bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcutaneous Osseo-integrated Auditory Devices: Analysis of Two Different Implants in Adults With Different Audiological Inclusion Criteria
Authors: Plasencia Daniel Perez , Suárez Antonia Alemán , Barreiro Silvia Borkoski , de Miguel Angel Ramos , Macias Angel Ramos
Published: September 2021

Objective:

To determine and compare audiological and speech/language discrimination results in patients with osteo-integrated auditory devices, by comparing two different systems including different audiological indications in adult population.

Study Design:

Descriptive and analytic, cross-sectional, cohort, and retrospective case review.

Setting:

Tertiary referral center.

Materials and Methods:

Fifty patients >14 years old, with conductive, mixed, or unilateral sensorineural hearing loss were compared. The variables studied were the following: pure tone audiometry results, air-bone gap, and the percentage of speech/language discrimination using Disyllabic Word Test. The patients were tested preoperative and 12 months after surgical procedure. Subsequently, a comparative analysis of the both systems was carried out.

Results:

With both implants, pure tone audiometry results and the difference in auditory thresholds and between the air-bone gap improved significantly. Speech discrimination increased significantly after implantation too. A significant difference was observed after implantation of both devices. Patients implanted with one of the implants showed better audiological results, but no significant differences were found with the other device. So, it was shown that the type of device and the type of hearing loss have no influence on the audiological results or complications.

Conclusion:

Both implants represent a good choice for audiological rehabilitation in patients with transmissive hearing loss, mixed hearing loss, or unilateral sensorineural hearing loss with a high success and low complication rates.
An Analysis of Ptosis following Subfascial Breast Augmentation: Calculations That Explain Dogma
Authors: Brown Tim
Published: September 2021

Background:

Implant placement can improve ptosis due to the position of the nipple, inframammary crease, and base of the breast acting together. The interrelationship between these was quantified via changes in morphometry following subfascial augmentation, and explains the circumstances under which dogma holds true.

Methods:

One hundred seventy-five patients underwent a series of static measurements before and 3 months after subfascial breast augmentation. Ptosis in the nipple and base of the breast was calculated before and after surgery.

Results:

All measurements except that of the the lateral sternal margin increased after surgery. All grades of ptosis reduced following surgery. There was lowering of the base in grade 1 patients, but not for other grades. Increased base ptosis correlated with reduced lateral sternal margin (1.9 cm compared with 2.9 cm; left, H5 = 24.7, p < 0.01; right, H5 = 24.5, p < 0.01). Implant volume did not correlate with change in ptosis at the nipple or base. Reduced ptosis was associated with implants that are a narrow match of implant to breast (0.52 to 0.95) (left, H5 = 28.3, p < 0.01; right, H5 = 24.9, p < 0.01). Decreasing ptosis correlated with lower lateral sternal margin compared to breasts that increased ptosis. Change in ptosis following surgery does not correlate with having children.

Conclusions:

Subfascial placement has varying effects on ptosis. Non-ptotic or mildly ptotic breasts appear to improve due to a disproportionate descent of the inframammary crease relative to the nipple and base. Patients with little breast tissue are more susceptible to an increase in "bottoming out," particularly if broad implants are used. A ratio matching implant to the base width has predictive value on outcome.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Safety, Immunogenicity, and Efficacy of COVID-19 Vaccine in Children and Adolescents: A Systematic Review
Authors: Lv Meng , Luo Xufei , Shen Quan , Lei Ruobing , Liu Xiao , Liu Enmei , Li Qiu , Chen Yaolong
Published: September 2021

Aim

To identify the safety, immunogenicity, and protective efficacy of COVID-19 vaccine in children and adolescents.

Methods

We conducted a systematic review. Databases including PubMed, Web of Science, WHO COVID-19 database, and CNKI were searched on 23 July 2021. International Clinical Trials Registry Platform (ICTRP) was also searched to collect ongoing trials. We included published researches or ongoing clinical trials related to the safety, immunogenicity, and efficacy of COVID-19 vaccine in children or adolescents (aged ≤18 years). Meta-analysis was performed if the consistency of the included studies was high. If not, descriptive analyses were performed.

Results

Eight published studies with 2851 children or adolescents and 28 ongoing clinical trials were included. Among eight published studies, two (25.0%) were RCTs, two (25.0%) case series, and four (50.0%) case reports. The results showed selected COVID-19 vaccines had a good safety profile in children and adolescents. Injection site pain, fatigue, headache, and chest pain were the most common adverse events. Some studies reported a few cases of myocarditis and pericarditis. Two RCTs showed that the immune response to BNT162b2 in adolescents aged 12-15 years was non-inferior to that in young people aged 16-25 years, while a stronger immune response was detected with 3μg CoronaVac injection. Only one single RCT showed the efficacy of BNT162b2 was 100% (95% CI: 75.3 to 100). Of the 28 ongoing clinical trials, twenty-three are interventional studies. Fifteen countries are conducting interventional clinical trials of COVID-19 vaccines in children and adolescents. Among them, China (10, 43.5%) and United Stated (9, 39.1%) were the top two countries with the most trials. BNT162b2 was the most common vaccine, which is under testing.

