bluuebunny/crossref_metadata_2025_split huggingface dataset:
An acylsugar-deficientNicotiana benthamianastrain for aphid and whitefly research
Authors: Feng Honglin , Acosta-Gamboa Lucia , Kruse Lars H. , Tracy Jake D. , Chung Seung Ho , Nava Fereira Alba Ruth , Shakir Sara , Xu Hongxing , Sunter Garry , Gore Michael A. , Casteel Clare L. , Moghe Gaurav D. , Jander Georg 
Published: August 2020

AbstractNicotiana benthamianais used extensively as a platform for transient gene expression and as a model system for studying plant-virus interactions. However, many tobacco-feeding generalist herbivores, includingMyzus persicae(green peach aphid),Bemisia tabaci(whitefly),Macrosiphum euphorbiae(potato aphid),Heliothis virescens(tobacco budworm),Trichoplusia ni(cabbage looper), andHelicoverpa zea(corn earworm), grow poorly onN. benthamiana, limiting its utility for research on plant-insect interactions. Using CRISPR/Cas9, we generated knockout mutations in twoN. benthamianaacylsugar acyltransferases,ASAT1andASAT2, which contribute to the biosynthesis of insect-deterrent acylsucroses. Whereasasat1mutations reduced the abundance of two predominant acylsucroses,asat2mutations caused almost complete depletion of foliar acylsucroses. The tested hemipteran and lepidopteran species survived, gained weight, and/or reproduced significantly better onasat2mutant plants than on wildtypeN. benthamiana. Furthermore, bothasat1andasat2mutations reduced the water content and increased the temperature of leaves, indicating that foliar acylsucroses can protect against desiccation. Two experiments demonstrated the utility of theN. benthamiana asat2mutant line for insect bioassays. Transmission of turnip mosaic virus byM. persicaewas significantly improved by anasat2mutation. Tobacco rattle virus constructs were used for virus-induced gene silencing ofacetylcholinesterase,squalene synthase,toll-like receptor 7, andtubulin-specific chaperon Dgenes inB. tabaci, an experiment that would have been difficult with wild-typeN. benthamianadue to high insect mortality. Additionally, the absence of acylsugars inasat2mutant lines will simplify transient expression assays for the functional analysis of acylsugar biosynthesis genes from other Solanaceae.
Impairment of the Hif-1α regulatory pathway in Foxn1-deficient (Foxn1−/−) mice affects the skin wound healing process
Authors: Machcinska Sylwia , Kopcewicz Marta , Bukowska Joanna , Walendzik Katarzyna , Gawronska-Kozak Barbara 
Published: August 2020

ABSTRACTHypoxia and hypoxia-regulated factors [e. g., hypoxia-inducible factor-1α (Hif-1α), factor inhibiting Hif-1α (Fih-1), thioredoxin-1 (Trx-1), aryl hydrocarbon receptor nuclear translocator 2 (Arnt-2)] have essential roles in skin wound healing. Using Foxn1−/−mice that can heal skin injuries in a unique scarless manner, we investigated the interaction between Foxn1 and hypoxia-regulated factors. The Foxn1−/−mice displayed impairments in the regulation of Hif-1α, Trx-1 and Fih-1 but not Arnt-2 during the healing process. An analysis of wounded skin showed that the skin of the Foxn1−/−mice healed in a scarless manner, displaying rapid re-epithelialization and an increase intransforming growth factor β(Tgfβ-3)andcollagen IIIexpression. Anin vitroanalysis revealed that Foxn1 overexpression in keratinocytes isolated from the skin of the Foxn1−/−mice led to reducedHif-1αexpression in normoxic but not hypoxic cultures and inhibitedFih-1expression exclusively under hypoxic conditions. These data indicate that in the skin, Foxn1 affects hypoxia-regulated factors that control the wound healing process and suggest that under normoxic conditions, Foxn1 is a limiting factor for Hif-1α.
A Review of Population Pharmacokinetic Studies of Levetiracetam
Authors: Li Zi-ran , Wang Chen-yu , Zhu Xiao , Jiao Zheng 
Published: August 2020

