bluuebunny/crossref_metadata_2025 huggingface dataset:
Antifungal activity of etomidate against growing biofilms of fluconazole-resistant Candida spp. strains, binding to mannoproteins and molecular docking with the ALS3 protein
Authors: Gurgel do Amaral Valente Sá Lívia , da Silva Cecília Rocha , Neto João Batista de Andrade , do Nascimento Francisca Bruna Stefany Aires , Barroso Fátima Daiana Dias , da Silva Lisandra Juvêncio , Cabral Vitória Pessoa de Farias , Barbosa Amanda Dias , Silva Jacilene , Marinho Emmanuel Silva , de Moraes Manoel Odorico , Rios Maria Erivanda França , Cavalcanti Bruno Coêlho , Lima Iri Sandro Pampolha , Júnior Hélio Vitoriano Nobre
Published: September 2020

This study evaluated the effect of etomidate against biofilms of Candida spp. and analysed through molecular docking the interaction of this drug with ALS3, an important protein for fungal adhesion. Three fluconazole-resistant fungi were used: Candida albicans, Candida parapsilosis and Candida tropicalis. Growing biofilms were exposed to etomidate at 31.25–500 µg ml−1. Then, an ALS3 adhesive protein from C. albicans was analysed through a molecular mapping technique, composed of a sequence of algorithms to perform molecular mapping simulation based on classic force field theory. Etomidate showed antifungal activity against growing biofilms of resistant C. albicans, C. parapsilosis and C. tropicalis at all concentrations used in the study. The etomidate coupling analysis revealed three interactions with the residues of interest compared to hepta-threonine, which remained at the ALS3 site. In addition, etomidate decreased the expression of mannoproteins on the surface of C. albicans. These results revealed that etomidate inhibited the growth of biofilms.
Prognostic accuracy of emergency department triage tools for adults with suspected COVID-19: The PRIEST observational cohort study
Authors: Thomas Ben , Goodacre Steve , Lee Ellen , Sutton Laura , Loban Amanda , Waterhouse Simon , Simmonds Richard , Biggs Katie , Marincowitz Carl , Schutter Jose , Connelly Sarah , Sheldon Elena , Hall Jamie , Young Emma , Bentley Andrew , Challen Kirsty , Fitzimmons Chris , Harris Tim , Lecky Fiona , Lee Andrew , Maconochie Ian , Walter Darren
Published: September 2020

Objectives

The World Health Organisation (WHO) and National Institute for Health and Care Excellence (NICE) recommend various triage tools to assist decision-making for patients with suspected COVID-19. We aimed to estimate the accuracy of triage tools for predicting severe illness in adults presenting to the emergency department (ED) with suspected COVID-19 infection.

Methods

We undertook a mixed prospective and retrospective observational cohort study in 70 EDs across the United Kingdom (UK). We collected data from people attending with suspected COVID-19 between 26 March 2020 and 28 May 2020, and used presenting data to determine the results of assessment with the following triage tools: the WHO algorithm, NEWS2, CURB-65, CRB-65, PMEWS and the swine flu adult hospital pathway (SFAHP). We used 30-day outcome data (death or receipt of respiratory, cardiovascular or renal support) to determine prognostic accuracy for adverse outcome.

Results

We analysed data from 20892 adults, of whom 4672 (22.4%) died or received organ support (primary outcome), with 2058 (9.9%) receiving organ support and 2614 (12.5%) dying without organ support (secondary outcomes). C-statistics for the primary outcome were: CURB-65 0.75; CRB-65 0.70; PMEWS 0.77; NEWS2 (score) 0.77; NEWS2 (rule) 0.69; SFAHP (6-point) 0.70; SFAHP (7-point) 0.68; WHO algorithm 0.61. All triage tools showed worse prediction for receipt of organ support and better prediction for death without organ support.

At the recommended threshold, PMEWS and the WHO criteria showed good sensitivity (0.96 and 0.95 respectively), at the expense of specificity (0.31 and 0.27 respectively). NEWS2 showed similar sensitivity (0.96) and specificity (0.28) when a lower threshold than recommended was used.

Conclusion

CURB-65, PMEWS and NEWS2 provide good but not excellent prediction for adverse outcome in suspected COVID-19, and predicted death without organ support better than receipt of organ support. PMEWS, the WHO criteria and NEWS2 (using a lower threshold than usually recommended) provide good sensitivity at the expense of specificity.

Registration

ISRCTN registry, ISRCTN28342533, http://www.isrctn.com/ISRCTN28342533
Parents’ and guardians’ views and experiences of accessing routine childhood vaccinations during the coronavirus (COVID-19) pandemic: A mixed-methods study in England
Authors: Bell Sadie , Clarke Richard , Paterson Pauline , Mounier-Jack Sandra
Published: September 2020

Objective

To explore parents’ and guardians’ views and experiences of accessing National Health Service (NHS) general practices for routine childhood vaccinations during the coronavirus (COVID-19) pandemic in England.

Design

Mixed methods approach involving an online cross-sectional survey (conducted between 19th April and 11th May 2020) and semi-structured telephone interviews (conducted between 27th April and 27th May 2020).

Participants

1252 parents and guardians (aged 16+ years) who reported living in England with a child aged 18 months or under completed the survey. Nineteen survey respondents took part in follow-up interviews.

Results

The majority of survey respondents (85.7%) considered it important for their children to receive routine vaccinations on schedule during the COVID-19 pandemic; however, several barriers to vaccination were identified. These included a lack of clarity around whether vaccination services were operating as usual, particularly amongst respondents from lower income households and those self-reporting as Black, Asian, Chinese, Mixed or Other ethnicity; difficulties in organising vaccination appointments; and fears around contracting COVID-19 while attending general practice.

