bluuebunny/crossref_metadata_2025 huggingface dataset:
Unexpected cryptic species among streptophyte algae most distant to land plants
Authors: Irisarri Iker , Darienko Tatyana , Pröschold Thomas , Fürst-Jansen Janine M. R. , Jamy Mahwash , de Vries Jan
Published: November 2021

Streptophytes are one of the major groups of the green lineage (Chloroplastida or Viridiplantae). During one billion years of evolution, streptophytes have radiated into an astounding diversity of uni- and multicellular green algae as well as land plants. Most divergent from land plants is a clade formed by Mesostigmatophyceae,Spirotaeniaspp. and Chlorokybophyceae. All three lineages are species-poor and the Chlorokybophyceae consist of a single described species,Chlorokybus atmophyticus.In this study, we used phylogenomic analyses to shed light into the diversity withinChlorokybususing a sampling of isolates across its known distribution. We uncovered a consistent deep genetic structure within theChlorokybusisolates, which prompted us to formally extend the Chlorokybophyceae by describing four new species. Gene expression differences amongChlorokybusspecies suggest certain constitutive variability that might influence their response to environmental factors. Failure to account for this diversity can hamper comparative genomic studies aiming to understand the evolution of stress response across streptophytes. Our data highlight that future studies on the evolution of plant form and function can tap into an unknown diversity at key deep branches of the streptophytes.
Limited replication of human cytomegalovirus in a trophoblast cell line
Authors: Hyde Kadeem , Sultana Nowshin , Tran Andy C. , Bileckaja Narina , Donald Claire L. , Kohl Alain , Stanton Richard J. , Strang Blair L.
Published: November 2021

Several viruses, including human cytomegalovirus (HCMV), are thought to replicate in the placenta. However, there is little understanding of the molecular mechanisms involved in HCMV replication in this tissue. We investigated replication of HCMV in the extravillous trophoblast cell line SGHPL-4, a commonly used model of HCMV replication in the placenta. We found limited HCMV protein expression and virus replication in SGHPL-4 cells. This was associated with a lack of trophoblast progenitor cell protein markers in SGHPL-4 cells, suggesting a relationship between trophoblast differentiation and limited HCMV replication. We proposed that limited HCMV replication in trophoblast cells is advantageous to vertical transmission of HCMV, as there is a greater opportunity for vertical transmission when the placenta is intact and functional. Furthermore, when we investigated the replication of other vertically transmitted viruses in SGHPL-4 cells we found some limitation to replication of Zika virus, but not herpes simplex virus. Thus, limited replication of some, but not all, vertically transmitted viruses may be a feature of trophoblast cells.
Sixteen cases of severe pneumonia caused by Chlamydia psittaci in South China investigated via metagenomic next-generation sequencing
Authors: Xiao Qiang , Shen Wei , Zou Yeqiang , Dong Susu , Tan Yafen , Zhang Xuan , Yao Lu , Li Qiuping , Pei Wenjun , Wang Tianli
Published: November 2021

Introduction.

Chlamydia psittaci

is an important cause of community-acquired pneumonia (CAP). The spectrum of CAP due to

Chlamydia psittaci

ranges from mild, self-limited to acute respiratory failure and the early identification of this disease can be challenging. Metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid has the potential to improve the pathogen identification in severe CAP.

Hypothesis/Gap Statement. Metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid has the potential to rapidly identify pathogens in severe CAP. The early identification and appropriate use of antibiotics can improve the prognosis of severe CAP caused by

Chlamydia psittaci

.

Aim. The aim of the study is to describe the clinical spectrum of severe psittacosis pneumonia to provide a better understanding of this disease and to demonstrate that mNGS is an effective method for pathogen detection.

Methodology. Retrospective case analysis from November 2019 to November 2020 was performed. Sixteen cases of severe psittacosis pneumonia were diagnosed through mNGS. Clinical features, laboratory findings, imaging features, treatment and outcome were summarized.