AbstractBackgroundLevetiracetam has been widely used as a treatment option for different types of epilepsy in both adults and children. Because of its large between-subject variability, several population pharmacokinetic studies have been performed to identify its pharmacokinetic covariates, and thus facilitate individualised therapy.ObjectiveThe aim of this review was to provide a synopsis for population pharmacokinetic studies of levetiracetam and explore the identified influencing covariates.MethodsWe systematically searched the PubMed and Embase databases from inception to 30 June, 2020. The information on study designs, target population, model characteristics, and identified covariates was summarised. Moreover, the pharmacokinetic profiles were compared among neonates, children, and adults.ResultsFourteen studies were included, among which 2 involved neonates, 4 involved children, 2 involved both children and adults, and 6 involved only adults. The median value of apparent clearance for children (0.074 [range: 0.038–0.079] L/h/kg) was higher than that for adults (0.054 [range: 0.039–0.061] L/h/kg). Body weight was found to significantly influence the apparent clearance and volume of distribution significantly, whereas renal function influenced the clearance. Likewise, co-administration with enzyme-inducing antiepileptic drugs (such as carbamazepine and phenytoin) increased the drug clearance by 9%–22%, whereas co-administration with valproate acid decreased it by 18.8%.ConclusionLevetiracetam dose regimen is dependent on the body size and renal function of patients. Further studies are needed to evaluate levetiracetam pharmacokinetics in neonates and pregnant women.Key pointsThis review identifies weight, renal function, daily dose, and postmenstrual age as the covariates that most likely influence the levetiracetam (LEV) pharmacokinetics.Children showed higher clearance per kilogram body weight than adults, indicating that a higher dosage is required for children per kilogram body weight.Further PPK studies are needed to evaluate LEV pharmacokinetics in special populations such as pregnant women and neonates.
The prevalence and associated factors of adverse pregnancy outcomes among Afghan women in Iran; the possible impacts of domestic violence, poor mental health, housing issues, and food security
Authors: Dadras Omid , Nakayama Takeo , Kihara Mashiro , Kihara Masako-Ono , Seyedalinaghi Seyedahmad , Dadras Fateme 
Published: August 2020

AbstractBackgroundsAfghans are the largest refugee population in Iran and an estimated 2.5 million Afghans are living in the country. Although Afghan women constitute less than half of this population, they are young and at the childbearing ages. Evidence indicates lower rates of antenatal care and higher incidence of pregnancy complications in Afghan compared to Iranian women. In the present study, we aimed to explore the prevalence and associated sociodemographic factors of adverse pregnancy outcomes and examine the impact of intimate partner violence (IPV), food insecurity, poor mental health, and housing issues on pregnancy outcome in Afghan women living in Iran.MethodsIn July 2019, we enrolled 424 Afghan women aged 18-44 years old using the time-location sampling at three community health centers in the south region of Tehran province. The data was collected through face to face interviews using the researcher-developed questionnaire.ResultsMore than half of Afghan women reported at least one pregnancy complication in their recent pregnancy. The results showed that illegal, illiterate, and unemployed Afghan women with lower socioeconomic status are more likely to experience adverse pregnancy outcomes. Furthermore, we observed lower prevalence of adverse pregnancy outcomes among legal immigrants with health insurance. It is also been found that food insecurity, poor antenatal care, IPV, and poor mental health could adversely impact the pregnancy outcome and we observed higher incidence of adverse outcomes among those suffering from these situations.ConclusionTo our knowledge, this is the first study that explored the prevalence and associated factors of adverse pregnancy outcomes and the impact of intimate partner violence, food insecurity, poor mental health on pregnancy outcomes among Afghan women in Iran. Enhancing the psychosocial support and empowering Afghan women through expanding the social network and safety net should be a priority for the central government and international parties. Psychological counseling could be incorporated into routine maternity care for Afghan refugees. Access to free antenatal care is a right for all Afghan women and it could be facilitated by universal health insurance for all Afghans regardless of their legal status.
Impact of prenatal exome sequencing for fetal genetic diagnosis on maternal psychological outcomes and decisional conflict in a prospective cohort
Authors: Talati Asha N. , Gilmore Kelly L. , Hardisty Emily , Lyerly Anne D. , Rini Christine , Vora Neeta L. 
Published: August 2020

