bluuebunny/crossref_metadata_2025_split huggingface dataset:
Towards environmental DNA-based bioassessment of freshwater reservoirs with small volumes of water: robust molecular protocols
Authors: Loh Rebecca K. , Kutty Sujatha N. , Yeo Darren C. J. , Meier Rudolf 
Published: November 2021

AbstractBioassessment of freshwater quality via eDNA is rapidly developing into a powerful alternative to traditional methods involving collecting, sorting, and identifying macroinvertebrates based on morphology. Particularly attractive would be methods that can use remote-controlled boats for sampling because it would allow for cost-effective, and frequent monitoring at multiple sites. The latter will be particularly important for tropical reservoirs that require year-around surveillance. We here optimize molecular protocols for capturing reservoir-specific differences in metazoan communities based on small water volumes (15 mL). The optimization is based on samples from two freshwater reservoirs with very different water qualities (“reservoir signal”). Each reservoir was sampled at three sites (“biological replicates”). For each water sample, the DNA was extracted twice (“technical replicates”). We then tested how much DNA template (0.1 ng to 15 ng) and how many PCR cycles (25 or 35) minimized variance between technical replicates. We find that 15 mL is sufficient for capturing the reservoir signal regardless of sampling time, template amounts, or PCR cycle numbers. Indeed, extrapolation from our results suggests that <1 mL would be sufficient because only 17 of 59 metazoan mOTUs (mainly planktonic crustaceans and rotifers) detected with a 313bp COI minibarcode were shared. We find that the use of 35 PCR cycles significantly lowered the number of detected species and that template amounts <0.5 ng yielded somewhat higher variance between technical replicates. Despite extensive trials, the variance between technical replicates remained high (Bray-Curtis: 5–20%; Jaccard: 10–40%) and we predict that it will be difficult to reduce this variance further. However, the overall reservoir differences are so strong that all biological and technical replicates can be correctly assigned.
Real-time and remote MCMC trace inspection with Beastiary
Authors: Wirth Wytamma , Duchene Sebastian 
Published: November 2021

1AbstractBayesian phylogenetic methods have gained substantial popularity in the last decade, due to their ability to incorporate independent information and fit complex models. Most Bayesian implementations rely on Markov chain Monte Carlo (MCMC), which in turn requires careful interpretation of the output to assess the statistical validity of any resulting inferences. Here we describe Beastiary, a package for real-time and remote inspection of log flies generated by MCMC analysis commonly utilised in Bayesian phylogenetic analysis. Beastiary is an easily deployed web-sever that can be used to summarise and visualise the output of many popular software packages including BEAST, BEAST2, RevBayes, and MrBayes. We describe the overall design and implementation of Beastiary and some typical use cases, with a particular focus on the capability of monitoring analyses from remote servers.
Distinct Adaptive Immunophenotypes in duodenal mucosa but not in peripheral blood of patients with functional dyspepsia
Authors: Burns Grace L. , Bruce Jessica , Minahan Kyra , Mathe Andrea , Fairlie Thomas , Cameron Raquel , Naudin Crystal , Nair Prema M. , Potter Michael D. E. , Irani Mudar Zand , Bollipo Steven , Foster Robert , Gan Lay T. , Shah Ayesha , Koloski Natasha , Foster Paul S. , Horvat Jay , Veysey Martin , Holtmann Gerald , Powell Nick , Walker Marjorie M. , Talley Nicholas J. , Keely Simon 
Published: November 2021