Conclusion

Some of the COVID-19 vaccines have potential protective effects in children and adolescents, but awareness is needed to monitor possible adverse effects after injection. Clinical trials of the COVID-19 vaccine in children and adolescents with long follow-up, large sample size, and different vaccines are still urgently needed.
Mask Interventions in K12 Schools Can Also Reduce Community Transmission in Fall 2021
Authors: Mele Jessica , Rosenstrom Erik , Ivy Julie , Mayorga Maria , Patel Mehul D. , Swann Julie
Published: September 2021

The dominance of the COVID-19 Delta variant has renewed questions about the impact of K12 school policies, including the role of masks, on disease burden.1 A recent study showed masks and testing could reduce infections in students, but failed to address the impact on the community,2 while another showed masking is critical to slow disease spread in communities, but did not consider school openings under Delta.3 We project the impact of school-masking on the community, which can inform policy decisions, and support healthcare system planning. Our findings indicate that the implementation of masking policies in school settings can reduce additional infections post-school opening by 23-36% for fully-open schools, with an additional 11-13% reduction for hybrid schooling, depending on mask quality and fit. Masking policies and hybrid schooling can also reduce peak hospitalization need by 71% and result in the fewest additional deaths post-school opening. We show that given the current vaccination rates within the community, the best option for children and the general population is to employ consistent high-quality masking, and use social distancing where possible.
Robust induction of B cell and T cell responses by a third dose of inactivated SARS-CoV-2 vaccine
Authors: Liu Yihao , Zeng Qin , Deng Caiguanxi , Li Mengyuan , Li Liubing , Liu Dayue , Liu Ming , Ruan Xinyuan , Mei Jie , Mo Ruohui , Zhou Qian , Liu Min , Peng Sui , Wang Ji , Zhang Hui , Xiao Haipeng
Published: September 2021

SARS-CoV-2 inactivated vaccines have shown remarkable efficacy in clinical trials, especially in reducing severe illness and casualty. However, the waning of humoral immunity over time has raised concern over the durability of immune memory following vaccination. Thus, we conducted a non-randomized trial among the healthcare professionals (HCWs) to investigate the long-term sustainability of SARS-CoV-2-specific B cells and T cells stimulated by inactivated vaccines and the potential need for a third booster dose. Although neutralizing antibodies elicited by the standard two-dose vaccination schedule dropped from a peak of 29.3 AU/ml to 8.8 AU/ml 5 months after the second vaccination, spike-specific memory B and T cells were still detectable, forming the basis for a quick recall response. As expected, the faded humoral immune response was vigorously elevated to 63.6 AU/ml by 7.2 folds 1 week after the third dose along with abundant spike-specific circulating follicular helper T cells in parallel. Meanwhile, spike-specific CD4+ and CD8+ T cells were also robustly elevated by 5.9 and 2.7 folds respectively. Robust expansion of memory pools by the third dose potentiated greater durability of protective immune responses. Another key finding in this trial was that HCWs with low serological response to 2 doses were not truly “non-responders” but fully equipped with immune memory that could be quickly recalled by a third dose even 5 months after the second vaccination. Collectively, these data provide insights into the generation of long-term immunological memory by the inactivated vaccine, which could be rapidly recalled and further boosted by a third dose.
A comparative study of Bacterial culture isolates, site of infections and drug resistance pattern between COVID and non COVID patients admitted in a tertiary care hospital: A Pilot study
Authors: Halder Arup , Mukherjee Deep Narayan , Seal Soumyadeep , Dasgupta Hindol , Chakraborty Mainak
Published: September 2021

Introduction

SARS-CoV2 which is a corona virus also predisposes patient to secondary bacterial infection by various mechanisms like-damaging the respiratory epithelium, profoundly affecting the innate and adaptive immunity, antagonising Interferon responses that enhance bacterial adherence, colonisation and invasion to respiratory tissue. In addition, prolonged hospital stay, invasive therapeutic devices, widespread use of empiric antibiotics and most importantly use of immune-suppressants like Steroid or Tocilizumab further increases the chances of bacterial infection. As opposed to this concept-physical distancing, frequent hand washing and use of gloves and protective gear by the healthcare workers also diminishes the chance of secondary bacterial infection. The present study is done to delineate the bacteriological profile, infection site predisposition or to gain knowledge on antibiotic sensitivity pattern.

Method

Retrospective data will be analyzed from June 2020, when the first COVID wave came to June 2021, corresponding to second COVID wave. The present study is a pilot study before collecting and analyzing the whole data Only those samples which were positive for bacterial isolates were randomly selected and the COVID status and drug resistance patterns were checked.

Results and discussion

The most common organism found was Klebsiella. Acinetobacter was also found in few patients. But most striking finding was that COVID positive patients showed higher incidence of antibiotic resistance with Acinetobacter. Though E Coli was also found commonly in COVID positive patients, they were not drug resistant.