Results. Frequent symptoms included fever (16/16, 100%), dyspnoea (16/16, 100%), cough (12/16, 75%), sputum (11/16, 69%) and headache (9/16, 56%). The median leukocytosis was within the normal range, while C-reactive proteins, CK, LDH, AST, D-Dimer were significantly elevated. The feature of computed tomography included ground-glass opacity with consolidation and multiple lobar distributions. The total number of sequences of

Chlamydia psittaci

identified from bronchoalveolar lavage by mNGS varied from 58 to 57115. Five patients underwent noninvasive mechanical ventilation, four patients underwent high flow humidified oxygen therapy and one patient underwent invasive mechanical ventilation. Two patients had septic shock needing vasoactive medications. All of the sixteen patients experienced full recoveries.

Conclusion. The symptoms of severe CAP caused by

Chlamydia psittaci

were not typical while laboratory results may have some clues. The mNGS technology can early detect of psittacosis, reduce unnecessary use of antibiotics and short the course of the disease.
Complete genome for Actinobacillus pleuropneumoniae serovar 8 reference strain 405: comparative analysis with draft genomes for different laboratory stock cultures indicates little genetic variation
Authors: Bossé Janine T. , Li Yanwen , Cohen Liza Miriam , Stegger Marc , Angen Øystein , Lacouture Sonia , Gottschalk Marcelo , Lei Liancheng , Koene Miriam , Kuhnert Peter , Bandara Aloka B. , Inzana Thomas J. , Holden Matthew T. G. , Harris David , Oshota Olusegun , Maskell Duncan J. , Tucker Alexander W. , Wren Brendan W. , Rycroft Andrew N. , Langford Paul R. ,   on behalf of the BRaDP1T consortium
Published: November 2021

We report here the complete genome sequence of the widely studied

Actinobacillus pleuropneumoniae

serovar 8 reference strain 405, generated using the Pacific Biosciences (PacBio) RS II platform. Furthermore, we compared draft sequences generated by Illumina sequencing of six stocks of this strain, including the same original stock used to generate the PacBio sequence, held in different countries and found little genetic variation, with only three SNPs identified, all within the degS gene. However, sequences of two small plasmids, pARD3079 and p405tetH, detected by Illumina sequencing of the draft genomes were not identified in the PacBio sequence of the reference strain.
Membrane lipid and osmolyte readjustment in the alkaliphilic micromycete Sodiomyces tronii under cold, heat and osmotic shocks
Authors: Ianutsevich Elena A. , Danilova Olga A. , Bondarenko Sofiya A. , Tereshina Vera M.
Published: November 2021

Previously, we showed for the first time that alkaliphilic fungi, in contrast to alkalitolerant fungi, accumulated trehalose under extremely alkaline conditions, and we have proposed its key role in alkaliphilia. We propose that high levels of trehalose in the mycelium of alkaliphiles may promote adaptation not only to alkaline conditions, but also to other stressors. Therefore, we studied changes in the composition of osmolytes, and storage and membrane lipids under the action of cold (CS), heat (HS) and osmotic (OS) shocks in the obligate alkaliphilic micromycete Sodiomyces tronii. During adaptation to CS, an increase in the degree of unsaturation of phospholipids was observed while the composition of osmolytes, membrane and storage lipids remained the same. Under HS conditions, a twofold increase in the level of trehalose and an increase in the proportion of phosphatidylethanolamines were observed against the background of a decrease in the proportion of phosphatidic acids. OS was accompanied by a decrease in the amount of membrane lipids, while their ratio remained unchanged, and an increase in the level of polyols (arabitol and mannitol) in the fungal mycelium, which suggests their role for adaptation to OS. Thus, the observed consistency of the composition of membrane lipids suggests that trehalose can participate in adaptation not only to extremely alkaline conditions, but also to other stressors – HS, CS and OS. Taken together, the data obtained indicate the adaptability of the fungus to the action of various stressors, which can point to polyextremotolerance.
Comprehensive genomic, immunological and clinical analysis of COVID-19 vaccine breakthrough infections: a prospective, comparative cohort study
Authors: Tian Di , Song Yang , Zhang Man , Pan Yang , Ge Ziruo , Zhang Yao , Ren Xingxiang , Wen Jing , Xu Yanli , Guo Hong , Yang Peng , Chen Zhihai , Xu Wenbo
Published: November 2021

Objectives

As the COVID-19 pandemic is still ongoing and SARS-CoV-2 variants are circulating worldwide, an increasing number of breakthrough infections have been detected despite the good efficacy of COVID-19 vaccines.

