bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real-time PCR assays for detection and quantification of early P. falciparum gametocyte stages
Authors: Gadalla Amal A.H. , Siciliano Giulia , Farid Ryan , Alano Pietro , Ranford-Cartwright Lisa , McCarthy James S , Thompson Joanne , Babiker Hamza 
Published: April 2021

AbstractIntroductionThe use of reverse transcription, quantitative qRT-PCR assays for detection and quantification of late gametocyte stages has revealed the high transmission capacity of the human malaria parasite, Plasmodium falciparum. A full understanding how the parasite adjusts its transmission in response to varying in-host environmental conditions during natural infections requires simultaneous quantification of early and late gametocytes. Here, we describe qRT-PCR assays that are specific for detection and quantification of early-stage gametocytes of P. falciparum.MethodsThe assays are based on expression of known early gametocyte genes (pfpeg4, pfg27, pfge1, pfge3 and pfgexp5). The specificity of the qRT-PCR assays was tested using purified stage II and stage V gametocytes. These validated assays were used with qRT-PCR assays targeting late stage (pfs25) and all-stage (pfs16) gametocyte-specific transcripts to quantify gametocytes in natural P. falciparum infections and in a controlled human clinical infection study.ResultsThe relative expression of pfpeg4, pfg27 and pfge3, but not of pfge1 and pfgexp5, was significantly higher in purified stage II compared to stage V gametocytes, indicating early gametocyte specificity. In natural infections, 71.2% of individuals had both early and late gametocyte transcripts (pfpeg4/pfg27 plus pfs25), 12.6% harboured only early gametocytes transcripts (pfpeg4/pfg27), and 15.2% had only late gametocytes transcripts (pfs25). In natural infections, the limit of detection was equivalent to 190 and 390 gametocytes/mL blood for pfpeg4 and pfg27, respectively. In infected volunteers, transcripts of pfpeg4 and pfg27 were detected shortly after the onset of blood stage infection, demonstrating the specificity of the assays.ConclusionThe pfpeg4 and pfg27 qRT-PCR assays can be used specifically to quantify circulating immature gametocytes. Quantification of early gametocytes will improve understanding of epidemiological processes that modulate P. falciparum transmission and enhance the evaluation of transmission blocking interventions.
A Vaccination Simulator for COVID-19: Effective and Sterilizing Immunization Cases
Authors: Karabay Aknur , Kuzdeuov Askat , Ospanova Shyryn , Lewis Michael , Varol Huseyin Atakan 
Published: April 2021

AbstractAccurate modeling provides a means by which a complex problem can be examined for informed decision-making. We present a particle-based SEIR epidemic simulator as a tool to assess the impact of vaccination strategies on viral propagation and to model both sterilizing and effective immunization outcomes. The simulator includes modules to support contact tracing of the interactions amongst individuals as well as epidemiological testing of the general population. The simulator particles are distinguished by age, thus enabling a more accurate representation of the rates of infection and mortality in accordance with differential demographic susceptibilities and medical outcomes. Moreover, thanks to the age differentiation of particles, the vaccination can be simulated based on the age group descending order or randomly across all age groups. The simulator can be calibrated by region of interest and variable vaccination strategies (i.e. random or prioritized by age) so as to enable locality-sensitive virus mitigation policy measures and resource allocation. The results described, based on the experience of the province of Lecco, Italy, indicate that the tool can be used to evaluate vaccination strategies in a way that incorporates local circumstances of viral propagation and demographic susceptibilities. Further, the simulator accounts for modeling the distinction between sterilizing immunization, in which immunized people are no longer contagious, and that of effective immunization, in which symptoms and mortality outcomes are diminished but individuals can still transmit the virus. The sterilizing-age-based vaccination scenario results in the least number of deaths compared to other scenarios. Furthermore, the results show that the vaccination of the most vulnerable portion of the population should be prioritized for the effective immunization case. As the vaccination rate increases, the mortality gap between the scenarios shrinks.
Evaluating the impact of Hazelwood mine fire event on students’ educational development with Bayesian interrupted time series hierarchical meta-regression
Authors: Gao Caroline X. , Broder Jonathan C. , Brilleman Sam , Campbell Tim C. H. , Berger Emily , Ikin Jillian , Smith Catherine L. , Wolfe Rory , Johnston Fay , Guo Yuming , Carroll Matthew 
Published: April 2021