Conclusion

MDR infections are common in COVID patients. Acinetobacter and Klebsiella are prone to develope MDR infections. While E.Coli is also common in COVID patients, chance of drug resistance is less among them.
RISK FACTORS FOR EARLY NATURAL MENOPAUSE: EVIDENCE FROM THE 1958 AND 1970 BRITISH BIRTH COHORTS
Authors: Peycheva Darina , Sullivan Alice , Hardy Rebecca , Bryson Alex , Conti Gabriella , Ploubidis George
Published: September 2021

Using data from two generations of British women followed from birth through childhood and into adulthood, we investigate risk factors for the onset of natural menopause before the age of 45 (known as early menopause). We focus on key stages during the life course to understand when risk factors are particularly harmful. We find that earlier cessation of menstruation is influenced by circumstances at birth. Women born in lower social class families, whose mother smoked during the pregnancy or who were short-term breastfed (one month or less) were more likely to undergo menopause before 45. Early menopause is also associated with poorer cognitive ability and smoking in childhood. Adult health behaviour also matters. Smoking is positively correlated with early menopause, while regular exercise (one to several times a week) and moderate frequency of alcohol drinking (one to three times a month) in women’s early thirties are associated with a reduced risk of early menopause. The occurrence of gynaecological problems by women’s early thirties is also linked to early menopause. We note that some of these factors (e.g. health behaviours) are modifiable and thus the risks may be preventable.
Pairwise genetic meta-analyses between schizophrenia and substance dependence phenotypes reveals novel association signals
Authors: Greco Laura A. , Reay William R. , Dayas Christopher V. , Cairns Murray J.
Published: September 2021

Almost half of individuals diagnosed with schizophrenia also present with a substance use disorder, however, little is known about potential molecular mechanisms underlying this comorbidity. We used genetic analyses to enhance our understanding of the molecular overlap between these conditions. Our analyses revealed a positive genetic correlation between schizophrenia and the following dependence phenotypes: alcohol (rg= 0.3685,SE= 0.0768,P =1.61 × 10−06), cannabis use disorder (rg= 0.309,SE= 0.0332,P =1.19 × 10−20) and nicotine dependence (rg= 0.1177,SE= 0.0436,P =7.0 × 10-03), as well as lifetime cannabis use (rg= 0.234,SE= 0.0298,P =3.73 × 10−15) and drinks per week (rg= 0.0688,SE= 0.0217,P =1.5 × 10−03). We further constructed latent causal variable (LCV) models to test for partial genetic causality and found evidence for a potential causal relationship between alcohol dependence and schizophrenia (GCP =0.6,SE= 0.22,P =1.6 × 10−03). This putative causal effect with schizophrenia was not seen using a continuous phenotype of drinks consumed per week, suggesting that distinct molecular mechanisms underlying dependence are involved in the relationship between alcohol and schizophrenia. To localise the specific genetic overlap between schizophrenia and substance use disorders, we conducted a gene-based and gene-set pairwise meta-analysis between schizophrenia and each of the four individual substance dependence phenotypes in up to 790,806 individuals. These bivariate meta-analyses identified 44 associations not observed in the individual GWAS, including five shared genes that play a key role in early central nervous system development. These genes may play an important role in substance dependence in schizophrenia, and, as a result, could represent important targets for future treatment or early intervention, as comorbid substance dependence is associated with poor treatment adherence, greater chronicity and increased mortality.
Behavior in mice subjected to a Token Slot-machine: effect of Unpredictable Chronic Mild Stress
Authors: Sfregola Arwen Emy , Brizard Bruno , Le Guisquet Anne-Marie , Tillet Clémence , Lefèvre Eulalie , Bruni Luigino , Belzung Catherine
Published: September 2021

Several studies have succeeded in teaching animals (primates, pigeons, rats, but not mice) the value of tokens by having them executing a task using a vending-machine apparatus, where in order to receive the primary reinforcement (food), the animals had to perform a specific action that allowed them to obtain the secondary reinforcement (tokens: metal balls). We tried to assess this kind of behavior in mice that had previously been trained to use some tokens, with the aim of rewarding them not with food, but with other tokens, as a result of a token economy task. We found that mice exhibit economic behavior. Further on, our research tried to investigate the effect of stress on their operant decision-making. Therefore, the mice were divided into two groups: a Control group (n=10) and a group subjected to an Unpredictable Chronic Mild Stress (UCMS) treatment (n=8). We found that chronic stress increases some aspects of sub-optimal economic activity.

Summary statement

We designed an original model enabling to assess behavior in mice that had previously been trained to use some tokens, with the aim of rewarding them not with food, but with other tokens. Further on, our research investigated the effect of stress on their operant decision-making.
Detailed Overview of the Buildout and Integration of an Automated High-Throughput CLIA Laboratory for SARS-CoV-2 Testing on a Large Urban Campus
Authors: Landaverde Lena , McIntyre David , Robson James , Fu Dany , Ortiz Luis , Chen Rita , Oliveira Samuel M.D. , Fan Andy , Barrett Amy , Burgay Stephen P. , Choate Stephen , Corbett David , Doucette-Stamm Lynn , Gonzales Kevin , Hamer Davidson H. , Huang Lilly , Huval Shari , Knight Christopher , Lindquist Diane , Lockard Kelly , Macdowell Trevor L. , Mauro Elizabeth , McGinty Colleen , Miller Candice , Monahan Maura , Moore Randall , Platt Judy , Roy Jeffrey , Schroeder Tracey , Tolan Dean R. , Zaia Ann , Brown Robert A. , Waters Gloria , Densmore Douglas , Klapperich Catherine M.
Published: September 2021

