bluuebunny/crossref_metadata_2025_split huggingface dataset:
The potential impact of Anopheles stephensi establishment on the transmission of Plasmodium falciparum in Ethiopia and prospective control measures
Authors: Hamlet Arran , Dengela Dereje , Tongren J. Eric , Tadesse Fitsum G , Bousema Teun , Sinka Marianne , Seyoum Aklilu , Irish Seth R. , Armistead Jennifer S. , Churcher Thomas 
Published: August 2021

AbstractBackgroundSub-Saharan Africa has seen substantial reductions in cases and deaths due to malaria over the past two decades. While this reduction is primarily due to an increasing expansion of interventions, urbanisation has played its part as urban areas typically experience substantially less malaria transmission than rural areas. However, this may be partially lost with the invasion and establishment of Anopheles stephensi. An. stephensi, the primary urban malaria vector in Asia, was first detected in Africa during 2012 in Djibouti and was subsequently identified in Ethiopia in 2016, and later in Sudan and Somalia. In Djibouti, malaria cases have increased 30-fold from 2012 to 2019 though the impact in the wider region remains unclear.MethodsHere we have adapted an existing model of mechanistic malaria transmission to estimate the increase in vector density required to explain the trends in malaria cases seen in Djibouti. To account for the observed plasticity in An. stephensi behaviour, and the unknowns of how it will establish in a novel environment, we sample behavioural parameters in order to account for a wide range of uncertainty. This quantification is then applied to Ethiopia, considering temperature-dependent extrinsic incubation periods, pre-existing vector-control interventions and Plasmodium falciparum prevalence in order to assess the potential impact of An. stephensi establishment on P. falciparum transmission. Following this, we estimate the potential impact of scaling up ITN (insecticide treated nets)/IRS (indoor residual spraying) and implementing piperonyl butoxide (PBO) ITNs and larval source management,, as well as their economic costs.ResultsWe estimate that annual P. falciparum malaria cases could increase by 50% (95% CI 14-90) if no additional interventions are implemented. The implementation of sufficient control measures to reduce malaria transmission to pre-stephensi levels will cost hundreds of millions of USD.ConclusionsSubstantial heterogeneity across the country is predicted and large increases in vector control interventions could be needed to prevent a major public health emergency.
Distance from home to motor vehicle crash location: Implications for license restrictions among medically-at-risk older drivers
Authors: Joyce Nina R. , Khan Marzan A. , Zullo Andrew R. , Pfeiffer Melissa R. , Metzger Kristina B. , Margolis Seth A. , Ott Brian R. , Curry Allison E. 
Published: August 2021

ABSTRACTBackground/ObjectivesThirty states allow licensing agencies to restrict the distance from home that “medically-at-risk” drivers are permitted to drive. However, there is little information on where older drivers crash relative to their home or how distance to crash varies by medical condition, and thus, what impact distance limits may have on motor vehicle crash rates for “medically-at-risk” drivers.DesignObservational study of crash-involved drivers.SettingMedicare fee-for-service claims linked to geocoded crash locations and residential addresses from police crash reports in the state of New Jersey from 2007 through 2017.ParticipantsNew Jersey Medicare fee-for-service beneficiaries aged 68 years and older involved in police-reported crashes.MeasurementsThe outcome was Euclidian distance from home to crash location. Covariates included driving-relevant medical conditions from Medicare claims, crash characteristics from police reports, and demographics from both sources.ResultsThere were 197,122 crash-involved older drivers for whom approximately 70% of crashes occurred within 5 miles and 95% within 25 miles of the driver’s residence. The mean distance to crash was 6.0 miles. Although distance from home to the crash was generally lower among drivers with (versus without) each of the medical conditions studied, the differences were small (maximum mean difference of 2.1 miles). The largest difference in distance was by licensure status, where unlicensed/suspended drivers crashed significantly farther from home than validly licensed drivers (8.8 miles, 95% Confidence Interval [CI]: 8.4-9.1 vs 5.9 miles, 95% CI: 5.9 – 6.0).ConclusionsFindings suggest that the majority of older adults who crash do so within a few miles from home and that the distance to crash does not differ substantially by the presence of a driving-relevant medical condition. Thus, distance restrictions may not reduce crash rates among older adults and the tradeoff between safety and mobility warrants consideration.KEYPOINTS30 states permit restriction of driving distance for medically-at-risk driversThe vast majority of crashes involving older drivers occur ≤ 25 miles of homeDistance to crash does not differ markedly across driving-relevant medical conditionsWhy does this matter?Distance restrictions are likely to impact mobility and autonomy but not crash rates
Predicting anti-cancer activity in flavonoids - a graph theoretic approach
Authors: Mukwembi Simon , Nyabadza Farai 
Published: August 2021