AbstractBackgroundClimate disasters such as wildfires, floods and droughts can introduce significant interruptions and trauma to impacted communities. Children and young people can be disproportionately affected with additional educational disruptions. However, evaluating the impact of disasters is challenging due to difficulties in establishing studies and recruitment post-disasters.ObjectivesWith the increasing threat of climate change, we aimed to (1) establish a new analytical framework to evaluate the impact of climate disasters on academic achievement and (2) evaluate the impact of the 2014 Hazelwood mine fire (a six-week fire event in Australia).MethodsBayesian hierarchical meta-regression was developed to evaluate the impact of the mine fire using only aggregated school-level data from the standardised National Assessment Program-Literacy and Numeracy (NAPLAN) test. NAPLAN results and school characteristics (2008-2018) from 69 primary/secondary schools with different levels of mine fire-related smoke exposure were used to estimate the impact of the event. Using an interrupted time series design, the model estimated immediate effects and post-interruption trend differences with full Bayesian statistical inference.ResultsMajor academic interruptions across NAPLAN domains were evident in high exposure schools in the year post-mine fire (greatest interruption in Writing: 11.09 [95%CI: 3.16-18.93], lowest interruption in Reading: 8.34 [95%CI: 1.07-15.51]). The interruption was comparable to a four to five-month delay in educational attainment and had not fully recovered after several years.DiscussionConsiderable academic delays were found as a result of a mine fire, highlighting the need to provide educational and community-based supports in response to future events. Importantly, this work provides a statistical method using readily available aggregated data to assess the educational impacts in response to other climate disasters.Graphical abstract
Estimates and determinants of SARS-CoV-2 seroprevalence and infection fatality ratio using latent class analysis: the population-based Tirschenreuth study in the hardest-hit German county in spring 2020
Authors: Wagner Ralf , Peterhoff David , Beileke Stephanie , Guenther Felix , Berr Melanie , Einhauser Sebastian , Schütz Anja , Niller Hans Helmut , Steininger Philipp , Knöll Antje , Tenbusch Matthias , Maier Clara , Korn Klaus , Stark Klaus J. , Gessner Andre , Burkhardt Ralph , Kabesch Michael , Schedl Holger , Küchenhoff Helmut , Pfahlberg Annette B. , Heid Iris M. , Gefeller Olaf , Überla Klaus 
Published: April 2021

AbstractSARS-CoV-2 infection fatality ratios (IFR) remain controversially discussed with implications for political measures, but the number of registered infections depends on testing strategies and deduced case fatality ratios (CFR) are poor proxies for IFR. The German county of Tirschenreuth suffered a severe SARS-CoV-2 outbreak in spring 2020 with particularly high CFR.To estimate seroprevalence, dark figure, and IFR for the Tirschenreuth population aged ≥14 years in June/July 2020 with misclassification error control, we conducted a population-based study, including home visits for elderly, and analyzed 4203 participants for SARS-CoV-2 antibodies via three antibody tests (64% of our random sample). Latent class analysis yielded 8.6% standardized county-wide seroprevalence, dark figure factor 5.0, and 2.5% overall IFR. Seroprevalence was two-fold higher among medical workers and one third among current smokers with similar proportions of registered infections. While seroprevalence did not show an age-trend, the dark figure was 12.2 in the young versus 1.7 for ≥85-year-old. Age-specific IFRs were <0.5% below 60 years of age, 1.0% for age 60-69, 13.2% for age 70+, confirming a previously reported age-model for IFR. Senior care homes accounted for 45% of COVID-19-related deaths, reflected by an IFR of 7.5% among individuals aged 70+ and an overall IFR of 1.4% when excluding senior care home residents from our computation.Our data underscore senior care home infections as key determinant of IFR additionally to age, insufficient targeted testing in the young, and the need for further investigations on behavioral or molecular causes of the fewer infections among current smokers.
Situation of COVID-19 in Brazil: An analysis via growth models as implemented in the ModInterv system for monitoring the pandemic
Authors: Vasconcelos Giovani L. , Duarte-Filho Gerson C. , Brum Arthur A. , Ospina Raydonal , Almeida Francisco A. G. , Macêdo Antônio M. S. 
Published: April 2021