In 2019, the first cases of SARS-CoV-2 were detected in Wuhan, China, and by early 2020 the cases were identified in the United States. SARS-CoV-2 infections increased in the US causing many states to implement stay-at-home orders and additional safety precautions to mitigate potential outbreaks. As policies changed throughout the pandemic and restrictions lifted, there was an increase in demand for Covid-19 testing which was costly, difficult to obtain, or had long turn-around times. Some academic institutions, including Boston University, created an on-campus Covid-19 screening protocol as part of planning for the safe return of students, faculty, and staff to campus with the option for in-person classes. At BU, we stood up an automated high-throughput clinical testing lab with the capacity to run 45,000 individual tests weekly by fall of 2020, with a purpose-built clinical testing laboratory, a multiplexed RT-PCR test, robotic instrumentation, and trained CLIA certified staff. There were challenges to overcome, including the supply chain issues for PPE testing materials, and equipment that were in high demand. The Boston University Clinical Testing Laboratory was operational at the start of the fall 2020 academic year. The lab performed over 1 million SARS-CoV-2 RT-PCR tests during the 2020-2021 academic year.
Molecular Programs of Glomerular Hyperfiltration in Early Diabetic Kidney Disease
Authors: Stefansson Vidar T. N. , Nair Viji , Melsom Toralf , Looker Helen C. , Mariani Laura H. , Fermin Damian , Eichinger Felix , Menon Rajasree , Subramanian Lalita , Harder Jennifer L. , Hodgin Jeffrey B. , Nelson Peter J. , Eriksen Bjørn O. , Nelson Robert G. , Kretzler Matthias
Published: September 2021

Hyperfiltration (HF) is a state of high glomerular filtration rate (GFR) observed in early diabetes that damages glomeruli, resulting in an iterative process of increasing filtration load on fewer and fewer remaining functional glomeruli. To delineate underlying cellular mechanisms of damage induced by HF, transcriptional profiles of kidney biopsies from Pima Indians with type 2 diabetes with or without early-stage diabetic kidney disease (DKD) were grouped into two HF categories based on annual iothalamate GFR measurements. Twenty-six participants with a peak GFR measurement within two years of biopsy were categorized as the “HF group”, and 26 in whom biopsy preceded peak GFR by >2 years were considered “pre-HF”. The HF group had higher hemoglobin A1c, higher urine albumin-to-creatinine ratio, increased glomerular basement membrane width and lower podocyte density compared to the pre-HF group. A glomerular 1240-gene transcriptional signature identified in the HF group was enriched for endothelial stress response signaling genes, including from endothelin-1, tec-kinase and TGF-β1 pathways, with the majority of the transcripts mapped to endothelial and inflammatory cell clusters in kidney single cell transcriptional data. This analysis reveals molecular pathomechanisms contributing to development of HF and early DKD and involving putative ligand-receptor pairs and downstream intracellular targets linked to cellular crosstalk between endothelial and mesangial cells.
Spread of SARS-CoV-2 Delta variant infections bearing the S:E484Q and S:T95I mutations in July and August 2021 in France
Authors: Verdurme Laura , Danesh Gonché , Trombert-Paolantoni Sabine , Sofonea Mircea T. , Noel Valérie , Foulongne Vincent , Montès Brigitte , Tuaillon Edouard , Haim-Boukobza Stéphanie , Roquebert Bénédicte , Alizon Samuel
Published: September 2021

Analysing 92,598 variant screening tests performed on SARS-CoV-2 positive samples collected in France between 1 July and 31 August 2021 shows an increase of Kappa-like infections. Full genome sequencing reveals that these correspond to Delta variants bearing the S:E484Q mutation. Most of these sequences belong to a phylogenetic cluster and also bear the S:T95I mutation. Further monitoring is needed to determine if this trend is driven by undocumented superspreading events or an early signal of future viral evolutionary dynamics.
Platelet polyphosphate and SARS-Cov-2 mRNA-vaccine-induced inflammatory side effects: a pilot study
Authors: Uematsu Takashi , Sato Atsushi , Aizawa Hachidai , Tsujino Tetsuhiro , Watanabe Taisuke , Isobe Kazushige , Kawabata Hideo , Kitamura Yutaka , Tanaka Takaaki , Kawase Tomoyuki
Published: September 2021

Background

Platelets have recently been recognized as immune cells. Platelets first contact invading pathogens and then induce immune reactions in cooperation with white blood cells. Platelet polyphosphate (polyP), which is classically recognized as a thrombotic and hemostatic biomolecule, has recently attracted attention as a ‘cytokine’ that modulates inflammation and is involved in intercellular communication between platelets and major immune cells.

Objective

To determine the involvement of polyP in SARS-Cov-2-mRNA vaccine-induced immune responses, this pilot study examined the effects of mRNA vaccines on platelet polyP levels.

Methods

Before and after vaccination (BNT162b2), blood samples were obtained from healthy, non-smoking individuals (relatively older male group, n=6 vs. younger female group, n=23), who did not have systemic diseases that required continuous treatment. Washed platelets were prepared and subjected to a fluorometric determination of platelet polyP levels using 4’,6-diamidino-2-phenylindole. The side effects of vaccination were recorded as scores.

