-EEG-fMRI project
Authors: Janssens Shanice E. W. , de Graaf Tom A. , Duecker Felix , Schuhmann Teresa , Sack Alexander T. 
Published: April 2022

AbstractHuman cognition arises from information exchange within and between functionally connected brain networks. Alterations in such signal propagation across networks are linked to numerous disorders. Brain-wide signal propagation can be experimentally studied with simultaneous transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI), where TMS pulses introduce a signal at a certain network node and fMRI charts its propagation through the network. Yet, this approach ignores the fact that the (network) impact of a TMS pulse depends on brain state, where brain state fluctuates spontaneously from moment to moment (e.g. oscillatory state) as well as depending on what a participant does (neurocognitive state). Here, we assessed TMS-evoked fMRI activations as a function of neurocognitive state (eyes open versus eyes closed in complete darkness) and oscillatory state (low versus high pre-TMS alpha power, as measured with simultaneous electroencephalography (EEG)). We applied supra-versus sub-threshold triple-pulse TMS to the right posterior parietal cortex in eight participants, while simultaneously recording EEG and fMRI during two different ocular states. In this first application of the multimodal TMS-EEG-fMRI paradigm to a cognitive network hub, we did not find evidence for a brain state modulation of TMS-induced signal propagation. Instead, we found state-independent TMS-evoked fMRI responses mostly in sensory areas such as the insula, superior temporal gyrus, anterior cingulate cortex, and thalamus, but also in the frontal eye fields. Interestingly, neurocognitive state did seem to modulate the fMRI response to indirect TMS effects such as sensory stimulation. These results lead to several important insights for future cognitive multimodal TMS experiments.
Evaluate the reliability of the apprenticeship in the first year of medical school: towards a reliable first level ultrasound examination
Authors: Turci Michela Cristina , Tassoni Massimo , Gajtani Florida , Previtera Antonino Michele , Magenta-Biasina Alberto , Biganzoli Elia Mario , Serrao Graziano 
Published: April 2022

AbstractObjectivesOur aim was to motivate apprentices’ sonographer needs, to appraise their own measurements, to reduce inconsistencies within and between operators. Deep knowledge of ultrasound sectional anatomy is mandatory for an appropriate performance.MethodsIn three different weekdays, 3 sonographer apprentices (rater), randomly selected from a cohort of San Paolo Medical School first year students participated in vertically integrated study of living anatomy through ultrasound examination, repeated lumbar multifidus cross-sections scans on 6 subjects at lumbar level. The Agreement R package 0.8-1 was used to monitored the performances of each apprentice.ResultsThe agreement (CCCintra 0.6749; CCCinter 0.556; CCCtotal is 0.5438) was further from least acceptable CCC of 0.92-0.95. The precision indices (precisionintra 0.6749; inter 0.801; total0.6274) were unsatisfactory, while the accuracy was high (0.9889 to 0.9913). The same occurred for the agreement on rater performances comparisons, where readings were high accurate (0.9537 to 0.9733) but moderately precise (0.7927 to 0.8895), not interchangeable TIR (1.173) but without rater supremacy. IIR (r1 vs r2 1.104, r1 vs r3 1.015, r2 vs r3 0.92) 95% confidence limits.ConclusionsApprentices were not reliable, repeatable, interchangeable. The weak link in the method seemed to be cultural weakness on vivo imaging morphologies, qualitative and quantitative measurement procedure on elementary statistical processing.
A systematic review of Hepatitis B virus (HBV) prevalence and genotypes in Kenya: Data to inform clinical care and health policy
Authors: Downs Louise O , Campbell Cori , Yonga Paul , Ansari M. Azim , Matthews Philippa C , Etyang Anthony O. 
Published: April 2022

AbstractMore than 20% of the global disease burden from chronic hepatitis B infection (CHB) is in Africa, however there is minimal high quality seroprevalence data from individual countries and little viral sequencing data available to represent the continent. We undertook a systematic review of the prevalence and genetic data available for hepatitis B virus (HBV) in Kenya using the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) 2020 checklist. We identified 23 studies reporting HBV prevalence and 25 studies that included HBV genetic data published in English between January 2000 and December 2021. We assessed study quality using the Joanna Briggs Institute critical appraisal checklist. Due to study heterogeneity, we divided the studies to represent low, moderate, high and very high-risk for HBV infection. We calculated pooled HBV prevalence within each group and evaluated available sequencing data. We also assessed whether reported HBV biomarkers could be applied to determine treatment eligibility. Eight studies were identified in the low-risk group, seven in the moderate risk group, five in the high-risk group and three in the very high-risk group for HBV infection. Pooled HBV prevalence was 3.31% (95% CI 2.62-4.01%), 5.58% (95% CI 3.46-7.7%), 6.17% (95% CI 4.4-9.94) and 31.39% (95% CI 9.5-53.09) respectively. Study quality was overall low, representing a small geographical location or a limited population subset. Only three studies detailed sample size calculation and 17/23 studies were cross sectional. Eight studies included genetic information on HBV, representing 247 individuals. Six studies sequenced one or two genes; two undertook whole genome sequencing, representing 22 participants. 92% people were infected with genotype A. Other genotypes included genotype D (6%), D/E recombinants (1%) or mixed populations (1%). Drug resistance mutations were reported by two studies. Seven studies presented additional biomarkers alongside HBsAg, however none provided sufficient information to deduce treatment eligibility.
A prospective observational study on BBV152 coronavirus vaccine use in adolescents and comparison with adults- first real-world safety analysis
Authors: Kaur Upinder , Anju KL , Chauhan Mayank , Joshi Aditi , Kansal Sangeeta , Jaisawal Vaibhav , Patwardhan Kishor , Chakrabarti Sankha Shubhra 
Published: April 2022