AbstractIn this work we analyze the cumulative curves of deaths attributed to COVID-19 in the 26 Brazilian States and the Federal District up until August 21, 2020. Mathematical growth models implemented by the application ModInterv COVID-19, which can be accessed via internet browser or via a mobile app, were used to investigate at which stage the epidemic is in each of the Brazilian federal units. The analysis revealed that almost all states in the Northern and Northeastern regions were already in the saturation phase, meaning that the epidemic was relatively under control, whereas in all Southern states and in most states in the Midwest the epidemic was still accelerating or showed only a slight deceleration. The Southeastern region presented a great diversity of epidemic stages, with each state being found at a different stage, ranging from acceleration to saturation. It is argued that understanding this heterogeneous geographical distribution of the epidemic is relevant for public health authorities, as it may help in devising more effective strategies against the COVID-19 pandemic in a continental country like Brazil.
Visuospatial neglect: Recovery & Functional outcome after 6 months
Authors: Moore Margaret Jane , Vancleef Kathleen , Riddoch M. Jane , Gillebert Celine R , Demeyere Nele 
Published: April 2021

AbstractBackground/ObjectiveThis study aims to investigate how complex visuospatial neglect behavioural phenotypes predict long-term outcomes, both in terms of neglect recovery and broader functional outcomes.MethodsThis study presents a secondary cohort study of acute and 6 month follow up data from 400 stroke survivors who completed the Oxford Cognitive Screen’s Cancellation Task. At follow-up, patients also completed the Stroke Impact Scale questionnaire. These data were analysed to identify whether any specific combination of neglect symptoms is more likely to result in long-lasting neglect or higher levels of functional impairment, therefore warranting more targeted rehabilitation.ResultsOverall, 98/142(69%) neglect cases recovered by follow-up and there was no significant difference in the persistence of egocentric/allocentric (X2(1)=0.66, p=0.418) or left/right neglect (X2(2)=0.781, p= 0.677). Egocentric neglect was found to follow a proportional recovery pattern with all patients demonstrating a similar level of improvement over time. Conversely, allocentric neglect followed a non-proportional recovery pattern with chronic neglect patients exhibiting a slower rate of improvement than those who recovered. A multiple regression analysis revealed that the initial severity of acute allocentric, but not egocentric, neglect impairment acted as a significant predictor of poor long-term functional outcomes (F(9,383)=3.96, p<0.001, R2=0.066).ConclusionsOur findings call for systematic neuropsychological assessment of both egocentric and allocentric neglect following stroke, as the occurrence and severity of these conditions may help predict recovery outcomes.
Using PARIHS framework to design a community-based COVID-19 intervention in rural Ghana
Authors: Frimpong Shadrack , Seidu Moro , Hilton Sam Kris 
Published: April 2021