Results

Compared with the male group, platelet polyP levels decreased in the relatively younger female group after the initial dose, while the side effect score increased in the female group after the second dose. Moderate correlation coefficients were observed between the reduction in polyP levels and the side effect scores or the original polyP levels.

Conclusions

Despite being a pilot study using a small sample size, this study suggests the possibility that platelet polyP may suppress the side effects induced by the mRNA vaccines after the initial dose, but not the second dose, in relatively young female subjects who generally have high immune responsiveness.

Essentials

The COVID-19 mRNA vaccines (BNT162b2) reduced platelet polyP levels after the initial dose, but not after the 2nddose, in relatively younger female subjects.

Relatively older male subjects did not respond to the vaccination by reducing platelet polyP.

These findings suggest that platelets release polyP to suppress vaccine-induced reactions, for example, inflammation, which is usually recognized as a side effect.

However, such suppression could be observed in subjects with higher immune responses, generally in relatively younger female subjects.
Social Capital Dimensions are Differentially Associated with COVID-19 Vaccinations, Masks, and Physical Distancing *
Authors: Ferwana Ibtihal , Varshney Lav R.
Published: September 2021

Background

Social capital has been associated with health outcomes in communities and can explain variations in different geographic localities. Social capital has also been associated with behaviors that promote better health and reduce the impacts of diseases. During the COVID-19 pandemic, social distancing, face masking, and vaccination have all been essential in controlling contagion. These behaviors have not been uniformly adopted by communities in the United States. Using different facets of social capital to explain the differences in public behaviors among communities during pandemics is lacking.

Objective

This study examines the relationship among public health behavior—vaccination, face masking, and physical distancing—during COVID-19 pandemic and social capital indices in counties in the United States.

Methods

We used publicly available vaccination data as of June 2021, face masking data in July 2020, and mobility data from mobile phones movements from the end of March 2020. Then, correlation analysis was conducted with county-level social capital index and its subindices (family unity, community health, institutional health, and collective efficacy) that were obtained from the Social Capital Project by the United States Senate.

Results

We found the social capital index and its subindices differentially correlate with different public health behaviors. Vaccination is associated with institutional health: positively with fully vaccinated population and negatively with vaccination hesitancy. Also, wearing masks negatively associates with community health, whereases reduced mobility associates with better community health. Further, residential mobility positively associates with family unity. By comparing correlation coefficients, we find that social capital and its subindices have largest effect sizes on vaccination and residential mobility.

Conclusion

Our results show that different facets of social capital are significantly associated with adoption of protective behaviors, e.g., social distancing, face masking, and vaccination. As such, our results suggest that differential facets of social capital imply a Swiss cheese model of pandemic control planning where, e.g., institutional health and community health, provide partially overlapping behavioral benefits.
MetaTrass: High-quality metagenome assembly on the human gut microbiome by co-barcoding sequencing reads
Authors: Qi Yanwei , Gu Shengqiang , Zhang Yue , Guo Lidong , Xu Mengyang , Cheng Xiaofang , Wang Ou , Chen Jianwei , Fang Xiaodong , Liu Xin , Deng Li , Fan Guangyi
Published: September 2021

With the development of sequencing technologies and computational analysis in metagenomics, the genetic diversity of non-conserved regions has been receiving intensive attention to unravel the human gut microbial community. However, it remains a challenge to obtain enough microbial draft genomes at a high resolution from a single sample. In this work, we presented MetaTrass with a strategy of binning first and assembling later to assemble high-quality draft genomes based on metagenomics co-barcoding reads and the public reference genomes. We applied the tool to the single tube long fragment reads datasets for four human faecal samples, and generated more high-quality draft genomes with longer contiguity and higher resolution than the common combination strategies of genome assembling and binning. A total of 178 high-quality genomes was successfully assembled by MetaTrass, but the maximum of 58 was generated by the optimal common combination strategy in our tests. These high-quality genomes paved the way for genetic diversity and lineage analysis among different samples. With the high capability of assembling high-quality genomes of metagenomics datasets, MetaTrass will facilitate the study of spatial characters and dynamics of complex microbial communities at high resolution. The open-source code of MetaTrass is available at https://github.com/BGI-Qingdao/MetaTrass.
In Silico Epitope Prediction And VP1 Modelling For Foot-And-Mouth Serotype SAT 2 For Vaccine Design In East Africa
Authors: Udahemuka Jean Claude , Accadius Lunayo , Obiero George , Aboge Gabriel , Lebea Phiyani
Published: September 2021

Foot and Mouth Disease Virus has seven distinct, geographically localized, serotypes and a vaccination targeting one serotype does not confer immunity against another serotype. The use of inactivated vaccines is not safe and confers an immunity with a relatively shorter time. Using the VP1 sequences isolated in East Africa, we have predicted epitopes able to induce humoral and cell-mediated immunity in cattle. The Wu-Kabat variability index calculated in this study reflects the variable, including the known GH loop, and conserved regions, with the latter being good candidates for region-tailored vaccine design. Furthermore, we modelled the identified epitopes on a 3D model (PDB ID:5aca) to represent the epitopes structurally. This study can be used for in vitro and in vivo experiments.
Confronting population models with experimental microcosm data: from trajectory matching to state-space models
Authors: Rosenbaum Benjamin , Fronhofer Emanuel A.
Published: September 2021

Population and community ecology traditionally has a very strong theoretical foundation with well-known dynamical models, such as the logistic and its variations, and many modification of the classical Lotka-Volterra predator-prey and interspecific competition models. More and more, these classical models are being confronted with data via fitting to empirical time series for purposes of projections or for estimating model parameters of interest. However, using statistical models to fit theoretical models to data is far from trivial, especially for time series data where subsequent measurements are not independent. This raises the question of whether statistical inferences using pure observation error models, such as simple (non-)linear regressions, are biased, and whether more elaborate process error models or state-space models have to be used to address this complexity.