AbstractIn drug design, there are two major causes of drug failure in the clinic. First, the drug has to work, and second, the drug should be safe. Identifying compounds that work for certain ailments require enormous experimental time and, in general, is cost intensive. In this paper, we are concerned with melanoma, a special type of cancer that affects the skin. In particular, we seek to provide a mathematical model that can predict the ability of flavonoids, a vast and natural class of compounds that are found in plants, in reversing or alleviating melanoma. The basis for our model is the conception of a new graph parameter called, for lack of better terminology, graph activity, which captures melanoma cancer healing properties of the flavonoids. With a superior coefficient of determination,R2= 1, the new model faithfully reproduces anti-cancer activities of some known data-sets. We demonstrate that the model can be used to rank the healing abilities of flavonoids which could be a powerful tool in the screening, and identification, of compounds for drug candidates.
Influence of age on the effectiveness and duration of protection in Vaxzevria and CoronaVac vaccines
Authors: Cerqueira-Silva Thiago , Oliveira Vinicius de Araújo , Pescarini Julia , Bertoldo Júnior Juracy , Machado Tales Mota , Flores-Ortiz Renzo , Penna Gerson , Ichihara Maria Yury , de Barros Jacson Venâncio , Boaventura Viviane S. , Barreto Mauricio L. , Werneck Guilherme Loureiro , Barral-Netto Manoel 
Published: August 2021

AbstractBackgroundHigh rates of virus transmission and the presence of variants of concern can affect vaccine effectiveness (VE). Both conditions occur in low-income countries, which primarily use viral vector or inactivated virus vaccine technologies. Such countries conducted few VE analyses, and most lack the power to evaluate effectiveness in subgroups.MethodsThe present retrospective cohort study evaluated the effectiveness of Vaxzevria and CoronaVac vaccines for COVID-19-related infection in 75,919,840 Brazilian vaccinees from January 18 to July 24, 2021.Study outcomes included documented infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), COVID-19–related hospitalization, ICU admission, and death. We estimated VE using Cox regression adjusted for individual demographic characteristics.ResultsVaccination with Vaxzevria or CoronaVac was effective against SARS-CoV-2 infection and highly effective against hospitalization, ICU admission, and death in individuals up to 79 years. From 80-89 years of age, Vaxzevria led to 89.9%(95CI:87.7-91.7) VE against death versus 67.2%(95CI:63.6-70.5) for CoronaVac. Above 90 years, 65.4%(95CI:46.1-77.8) protection was conferred to Vaxzevria-vaccinated individuals versus 33.6%(95CI:21.9-43.5) in CoronaVac-vaccinated individuals. Furthermore, the post-vaccination daily incidence rate shows a stepwise increase from younger to elder decades of life.ConclusionsVaxzevria demonstrated overall effectiveness against severe COVID-19 up to 89 years and CoronaVac up to 79 years of age. There is a stepwise effectiveness reduction for both vaccines for each decade of life. Our results suggest that individuals aged 80 years or older may benefit from an expedited booster dose. Ongoing evaluations, including any additional vaccines authorized, are crucial to monitoring long-term vaccine effectiveness.
HMOX1 genetic polymorphisms and outcomes in infectious disease: a systematic review
Authors: Hamilton Fergus , Somers Julia , Mitchell Ruth , Ghazal Peter , Timpson Nic 
Published: August 2021