Concerns about catching COVID-19 while accessing general practice were weighed against concerns about children acquiring a vaccine-preventable disease if they did not receive scheduled routine childhood vaccinations. Many parents and guardians felt their child’s risk of acquiring a vaccine-preventable disease was low as the implementation of stringent physical distancing measures (from March 23rd 2020) meant they were not mixing with others.

Conclusion

To promote routine childhood vaccination uptake during the current COVID-19 outbreak, further waves of COVID-19 infection, and future pandemics, prompt and sustained national and general practice level communication is needed to raise awareness of vaccination service continuation and the importance of timely vaccination, and invitation-reminder systems for vaccination need to be maintained. To allay concerns about the safety of accessing general practice, practices should communicate the measures being implemented to prevent COVID-19 transmission.
Serological Responses to Human Virome Define Clinical Outcomes of Italian Patients Infected with SARS-CoV-2
Authors: Wang Limin , Candia Julián , Ma Lichun , Zhao Yongmei , Imberti Luisa , Sottini Alessandra , Dobbs Kerry ,   NIAID-NCI COVID Consortium, Lisco Andrea , Sereti Irini , Su Helen C. , Notarangelo Luigi D. , Wang Xin Wei
Published: September 2020

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the pandemic respiratory infectious disease COVID-19. However, clinical manifestations and outcomes differ significantly among COVID-19 patients, ranging from asymptomatic to extremely severe, and it remains unclear what drives these disparities. Here, we studied 159 hospitalized Italian patients with pneumonia from the NIAID-NCI COVID-19 Consortium using a phage-display method to characterize circulating antibodies binding to 93,904 viral peptides encoded by 1,276 strains of human viruses. SARS-CoV-2 infection was associated with a marked increase in individual’s immune memory antibody repertoires linked to trajectories of disease severity from the longitudinal analysis also including anti-spike protein antibodies. By applying a machine-learning-based strategy, we developed a viral exposure signature predictive of COVID-19-related disease severity linked to patient survival. These results provide a basis for understanding the roles of memory B-cell repertoires in COVID-19-related symptoms as well as a predictive tool for monitoring its clinical severity.
Computer-aided interpretation of chest radiography reveals the spectrum of tuberculosis in rural South Africa
Authors: Fehr Jana , Konigorski Stefan , Olivier Stephen , Gunda Resign , Surujdeen Ashmika , Gareta Dickman , Smit Theresa , Baisley Kathy , Moodley Sashen , Moosa Yumna , Hanekom Willem , Koole Olivier , Ndung’u Thumbi , Pillay Deenan , Grant Alison D. , Siedner Mark J. , Lippert Christoph , Wong Emily B. ,   the Vukuzazi Team
Published: September 2020

Computer-aided digital chest radiograph interpretation (CAD) can facilitate high-throughput screening for tuberculosis (TB), but its use in population-based active case finding programs has been limited. In an HIV-endemic area in rural South Africa, we used a CAD-algorithm (CAD4TBv5) to interpret digital chest x-rays (CXR) as part of a mobile health screening effort. Participants with TB symptoms or CAD4TBv5 score above the triaging threshold were referred for microbiological sputum assessment. During an initial pilot phase, a low CAD4TBv5 triaging threshold of 25 was selected to maximize TB case finding. We report the performance of CAD4TBv5 in screening 9,914 participants, 99 (1.0%) of whom were found to have microbiologically proven TB. CAD4TBv5 was able to identify TB cases at the same sensitivity but lower specificity as a blinded radiologist, whereas the next generation of the algorithm (CAD4TBv6) achieved comparable sensitivity and specificity to the radiologist. The CXRs of people with microbiologically-confirmed TB spanned a range of lung field abnormality, including 19 (19.2%) cases deemed normal by the radiologist. HIV-serostatus did not impact CAD4TB’s performance. Notably, 78.8% of the TB cases identified during this population-based survey were asymptomatic and therefore triaged for sputum collection on the basis of CAD4TBv5 score alone. While CAD4TBv6 has the potential to replace radiologists for triaging CXRs in TB prevalence surveys, population-specific piloting is necessary to set the appropriate triaging thresholds. Further work on image analysis strategies is needed to identify radiologically-subtle active TB.
Successful Tracheal Extubation within Eleven Minutes in the Post Anesthesia Care Unit in Children after Adenotonsillectomy
Authors: Gupta Deepak , Tukel Matthew Ryan , Mukhija Divya , Kaminski Edward , Markakis Zestos Maria
Published: September 2020

Background

Some pediatric centers prefer to extubate their patients in the operating rooms (ORs) while others prefer post-anesthesia care units (PACUs) for the same.

Objectives

To share our retrospective experience of 214 pediatric adenotonsillectomy (T&A) patients’ cohort extubated in our pediatric PACU during a seven-month retrospective study-period.

Materials and Methods

After institutional review board approval for retrospective chart review, institutional electronic surgical database was used to identify patients who underwent T&A and the peri-anesthetic records were obtained from patients’ electronic medical records and/or from hospital paper records.

Results

Patients’ tracheas were extubated in average 11 minutes (standard deviation 8 minutes) after arrival to PACU care and only one patient required tracheal re-intubation. Patients were ready for discharge from PACU in average 56 minutes (standard deviation 20 minutes) thus averaging only 44 minutes (standard deviation 20 minutes) after their tracheas had been extubated.