In order to help empiricists, especially researchers working with experimental laboratory populations in micro- and mesocosms, make informed decisions about the statistical formalism to use, we here compare different error structures one could use when fitting classical deterministic ODE models to empirical data. We consider a large range of biological scenarios and theoretical models, from single species to community dynamics and trophic interactions. In order to compare the performance of different error structure models, we use both realistically simulated data and empirical data from microcosms in a Bayesian framework.

We find that many model parameters can be estimated precisely with an appropriate choice of error structure using pure observation error or state-space models, if observation errors are not too high. However, Allee effect models are typically hard to identify and state-space models should be preferred when model complexity increases.

Our work shows that, at least in the context of low environmental stochasticity and high quality observations, deterministic models can be used to describe stochastic population dynamics that include process variability and observation error. We discuss when more complex state-space model formulations may be required for obtaining accurate parameter estimates. Finally, we provide a comprehensive tutorial for fitting these models in R.

Open research

Code for stochastic individual-based simulations is available fromhttps://doi.org/10.5281/zenodo.5500442. A tutorial for fitting ODE models to time series data in R is presented in the Supplementary Information and is also available onlinehttps://github.com/benjamin-rosenbaum/fittingdeterministic population models. Data (Fronhofer et al., 2020) will be provided via GitHub and Zenodo.
Predictors of human-infective RNA virus discovery in the United States, China and Africa, an ecological study
Authors: Zhang Feifei , Chase-Topping Margo , Guo Chuan-Guo , Woolhouse Mark E.J.
Published: September 2021

Background

The variation in the pathogen type as well as the spatial heterogeneity of predictors make the generality of any associations with pathogen discovery debatable. Our previous work confirmed that the association of a group of predictors differed across different types of RNA viruses, yet there have been no previous comparisons of the specific predictors for RNA virus discovery in different regions. The aim of the current study was to close the gap by investigating whether predictors of discovery rates within three regions—the United States, China and Africa—differ from one another and from those at the global level.

Methods

Based on a comprehensive list of human-infective RNA viruses, we collated published data on first discovery of each species in each region. We used a Poisson boosted regression tree (BRT) model to examine the relationship between virus discovery and 33 predictors representing climate, socio-economics, land use, and biodiversity across each region separately. The discovery probability in three regions in 2010–2019 was mapped using the fitted models and historical predictors.

Results

The numbers of human-infective virus species discovered in the United States, China and Africa up to 2019 were 95, 80 and 107 respectively, with China lagging behind the other two regions. In each region, discoveries were clustered in hotspots. BRT modelling suggested that in all three regions RNA virus discovery was best predicted by land use and socio- economic variables, followed by climatic variables and biodiversity, though the relative importance of these predictors varied by region. Map of virus discovery probability in 2010– 2019 indicated several new hotspots outside historical high-risk areas. Most new virus species since 2010 in each region (6/6 in the United States, 19/19 in China, 12/19 in Africa) were discovered in high risk areas as predicted by our model.

Conclusions

The drivers of spatiotemporal variation in virus discovery rates vary in different regions of the world. Within regions virus discovery is driven mainly by land-use and socio- economic variables; climate and biodiversity variables are consistently less important predictors than at a global scale. Potential new discovery hotspots in 2010–2019 are identified. Results from the study could guide active surveillance for new human-infective viruses in local high risk areas.

Funding

Darwin Trust of Edinburgh; European Union.
Mapping brain-wide excitatory projectome of primate prefrontal cortex at submicron resolution: relevance to diffusion tractography
Authors: Yan Mingchao , Yu Wenwen , Lv Qian , Lv Qiming , Bo Tingting , Chen Xiaoyu , Liu Yilin , Zhan Yafeng , Yan Shengyao , Shen Xiangyu , Yang Baofeng , Qiu Zilong , Feng Yuanjing , Zhang Xiaoyong , Wang He , Xu Fuqiang , Wang Zheng
Published: September 2021