ABSTRACTBackground and aimsFunctional dyspepsia is characterised by chronic symptoms of post- prandial distress or epigastric pain not associated with defined structural pathology. Increased peripheral gut-homing T cell have been previously identified in patients. To date, it is unknown if these T cells were antigen-experienced, or if a specific immunophenotype was associated with FD. This study aimed to characterise immune populations in the blood and duodenal mucosa of FD patients that may be implicated in disease pathophysiology.MethodsWe identified duodenal T cell populations from 23 controls and 49 Rome III FD patients by flow cytometry. We also analysed duodenal eosinophils and T cell populations in peripheral blood from 37 controls and 49 patients and investigated if subtyping patients based on reported symptoms or co-morbidity identified specific immunophenoptypes.ResultsIn addition to increased duodenal mucosal CD4+effector cells, FD patients demonstrated a shift in the T helper cell balance compared to controls. Patients had increased duodenal mucosal Th2 populations in the effector (13.03±16.11, 19.84±15.51,p=0.038), central memory (23.75±18.97, 37.52±17.51,p=0.007) and effector memory (9.80±10.50 vs 20.53±14.15,p=0.001) populations. Th17 populations were also increased in the effector (31.74±24.73 vs 45.57±23.75,p=0.03) and effector memory (11.95±8.42 vs 18.44±15.63,p=0.027) subsets.ConclusionOur findings confirm the involvement of adaptive responses in the aetiopathogenesis of FD, specifically a Th2 and Th17 signature in the duodenal mucosa. The presence of effector and memory cells suggest that the microinflammation in FD is antigen driven.
Comparing health care use after hospital visit for SARS-CoV-2, respiratory syncytial virus, and other respiratory tract infections in children
Authors: Larsen Vilde Bergstad , Størdal Ketil , Telle Kjetil , Methi Fredrik , Magnusson Karin 
Published: November 2021

AbstractAimTo explore whether children in specialist care with COVID-19 have increased post-discharge health care use when compared to children in specialist care with 1) respiratory syncytial virus (RSV) infection, and 2) other respiratory tract infections (RTIs).MethodsIn 34,214 children aged 1 month to 5 years who were registered with one or more hospital visit (outpatient or inpatient) with a diagnosis of COVID-19 (N=128), RSV infection (N=4,009), or other RTIs (N=34,458) from 2017-2021, we used a difference-in-differences study design to investigate the individual all-cause primary and specialist health care use from 12 weeks prior to 12 weeks after the hospital visit, stratified on infants (1-12 months) and children (1-5 years).ResultsWe found a slight increase in primary health care use in the first four weeks after the hospital visit for infants with COVID-19 when compared to infants with RSV infection (6 [95%CI=2 to 13] per 10,000, 0.52% relative increase). For infants diagnosed with COVID-19, we found a similar post-visit increase in inpatients when compared to infants with RSV infection, which lasted for 12 weeks.ConclusionsOur findings imply slightly increased health care use among infants after hospital visit for COVID-19 than among infants with other respiratory tract infections, for which potential etiological mechanisms deserve future clinical research. Severe COVID-19 in young children will not represent any markedly increased burden on the health services.
The role of multi-generational household clusters in COVID-19 in England
Authors: Thelwall Simon , Zaidi Asad , Nsonwu Olisaeloka , Rice Wendy , Chudasama Dimple , Lamagni Theresa , Dabrera Gavin 
Published: November 2021

ABSTRACTBackgroundHousehold transmission has been demonstrated to be an important factor in the population-level growth of COVID-19. UK Health Security Agency (UKHSA) maintains data on positive tests for COVID-19 and the residential addresses of cases. We sought to use this information to characterise clusters of COVID-19 in multi-generational households in England.MethodsUsing cross-sectional design, cases of COVID-19 were assigned to clusters if they occurred in the same residential property in a 14-day rolling window. Patient demographic data were supplemented with reference to the ONS index of multiple deprivation and population density. Multi-generational households were defined as a cluster with at least three people, with one case in a person who was 0-16 years old and one case in a person who was ≥ 60 years old, with at least 16 years between two members of each age group.ResultsA total of 3,647,063 COVID-19 cases were reported between 01 April 2020 and 20 May 2021. Of these, 1,980,527 (54.3 %) occurred in residential clusters. Multi-generational households formed 1.5 % of clusters, with these more likely to occur in areas of higher population density and higher relative deprivation. Multi-generational clusters were more common among households of non-White ethnicity and formed larger clusters than non-multi-generational clusters (median cluster size 6, IQR 4-11 vs 3, IQR 3-4, respectively).ConclusionMulti-generational clusters were not highly prevalent in England during the study period, however were more common in certain populations.BOX TEXTWhat is already known on this subjectGreater risk of infection with SARS-CoV-2 in England is associated with being of non-White ethnicity, residence in an area of greater deprivation and higher population density. What is less clear is the role of household composition in the risk of COVID-19 transmission. It has been hypothesised that multi-generational housing (in which at least three different generations are resident in the same property) accounted for a substantial proportion of COVID-19 cases. We sought to test this hypothesis.What this study addsThis study provides descriptive evidence around the role of multi-generational households in the COVID-19 pandemic in England between April 2020 and March 2021. It does not support the hypothesis that this period (a period of low incidence in England), a substantial proportion of COVID-19 cases occurred in multi-generational households.
Impacts of vaccination and asymptomatic testing on SARS-CoV-2 transmission dynamics in a university setting
Authors: Nixon Emily , Thomas Amy , Stocks Daniel , Barreaux Antoine M.G. , Hemani Gibran , Trickey Adam , Kwiatkowska Rachel , Walker Josephine , Ellis David , Danon Leon , Relton Caroline , Christensen Hannah , Brooks-Pollock Ellen 
Published: November 2021