Conclusion

Summarily for re-validating or refuting our results, institutions can prospectively create PACU extubation quality improvement projects to discern if tracheal extubation in PACU of all or some pediatric surgical patients is beneficial when their rapid turnover surgeries warrant anesthesia providers to not attempt their tracheal extubation in ORs.
50 policies, 1 pandemic, 500,000 deaths: Associations between state-level COVID-19 testing recommendations, tests per capita, undercounted deaths, vaccination policies, and doses per capita in the United States
Authors: Perniciaro Stephanie R. , Weinberger Daniel M.
Published: September 2020

Background

State health departments have been responsible for prioritizing and allocating SARS-CoV-2 tests and vaccines. Testing and vaccination recommendations in the United States varied by state and over time, as did vaccine rollouts, COVID-19 cases, and estimates of excess mortality.

Methods

We compiled data about COVID-19 testing, cases, and deaths, and excess pneumonia + influenza + COVID-19 deaths to assess relationships between testing recommendations, per capita tests performed, epidemic intensity, and excess mortality during the early months of the COVID-19 pandemic in the United States. We compiled further data about state-level SARS-CoV-2 vaccination policies and doses administered during the early months of the vaccine rollout.

Results

As of July 2020, 16 states recommended testing asymptomatic members of the general public. The rate of COVID-19 tests reported in each state correlated with more inclusive testing recommendations and with higher epidemic intensity. Higher per capita testing was associated with more complete reporting of COVID-19 deaths, which is a fundamental requirement for analyzing the pandemic. Testing per capita during the first three months was associated with vaccination per capita in the first three months of rollout. Per capita vaccine doses in each state were not associated with adherence to national guidelines.

Conclusions

Reported deaths due to COVID-19 likely represent an undercount of the true burden of the pandemic. States that struggled with testing rollout have also frequently struggled with vaccine rollout. Coordinated, consistent guidelines for COVID-19 testing and vaccine administration should be a high priority for state and national health systems.
Modeling COVID-19 dynamics in the sixteen West African countries
Authors: Honfo Sewanou H. , Taboe Hémaho B. , Glèlè Kakaï Romain
Published: September 2020

The COVID-19 pandemic is currently causing several damages to the world, especially in the public health sector. Due to identifiability problems in parameters’ estimation of complex compartmental models, this study considered a simple deterministic susceptible–infectious–recovered (SIR)-type model to characterize and predict the future course of the pandemic in the West African countries. We estimated some specific characteristics of the disease’s dynamics such as its initial conditions, reproduction numbers, true peak and peak of the reported cases, with their corresponding times, final epidemic size and time-varying attack ratio. Our findings revealed a relatively low proportion of susceptible individuals in the region and in the different countries (1.2% across West Africa). The detection rate of the disease was also relatively low (0.9% for West Africa as a whole) and < 2% for most countries, except for Gambia (12.5 %), Cape-Verde (9.5%), Mauritania (5.9%) and Ghana (4.4%). The reproduction number varied between 1.15 (Burkina-Faso) and 4.45 (Niger), and the peak time of the pandemic was between June and July for most countries. Generally, the peak time of the reported cases came a week (7-8 days) after the true peak time. The model predicted 222,100 actual active cases in the region at the peak time, while the final epidemic size accounted for 0.6% of the West African population (2,526,700 individuals). The results obtained showed that COVID-19 has not severely affected West Africa as noticed in other regions of the world. However, current control measures and standard operating procedures should be maintained over time to accelerate a decline in the observed trends of the pandemic.
Contact tracing efficiency, transmission heterogeneity, and accelerating COVID-19 epidemics
Authors: Gardner Billy J. , Kilpatrick A. Marm
Published: September 2020

Simultaneously controlling COVID-19 epidemics and limiting economic and societal impacts presents a difficult challenge, especially with limited public health budgets. Testing, contact tracing, and isolating/quarantining is a key strategy that has been used to reduce transmission of SARS-CoV-2, the virus that causes COVID-19. However, manual contact tracing is a time-consuming process and as case numbers increase it takes longer to reach each cases’ contacts, leading to additional virus spread. Delays between symptom onset and being tested (and receiving results), and a low fraction of symptomatic cases being tested and traced can also reduce the impact of contact tracing on transmission. We examined the relationship between cases and delays and the pathogen reproductive number Rt, and the implications for infection dynamics using a stochastic compartment model of SARS-CoV-2. We found that Rt increases sigmoidally with the number of cases due to decreasing contact tracing efficacy. This relationship results in accelerating epidemics because Rt increases, rather than declines, as infections increase. Shifting contact tracers from locations with high and low case burdens relative to capacity to locations with intermediate case burdens maximizes their impact in reducing Rt (but minimizing total infections is more complicated). Contact tracing efficacy also decreased with increasing delays between symptom onset and tracing and with lower fraction of symptomatic infections being tested. Finally, testing and tracing reductions in Rt can sometimes greatly delay epidemics due to the highly heterogeneous transmission dynamics of SARS-CoV-2. These results demonstrate the importance of having an expandable or mobile team of contact tracers that can be used to control surges in cases, and the value of easy access, high testing capacity and rapid turn-around of testing results, as well as outreach efforts to encourage symptomatic infections to be tested immediately after symptom onset.