Resolving trajectories of axonal pathways in the primate prefrontal cortex remains crucial to gain insights into higher-order processes of cognition and emotion, which requires a comprehensive map of axonal projections linking demarcated subdivisions of prefrontal cortex and the rest of brain. Here we report a mesoscale excitatory projectome issued from the ventrolateral prefrontal cortex (vlPFC) to the entire macaque brain by using viral-based genetic axonal tracing in tandem with high-throughput serial two-photon tomography, which demonstrated prominent monosynaptic projections to other prefrontal areas, temporal, limbic and subcortical areas, relatively weak projections to parietal and insular cortices but no projections directly to the occipital lobe. In a common 3D space, we quantitatively validated an atlas of diffusion tractography-derived vlPFC connections with correlative enhanced green fluorescent protein-labelled axonal tracing, and observed generally good agreement except a major difference in the posterior projections of inferior fronto-occipital fasciculus. These findings raise an intriguing question as to how neural information passes along long-range association fiber bundles in macaque brains, and call for the caution of using diffusion tractography to map the wiring diagram of brain circuits.
DNA metabarcoding reveals host-specific communities of arthropods residing in fungal fruit bodies
Authors: Lunde Lisa Fagerli , Birkemoe Tone , Kauserud Håvard , Boddy Lynne , Jacobsen Rannveig M. , Sverdrup-Thygeson Anne , Maurice Sundy
Published: September 2021

Biological communities within living organisms are structured by their host’s traits. How host traits affect biodiversity and community composition is poorly explored for some associations, such as arthropods within fungal fruit bodies. Using DNA metabarcoding, we revealed the arthropod communities in living fruit bodies of eleven wood-decay fungi from boreal forests and investigated how they were affected by different fungal traits. Arthropod diversity was higher in fruit bodies with a larger surface area-to-volume ratio, suggesting that colonisation is crucial to maintain arthropod populations. Diversity was not higher in long-lived fruit bodies, most likely because these fungi invest in physical or chemical defences against arthropods. Arthropod community composition was structured by all measured host traits, namely fruit body size, thickness, surface area, morphology and toughness. Notably, we identified a community gradient where soft and short-lived fruit bodies harboured more true flies, while tougher and long-lived fruit bodies had more oribatid mites and beetles, which might reflect different development times of the arthropods. Ultimately, close to 75% of the arthropods were specific to one or two fungal hosts. Besides revealing surprisingly diverse and host-specific arthropod communities within fungal fruit bodies, our study provided insight on how host traits structure communities.
Convex-PLR – Revisiting affinity predictions and virtual screening using physics-informed machine learning
Authors: Kadukova Maria , Chupin Vladimir , Grudinin Sergei
Published: September 2021

Virtual screening is an essential part of the modern drug design pipeline, which significantly accelerates the discovery of new drug candidates. Structure-based virtual screening involves ligand conformational sampling, which is often followed by re-scoring of docking poses. A great variety of scoring functions have been designed for this purpose. The advent of structural and affinity databases and the progress in machine-learning methods have recently boosted scoring function performance. Nonetheless, the most successful scoring functions are typically designed for specific tasks or systems. All-purpose scoring functions still perform poorly on the virtual screening tests, compared to precision with which they are able to predict co-crystal binding poses. Another limitation is the low interpretability of the heuristics being used.

We analyzed scoring functions’ performance in the CASF benchmarks and discovered that the vast majority of them have a strong bias towards predicting larger binding interfaces. This motivated us to develop a physical model with additional entropic terms with the aim of penalizing such a preference. We parameterized the new model using affinity and structural data, solving a classification problem followed by regression. The new model, called Convex-PLR, demonstrated high-quality results on multiple tests and a substantial improvement over its predecessor Convex-PL. Convex-PLR can be used for molecular docking together with VinaCPL, our version of AutoDock Vina, with Convex-PL integrated as a scoring function. Convex-PLR, Convex-PL, and VinaCPL are available at https://team.inria.fr/nano-d/convex-pl/.
Addition of a carboxy terminal tail to the normally tailless gonadotropin-releasing hormone receptor impairs fertility in female mice
Authors: Toufaily Chirine , Fortin Jérôme , Alonso Carlos A. I. , Lapointe Evelyn , Zhou Xiang , Santiago-Andres Yorgui , Lin Yeu-Farn , Cui Yimming , Wang Ying , Devost Dominic , Roelfsema Ferdinand , Steyn Frederik , Hanyaloglu Aylin C. , Hébert Terence E. , Fiordelisio Tatiana , Boerboom Derek , Bernard Daniel J.
Published: September 2021

Gonadotropin-releasing hormone (GnRH) is the primary neuropeptide controlling reproduction in vertebrates. GnRH stimulates follicle-stimulating hormone (FSH) and luteinizing hormone (LH) synthesis via a G protein-coupled receptor, GnRHR, in the pituitary gland. In mammals, GnRHR lacks a C-terminal cytosolic tail (Ctail) and does not exhibit homologous desensitization. This might be an evolutionary adaptation that enables LH surge generation and ovulation. To test this idea, we fused the chicken GnRHR Ctail to the endogenous murine GnRHR in a transgenic model. The LH surge was blunted, but not blocked in these mice. In contrast, they showed reductions in FSH production, ovarian follicle development, and fertility. Addition of the Ctail altered the nature of agonist-induced calcium signaling required for normal FSH production. The loss of the GnRHR Ctail during mammalian evolution is unlikely to have conferred a selective advantage by enabling the LH surge. The adaptive significance of this specialization remains to be determined.
Population dynamics of Amazonian floodplain forest species support spatial variation on genetic diversity but not range expansions through time
Authors: Thom Gregory , Ribas Camila C. , Shultz Eduardo , Aleixo Alexandre , Miyaki Cristina Y.
Published: September 2021

Aim

We tested if historical demographic changes of populations occurring on the floodplains of a major Amazon Basin tributary could be associated with range expansions from upper and middle sections of the river, following the establishment of widespread river-created environments during the Late Pleistocene and Holocene.