IntroductionHeme-oxygenase 1 (HMOX1) is a critical stress response gene that catalyzes the multistep oxidation of heme. A GT(n) repeat of variable length in the promoter in has been associated with a wide range of human diseases, including infections. This paper aims to summarise and systematically review associations between the length of the HMOX1 GT(n) promoter and infectious disease in humans.MethodsA search using relevant terms was performed in PubMED and EMBASE through to 15/01/21 identifying all research that studied an association between the HMOX1 GT(n) repeat polymorphism and the incidence and/or outcome of any human infectious disease. Citations were screened for additional studies. Potential studies were screened for inclusion by two authors. Data was extracted on allele frequency, genotype, strength of association, mechanism of genotyping, and potential biases. A narrative review was performed across each type of infection.Results1,533 studies were identified in the search, and one via citation screening. Sixteen studies were ultimately included, seven in malaria, three in HIV, three in sepsis, and one each in pneumonia, hepatitis C, and acute respiratory distress syndrome (ARDS). Sample sizes for nearly all studies were small (biggest study, n = 1,646). Allelic definition was different across all included studies.In malaria, three studies suggested that longer alleles were associated with reduced risk of severe malaria, particularly malaria-induced renal dysfunction, with four studies identifying a null association. In sepsis, two studies suggested an association with longer alleles and better outcomes.ConclusionsDespite the importance of HMOX1 in survival from infection, and the association between repeat length and gene expression, the clinical data supporting an association between repeat length and incidence and/or outcome of infection remain inconclusive. The most promising data supports a potential association with protection from severe malaria, although this was not found in all studies.
Computer-delivered Cognitive Training and Transcranial Direct Current Stimulation in Patients with HIV-associated Neurocognitive Disorder: A Randomized Trial
Authors: Ownby Raymond L. , Kim Jae 
Published: August 2021

AbstractObjectiveHIV infection is associated with impaired cognition, and as individuals grow older, they may also experience age-related changes in mental abilities. Previous studies have shown that computer-based cognitive training (CCT) and transcranial direct current stimulation (tDCS) may be useful in improving cognition in older persons. This study evaluated the acceptability of CCT and tDCS to older adults with HIV-associated neurocognitive disorder, and assessed their impact on reaction time, attention, and psychomotor speed.MethodsIn a single-blind randomized study, 46 individuals with HIV-associated mild neurocognitive disorder completed neuropsychological assessments and six 20-minute training sessions to which they had been randomly assigned to one of the following conditions: (1) CCT with active tDCS; (2) CCT with sham tDCS, or (3) watching educational videos with sham tDCS. Immediately after training and again one month later, participants completed follow-up assessments. Outcomes were evaluated via repeated measures mixed effects models.ResultsParticipant ratings of the intervention were positive. Effects on reaction time were not significant, but measures of attention and psychomotor speed suggested positive effects of the intervention.ConclusionBoth CCT and tDCS were highly acceptable to older persons with HIV infection. CCT and tDCS may improve cognitive in affected individuals.Registered atClinicalTrials.gov(NCT03440840).
Constitutive expression of JASMONATE RESISTANT 1 elevates content of several jasmonates and primes Arabidopsis thaliana to better withstand drought
Authors: Mahmud Sakil , Ullah Chhana , Kortz Annika , Bhattacharyya Sabarna , Yu Peng , Gershenzon Jonathan , Vothknecht Ute C. 
Published: August 2021