Methods

A prospective, comparative cohort study was conducted in Beijing Ditan Hospital to evaluate the clinical, immunological and genomic characteristics of COVID-19 breakthrough infections. Data on 88 COVID-19 breakthrough cases (vaccinated group) and 41 unvaccinated cases (unvaccinated group) from June 1 to August 20, 2021 were extracted from a cloud database. Among these 129 COVID-19 cases, we successfully sequenced 33 whole genomes, including 16 from the vaccinated group and 17 from the unvaccinated group.

Results

Asymptomatic and mild cases predominated in both groups, but 2 patients developed severe disease in the unvaccinated group. Between the two groups, the median time of viral shedding in the vaccinated group were significantly lower than those in the unvaccinated group (p = 0.003). A comparison of dynamic IgG titres of cases in the two groups indicated that IgG titres in the vaccinated group showed a significantly increasing trend (P =0.028). The CD4+T lymphocyte count was lower in the unvaccinated group, and there was a significant difference between the two groups (p=0.018). In the vaccinated group, the number of moderate cases who received Sinopharm BBIBP (42 cases) was significantly higher than those who received Sinovac Coronavac (p=0.020). Whole-genome sequencing revealed 23 cases of delta variants, including 15 patients from the vaccinated group. However, no significant difference was observed in either the RT-qPCR results or viral shedding time.

Conclusions

COVID-19 vaccine breakthrough infections were mainly asymptomatic and mild, the IgG titres were significantly higher and increased rapidly, and the viral shedding was short. Delta variants may be more likely to cause breakthrough infections, and vaccination may not reduce the viral loads and shedding time.
Protocol for Development of a Reporting Guideline for Causal and Counterfactual Prediction Models
Authors: Xu Jie , Guo Yi , Wang Fei , Xu Hua , Lucero Robert , Bian Jiang , Prosperi Mattia
Published: November 2021

Introduction

While there are protocols for reporting on observational studies (e.g., STROBE, RECORD), estimation of causal effects from both observational data and randomized experiments (e.g., AGREMA, CONSORT), and on prediction modelling (e.g., TRIPOD), none is purposely made for assessing the ability and reliability of models to predict counterfactuals for individuals upon one or more possible interventions, on the basis of given (or inferred) causal structures. This paper describes methods and processes that will be used to develop a reporting guideline for causal and counterfactual prediction models (tentative acronym: PRECOG).

Materials and Methods

PRECOG will be developed following published guidance from the EQUATOR network, and will comprise five stages. Stage 1 will be bi-weekly meetings of a working group with external advisors (active until stage 5). Stage 2 will comprise a scoping/systematic review of literature on counterfactual prediction modelling for biomedical sciences (registered in PROSPERO). In stage 3, we will perform a computer-based, real-time Delphi survey to consolidate the PRECOG checklist, involving experts in causal inference, statistics, machine learning, prediction modelling and protocols/standards. Stage 4 will involve the write-up of the PRECOG guideline (including its checklist) based on the results from the prior stages. In stage 5, we will work on the publication of the guideline and of the scoping/systematic review as peer-reviewed, open-access papers, and on their dissemination through conferences, websites, and social media.

Conclusions

PRECOG can help researchers and policymakers to carry out and critically appraise causal and counterfactual prediction model studies. PRECOG will also be useful for designing interventions, and we anticipate further expansion of the guideline for specific areas, e.g., pharmaceutical interventions.
Spatiotemporal mapping of major trauma in Victoria, Australia
Authors: Beck Ben , Zammit-Mangion Andrew , Fry Richard , Smith Karen , Gabbe Belinda
Published: November 2021

Background

Spatiotemporal modelling techniques allow one to predict injury across time and space. However, such methods have been underutilised in injury studies. This study demonstrates the use of statistical spatiotemporal modelling in identifying areas of significantly high injury risk, and areas witnessing significantly increasing risk over time.