AbstractObjectiveTo evaluate associations between prenatal trio exome sequencing (trio-ES) and psychological outcomes among women with an anomalous pregnancy.MethodsTrio-ES study enrolling patients with major fetal anomaly and normal microarray. Women completed self-reported measures and free response interviews at two time points, pre- (1) and post- (2) sequencing. Pre-sequencing responses were compared to post-sequencing responses; post-sequencing responses were stratified by women who received trio-ES results that may explain fetal findings, secondary findings (medically actionable or carrier couple status), or negative results. Free responses were content analyzed.Results115 trios were enrolled. Of those, 41/115 (35.7%) received results from trio-ES, including 36 (31.3%) who received results that may explain the fetal phenotype. These women had greater post-sequencing distress compared to women who received negative results, including generalized distress (p=0.03) and test-related distress (p=0.2); they also had worse psychological adaptation to results (p=0.001). Genomic knowledge did not change from pre- to post-sequencing (p=0.51). Major themes from content analyses included closure, future pregnancy, altruism, anxiety, and gratitude.ConclusionsWomen show more distress after receiving trio-ES results compared to those who do not.
U.S. Field Hospitals: A Study on Public Health Emergency Response to COVID-19
Authors: Yuan Luorongxin , Sherryn Sherryn , Hu Peter , Chen Fenghao 
Published: August 2020

AbstractWith the number of confirmed COVID-19 cases rapidly growing in the U.S., many states are experiencing a shortage of hospital—especially ICU—beds. In addition to discharging non-critical patients, expanding local hospitals’ capacity as well as re-opening closed healthcare facilities, these states are actively building or converting public venues into field hospitals to fill the gap1. By studying these makeshift hospitals, we found that the states most severely impacted by the pandemic are fast at responding with the first wave of hospitals opening around the date of peak demand and the majority ready to use by the end of April. However, depending on the types of patients the field hospitals accept (COVID-19 vs. non-COVID-19) and how they are incorporated to local healthcare system, these field hospitals have utilization rate ranging from 100% to 0%. The field hospitals acting as alternative site to treat non-COVID-19 patients typically had low utilization rate and often faced the risk of COVID-19 outbreak in the facility. As overflow facilities, the field hospitals providing intensive care were highly relied on by local healthcare systems whereas the field hospitals dedicated to patients with mild symptoms often found it hard to fill the beds due to a combination of factors such as strict regulation on transferring patients from local hospitals, complication of health insurance discouraging health-seeking behavior, and effective public health measure to “flatten the curve” so that the additional beds were no longer needed.
Time-to-event estimation of birth prevalence trends: a method to enable investigating the etiology of childhood disorders including autism
Authors: MacInnis Alexander G. 
Published: August 2020

AbstractAn unbiased, widely accepted estimate of the rate of occurrence of new cases of autism over time would facilitate progress in understanding the causes of autism. The same may also apply to other disorders. While incidence is a widely used measure of occurrence, birth prevalence—the proportion of each birth year cohort with the disorder—is the appropriate measure for disorders and diseases of early childhood. Studies of autism epidemiology commonly speculate that estimates showing strong increases in rate of autism cases result from an increase in diagnosis rates rather than a true increase in cases. Unfortunately, current methods are not sufficient to provide a definitive resolution to this controversy. Prominent experts have written that it is virtually impossible to solve.This paper presents a novel method, time-to-event birth prevalence estimation (TTEPE), to provide accurate estimates of birth prevalence properly adjusted for changing diagnostic factors. It addresses the shortcomings of prior methods. TTEPE is based on well-known time-to-event (survival) analysis techniques. A discrete survival process models the rates of incident diagnoses by birth year and age. Diagnostic factors drive the probability of diagnosis as a function of the year of diagnosis. TTEPE models changes in diagnostic criteria, which can modify the effective birth prevalence when new criteria take effect. TTEPE incorporates the development of diagnosable symptoms with age. General-purpose optimization software estimates all parameters, forming a non-linear regression. The paper specifies all assumptions underlying the analysis and explores potential deviations from assumptions and optional additional analyses.A simulation study shows that TTEPE produces accurate parameter estimates, including trends in both birth prevalence and the probability of diagnosis in the presence of sampling effects from finite populations. TTEPE provides high power to resolve small differences in parameter values by utilizing all available data points.
Phenotyping the preterm brain: characterising individual deviations from normative volumetric development in two large infant cohorts
Authors: Dimitrova Ralica , Arulkumaran Sophie , Carney Olivia , Chew Andrew , Falconer Shona , Ciarrusta Judit , Wolfers Thomas , Batalle Dafnis , Cordero-Grande Lucilio , Price Anthony N. , Teixeira Rui PAG , Hughes Emer , Egloff Alexia , Hutter Jana , Makropoulos Antonios , Robinson Emma C. , Schuh Andreas , Vecchiato Katy , Steinweg Johannes K. , Macleod Russell , Marquand Andre F. , McAlonan Grainne , Rutherford Mary A. , Counsell Serena J. , Smith Stephen M. , Rueckert Daniel , Hajnal Joseph V. , O’Muircheartaigh Jonathan , Edwards A. David 
Published: August 2020

