bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genomic signatures of local adaptation in recent invasiveAedes aegyptipopulations in California
Authors: Soudi Shaghayegh , Crepeau Marc , Collier Travis C. , Lee Yoosook , Cornel Anthony J. , Lanzaro Gregory C. 
Published: December 2022

AbstractBackgroundRapid adaptation to new environments can facilitate species invasions and range expansions. Understanding the mechanisms of adaptation used by invasive disease vectors in new regions has key implications for mitigating the prevalence and spread of vector-borne disease, although they remain relatively unexplored.ResultsHere, we use whole-genome sequencing data from 103Aedes aegyptimosquitoes collected from various sites in southern and central California to infer the genetic structure of invasive populations. We integrate genome data with 25 topo-climate variables to investigate genome-wide signals of local adaptation among populations. Patterns of population structure, as inferred using principle components and admixture analysis, were consistent with three genetic clusters, likely resulting from multiple independent introductions. Using various landscape genomics approaches, which all remove the confounding effects of shared ancestry on correlations between genetic and environmental variation, we identified 112 genes showing strong signals of local environmental adaptation associated with one or more topo-climate factors. Some of them have known effects in climate adaptation, such as heat-shock proteins, which shows selective sweep and recent positive selection acting on these genomic regions.ConclusionsOur results provide a genome wide perspective on the distribution of adaptive loci and lay the foundation for future work to understand how environmental adaptation inAe. aegyptiimpacts the arboviral disease landscape and how such adaptation could help or hinder efforts at population control.
Fetal cannabidiol (CBD) exposure alters thermal pain sensitivity, cognition, and prefrontal cortex excitability
Authors: Swenson Karli S. , Wulschner Luis E. Gomez , Hoelscher Victoria M. , Folts Lillian , Korth Kamryn M. , Oh Won Chan , Bates Emily Anne 
Published: December 2022

AbstractThousands of people suffer from nausea with pregnancy each year. Nausea can be alleviated with cannabidiol (CBD), a primary component of cannabis that is widely available. However, is it unknown how fetal CBD exposure affects embryonic development and postnatal outcomes. CBD binds and activates receptors that are important for fetal development and are expressed in the fetal brain, including serotonin receptors (5HT1A), voltage-gated potassium (Kv)7 receptors, and the transient potential vanilloid 1 receptor (TRPV1). Excessive activation of each of these receptors during fetal development can disrupt neurodevelopment. Here, we test the hypothesis that intrauterine CBD exposure alters offspring neurodevelopment and postnatal behavior. We show that fetal CBD exposure sensitizes male offspring to thermal pain in a TRPV1 dependent manner. We show that fetal CBD exposure decreases cognitive function in female CBD-exposed offspring. We demonstrate that fetal CBD exposure increases the minimum current required to elicit action potentials and decreases the number of action potentials in female offspring layer 2/3 prefrontal cortex (PFC) pyramidal neurons. Fetal CBD exposure reduces the amplitude of glutamate uncaging-evoked excitatory post-synaptic currents. Combined, these data show that fetal CBD exposure disrupts neurodevelopment and postnatal behavior in a sex-dependent manner.One Sentence SummaryCannabidiol (CBD) consumption during pregnancy alters offspring behavior and neuronal excitability in a sex dependent manner in mice.
Defining the role of host biomarkers in the diagnosis and prognosis of childhood pneumonia – a prospective cohort study
Authors: Chandna Arjun , Lubell Yoel , Mwandigha Lazaro , Tanunchai Phattaranit , Vinitsorn Asama , Richard-Greenblatt Melissa , Koshiaris Constantinos , Limmathurotsakul Direk , Nosten Francois , Abdad Mohammad Yazid , Perera-Salazar Rafael , Turner Claudia , Turner Paul 
Published: December 2022