AbstractWe investigate the impact of vaccination and asymptomatic testing uptake on SARS-CoV-2 transmission in a university student population using a stochastic compartmental model. We find that the magnitude and timing of outbreaks is highly variable depending on the transmissibility of the most dominant strain of SARS CoV-2 and under different vaccine uptake levels and efficacies. When delta is the dominant strain, low level interventions (no asymptomatic testing, 30% vaccinated with a vaccine that is 80% effective at reducing infection) lead to 53-71% of students become infected during the first term. Asymptomatic testing is most useful when vaccine uptake is low: when 30% of students are vaccinated, 90% uptake of asymptomatic testing leads to almost half the case numbers. With high interventions (90% using asymptomatic testing, 90% vaccinated) cumulative incidence is 7-9%, with around 80% of these cases estimated to be asymptomatic. However, under emergence of a new variant that is at least twice as transmissible as delta and with the vaccine efficacy against infection reduced to 55%, large outbreaks are likely in universities, even with very high (90%) uptake of vaccination and 100% uptake of asymptomatic testing. If vaccine efficacy against infection against this new variant is higher (70%), then outbreaks can be mitigated if there is least 50% uptake of asymptomatic testing additional to 90% uptake of vaccination. Our findings suggest that effective vaccination is critical for controlling SARS-CoV-2 transmission in university settings with asymptomatic testing ranging from additionally useful to critical, depending on effectiveness and uptake of vaccination. Other measures may be necessary to control outbreaks under the emergence of a more transmissible variant with vaccine escape.
Impact of the Liberian National Community Health Assistant Program on Childhood Illness Treatment in Grand Bassa County, Liberia: A Difference-in-Differences Analysis of Population-Based Data
Authors: White Emily , Mendin Savior , Kolubah Featha R. , Karlay Robert , Grant Ben , Jacobs George P. , Subah Marion , Siedner Mark J. , Kraemer John D. , Hirschhorn Lisa R. 
Published: November 2021

AbstractLiberia launched its National Community Health Assistant Program in 2016, which seeks to ensure that all people living 5 kilometers or farther from a health facility have access to trained, supplied, supervised, and paid community health workers (CHWs). This study aims to evaluate the impact of the national program following implementation in Grand Bassa County in 2018 using data from population-based surveys.We measured before-to-after changes in childhood treatment from qualified providers in a portion of the county that implemented in a first phase compared to those which had not yet implemented. We also assessed changes in whether children received oral rehydration therapy for diarrhea and malaria rapid diagnostic tests if they had a fever by a qualified provider (facility based or CHW). For these analyses, we used a difference-in-differences approach and adjusted for potential confounding using inverse probability of treatment weighting. We also assessed changes in the source from which care was received and examined changes by key dimensions of equity (distance from health facilities, maternal education, and household wealth).We found that treatment of childhood illness by a qualified provider increased by 60.3 percentage points (95%CI 44.7-76.0) more in intervention than comparison areas. Difference-in-differences for oral rehydration therapy and malaria rapid diagnostic tests were 37.6 (95%CI 19.5-55.8) and 38.5 (95%CI 19.9-57.0) percentage points, respectively.In intervention areas, treatment by a CHW increased from 0 to 81.6% and care from unqualified providers dropped. Increases in treatment by a qualified provider did not vary significantly by household wealth, remoteness, or maternal education.This evaluation found evidence that the Liberian National Community Health Assistant Program has increased access to effective treatment in rural Grand Bassa County. Improvements were approximately equal across three measured dimensions of marginalization.
SARS-CoV-2 genome-based severity predictions correspond to lower qPCR values and higher viral load
Authors: Skarzynski Martin , McAuley Erin M. , Maier Ezekiel J. , Fries Anthony C. , Voss Jameson D. , Chapleau Richard R. 
Published: November 2021