Author Summary

A key tool in the control of infectious diseases is contact tracing – the identification of individuals who have contacted the case and may have been infected by a newly detected case. However, to successfully contact and quarantine individuals requires time, and as cases rise, this can result in delays in reaching contacts during which time they may infect other people. Here we examine the quantitative relationships between increasing case numbers, contact tracing efficiency, and the pathogen reproductive number Rt (the number of cases infected by each case) and how these relationships vary with delays and incomplete participation in the testing and tracing process. We built
Efficacy and safety of dihydroartemisinin-piperaquine for the treatment of uncomplicated Plasmodium falciparum and Plasmodium vivax malaria in Northern Papua and Jambi, Indonesia
Authors: Asih Puji BS , Rozi Ismail E , Dewayanti Farahana K , Wangsamuda Suradi , Zulfah Syarifah , Robaha Marthen , Hutahaean Jonny , Anggraeni Nancy D , Kusumaningsih Marti , Mulyani Pranti S , Sariwati Elvieda , Basri Herdiana H , Bustos Maria Dorina G , Syafruddin Din
Published: September 2020

Dihydroartemisinin-piperaquine (DHA-PPQ) has been adopted as first-line therapy for uncomplicated falciparum malaria in Indonesia since 2010. The efficacy of DHA-PPQ was evaluated in 2 sentinel sites in Keerom District, Papua and Merangin District, Jambi Provinces from April 2017 to April 2018. Clinical and parasitological parameters were monitored over a 42-day period following the WHO standard in vivo protocol and subjects meeting the inclusion criteria were treated with DHA-PPQ once daily for 3 days, administered orally. In Keerom District, 6339 subjects were screened through active and passive cases detection. A total of 114 subjects infected by P. falciparum and 83 subjects infected by P. vivax agreed to take a part through written informed consent. Kaplan-Meier analysis of microscopy readings and PCR-corrected falciparum cases revealed a 93.1% (95%CI:86.4-97.2) and 97.9% (95%CI:92.7-99.7) DHA-PPQ efficacy, respectively and were classified as Adequate Clinical Parasitological Responses (ACPRs). For vivax malaria, the DHA-PPQ efficacy were 89% (95%CI: 80.2 - 94.9) and 100% (95%CI: 95.1-100) respectively. In Merangin District, 751 subjects were screened and 41 subjects infected by P. vivax were recruited. Microscopy reading and PCR-corrected analysis revealed a 97.4% (95%CI:86.2-99.9) and 100% (95%CI: 90.5-100) DHA-PPQ efficacy, respectively. No severe adverse events were found in both sites. In both sites, there was no delay in parasite clearance and no mutations in the PfK13 and PvK12 genes. Of the 6 recurrent P. falciparum found, 2 indicated recrudescent and 4 cases were re-infection. Analysis of the PfPM2 gene at day 0 and day of recurrence in recrudescent cases revealed the same single copy number, whereas 3 of the 4 re-infection cases carried 2-3 copy numbers. In conclusion, treatment of falciparum and vivax malaria cases with DHA-PPQ showed a high efficacy and safety. DHA-PPQ regimen is also efficacious against P. vivax cases in the absence of primaquine.
Embeddings from deep learning transfer GO annotations beyond homology
Authors: Littmann Maria , Heinzinger Michael , Dallago Christian , Olenyi Tobias , Rost Burkhard
Published: September 2020

Knowing protein function is crucial to advance molecular and medical biology, yet experimental function annotations through the Gene Ontology (GO) exist for fewer than 0.5% of all known proteins. Computational methods bridge this sequence-annotation gap typically through homology-based annotation transfer by identifying sequence-similar proteins with known function or through prediction methods using evolutionary information. Here, we propose predicting GO terms through annotation transfer based on proximity of proteins in the SeqVec embedding rather than in sequence space. These embeddings originate from deep learned language models (LMs) for protein sequences (SeqVec) transferring the knowledge gained from predicting the next amino acid in 33 million protein sequences. Replicating the conditions of CAFA3, our method reaches an Fmaxof 37±2%, 50±3%, and 57±2% for BPO, MFO, and CCO, respectively. Numerically, this appears close to the top ten CAFA3 methods. When restricting the annotation transfer to proteins with <20% pairwise sequence identity to the query, performance drops (FmaxBPO 33±2%, MFO 43±3%, CCO 53±2%); this still outperforms naïve sequence-based transfer. Preliminary results from CAFA4 appear to confirm these findings. Overall, this new concept is likely to change the annotation of proteins, in particular for proteins from smaller families or proteins with intrinsically disordered regions.
The interplay of wind and uplift facilitates over-water flight in facultative soaring birds
Authors: Nourani Elham , Bohrer Gil , Becciu Paolo , Bierregaard Richard O. , Duriez Olivier , Figuerola Jordi , Gangoso Laura , Giokas Sinos , Higuchi Hiroyoshi , Kassara Christina , Kulikova Olga , Lecomte Nicolas , Monti Flavio , Pokrovsky Ivan , Sforzi Andrea , Therrien Jean-François , Tsiopelas Nikos , Vansteelant Wouter M.G. , Viana Duarte S. , Yamaguchi Noriyuki M. , Wikelski Martin , Safi Kamran
Published: September 2020

Flying over the open sea is energetically costly for terrestrial birds. Despite this, over-water journeys of many birds, sometimes hundreds of kilometers long, are uncovered by bio-logging technology. To understand how these birds afford their flights over the open sea, we investigated the role of atmospheric conditions, specifically wind and uplift, in subsidizing over-water flight at the global scale. We first established that ΔT, the temperature difference between sea surface and air, is a meaningful proxy for uplift over water. Using this proxy, we showed that the spatio-temporal patterns of sea-crossing in terrestrial migratory birds is associated with favorable uplift conditions. We then analyzed route selection over the open sea for five facultative soaring species, representing all major migratory flyways. The birds maximized wind support when selecting their sea-crossing routes and selected higher uplift when suitable wind support was available. They also preferred routes with low long-term uncertainty in wind conditions. Our findings suggest that, in addition to wind, uplift may play a key role in the energy seascape for bird migration that in turn determines strategies and associated costs for birds crossing ecological barriers such as the open sea.
Effects of phylogeny on coexistence in model communities
Authors: Serván Carlos A. , Capitán José A. , Miller Zachary R. , Allesina Stefano
Published: September 2020