AbstractThe diverse cerebral consequences of preterm birth create significant challenges for understanding pathogenesis or predicting later outcome. Instead of focusing on describing effects common to the group, comparing individual infants against robust normative data offers a powerful alternative to study brain maturation. Here we used Gaussian process regression to create normative curves characterising brain volumetric development in 274 term-born infants, modelling for age at scan and sex. We then compared 89 preterm infants scanned at termequivalent age to these normative charts, relatingindividualdeviations from typical volumetric development to perinatal risk factors and later neurocognitive scores. To test generalisability, we used a second independent dataset comprising of 253 preterm infants scanned using different acquisition parameters and scanner. We describe rapid, non-uniform brain growth during the neonatal period. Inbothpreterm cohorts, cerebral atypicalities were widespread, often multiple, and varied highly between individuals. Deviations from normative development were associated with respiratory support, nutrition, birth weight, and later neurocognition, demonstrating their clinical relevance. Group-level understanding of the preterm brain disguise a large degree of individual differences. We provide a method and normative dataset that offer a more precise characterisation of the cerebral consequences of preterm birth by profiling theindividualneonatal brain.
Antigen-specific induction of CD4+CD8αα+intraepithelial T lymphocytes byBacteroidetesspecies
Authors: Bousbaine Djenet , Bhagchandani Preksha , London Mariya , Mimee Mark , Olesen Scott , Poyet Mathilde , Cheloha Ross W. , Sidney John , Ling Jingjing , Gupta Aaron , Lu Timothy K. , Sette Alessandro , Alm Eric J. , Mucida Daniel , Bilate Angelina M. , Ploegh Hidde L. 
Published: August 2020

AbstractThe microbiome contributes to the development and maturation of the immune system1–3In response to commensal bacteria, CD4+T cells can differentiate into distinct functional subtypes with regulatory or effector functions along the intestine. Peripherally-induced Foxp3+-regulatory T cells (pTregs) maintain immune homeostasis at the intestinal mucosa by regulating effector T cell responses against dietary antigens and microbes4. Similarly to pTregs, a subset of small intestine intraepithelial lymphocytes CD4+CD8αα+(CD4IELS) exhibit regulatory properties and promote tolerance against dietary antigens5. Development of CD4IELSfrom conventional CD4+T cells or from Treg precursors depends on the microbiota5,6. However, the identity of the microbial antigens recognized by CD4IELsremains unknown. We identified species belonging to theBacteroidetesphylum as commensal bacteria capable of generating CD4IELfrom naïve CD4+T cells expressing the pTreg transnuclear (TN) monoclonal TCR6as well as from polyclonal WT T cells. We found that β-hexosaminidase, a widely conserved carbohydrate-metabolizing enzyme in theBacteroidetesphylum, is recognized by TN T cells, which share their TCR specificity with CD4+T cells found in the intraepithelial compartment of polyclonal specific-pathogen-free (SPF) mice. In a mouse model of colitis, β-hexosaminidase-specific CD4IELsprovided protection from ulceration of the colon and weight loss. Thus, a single T cell clone can recognize a variety of abundant commensal bacteria and elicit a regulatory immune response at the intestinal epithelial surface.
Ventralis intermedius nucleus anatomical variability assessment by MRI structural connectivity
Authors: Ferreira Francisca , Akram Harith , Ashburner John , Zrinzo Ludvic , Zhang Hui , Lambert Christian 
Published: August 2020