AbstractThe 2019 coronavirus disease (COVID-19) pandemic has demonstrated the importance of predicting, identifying, and tracking mutations throughout a pandemic event. As the COVID-19 global pandemic surpassed one year, several variants had emerged resulting in increased severity and transmissibility. In order to reduce the impact on human life, it is critical to rapidly identify which genetic variants result in increased virulence or transmission. To address the former, we evaluated if a genome-based predictive algorithm designed to predict clinical severity could predict polymerase chain reaction (PCR) results, as a surrogate for viral load and severity. Using a previously published algorithm, we compared the viral genome-based severity predictions to clinically-derived PCR-based viral load of 716 viral genomes. For those samples predicted to be “severe” (predicted severity score > 0.5), we observed an average cycle threshold (Ct) of 18.3, whereas those in in the “mild” category (severity prediction < 0.5) had an average Ct of 20.4 (P = 0.0017). We found a non-trivial correlation between predicted severity probability and cycle threshold (r = −0.199). Additionally, when divided into quartiles by prediction severity probability, the most probable quartile (≥75% probability) had a Ct of 16.6 (n=10) as compared to those least probable to be severe (<25%) of 21.4 (n=350) (P = 0.0045). Taken together, our results suggest that the severity predicted by a genome-based algorithm can be related to the metrics from the clinical diagnostic test, and that relative severity may be inferred from diagnostic values.
Preclinical evaluation of a COVID-19 vaccine candidate based on a recombinant RBD fusion heterodimer of SARS-CoV-2
Authors: Barreiro Antonio , Prenafeta Antoni , Bech-Sabat Gregori , Roca Mercè , Mur Eva Perozo , March Ricard , González-González Luis , Madrenas Laia , Corominas Júlia , Fernández Alex , Moros Alexandra , Cañete Manuel , Molas Mercè , Pentinat-Pelegrin Thais , Panosa Clara , Moreno Alberto , Molas Ester Puigvert , Vilarrassa Eva Pol , Palmada Jordi , Garriga Carme , Cabañas Teresa Prat , Iglesias-Fernández Javier , Vergara-Alert Júlia , Lorca-Oró Cristina , Roca Núria , Fernández-Bastit Leira , Rodon Jordi , Pérez Mònica , Segalés Joaquim , Pradenas Edwards , Marfil Silvia , Trinité Benjamin , Ortiz Raquel , Clotet Bonaventura , Blanco Julià , Pedroza Jorge Díaz , Carrasco Rosa Ampudia , Salgado Yaiza Rosales , Loubat-Casanovas Jordina , Larripa Sara Capdevila , Prado Julia Garcia , Barretina Jordi , Sisteré-Oró Marta , Rica Paula Cebollada , Meyerhans Andreas , Ferrer Laura 
Published: November 2021

SummaryCurrent C0VID-19 vaccines have been associated with a decline in infection rates, prevention of severe disease and a decrease in mortality rates. However, SARS-CoV-2 variants are continuously evolving, and development of new accessible COVID-19 vaccines is essential to mitigate the pandemic. Here, we present data on preclinical studies in mice of a receptor-binding domain (RBD)-based recombinant protein vaccine (PHH-1V) consisting of an RBD fusion heterodimer comprising the B.1.351 and B.1.1.7 SARS-CoV-2 variants formulated in SQBA adjuvant, an oil-in-water emulsion. A prime-boost immunisation with PHH-1V in BALB/c and K18-hACE2 mice induced a CD4+and CD8+T cell response and RBD-binding antibodies with neutralising activity against several variants, and also showed a good tolerability profile. Significantly, RBD fusion heterodimer vaccination conferred 100% efficacy, preventing mortality in SARS-CoV-2 infected K18-hACE2 mice, but also reducing Beta, Delta and Omicron infection in lower respiratory airways. These findings demonstrate the feasibility of this recombinant vaccine strategy.
Mapping climate change and health into the medical curriculum: co-development of a “planetary health – organ system map” for graduate medical education
Authors: Burch Hayden , Watson Benjamin , Simpson Grace , Beaton Laura J. , Maxwell Janie , Winkel Ken 
Published: November 2021