AbstractThis study utilized the Promoting Action on Research Implementation in Health Services (PARIHS) framework to guide the design of the evidence-based practice – COVID Preparedness & Outbreak Prevention Plan (CoCoPOPP) for rural communities in Ghana. Through a participatory academic-community team discussion, interactive dissemination, review of evidence about community-based interventions during Ebola, HIV/AIDS, and Influenza outbreaks via snowball sampling, continuous discourse within the design team, feedback from other local stakeholders and national experts, the evidence-based intervention was developed consistent with the PARIHS framework. By applying the three core elements of the PARIHS framework (that is, evidence, context and facilitation), the study developed orientation, logistic needs and planning as well as social mobilization. The components also included participants recruitment and training, communication, research and M&E plan, execution and technical assistance and facilitation with three overall aims: (1) meet a pressing health need during the COVID-19 pandemic in local underserved settings, (2) ensure that the strategy is informed by high-quality evidence from similar interventions in past outbreaks and (3) evaluate and learn from research on interventions to garner data for organizational use and to share insights on pandemic management and control with the Ghanaian government, wider global health and education community. Hence, CoCoPOPP can be implemented across other rural communities in Ghana and beyond, particularly in other Sub-Saharan African countries with similar cultural settings.
Dynamics of amygdala connectivity in bipolar disorders: A longitudinal study across mood states
Authors: Rey Gwladys , Bolton Thomas A.W. , Gaviria Julian , Piguet Camille , Preti Maria Giulia , Favre Sophie , Aubry Jean-Michel , Van De Ville Dimitri , Vuilleumier Patrik 
Published: April 2021

AbstractAlterations in activity and connectivity of brain circuits implicated in emotion processing and emotion regulation have been observed during resting-state for different clinical phases of bipolar disorders (BD), but longitudinal investigations across different mood states in the same patients are still rare. Furthermore, measuring dynamics of functional connectivity patterns offers a powerful method to explore changes in the brain’s intrinsic functional organization across mood states. We used a novel co-activation pattern (CAP) analysis to explore the dynamics of amygdala connectivity at rest in a cohort of 20 BD patients prospectively followed-up and scanned across distinct mood states: euthymia (20 patients; 39 sessions), depression (12 patients; 18 sessions), or mania/hypomania (14 patients; 18 sessions). We compared them to 41 healthy controls scanned once or twice (55 sessions). We characterized temporal aspects of dynamic fluctuations in amygdala connectivity over the whole brain as a function of current mood. We identified 6 distinct networks describing amygdala connectivity, among which an interoceptive-sensorimotor CAP exhibited more frequent occurrences during hypomania compared to other mood states, and predicted more severe symptoms of irritability and motor agitation. In contrast, a limbic CAP comprising the hippocampus and ventral tegmental area exhibited fewer occurrences during both depression and hypomania compared to euthymia. Our results reveal distinctive interactions between amygdala and distributed brain networks in different mood states, and foster research on interoception systems especially during the manic phase. Our study also demonstrates the benefits of assessing brain dynamics in BD.
Multilevel and Quasi Monte Carlo methods for the calculation of the Expected Value of Partial Perfect Information
Authors: Fang Wei , Wang Zhenru , Giles Michael B. , Jackson Chris H. , Welton Nicky J. , Andrieu Christophe , Thom Howard 
Published: April 2021

AbstractThe expected value of partial perfect information (EVPPI) provides an upper bound on the value of collecting further evidence on a set of inputs to a cost-effectiveness decision model. Standard Monte Carlo (MC) estimation of EVPPI is computationally expensive as it requires nested simulation. Alternatives based on regression approximations to the model have been developed, but are not practicable when the number of uncertain parameters of interest is large and when parameter estimates are highly correlated. The error associated with the regression approximation is difficult to determine, while MC allows the bias and precision to be controlled. In this paper, we explore the potential of Quasi Monte-Carlo (QMC) and Multilevel Monte-Carlo (MLMC) estimation to reduce computational cost of estimating EVPPI by reducing the variance compared with MC, while preserving accuracy. In this paper, we develop methods to apply QMC and MLMC to EVPPI, addressing particular challenges that arise where Markov Chain Monte Carlo (MCMC) has been used to estimate input parameter distributions. We illustrate the methods using a two examples: a simplified decision tree model for treatments for depression, and a complex Markov model for treatments to prevent stroke in atrial fibrillation, both of which use MCMC inputs. We compare the performance of QMC and MLMC with MC and the approximation techniques of Generalised Additive Model regression (GAM), Gaussian process regression (GP), and Integrated Nested Laplace Approximations (INLA-GP). We found QMC and MLMC to offer substantial computational savings when parameter sets are large and correlated, and when the EVPPI is large. We also find GP and INLA-GP to be biased in those situations, while GAM cannot estimate EVPPI for large parameter sets.
Effect of telomerization on the growth patterns of adult cutaneous diploid fibroblasts
Authors: Zgurskiy Alexander A. , Prokhorov Leonid Yu. 
Published: April 2021