A species’ traits influence the way in which it interacts with the environment. Thus, we expect traits to play a role in determining whether a given set of species coexists. Traits are, in turn, the outcome of an eco-evolutionary process summarized by a phylogenetic tree. Therefore, the phylogenetic tree associated with a set of species should encode information about the assembly properties of the community. Many studies have high-lighted the potentially complex ways in which phylogenetic information is translated into species’ ecological properties. However, much less emphasis has been placed on developing expectations for community properties under a particular hypothesis.

In this work, we couple a simple model of trait evolution on a phylogenetic tree with local community dynamics governed by Lotka-Volterra equations. This allows us to derive properties of the community of coexisting species as a function of the number of traits, tree topology and the size of the species pool. Our results highlight how phylogenies and traits, in concert, affect the coexistence of a set of species.

In this way, our work provides new baseline expectations for the ways in which phylogenetic information is reflected in the structure of and coexistence within local communities.
Pre-clinical studies of a recombinant adenoviral mucosal vaccine to prevent SARS-CoV-2 infection
Authors: Moore Anne C. , Dora Emery G. , Peinovich Nadine , Tucker Kiersten P. , Lin Karen , Cortese Mario , Tucker Sean N.
Published: September 2020

There is an urgent need to develop efficacious vaccines against SARS-CoV-2 that also address the issues of deployment, equitable access, and vaccine acceptance. Ideally, the vaccine would prevent virus infection and transmission as well as preventing COVID-19 disease. We previously developed an oral adenovirus-based vaccine technology that induces both mucosal and systemic immunity in humans. Here we investigate the immunogenicity of a range of candidate adenovirusbased vaccines, expressing full or partial sequences of the spike and nucleocapsid proteins, in mice. We demonstrate that, compared to expression of the S1 domain or a stabilized spike antigen, the full length, wild-type spike antigen induces significantly higher neutralizing antibodies in the periphery and in the lungs, when the vaccine is administered mucosally. Antigen-specific CD4+ and CD8+ T cells were induced by this leading vaccine candidate at low and high doses. This fulllength spike antigen plus nucleocapsid adenovirus construct has been prioritized for further clinical development.
Self-Supervised Contrastive Learning of Protein Representations By Mutual Information Maximization
Authors: Lu Amy X. , Zhang Haoran , Ghassemi Marzyeh , Moses Alan
Published: September 2020

Pretrained embedding representations of biological sequences which capture meaningful properties can alleviate many problems associated with supervised learning in biology. We apply the principle of mutual information maximization between local and global information as a self-supervised pretraining signal for protein embeddings. To do so, we divide protein sequences into fixed size fragments, and train an autoregressive model to distinguish between subsequent fragments from the same protein and fragments from random proteins. Our model, CPCProt, achieves comparable performance to state-of-the-art self-supervised models for protein sequence embeddings on various downstream tasks, but reduces the number of parameters down to 2% to 10% of benchmarked models. Further, we explore how downstream assessment protocols affect embedding evaluation, and the effect of contrastive learning hyperparameters on empirical performance. We hope that these results will inform the development of contrastive learning methods in protein biology and other modalities.
An early Cambrian ecdysozoan with a terminal mouth but no anus
Authors: Liu Yunhuan , Zhang Huaqiao , Xiao Shuhai , Shao Tiequan , Duan Baichuan
Published: September 2020

The ecdysozoans are the most diverse animal group on Earth1, 2. Molecular clock studies indicate that the ecdysozoans may have diverged and diversified in the Ediacaran Period3, 4, but unambiguous ecdysozoan fossils first appear in the earliest Cambrian and are limited to cycloneuralians5–7. Here we report new material of the early Cambrian microscopic animalSaccorhytus coronarius, which was previously interpreted as a deuterostome8.Saccorhytus coronariusis reconstructed as a millimetric and ellipsoidal meiobenthic animal with a spinose armor and an anterior mouth but no anus. Purported pharyngeal gills in support of the deuterostome hypothesis8are shown to be taphonomic artifacts. Phylogenetic analyses indicate thatSaccorhytus coronariusbelongs to the total-group Ecdysozoa, highlighting the morphological and ecological diversity of early Cambrian ecdysozoans.
The association between COVID-19 and preterm delivery: A cohort study with a multivariate analysis
Authors:   Spanish Obstetric Emergency Group, Pérez Oscar Martínez
Published: September 2020

Structured Abstract

Objective

To determine whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, the cause of COVID-19 disease) exposure in pregnancy, compared to non-exposure, is associated with infection-related obstetric morbidity.

Design and setting

Throughout Spain, 45 hospitals took part in universal screening of pregnant women going into labour using polymerase-chain-reaction (PCR) for COVID-19 since late March 2020.

Methods

The cohort of exposed and unexposed pregnancies was followed up until 6-weeks post-partum. Multivariate logistic regression analysis, adjusting for known confounding variables, determined the adjusted odds ratio (aOR) with 95% confidence intervals (95% CI) of the association of COVID-19 exposure, compared to non-exposure, with infection-related obstetric outcomes.