Methods

We performed a retrospective review of hospitalised major trauma patients from the Victorian State Trauma Registry, Australia, between 2007 and 2019. Geographical locations of injury events were mapped to the 79 local government areas (LGAs) in the state. We employed Bayesian spatiotemporal models to quantify spatial and temporal patterns, and analysed the results across a range of geographical remoteness and socioeconomic levels.

Results

There were 31,317 major trauma patients included. For major trauma overall, we observed substantial spatial variation in injury incidence and a significant 2.1% increase in injury incidence per year. Area-specific risk of injury by motor vehicle collision was higher in regional areas relative to metropolitan areas, while risk of injury by low fall was higher in metropolitan areas. Significant temporal increases were observed in injury by low fall, and the greatest increases were observed in the most disadvantaged LGAs.

Conclusions

These findings can be used to inform injury prevention initiatives, which could be designed to target areas with relatively high injury risk and with significantly increasing injury risk over time. Our finding that the greatest year-on-year increases in injury incidence were observed in the most disadvantaged areas highlights the need for a greater emphasis on reducing inequities in injury.
Conserved recombination patterns across coronavirus subgenera
Authors: de Klerk Arné , Swanepoel Phillip , Lourens Rentia , Zondo Mpumelelo , Abodunran Isaac , Lytras Spyros , MacLean Oscar A , Robertson David , Kosakovsky Pond Sergei L , Zehr Jordan D , Kumar Venkatesh , Stanhope Michael J. , Harkins Gordon , Murrell Ben , Martin Darren P
Published: November 2021

Recombination contributes to the genetic diversity found in coronaviruses and is known to be a prominent mechanism whereby they evolve. It is apparent, both from controlled experiments and in genome sequences sampled from nature, that patterns of recombination in coronaviruses are non-random and that this is likely attributable to a combination of sequence features that favour the occurrence of recombination breakpoints at specific genomic sites, and selection disfavouring the survival of recombinants within which favourable intra-genome interactions have been disrupted. Here we leverage available whole-genome sequence data for six coronavirus subgenera to identify specific patterns of recombination that are conserved between multiple subgenera and then identify the likely factors that underlie these conserved patterns. Specifically, we confirm the non-randomness of recombination breakpoints across all six tested coronavirus subgenera, locate conserved recombination hot- and cold-spots, and determine that the locations of transcriptional regulatory sequences are likely major determinants of conserved recombination breakpoint hot-spot locations. We find that while the locations of recombination breakpoints are not uniformly associated with degrees of nucleotide sequence conservation, they display significant tendencies in multiple coronavirus subgenera to occur in low guanine-cytosine content genome regions, in non-coding regions, at the edges of genes, and at sites within the Spike gene that are predicted to be minimally disruptive of Spike protein folding. While it is apparent that sequence features such as transcriptional regulatory sequences are likely major determinants of where the template-switching events that yield recombination breakpoints most commonly occur, it is evident that selection against misfolded recombinant proteins also strongly impacts observable recombination breakpoint distributions in coronavirus genomes sampled from nature.
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

Bioassessment 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

1

Bayesian 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

Background and aims

Functional 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.

Methods

We 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.

Results

In 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.

Conclusion

Our 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

Aim

To 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).

Methods

In 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).

Results

We 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.

Conclusions

Our 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

Background

Household 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.

Methods

Using 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.

Results

A 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).

Conclusion

Multi-generational clusters were not highly prevalent in England during the study period, however were more common in certain populations.

BOX TEXT

What is already known on this subject

Greater 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 adds

This 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

We 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

Liberia 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

The 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

Current 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

Purpose

Within 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.

Method

We 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.

Results

Participatory 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.

Conclusions

The 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

Objectives

To appraise the causal effect of systemic lupus erythematosus (SLE) for risk of Coronary heart disease (CHD).