AbstractThe article describes effects of telomerization on proliferative activity in cultured cutaneous diploid fibroblasts obtained from an adult men aged 57 years. It is shown that the cells in the control culture initially divide quite actively, but starting from the 27th to the 40th passages, the rate of their division decreases and the time to reach the monolayer increases by about 2 times, and starting from the 42nd passage, the time to reach the monolayer increases by 4-10 times (up to 16-40 days). In a single case, an increase in the doubling time of control non-thelomerized cells was recorded up to 30 times (136 days). The introduction of the telomerase gene allowed cells maintain a high rate of cell division to about 45-47 passages. At the same time, the culture with the telomerase gene exceeds the control culture by 10 passages. Rate of growth the cells with telomerase gene after 48 and up to 57 passages slowed down by 10-18 times (up to 40-73 days). At the 47th passage in the control culture and at the 57th passage in the experimental culture, the cells practically stopped dividing and their number did not increase. The results show that the inclusion of the telomerase gene in adult fibroblasts does not always cancel the limit of cell divisions.
Single extracellular vesicle analysis performed by imaging flow cytometry in contrast to NTA rigorously assesses the accuracy of urinary extracellular vesicle preparation techniques
Authors: Droste Marvin , Tertel Tobias , Jeruschke Stefanie , Dittrich Robin , Kontopoulou Evangelia , Walkenfort Bernd , Börger Verena , Hoyer Peter F. , Büscher Anja K. , Thakur Basant K. , Giebel Bernd 
Published: April 2021

AbstractExtracellular vesicles (EVs) from several body fluids, including urine, appear as promising biomarkers. Within the last decade, numerous groups have compared the efficacy of EV preparation protocols. Frequently, the efficacy of EV preparation methods is judged by the recovery of particles as estimated by conventional nanoparticle tracking analysis (NTA) or other particle quantification devices. Here, at the example of different urinary EV (uEV) preparation methods, we determined the particle yield in obtained samples with conventional NTA, analyzed their EV content by imaging flow cytometry (IFCM) and quantified the intensity of TSG101 and the contaminant protein uromodulin (UMOD) in Western blots. Our results demonstrate a correlation among CD9-positive objects detected by IFCM and TSG101 Western blot intensities, while particle numbers as determined by NTA correlated with the amount of UMOD.Consequently, our results question the reliability of conventional NTA analyses for identifying the optimal EV preparation method. Here, in our method comparison, a combination of size exclusion chromatography followed by ultra-filtration showed the highest CD9-positive object and TSG101 protein recovery, and in relation to the number of CD9-positive objects, the lowest amount of UMOD contamination.
Privacy Preserving RNA-Model Validation Across Laboratories
Authors: Ahmed Talal , Carty Mark A , Wenric Stephane , Dry Jonathan R , Salahudeen Ameen Abdulla , Khan Aly A. , Lefkofsky Eric , Stumpe Martin C , Pelossof Raphael 
Published: April 2021

AbstractReproducibility of results obtained using RNA data across labs remains a major hurdle in cancer research. Often, molecular predictors trained on one dataset cannot be applied to another due to differences in RNA library preparation and quantification. While current RNA correction algorithms may overcome these differences, they require access to all patient-level data, which necessitates the sharing of training data for predictors when sharing predictors. Here, we describe SpinAdapt, an unsupervised RNA correction algorithm that enables the transfer of molecular models without requiring access to patient-level data. It computes data corrections only via aggregate statistics of each dataset, thereby maintaining patient data privacy. Furthermore, SpinAdapt can correct new samples, thereby enabling evaluation of validation cohorts. Despite an inherent tradeoff between privacy and performance, SpinAdapt outperforms current correction methods that require patient-level data access. We expect this novel correction paradigm to enhance research reproducibility and patient privacy. Finally, SpinAdapt lays a mathematical framework that can be extended to other -omics modalities.