Main outcome measures

Preterm delivery (primary), premature rupture of membranes and neonatal intensive care unit admissions.

Results

In the cohort of 1,009 screened pregnancies, 246 were COVID-19 positive. Compared to non-exposure, COVID-19 exposure increased the odds of preterm birth (34 vs 51, 13.8% vs 6.7%, aOR 2.12, 95% CI 1.32–3.36, p = 0.002), premature rupture of membranes at term (39 vs 75, 15.8% vs 9.8%, aOR 1.70, 95% CI 1.11–2.57, p = 0.013) and neonatal intensive care unit admissions (23 vs 18, 9.3% vs 2.4%, aOR 4.62, 95% CI 2.43 – 8.94, p< 0.001).

Conclusion

This first prospective cohort study demonstrated that pregnant women infected with SARS- CoV-2 have more infection-related obstetric morbidity. This hypothesis merits evaluation of a causal association in further research.
Discovery of a Potent and Dual-Selective Bisubstrate Inhibitor for Protein Arginine Methyltransferase 4/5
Authors: Al-Hamashi Ayad A. , Chen Dongxing , Deng Youchao , Dong Guangping , Huang Rong
Published: September 2020

Protein arginine methyltransferases (PRMTs) have been implicated in the progression of many diseases. Understanding substrate recognition and specificity of individual PRMT would facilitate the discovery of selective inhibitors towards future drug discovery. Herein, we reported the design and synthesis of bisubstrate analogues for PRMTs that incorporate a S-adenosylmethionine (SAM) analogue moiety and a tripeptide through an alkyl substituted guanidino group. CompoundAH237is a potent and selective inhibitor for PRMT4 and PRMT5 with a half-maximal inhibition concentration (IC50) of 2.8 nM and <1.5 nM, respectively. Computational studies provided a plausible explanation for the high potency and selectivity ofAH237for PRMT4/5 over other 40 methyltransferases. This proof-of-principle study outlines an applicable strategy to develop potent and selective bisubstrate inhibitors for PRMTs, providing valuable probes for future structural studies.
Characterization of gustatory receptor 7 in the brown planthopper reveals functional versatility
Authors: Ojha Abhishek , Zhang Wenqing
Published: September 2020

Insect pests consume tastants as their necessary energy and nutrient sources. Gustatory receptors play important roles in insect life and can form within an extremely complicated regulatory network. However, there are still many gustatory genes that have a significant impact on insect physiology, but their functional mechanism is still unknown. Here, we purified and characterized a gustatory receptor (protein) coding gene,NlGr7, from the brown planthopper (BPH)Nilaparvata lugens, which is an important insect pest of rice. Our results revealed thatNlGr7 has an active association with various ligands, such as lectins, lipids (phospho- and sphingolipid) and copper. The mass-spectrometry result showed thatNlGr7 is a sugar receptor, andNlGr7 is validated by different types of insoluble polysaccharides and a varied range of tastants. Furthermore, we observed thatNlGr7-bound ATP hydrolysed on the ATPase activity assay, which indicated thatNlGr7 may be associated with important biological functions in the BPH. The importantNlGr7 for chemoreception has now been characterized in the BPH. We showed thatNlGr7 in the BPH is required for various protein-ligands, as well as protein-sugars interactions, to play crucial roles in this pest. This study will provide valuable information for further functional studies of chemoreception mechanisms in this important agricultural pest.
BacAnt: A Combination Annotation Server for Bacterial DNA Sequences to Identify Antibiotic Resistance Genes, Integrons, and Transposable Elements
Authors: Hua Xiaoting , Liang Qian , Deng Min , He Jintao , Wang Meixia , Hong Wenjie , Wu Jun , Lu Bian , Leptihn Sebastian , Yu Yunsong , Chen Huan
Published: September 2020

Whole genome sequencing (WGS) of bacteria has become a routine method in diagnostic laboratories. One of the clinically most useful advantages of WGS is the ability to predict antimicrobial resistance genes (ARGs) and mobile genetic elements (MGEs) in bacterial sequences. This allows comprehensive investigations of such genetic features but can also be used for epidemiological studies. A plethora of software programs have been developed for the detailed annotation of bacterial DNA sequences, such as RAST (Rapid Annotation using Subsystem Technology), Resfinder, ISfinder, INTEGRALL and The Transposon Registry. Unfortunately, to this day, a reliable annotation tool of the combination of ARGs and MGEs is not available, and the generation of genbank files requires much manual input. Here, we present a new webserver which allows the annotation of ARGs, integrons, and transposable elements at the same time. The pipeline generates genbank files automatically, which are compatible with easyfig for comparative genomic analysis. Our BacAnt code and standalone software package are available athttps://github.com/xthua/bacantwith an accompanying web application athttp://bacant.net.