Methods

We 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.

Results

Genetically 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.

Conclusion

SLE 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.
Efficacy of Sofosbuvir, Daclatasvir and Ribavirin combination therapy in treatment naïve hepatitis C patients at tertiary care hospital of South Punjab
Authors: Umar Qasim , Gul Muhammad Asif , Din Chaudhary Farooq Mohyud , Kanju Shehryar , Hameed Rizwan , Shahwar Dure
Published: November 2021

Introduction

Hepatitis C has gradually become endemic in Pakistan, with infectivity rates one of the highest in the world. The emergence of direct acting antivirals (DAAs) has become a ray of sunshine in eradicating this menace from this region. The combination of sofosbuvir, daclatasvir and ribavirin (SOF/DACLA/RIBA) has had phenomenal success all over the world in eradicating this virus. Our study aims to see the effectiveness of this regime in this part of the world.

Methods

After approval from the institutional review board (IRB), retrospective analysis of data of treatment naïve patients who have been treated with the above mentioned regimen was collected to assess the efficacy by calculating the sustained virological response (SVR) at 12 weeks after completion of therapy.

Results

Data of 300 patients (172 females, 128 males) was collected. Mean age was 39.66 years. Majority (almost 90%) of patients were from District Multan Age range was from 18 years to 60 years. Eighty-three percent of the patients were non-cirrhotics, 15.7% had compensated cirrhosis, while only 1 % had decompensated cirrhosis. Out of the 300 patients, 291 patients had undetectable HCV RNA on polymerase chain reaction (PCR) at 12 weeks after completion of treatment, achieving SVR rates of 97%. There was no significant association of SVR rates with gender and age of patients.

Conclusion

The combination of SOF/DACA/RIBA is highly efficacious for treatment of hepatitis C patients.
amica: an interactive and user-friendly web-platform for the analysis of proteomics data
Authors: Didusch Sebastian , Madern Moritz , Hartl Markus , Baccarini Manuela
Published: November 2021

Quantitative proteomics has become an increasingly prominent tool in the study of life sciences. A substantial hurdle for many biologists are, however, the intricacies involved in the associated high throughput data analysis. In order to facilitate this task for users with limited background knowledge, we have developed amica, a freely available open-source web-based software that accepts proteomic input files from different sources and provides quality control, differential expression, biological network and over-representation analysis on the basis of minimal user input. Scientists can use amica interactively to compare proteins across multiple groups, create customized output graphics, and ultimately export the results in a tab-separated format that can be shared with collaborators.

Availability and Implementation

The code for the application, input data and documentation can be accessed online at https://github.com/tbaccata/amica and is also incorporated in the web application. A freely available version of amica is available at https://bioapps.maxperutzlabs.ac.at/app/amica.
A chromosome-level reference genome of Ensete glaucum gives insight into diversity, chromosomal and repetitive sequence evolution in the Musaceae
Authors: Wang Ziwei , Rouard Mathieu , Biswas Manosh Kumar , Droc Gaetan , Cui Dongli , Roux Nicolas , Baurens Franc-Christophe , Ge Xue-Jun , Schwarzacher Trude , Heslop-Harrison Pat (J.S.) , Liu Qing
Published: November 2021

Background

Ensete glaucum (2n = 2x = 18) is a giant herbaceous monocotyledonous plant in the small Musaceae family along with banana (Musa). A high-quality reference genome sequence of E. glaucum offers a vital genomic resource for functional and evolutionary studies of Ensete, the Musaceae, and more widely in the Zingiberales.