ABSTRACTJasmonates have a well-documented role in balancing the trade-off between plant growth and defense against biotic stresses. However, the role of jasmonate signaling under abiotic stress is less well studied. Here, we investigated the function of JASMONATE RESISTANT 1 (JAR1) in drought stress in Arabidopsis thaliana. JAR1 converts jasmonic acid (JA) to jasmonyl-L-isoleucine (JA-Ile), the major bioactive form of jasmonates. Comparison of a newly generated over-expression line (JAR1-OE) with jar1-11, a T-DNA insertion line in the JAR1 locus, and Col-0 revealed that constitutively increased JA-Ile production results in stunted growth and a delay in flowering. Upon water limitation, JAR1-OE plants retained more water in their leaves, showed reduced wilting and recovered better from drought stress than the wild type. By contrast, jar1-11 mutant plants were hypersensitive to drought. RNA-seq analysis and hormonal profiling of plants under control and drought stress conditions provided insight into the molecular reprogramming caused by the alteration in JA-Ile content. Especially JAR1-OE plants were affected in many adaptive systems related to drought stress, including stomatal density, stomatal aperture or the formation of reactive oxygen species (ROS). Overall, our data suggest that constitutively increased expression of JAR1 can prime Arabidopsis towards improved drought tolerance.One sentence summaryConstitutive expression of JAR1primes Arabidopsis thaliana to better withstand drought stress
Discovery of Antiviral Cyclic Peptides Targeting the Main Protease of SARS-CoV-2 via mRNA Display
Authors: Johansen-Leete Jason , Ullrich Sven , Fry Sarah E. , Frkic Rebecca , Bedding Max J. , Aggarwal Anupriya , Ashhurst Anneliese S. , Ekanayake Kasuni B. , Mahawaththa Mithun C. , Sasi Vishnu M. , Passioura Toby , Larance Mark , Otting Gottfried , Turville Stuart , Jackson Colin J. , Nitsche Christoph , Payne Richard J. 
Published: August 2021

AbstractAntivirals that specifically target SARS-CoV-2 are needed to control the COVID-19 pandemic. The main protease (Mpro) is essential for SARS-CoV-2 replication and is an attractive target for antiviral development. Here we report the use of the Random nonstandard Peptide Integrated Discovery (RaPID) mRNA display on a chemically cross-linked SARS-CoV-2 Mpro dimer, which yielded several high-affinity thioether-linked cyclic peptide inhibitors of the protease. Structural analysis of Mpro complexed with a selenoether analogue of the highest-affinity peptide revealed key binding interactions, including glutamine and leucine residues in sites S1 and S2, respectively, and a binding epitope straddling both protein chains in the physiological dimer. Several of these Mpro peptide inhibitors possessed antiviral activity against SARS-CoV-2 in vitro with EC50 values in the low micromolar range. These cyclic peptides serve as a foundation for the development of much needed antivirals that specifically target SARS-CoV-2.
The Chloroflexi supergroup is metabolically diverse and representatives have novel genes for non-photosynthesis based CO2 fixation
Authors: West-Roberts Jacob A. , Matheus-Carnevali Paula B. , Schoelmerich Marie Charlotte , Al-Shayeb Basem , Thomas Alex D. , Sharrar Allison , He Christine , Chen Lin-Xing , Lavy Adi , Keren Ray , Amano Yuki , Banfield Jillian F. 
Published: August 2021

AbstractThe Chloroflexi superphylum have been investigated primarily from the perspective of reductive dehalogenation of toxic compounds, anaerobic photosynthesis and wastewater treatment, but remain relatively little studied compared to their close relatives within the larger Terrabacteria group, including Cyanobacteria, Actinobacteria, and Firmicutes. Here, we conducted a detailed phylogenetic analysis of the phylum Chloroflexota, the phylogenetically proximal candidate phylum Dormibacteraeota, and a newly defined sibling phylum proposed in the current study, Eulabeiota. These groups routinely root together in phylogenomic analyses, and constitute the Chloroflexi supergroup. Chemoautotrophy is widespread in Chloroflexi. Two Form I Rubisco ancestral subtypes that both lack the small subunit are prevalent in ca. Eulabeiota and Chloroflexota, suggesting that the predominant modern pathway for CO2 fixation evolved in these groups. The single subunit Form I Rubiscos are inferred to have evolved prior to oxygenation of the Earth’s atmosphere and now predominantly occur in anaerobes. Prevalent in both Chloroflexota and ca. Eulabeiota are capacities related to aerobic oxidation of gases, especially CO and H2. In fact, aerobic and anaerobic CO dehydrogenases are widespread throughout every class-level lineage, whereas traits such as denitrification and reductive dehalogenation are heterogeneously distributed across the supergroup. Interestingly, some Chloroflexota have a novel clade of group 3 NiFe hydrogenases that is phylogenetically distinct from previously reported groups. Overall, the analyses underline the very high level of metabolic diversity in the Chloroflexi supergroup, suggesting the ancestral metabolic platform for this group enabled highly varied adaptation to ecosystems that appeared in the aerobic world.
Informative RNA-base embedding for functional RNA structural alignment and clustering by deep representation learning
Authors: Akiyama Manato , Sakakibara Yasubumi 
Published: August 2021