AbstractPurposeWithin the context of a review of a Doctor of Medicine graduate curriculum, medical students partnered with faculty staff to co-develop a novel curriculum resource exemplifying the integration of planetary determinants of health into existing medical curricula.MethodWe undertook qualitative methodologies involving a planetary health literature review and curriculum mapping exercise in three parts between April 2018 - May 2021. In part one, a student focus group sought students’ perceptions on opportunities for climate-change related teaching. Part two involved two 5-hour workshops that mapped planetary health principles to classical organ systems-based teaching areas. Part three consisted of curriculum mapping expert review.ResultsParticipatory workshops involved 26 students and positioned students as leaders and partners in curriculum development alongside academics and clinicians. Final synthesis produced a comprehensive infographic rich document covering seven organ systems plus healthcare’s ecological footprint, the role of medical students and opportunities for applied skills and behaviours.ConclusionsThe student-staff co-production method adopted here promotes higher order relational and extended abstract reasoning by students, the ultimate task of any higher education. This approach, and the open access resource generated, provides an integrated and novel planetary health framework, supporting students to be leaders for a sustainable future.Practice Points[1]This project provides a methodology to overcome barriers to curriculum-wide integration of planetary determinants of health and a template to move beyond stand-alone planetary health workshops or population health case studies.[2]Student and educator co-development of planetary health teaching and learning resources promotes higher order relational and extended abstract reasoning by students, the ultimate task of any higher education.[3]Integrating planetary health supports emerging clinicians in all areas of medicine to be leaders for a sustainable future.
Association between Systemic Lupus Erythematosus and Coronary Heart Disease: a retrospective case-control analysis and Mendelian Randomization Study
Authors: Chen Jinyun , Tian Junmei , Wang Wen , Zhou Shiliang , Zhang Lu , Jiang Wanlan , Cai Mingyuan , Zhang Peirong , Xu Ting , Wu Min 
Published: November 2021

AbstractObjectivesTo appraise the causal effect of systemic lupus erythematosus (SLE) for risk of Coronary heart disease (CHD).MethodsWe selected single nucleotide polymorphisms (SNPs) associated with SLE as instrumental variables (IVs) from three independent genome-wide association studies (GWAS), the three largest to date for SLE of European ancestry. Then we conducted two-sample Mendelian randomization (2SMR) analyses to estimate the effects of IVs on the odds of CHD and traditional coronary risk factors (including high LDL cholesterol levels, low HDL cholesterol levels, Apolipoprotein A-I, Apolipoprotein B, diabetes mellitus, and hypertension). Additionally, we searched for common risk loci between SLE and premature coronary atherosclerosis. Furthermore, we retrospectively reviewed the lipid profile of treatment-naïve SLE patients and age-matched healthy controls.ResultsGenetically predicted SLE did not increase the odds of CHD. Nevertheless, we found mild causal relationships between SLE and decreased HDL cholesterol levels, and between SLE and decreased apolipoprotein A-I. There was one common risk locus (rs597808) between SLE and premature coronary atherosclerosis at a genome-wide significance level (P<5 × 10−8). Retrospective analysis showed decreased HDL-cholesterol (0.98±0.516mmol/L vs. 1.46±0.307mmol/L in female, 0.76±0.199mmol/L vs. 1.19±0.257mmol/L in male; both P<0.001) and apolipoprotein A-I (1.06±0.314g/L vs. 1.37±0.205g/L in female, 0.87±0.174g/L vs. 1.24±0.200g/L in male; both P<0.001) in naïve SLE patients.ConclusionSLE may accelerate coronary atherosclerosis in young patients by reducing HDL cholesterol and apolipoprotein A-I intrinsically, but it seems not to play a predominant role in CHD development in old patients.