AbstractThe ventralis intermedius nucleus (Vim) is centrally placed in the dentato-thalamo-cortical pathway (DTCp) and is a key surgical target in the treatment of severe medically refractory tremor. It is not visible on conventional MRI sequences; consequently, stereotactic targeting currently relies on atlas-based coordinates. This fails to capture individual anatomical variability, which may lead to poor long-term clinical efficacy. Probabilistic tractography, combined with known anatomical connectivity, enables localisation of thalamic nuclei at an individual subject level. There are, however, a number of confounds associated with this technique that may influence results.Here we focused on an established method, using probabilistic tractography to reconstruct the DTCp, to identify the connectivity-defined Vim (cd-Vim)in vivo. Using 100 healthy individuals from the Human Connectome Project, our aim was to quantify cd-Vim variability across this population, measure the discrepancy with atlas-defined Vim (ad-Vim), and assess the influence of potential methodological confounds.We found no significant effect of any of the confounds. The mean cd-Vim coordinate was located within 1.9 mm (left) and 2.1 mm (right) of the average midpoint and 4.9 mm (left) and 5.4 mm (right) from the ad-Vim coordinates. cd-Vim location was more variable on the right, which reflects hemispheric asymmetries in the probabilistic DTCp reconstructed. The superior cerebellar peduncle was identified as a potential source of artificial variance.This work demonstrates significant individual anatomical variability of the cd-Vim that atlas-based approaches fail to capture. This variability was not related to any methodological confound tested. Lateralisation of cerebellar functions, such as speech, may contribute to the observed asymmetry. Tractography-based methods seem sensitive to individual anatomical variability that is missed by conventional neurosurgical targeting; These findings may form the basis for translational tools to improve efficacy and reduce side-effects of thalamic surgery for tremor.HighlightsConnectivity-based Vim position varied markedly between subjects and from atlas-defined coordinates.This positional variability was not related to any methodological confound tested.Hemispheric asymmetry was observed in connectivity-based Vim position.We hypothesise lateralization of cerebellar functions, such as language, may contribute to asymmetry.Knowledge of Vim position variability could help inform neurosurgical planning in the management of tremor.
H3 K27M and EZHIP impede H3K27-methylation spreading by inhibiting allosterically stimulated PRC2
Authors: Jain Siddhant U. , Rashoff Andrew Q. , Krabbenhoft Samuel D. , Hoelper Dominik , Do Truman J. , Gibson Tyler J. , Lundgren Stefan M , Bondra Eliana R. , Deshmukh Shriya , Harutyunyan Ashot S. , Juretic Nikoleta , Jabado Nada , Harrison Melissa M. , Lewis Peter W. 
Published: August 2020

AbstractDiffuse midline gliomas and posterior fossa type-A ependymomas contain the highly recurrent histone H3 K27M mutation and the H3 K27M-mimic EZHIP, respectively.In vitro, H3 K27M and EZHIP are competitive inhibitors of Polycomb Repressive Complex 2 (PRC2) lysine methyltransferase activity.In vivo, these proteins reduce overall H3K27me3 levels, however residual peaks of H3K27me3 remain at CpG islands through an unknown mechanism. Here, we report that EZHIP and H3 K27M preferentially interact with an allosterically activated form of PRC2in vivo. The formation of H3 K27M- and EZHIP-PRC2 complexes occurs at CpG islands containing H3K27me3 and impedes PRC2 and H3K27me3 spreading. While EZHIP is not found outside of placental mammals, we find that expression of human EZHIP reduces H3K27me3 inDrosophila melanogasterthrough a conserved molecular mechanism. Our results highlight the mechanistic similarities between EZHIP and H3 K27Min vivoand provide mechanistic insight for the retention of residual H3K27me3 in tumors driven by these oncogenes.