ABSTRACTEffective embedding is being actively conducted by applying deep learning to biomolecular information. Obtaining better embedding enhances the quality of downstream analysis such as DNA sequence motif detection and protein function prediction. In this study, we adopt a pre-training algorithm for the effective embedding of RNA bases to acquire semantically rich representations, and apply it to two fundamental RNA sequence problems: structural alignment and clustering. By using the pre-learning algorithm to embed the four bases of RNA in a position-dependent manner using a large number of RNA sequences from various RNA families, a context-sensitive embedding representation is obtained. As a result, not only base information but also secondary structure and context information of RNA sequences are embedded for each base. We call this “informative base embedding” and use it to achieve accuracy superior to that of existing state-of-the-art methods in RNA structural alignment and RNA family clustering tasks. Furthermore, by performing RNA sequence alignment combining this informative base embedding with a simple Needleman-Wunsch alignment algorithm, we succeed in calculating a structural alignment in a time complexity O(n2) instead of the O(n6) time complexity of Sankoff-style algorithms.
Wolbachia in scale insects: a distinct pattern of infection frequencies and potential transfer routes via ant associates
Authors: Sanaei Ehsan , Lin Yen-Po , Cook Lyn G , Engelstädter Jan 
Published: August 2021

SummaryWolbachia is one of the most successful endosymbiotic bacteria of arthropods. Known as the “master of manipulation”, Wolbachia can induce a wide range of phenotypes in its host that can have far-reaching ecological and evolutionary consequences and may be exploited for disease and pest control. However, our knowledge of Wolbachia’s distribution and infection rate is unevenly distributed across arthropod groups such as scale insects. We fitted a distribution of within-species prevalence of Wolbachia to our data and compared it to distributions fitted to an up-to-date dataset compiled from surveys across all arthropods. The estimated distribution parameters indicate a Wolbachia infection frequency of 43.6% (at a 10% prevalence threshold) in scale insects. Prevalence of Wolbachia in scale insects follows a distribution similar to exponential decline (most species are predicted to have low prevalence infections), in contrast to the U-shaped distribution estimated for other taxa (most species have a very low or very high prevalence). We observed no significant associations between Wolbachia infection and scale insect traits. Finally, we screened for Wolbachia in scale insect’s ecological associates. We found a positive correlation between Wolbachia infection in scale insects and their ant associates, pointing to a possible route of horizontal transfer of Wolbachia.Originality-Significance StatementBy creating metadata of Wolbachia infection in arthropods and applying a fitting an advanced mathematical model on the estimated infection frequency in scale insects, a unique pattern of infection prevalence was detected. In addition, ant-scale insect trophallaxis interaction was suggested as a plausible route of Wolbachia transfer
Characterization of the flagellar collar reveals structural plasticity essential for spirochete motility
Authors: Chang Yunjie , Xu Hui , Motaleb Md A. , Liu Jun 
Published: August 2021

AbstractSpirochetes are a remarkable group of bacteria with distinct morphology and periplasmic flagella that enable motility in viscous environments, such as host connective tissues. The collar, a spirochete-specific complex of the periplasmic flagellum, is required for the unique spirochete motility, yet it has not been clear how the collar assembles and enables spirochetes to transit between complex host environments. Here, we characterize the collar complex in the Lyme disease spirochete Borrelia burgdorferi. We discover as well as delineate the distinct functions of two novel collar proteins, FlcB and FlcC, by combining subtractive bioinformatic, genetic, and cryo-electron tomography approaches. Our high-resolution in-situ structures reveal that the multi-protein collar has a remarkable structural plasticity essential not only for assembly of flagellar motors in the highly curved membrane of spirochetes but also for generation of the high torque necessary for spirochete motility.