ABSTRACTBackgroundReliable tools to inform outpatient management of childhood pneumonia in resource-limited settings are needed. We investigated the value added by biomarkers of host infection response to the performance of the Liverpool quick Sequential Organ Failure Assessment score (LqSOFA), for triage of children presenting with pneumonia to a primary care clinic in a refugee camp on the Thailand-Myanmar border.Methods900 presentations of children aged ≤ 24 months meeting WHO pneumonia criteria were included. The primary outcome was receipt of supplemental oxygen. We compared discrimination of a clinical risk score (LqSOFA) to markers of endothelial injury (Ang-1, Ang-2, sFlt-1), immune activation (CHI3L1, IP-10, IL-1ra, IL-6, IL-8, IL-10, sTNFR-1, sTREM-1), and inflammation (CRP, PCT), and quantified the net-benefit of including biomarkers alongside LqSOFA. We evaluated the differential contribution of LqSOFA and host biomarkers to the diagnosis and prognosis of severe pneumonia.Results49/900 (5.4%) presentations met the primary outcome. Discrimination of LqSOFA and Ang-2, the best performing biomarker, were comparable (AUC 0.82 [95% CI 0.76-0.88] and 0.81 [95% CI 0.74-0.87] respectively). Combining Ang-2 with LqSOFA improved discrimination (AUC 0.91; 95% CI 0.87-0.94; p < 0.001), and resulted in greater net-benefit, with 10-30% fewer children requiring oxygen supplementation incorrectly identified as safe for community-based management. Ang-2 had greater prognostic utility than LqSOFA to identify children requiring supplemental oxygen later in their illness course.ConclusionsCombining Ang-2 and LqSOFA could guide referrals of childhood pneumonia from resource-limited community settings. Further work on integration into patient triage is required.
Compositional coding of individual finger movements in human posterior parietal cortex and motor cortex enables ten-finger decoding
Authors: Guan Charles , Aflalo Tyson , Kadlec Kelly , Gámez de Leon Jorge , Rosario Emily R. , Bari Ausaf , Pouratian Nader , Andersen Richard A. 
Published: December 2022

AbstractObjectiveEnable neural control of individual prosthetic fingers for participants with upper-limb paralysis.ApproachTwo tetraplegic participants were each implanted with a 96-channel array in the left posterior parietal cortex (PPC). One of the participants was additionally implanted with a 96-channel array near the hand knob of the left motor cortex (MC). Across tens of sessions, we recorded neural activity while the participants attempted to move individual fingers of the right hand. Offline, we classified finger movements from neural firing rates using linear discriminant analysis (LDA) with cross-validation. The participants then used the neural classifier online to control individual fingers of a brain-machine interface (BMI). Finally, we characterized the neural representational geometry during individual finger movements of both hands.Main ResultsThe two participants achieved 86% and 92% online accuracy during BMI control of the contralateral fingers (chance = 17%). Offline, a linear decoder achieved ten-finger decoding accuracies of 70% and 66% using respective PPC recordings and 75% using MC recordings (chance = 10%). A compositional code linked corresponding finger movements of the contralateral and ipsilateral hands.SignificanceThis is the first study to decode both contralateral and ipsilateral finger movements from PPC. Online BMI control of contralateral fingers exceeded that of previous finger BMIs. PPC and MC signals can be used to control individual prosthetic fingers, which may contribute to a hand restoration strategy for people with tetraplegia.
Healthy behaviors and circadian patterns determined by actigraphy in researchers and administrative personnel as protective factors against metabolic disease and obesity
Authors: Espitia-Bautista Estefania , Morales-Bautista Francisco , Rizo-Pastrana Ivette , Escobar Carolina , Stephens Christopher R. 
Published: December 2022

ABSTRACTObjectivesThree important, directly-causal, behavioral risk factors for obesity and its metabolic consequences are: food consumption, sedentary lifestyle and circadian disruption, such as social jet-lag, which should also partially explain the relevance of known, indirectly-causal, such as educational level, socio-economic status and/or type of job and its conditions. In this study we use actigraphy as a means to quantify and understand those differences in behaviors or conducts, related to 1) physical activity and 2) circadian disruption, which can explain observed differences in metabolic health in two different populations.MethodsMetabolic and anthropometric data were taken from a population of university workers segmented by educational level – administrative workers (bachelor’s degree) and researchers (Masters or PhD degree) – Actigraphs collected temperature, acceleration, luxes and time in movement; participants use them for at least 1 week. Actigraphy data were divided in weekdays and weekends for analysis.ResultsWe show that body mass index and metabolic syndrome criteria were significantly worse for the lower educational level group. Correspondingly, significant differences were found between administrative personnel and researchers across all measured actigraphy parameters – activity level, acceleration, light exposure and temperature. The most relevant differences are that researchers presented significantly more/less time in high/low-activity conducts, less differences in activity level between weekdays and weekends, and less social jet-lag than administrative personnel.ConclusionsResearchers have healthier habits both in terms of voluntary physical activity and less circadian disruption, showing how work environment can be an important determinant of the degree to which healthy habits can be adopted.HighlightsEducational level and work environment are relevant factors to contribute to the development of metabolic syndrome and obesity.Administrative personnel showed worse metabolic health than Researchers, and also Administrative workers showed less healthy behaviors in actigraphy.Differences between weekdays and weekends are a good parameter to measure social jet lag, but also for habits.Administrative personnel presented more Social jet lag than researchers, and more differences between weekdays and weekends in activity and temperature.
Developing and validating a multi-criteria decision analytic tool to assess the value of cancer clinical trials
Authors: Gillett Piers , Mahar Robert K , Tran Nancy R , Rosenthal Mark , IJzerman Maarten 
Published: December 2022