Location

Solimoes River, Western Amazon, South America

Taxon

Myrmoborus lugubris, Thamnophilus cryptoleucus and Myrmotherula assimilisMethods: We analyzed thousands of UltraConserved Elements to explore spatial patterns of genetic diversity and connectivity between individuals. Range expansions were tested with alternative methods. We quantified habitat preference for the analyzed species in order to test if the occupation of dynamic habitats could predict spatial patterns of genetic diversity.

Results

Our study did not support shared population range expansions related to historical regionalized changes in habitat availability. We found considerable variation in the spatial distribution of the genetic diversity between studied taxa, and that species with higher levels of specialization to dynamic environments have a more heterogeneous distribution of genetic diversity and reduced levels of gene flow across space.

Main conclusions

Our results suggest that demographic expansions along the Solimões River might be linked to geographic homogeneous oscillation in the distribution of floodplain environments, promoting effective population size changes but not range expansion. We found that habitat specificity might be a good predictor of population connectivity along the Amazonian floodplains.
The conventional dendritic cell 1 subset primes CD8+ T cells and traffics tumor antigen to drive anti-tumor immunity in the brain
Authors: Bowman-Kirigin Jay A. , Saunders Brian T. , Desai Rupen , Wang Anthony Z. , Schaettler Max O. , Liu Connor J. , Livingstone Alexandra J. , Kobayashi Dale K. , Durai Vivek , Kretzer Nicole M. , Zipfel Gregory J. , Leuthardt Eric C. , Osbun Joshua W. , Chicoine Michael R. , Kim Albert H. , Murphy Kenneth M. , Johanns Tanner M. , Zinselmeyer Bernd H. , Dunn Gavin P.
Published: September 2021

The central nervous system (CNS) antigen presenting cell (APC) which primes anti-tumor CD8+ T cell responses remains undefined. Elsewhere, the conventional dendritic cell 1 (cDC1) performs this role. However, steady-state brain cDC1 are rare; cDC localize to choroid plexus and dura. Using preclinical glioblastoma models and cDC1-deficient mice, we explored the role of cDC1 in CNS anti-tumor immunity. We determined that cDC1 mediate checkpoint blockade-induced survival benefit and prime neoantigen-specific CD8+ T cells against brain tumors. We observed that cDC, including cDC1, isolated from the tumor, the dura, and the CNS-draining cervical lymph nodes harbored a traceable fluorescent tumor-antigen. In patient samples, we observed several APC subsets (including the CD141+ cDC1-equivalent) infiltrating glioblastomas, meningiomas, and dura. In these same subsets, we identified a tumor-specific fluorescent metabolite of 5- aminolevulinic acid, which labels tumor cells during fluorescence-guided glioblastoma resection. Together, these data elucidate the specialized behavior of cDC1 and suggest cDC1 play a significant role in CNS anti-tumor immunity.

One Sentence Summary

CNS cDC1 engage in previously undefined behavior to establish immune responses against brain tumors.
Pasture age impacts soil fungal composition while bacteria respond to soil chemistry
Authors: Seaton Fiona M. , Griffiths Robert I. , Goodall Tim , Lebron Inma , Norton Lisa R.
Published: September 2021

Pasture is a globally important managed habitat providing both food and income. The way in which it is managed leads to a wide range of impacts on soil microbial communities and associated soil health. While there have been several studies comparing pasture farming to other forms of land use, we still have limited understanding of how the soil microbial communities vary between pasture farms and according to management practices. Here we present the results of a field survey across 56 UK livestock farms that are managed by members of the Pasture fed Livestock Association, using amplicon sequencing of the 16S and ITS regions to characterise the soil bacterial and fungal community within fields that have been under pasture for differing durations. We show that grazing management intensity has only limited effects upon microbial community structure, while the duration of pasture since ploughing (ranging from 1 year to over 100 years) impacted the fungal community structure. The impact of management duration was conditional upon soil physicochemical properties, particularly pH. Plant community effects on upon soil bacterial and fungal composition appear to also interact with the soil chemistry, highlighting the importance of plant-soil interactions in determining microbial community structure. Analyses of microbial indicators revealed proportionally more fungal taxa that responded to multiple ecosystem health associated properties than bacterial taxa. We also identified several fungal taxa that both acted as indicators of soil health related properties within our dataset and showed differentiation between grassland types in a national survey, indicating the generality of some fungal indicators to the national level. Members of the Agaricomycetes were associated with multiple indicators of soil health. Our results show the importance of maintaining grassland for the development of plant-soil interactions and microbial community structure with concomitant effects on soil and general ecosystem health.

Highlights

Soil bacteria and fungi from >50 pastures were analysed using DNA metabarcoding

Duration of pasture since ploughing impacted fungal community composition

Bacteria were more associated with soil physicochemical properties than fungi

Plant effects on soil microbes were through interactions with soil chemistry

Microbial indicators of soil health were disproportionately fungal taxa