Graphical Abstract
Transcription initiation mapping in 31 bovine tissues reveals complex promoter activity, pervasive transcription, and tissue-specific promoter usage
Authors: Goszczynski D.E. , Halstead M.M. , Islas-Trejo A.D. , Zhou H. , Ross P.J.
Published: September 2020

Characterizing transcription start sites is essential for understanding the regulatory mechanisms that control gene expression. Recently, a new bovine genome assembly (ARS-UCD1.2) with high continuity, accuracy, and completeness was released; however, the functional annotation of the bovine genome lacks precise transcription start sites and contains a low number of transcripts in comparison to human and mouse. Using the RAMPAGE approach, this study identified transcription start sites at high resolution in a large collection of bovine tissues. We found several known and novel transcription start sites attributed to promoters of protein coding and lncRNA genes that were validated through experimental andin silicoevidence. With these findings, the annotation of transcription start sites in cattle reached a level comparable to the mouse and human genome annotations. In addition, we identified and characterized transcription start sites for antisense transcripts derived from bidirectional promoters, potential lncRNAs, mRNAs, and pre-miRNAs. We also analyzed the quantitative aspects of RAMPAGE to produce a promoter activity atlas, reaching highly reproducible results comparable to traditional RNA-seq. Co-expression networks revealed considerable use of tissue specific promoters, especially between brain and testicle, which expressed several genes in common from alternate loci. Furthermore, regions surrounding co-expressed modules were enriched in binding factor motifs representative of each tissue. The comprehensive annotation of promoters in such a large collection of tissues will substantially contribute to our understanding of gene expression in cattle and other mammalian species, shortening the gap between genotypes and phenotypes.
Functional metagenomics of bark microbial communities from avocado trees (Persea americana Mill.) reveals potential for bacterial primary productivity
Authors: Aguirre-von-Wobeser Eneas
Published: September 2020

Bark microbial communities are poorly understood, and information on the metabolic capacities of their inhabitants is lacking. Bark microbial communities share part of their taxonomic composition with soil, but the functional differences and similarities are unknown. By comparing bark microbial communities of avocado trees (Persea americana, Mill.) with rhizospheric soil, functional processes relevant to the bark environment were identified. DNA from bark and soil communities was extracted from the same trees, and shotgun metagenomics sequencing was performed using nextSeq technology. Genes were identified by BLAST methods, and functional annotation was performed with KEGG databases as a reference. Bacterial oxygenic and anoxygenic photosynthesis genes were highly abundant in bark as compared to soil. Furthermore, increased presence of nitrogenase genes suggests a potential for nitrogen fixation. Genes for methanol utilization were abundant in bark, but no evidence of methane utilization potential was observed. Bark microbial communities have the genetic information for potential primary productivity, which might contribute to microbial growth independent of plant-derived carbon substrates.
Systematic functional analysis of Leishmania protein kinases identifies regulators of differentiation or survival
Authors: N. Baker , C.M.C. Catta-Preta , R. Neish , J. Sadlova , B. Powell , E.V.C. Alves-Ferreira , V. Geoghegan , J.B.T. Carnielli , K. Newling , C. Hughes , B. Vojtkova , J. Anand , A. Mihut , P.B. Walrad , L.G. Wilson , J.W. Pitchford , P. Volf , J.C. Mottram
Published: September 2020

Differentiation between distinct stages is fundamental for the life cycle of intracellular protozoan parasites and for transmission between hosts, requiring stringent spatial and temporal regulation. Here we applied kinome-wide gene deletion and gene tagging in Leishmania mexicana promastigotes to define protein kinases with life cycle transition roles. Whilst 162 were dispensable, 44 protein kinase genes were refractory to deletion in promastigotes and are likely core genes required for parasite replication. Phenotyping of pooled gene deletion mutants using bar-seq and projection pursuit clustering revealed functional phenotypic groups of protein kinases involved in differentiation from metacyclic promastigote to amastigote, growth and survival in macrophages and mice, colonisation of the sand fly and motility. This unbiased interrogation of protein kinase function in Leishmania allows targeted investigation of organelle-associated signalling pathways required for successful intracellular parasitism.
Detection ofPlasmodium vivaxin a liver sample of a howler-monkey: one evidence more in favour of the identity betweenPlasmodium simiumandP. vivax
Authors: Buery J.C. , Duarte A.M.R.C. , Alencar F.E.C. , Furieri C. , Mendes S.L. , Loss A.C. , Vicente C.R. , Fux B. , Rezende H.R. , Cravo P.V. , Medeiros M.M. , Arez A.P. , Cerutti C.
Published: September 2020

Introduction

The residual malaria of Atlantic Forest systems in Brazil occurs as an endemic disease with low frequency of cases. The chronological and spatial distance among the cases indicate an absence of fitness to the classical malaria cycle. This peculiar condition raised the suspicion of a reservoir, possibly the non-human primates. Simian and human malaria occur at the same places in that region, and there is already evidence of molecular identity between the simian parasites,Plasmodium simiumandPlasmodium brasilianum, and the human parasites,Plasmodium vivaxandPlasmodium malariae, respectively. Two different SNPs identified in the COX1 region of thePlasmodium vivax/simiumof the Atlantic Forest reinforced its characterization as a zoonotic parasite. This finding supported the development of a PCR-RFLP protocol to identify such polymorphisms, and to monitor zoonotic malaria transmission.

Methods

In the present work, we tested the above-mentioned PCR-RFLP protocol in unprecedented mosquitoes and simian samples collected in Espírito Santo State, Brazil (ES).

Results

The parasite found in the simian sample wasP. vivax, contrary to what the protocol should indicate. In the mosquito samples, the protocol disclosed both forms of the parasite.