AbstractBackgroundDemonstrating safety and efficacy of new medical treatments requires clinical trials. But clinical trials are costly and may not provide value proportionate to their costs. In health systems with limited resources, it is important to identify the trials with the highest value. Tools exist to assess elements of a clinical trial such as statistical validity but are not wholistic in their valuation of a clinical trial. This study aims to develop a measure of clinical trials value and provide an online tool for clinical trial prioritisation.MethodsA search of the academic and grey literature and expert consultation was undertaken to identify a set of metrics to aid clinical trial valuation using multi-criteria decision analysis. Swing weighting and ranking exercises were used to calculate appropriate weights of each of the included metrics and to estimate the partial-value function for each underlying metric. The set of metrics and their respective weights were applied to the results of six different clinical trials to calculate their value.ResultsSeven metrics were identified: ‘unmet need’, ‘size of target population’, ‘eligible participants can access the trial’, ‘patient outcomes’, ‘total trial cost’, ‘academic impact’ and ‘use of trial results’. The survey had 80 complete sets of responses (51% response rate). A trial designed to address an ‘Unmet Need’ was most commonly ranked as the most important with a weight of 24.4%, followed by trials demonstrating improved ‘Patient Outcomes’ with a weight of 21.2%. The value calculated for each trial allowed for their clear delineation and thus a final value ranking for each of the six trials.ConclusionWe confirmed that the use of the decision tool for valuing clinical trials is feasible and that the results are face valid based on the evaluation of six trials. A proof-of-concept applying this tool to a larger set of trials with an external validation is currently underway.
Multiscale modelling of invasive species control: the cane toad in Australia
Authors: Pham Anh D. , Baker Christopher M. , Geard Nicholas 
Published: December 2022

AbstractThe cane toad (Bufo marinus) is an invasive species in Australia that has a negative impact on native species. Control methods such as trapping, fencing, and water exclusion have been devised to contain the spread of cane toads and reduce their ecological impact. However, implementing these interventions is expensive, and estimating the likely impact of a proposed intervention on spread at a large spatial scale, comprising one or more control methods, is challenging due to the lack of large-scale data and the computational cost of modelling a large number of toads.To address this challenge, we developed a multiscale model which uses individual-level data on cane toad behaviour to estimate the impact of trapping, fencing, and water exclusion when applied at scale in the Pilbara region in north-western Australia. Compared to previous work, our model allows us to explore more complex combinations and tradeoffs of control methods by utilising data sources at different scales.Our results suggest that exclusion of toads from water points is the most effective method for containing the spread of cane toads, and that trapping and fencing alone are unlikely to be sufficient. However, trapping and fencing are still useful supplementary measures in scenarios where exclusion cannot be broadly applied to a large number of water points.Synthesis and applications. Our analyses highlight the importance of limiting access to sheltering and breeding sites in invasive species control. Furthermore, this study illustrates the value of multiscale computational models for exploring scenarios where parameters and calibration data are available at the scale of individuals and small groups, but management questions are framed at a much larger scale.
A unified classification system for HIV-1 5’ long terminal repeats
Authors: Guo Xing , Yu Dan , Liu Mengying , Li Hanping , Chen Mingyue , Wang Xinyu , Zhai Xiuli , Zhang Bohan , Wang Yanglan , Yang Caiqing , Wang Chunlei , Liu Yongjian , Han Jingwan , Wang Xiaolin , Li Tianyi , Li Jingyun , Jia Lei , Li Lin 
Published: December 2022

AbstractThe HIV-1 provirus mainly consists of internal coding region flanked by the 2 same long terminal repeats (LTRs) at each terminus. The LTRs play important roles in HIV-1 reverse transcription, integration, and transcription by the association with host factors. However, despite of the significant study advances of the internal coding regions of HIV-1 by using definite reference classification, there are no systematic classifications for HIV-1 5’ LTRs, which hinders our elaboration on 5’ LTR and a better understanding of the viral origin, spread and therapy. Here, by analyzing all available resources of 5’ LTR sequences in public databases following 4 recognized principles for the reference classification, 83 representatives and 14 consensus sequences were identified as representatives of 2 groups, 6 subtypes, 6 sub-subtypes, and 9 CRFs. To test the reliability of our established classification system, the constructed references were applied to identify the 5’ LTR assignment of the 22 clinical isolates in China. The results revealed that 16 out of 22 tested strains showed a consistent subtype classification with the previous LTR-independent classification system. However, 6 strains, for which recombination events within 5’ LTR were demonstrated, unexpectedly showed a different subtype classification, leading a significant change of binding sites for important transcription factors including SP1, p53, and NF-κB. The binding change of these transcriptional factors would probably affect the transcriptional activity of 5’ LTR. This study established a unified classification system for HIV-1 5’ LTRs, which will facilitate HIV-1 characterization and be helpful for both basic and clinical research fields.IMPORTANCEHere, a scientific, reliable, and usable classification system based on the 5’ LTR sequences was established, which will allow us to effectively facilitate the precise typing of HIV-1 strains. This classification system was applied to 22 HIV-1 strains circulating in China, we found that 6 out of 22 strains analyzed, belonged to a different subtype when our results were compared to those obtained with the previous LTR-independent classification system. Thus, these data demonstrated that our classification method could greatly improve the HIV-1 subtype classification. We found that 6 5’ LTR sequences showed recombination events, leading to a significant exchange of the binding sites of transcriptional factors. Thus, this work established a comprehensive HIV-1 5’ LTR classification system, which will help the scientific community to precisely characterize HIV-1 variants, and better understand the origin and spread of HIV-1 strains, and it also may be helpful for pathogenicity and transmissibility evaluation studies.
Quantitative proteomics of cerebrospinal fluid from African Americans and Caucasians reveals shared and divergent changes in Alzheimer’s disease
Authors: Modeste Erica , Ping Lingyan , Watson Caroline M. , Duong Duc M. , Dammer Eric B. , Johnson Erik C.B. , Roberts Blaine R. , Lah James J. , Levey Allan I. , Seyfried Nicholas T. 
Published: December 2022