AbstractBackgroundThe BBV152 COVID-19 vaccine (COVAXIN) has recently been approved for adolescents. We provide the first real world safety data of COVAXIN use in adolescents and compare this with adults.MethodsA prospective observational study is being conducted since January 2022. Enrolled adolescents and adults were contacted telephonically after 14 days of receiving the BBV152 vaccine. Primary outcome was vaccine safety assessed as rates of adverse events following immunization (AEFI). Severity grading of AEFIs was done using the FDA scale.FindingsA total of 698 adolescents and 326 adults were enrolled. AEFIs occurred in 36.3% adolescents after first and in 37.9% after second dose. Systemic involvement was seen in 15-17% adolescents. Injection site pain and fever were the common AEFIs. Majority of AEFIs were mild-moderate. Severe and atypical AEFIs were observed in 0.9% and 0.6% adolescents respectively. Majority of AEFIs recovered in 1-2 days. In >2% adolescents, AEFIs were persisting at 14-day follow-up since the second dose. No difference in AEFI incidence and patterns was observed between adolescents and adults. Regression analysis showed females and those with history of allergy to be respectively at 1.5-times and 3-times increased risk of AEFIs among adolescents.InterpretationCOVAXIN carries an overall favorable short term safety profile in adolescents. The observed AEFI rates in adolescents are much lower than that reported with mRNA vaccines. Female adolescents and those with history of allergy need watchfulness. With some AEFIs persisting at 14 days, a longer follow-up is recommended to strengthen the safety data of these vaccines.FundingNo funding support
Dynamic rewiring of electrophysiological brain networks during learning
Authors: Ruggeri Paolo , Miehlbradt Jenifer , Kabbara Aya , Hassan Mahmoud 
Published: April 2022

ABSTRACTHuman learning is an active and complex process. However, the brain mechanisms underlying human skill learning and the effect of learning on the communication between brain regions, at different frequency bands, are still largely unknown. Here, we tracked changes in large-scale electrophysiological networks over a 6-week training period during which participants practiced a series of motor sequences during 30 home training sessions. Our findings showed that brain networks become more flexible with learning in all the frequency bands from theta to gamma ranges. We found consistent increase of flexibility in the prefrontal and limbic areas in the theta and alpha band, and over somatomotor and visual areas in the alpha band. Specific to the beta rhythm, we revealed that higher flexibility of prefrontal regions during the early stage of learning strongly correlated with better performance measured during home training sessions. Our findings provide novel evidence that prolonged motor skill practice results in higher, frequency-specific, temporal variability in brain network structure.AUTHOR SUMMARYWe investigated the large-scale organization of electrophysiological brain networks of a cohort of 30 participants practicing a series of motor sequences during 6 weeks of training. With learning, we observed a progressive modulation of the dynamics of prefrontal and limbic regions from theta to alpha frequencies, and of centro-parietal and occipital regions within visuomotor networks in the alpha band. In addition, higher prefrontal regional flexibility during early practice correlated with learning occurring during the 6 weeks of training. This provides novel evidence of a frequency-specific reorganization of brain networks with prolonged motor skill learning and an important neural basis for non-invasive research into the role of cortical functional interactions in (visuo)motor learning.
An oligogenic inheritance test detects risk genes and their interactions in congenital heart defects and developmental comorbidities
Authors: Pittman Maureen , Lee Kihyun , Srivastava Deepak , Pollard Katherine S. 
Published: April 2022

AbstractExome sequencing of thousands of families has revealed many individual risk genes for congenital heart defects (CHD), yet most cases cannot be explained by a single causal mutation. Further, those who carryde novoand inherited mutations in known risk genes often demonstrate variable phenotypes even within the same family, indicating the presence of genetic modifiers. To explore oligogenic causes of CHD without assessing billions of variant combinations, we developed an efficient, simulation-based method to detect gene sets that carry damaging variants in probands at a higher rate than expected given parental genotypes. We implemented this approach in software called Gene Combinations in Oligogenic Disease (GCOD) and applied it to a cohort of 3382 trios with exome sequencing. This analysis detected 353 high-confidence risk genes in 202 pairs that appear together in multiple probands but rarely or never appear in combination in their unaffected parents. Stratifying analyses by specific CHD diagnosis and considering gene combinations of higher orders yielded an additional 244 gene sets. The oligogenic genes we discovered cluster in pathways specific to heart development and suggest new molecular disease mechanisms, such as arylsulfatase activity andde novonucleotide biosynthesis. Finally, by combining CHD families with an autism spectrum disorder cohort, we were able to detect 925 oligogenic sets transmitted in renal disease, a known co-morbidity of both conditions. As genome sequencing is applied to more families and other disorders, GCOD will enable detection of increasingly large, novel gene combinations, shedding light on combinatorial causes of genetic diseases.