Findings

Using a combination of Illumina and Oxford Nanopore Technologies (ONT) sequencing, genome-wide chromosome conformation capture (Hi-C), and RNA survey sequence, we report a high-quality assembly of the 481.5Mb genome with 9 pseudochromosomes and 36,836 genes (BUSCO 94.7%). A total of 55% of the genome is composed of repetitive sequences with LTR-retroelements (37%) and DNA transposons (7%) predominant. The 5S and 45S rDNA were each present at one locus, and the 5S rDNA had an exceptionally long monomer length of c.1,056 bp, contrasting with the c. 450 bp monomer at multiple loci in Musa. A tandemly repeated c. 134 bp satellite, 1.1% of the genome (with no similar sequence in Musa), was present around all nine centromeres, with a LINE retroelement also found at Musa centromeres. The assembly, including centromeric positions, enabled us to characterize in detail the chromosomal rearrangements occurring between the x = 9 species and x = 11 species of Musa. Only one chromosome has the same gene content as M. acuminata (ma). Three ma chromosomes represent part of only one E. glaucum (eg) chromosome, while the remaining seven ma chromosomes are fusions of parts of two, three, or four eg chromosomes, demonstrating complex and multiple evolutionary rearrangements in the change between x = 9 and x = 11.

Conclusions

The advance towards a Musaceae pangenome including E. glaucum, tolerant of extreme environments, makes a complete set of gene alleles available for crop breeding and understanding environmental responses. The chromosome-scale genome assembly show how chromosome number evolves, and features of the rapid evolution of repetitive sequences.
A bioactive phlebovirus-like envelope protein in a hookworm endogenous retrovirus
Authors: Merchant Monique , Mata Carlos P. , Liu Yangci , Zhai Haoming , Protasio Anna V. , Modis Yorgo
Published: November 2021

Endogenous retroviruses (ERVs), accounting for 14% of our genome, serve as a genetic reservoir from which new genes can emerge. Nematode ERVs are particularly diverse and informative of retrovirus evolution. We identify Atlas virus – a novel, intact ERV in the human hookworm Ancylostoma ceylanicum with an envelope protein genetically related to GN-GC glycoproteins from phleboviruses. A cryo-EM structure of Atlas GC reveals a class II viral membrane fusion protein fold not previously seen in retroviruses. Atlas GC has the structural hallmarks of an active fusogen. Atlas GC trimers insert into membranes with endosomal lipid compositions and low pH. When expressed on the plasma membrane, Atlas GC has cell-cell fusion activity. Atlas virus is transcriptionally active at specific stages of hookworm development. The preserved activities and expression pattern of Atlas GC suggest it has acquired a cellular function. Our work reveals an unexpected degree of structural and genetic plasticity in retroviruses.
Inferring kinetic rate constants from single-molecule FRET trajectories – a blind benchmark of kinetic analysis tools
Authors: Götz Markus , Barth Anders , Bohr Søren S.-R. , Börner Richard , Chen Jixin , Cordes Thorben , Erie Dorothy A. , Gebhardt Christian , Hadzic Mélodie C.A.S. , Hamilton George L. , Hatzakis Nikos S. , Hugel Thorsten , Kisley Lydia , Lamb Don C. , de Lannoy Carlos , Mahn Chelsea , Dunukara Dushani , de Ridder Dick , Sanabria Hugo , Schimpf Julia , Seidel Claus A.M. , Sigel Roland K.O. , Sletfjerding Magnus Berg , Thomsen Johannes , Vollmar Leonie , Wanninger Simon , Weninger Keith R. , Xu Pengning , Schmid Sonja
Published: November 2021

Single-molecule FRET (smFRET) is a versatile technique to study the dynamics and function of biomolecules since it makes nanoscale movements detectable as fluorescence signals. The powerful ability to infer quantitative kinetic information from smFRET data is, however, complicated by experimental limitations. Diverse analysis tools have been developed to overcome these hurdles but a systematic comparison is lacking. Here, we report the results of a blind benchmark study assessing eleven analysis tools used to infer kinetic rate constants from smFRET trajectories. We tested them against simulated and experimental data containing the most prominent difficulties encountered in analyzing smFRET experiments: different noise levels, varied model complexity, non-equilibrium dynamics, and kinetic heterogeneity. Our results highlight the current strengths and limitations in inferring kinetic information from smFRET trajectories. In addition, we formulate concrete recommendations and identify key targets for future developments, aimed to advance our understanding of biomolecular dynamics through quantitative experiment-derived models.