ABSTRACTDespite being twice as likely to get Alzheimer’s disease (AD), African Americans have been grossly underrepresented in AD research. While emerging evidence indicates that African Americans with AD have lower cerebrospinal fluid (CSF) levels of Tau compared to Caucasians, other differences in AD CSF biomarkers have not been fully elucidated. Here, we performed unbiased proteomic profiling of CSF from African Americans and Caucasians with and without AD to identify both common and divergent AD CSF biomarkers. Multiplex tandem mass tag-based mass spectrometry (TMT-MS) quantified 1,840 proteins from 105 control and 98 AD patients of which 100 identified as Caucasian while 103 identified as African American. Consistent with previous findings, the increase of Tau levels in AD was greater in Caucasians than in African Americans by both immunoassay and TMT-MS measurements. Network analysis organized the CSF proteome into 14 modules associated with brain cell-types and biological pathways. CSF modules which included 14-3-3 proteins (YWHAZ and YWHAG), demonstrated equivalent disease-related elevations in both African Americans and Caucasians with AD, whereas other modules demonstrated more profound disease changes within race. Modules enriched with proteins involved with glycolysis and neuronal/cytoskeletal proteins, including Tau, were more increased in Caucasians than in African Americans with AD. In contrast, a module enriched with synaptic proteins including VGF, SCG2, and NPTX2 was significantly lower in African Americans than Caucasians with AD. Using a targeted proteomic approach (selected reaction monitoring) followed by a receiver operating characteristic curve (ROC) analysis we measured levels of VGF, SCG2, and NPTX2, which were significantly better at classifying African Americans than Caucasians with AD. Collectively, our findings provide insight into additional protein biomarkers and pathways reflecting underlying brain pathology that are shared or differ by race.
Interior pH Sensing Residue of Human Voltage-Gated Proton Channel Hv1 is Histidine 168
Authors: Shen Mingzhe , Huang Yandong , Cai Zhitao , Cherny Vladimir V. , DeCoursey Thomas E. , Shen Jana 
Published: December 2022

ABSTRACTThe molecular mechanisms governing the human voltage-gated proton channel hHv1 remain elusive. Here we used membrane-enabled hybrid-solvent continuous constant pH molecular dynamics (CpHMD) simulations with pH replica exchange to further evaluate the recently obtained structural models of hHv1 in hyperpolarized (closed channel) and depolarized (open channel) states (Geragotelis, Tobias et al., Proc. Natl. Acad. Sci. USA 2020) and explore potential pH-sensing residues. The CpHMD titration at a set of symmetric pH conditions revealed three residues that can gain or lose protons upon channel depolarization. Among them residue H168 at the intracellular end of the S3 helix switches from the deprotonated to the protonated state and its protonation is correlated with the increased tilting of the S3 helix during the transition from the hyper-to the depolarized state. Thus, the simulation data suggest H168 as an interior pH sensor, in support of a recent finding based on electrophysiological experiments of Hv1 mutants (Cherny, DeCoursey et al., J. Gen. Physiol. 2018). Our work represents an important step towards deciphering the pH-dependent gating mechanism of hHv1.SIGNIFICANCEThe human voltage-gated proton channel hHv1 is comprised of a proton-selective voltage sensing domain and responsible for cellular pH homeostasis. Despite intense experimental and theoretical investigations, its pH-dependent gating mechanism is not understood. Our simulation data offer strong evidence supporting the role of H168 as a pHisensor (Cherny, DeCoursey et al., J. Gen. Physiol. 2018). Deciphering the interior pH sensor moves us a step closer to elucidating the structure-function relationship of hHv1.