Conclusion

This result suggests that the previously published pair of SNPs, and, consequently, the PCR-RFLP protocol, are not able to distinguish the dynamics ofPlasmodiumspp. circulation in the Atlantic Forest endemic area of ES.
Protective efficacy of calcium phosphate nanoparticle adsorbed bivalent subunit vaccine ofPasteurella multocidaagainst homologous challenge in mice
Authors: Shyam Songyukta , Tamuly Shantanu , Borah Probodh , Sharma Rajeev Kumar
Published: September 2020

Swine pasteurellosis, caused byPasteurella multocidacapsular types A and D, causes heavy economic loss to the pig farmers. The vaccine presently used is abacterin ofPasteurella multocidacapsular type B that is proven to be effective against bovine pasteurellosis. However, its efficacy against swine pasteurellosis is questionable. The present study was carried out to evaluate the efficacy of calcium phosphate nanoparticle adjuvanted bivalent subunit vaccine prepared fromPasteurella multocidacapsular types A and D along with a monovalent subunit vaccine prepared fromPasteurella multocidacapsular type B in mice. The Alum precipitated bacterin vaccine was used as the control. The bivalent subunit vaccine comprising the immune components of both the capsular types showed significantly higher IgG response than either of the other two vaccines. Both the calcium phosphate nanoparticle adjuvanted vaccines could elicit 100% protection in mice against homologous challenges but the aluminum hydroxide adjuvanted bacterin vaccine could not elicit significant protection. Based on this preliminary work, it was concluded that the bivalent subunit vaccine would be a better option for immunization of swine against swine pasteurellosis.

IMPORTANCE OF THE WORK

The swine pasteurellosis is an important economic disease affecting the pig population in the North-eastern part of India that contributes the major pig population. The disease is caused by Serotype A and D ofPasteurella multocida. At present the inactivated vaccine is used that is actually developed against P52strain of serotype B:2 ofPasteurella multocida, which is mainly involved in haemorrhagic septicaemia (or bovine pasteurellosis) that affects the cattle, buffaloe, sheep and goat. As a result, the present vaccine does not give sufficient protection in pigs but gives significant protection in cattle, buffaloe, sheep and goat. Hence, there is a need of development of vaccine that can address specifically swine pasteurellosis by targeting serotype A and D ofPasteurella multocida.
Transgenic pyrimethamine-resistantP. falciparumreveals transmission blocking potency of P218, a novel antifolate
Authors: Posayapisit Navaporn , Pengon Jutharat , Prommana Parichat , Shoram Molnipha , Yuthavong Yongyuth , Uthaipibull Chairat , Kamchonwongpaisan Sumalee , Jupatanakul Natapong
Published: September 2020

Antimalarial drug which target more than one life stage of the parasite are valuable tools in the fight against malaria. Previous generation of antifolate drugs are able to inhibit replicative stages of drug-sensitive, but not resistant parasites in humans, and mosquitoes. The lack of reliable gametocyte-producing, antifolate resistantP. falciparumhindrance the development of new antifolate compounds against mosquito stages. We used CRISPR-Cas9 technology to develop transgenic gametocyte producingP. falciparumwith quadruple mutations indhfrgene, using NF54 as a parental strain. The transgenic parasites gained pyrimethamine resistance while maintaining the gametocyte producing activity. In contrast to pyrimethamine that cannot inhibit exflagellation of the quadrupledhfrmutant parasite, the novel antifolate P218 showed a good potency for exflagellation inhibition (exflagellation IC5010.74 ± 4.22 nM). The exflagellation IC50was 5.3 times lower than erythrocytic IC50suggesting that the human to mosquito transmission poses as a strong barrier to prevent P218 resistant parasite among population. This study demonstrates that P218 can be considered as a highly potent tool to prevent the spread of antifolate resistant parasites.

Graphical Abstract

Research Highlights

- Transgenic gametocyte producing pyrimethamine resistantP. falciparumwas generated.

- P218 asexual stage IC50in NF54-4mutPfdhfrwas 56.94 ± 15.69 nM.

- P218 exflagellation IC50in NF54-4mutPfdhfrwas 10.74 ± 4.22 nM.

- P218 exflagellation IC50in NF54-4mutPfdhfris 5.3 times lower than erythrocytic IC50.

- P218 is an invaluable tool for malaria treatment and transmission control.
Loss of Kallmann syndrome-associated gene WDR11 disrupts primordial germ cell development by affecting canonical and non-canonical Hedgehog signalling
Authors: Lee Jiyoung , Kim Yeonjoo , Ataliotis Paris , Kim Hyung-Goo , Kim Dae-Won , Bennett Dorothy C. , Brown Nigel A. , Layman Lawrence C. , Kim Soo-Hyun
Published: September 2020

Mutations ofWDR11are associated with Kallmann syndrome (KS) and congenital hypogonadotrophic hypogonadism (CHH), typically caused by defective functions of gonadotrophin-releasing hormone (GnRH) neurones in the brain. We previously reported that Wdr11 knockout mice show profound infertility with significantly fewer germ cells present in the gonads. To understand the underlying mechanisms mediated by WDR11 in these processes, we investigated the effects ofWdr11deletion on primordial germ cell (PGC) development. Using live-tracking of PGCs and primary co-cultures of genital ridges (GR), we demonstrated thatWdr11-deficient embryos contained reduced numbers of PGCs which had delayed migration due to significantly decreased proliferation and motility. We found primary cilia-dependent canonical Hedgehog (Hh) signalling was required for proliferation of the somatic mesenchymal cells of GR, while primary cilia-independent non-canonical Hh signalling mediated by Ptch2/Gas1 and downstream effectors Src and Creb was required for PGC proliferation and migration, which was disrupted by the loss of function mutations of WDR11. Therefore, canonical and non-canonical Hh signalling are differentially involved in the development of somatic and germ cell components of the gonads, and WDR11 is required for both of these pathways operating in parallel in GR and PGCs, respectively, during normal PGC development. Our study provides a mechanistic link between the development of GnRH neurones and germ cells mediated by WDR11, which may underlie some cases of KS/CHH and ciliopathies.