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Background: We aimed to assess perioperative changes in fibrinogen in the cerebrospinal fluid (CSF), their association with markers of blood–brain barrier breakdown and neuroinflammation, and their association with postoperative delirium severity. Methods: We conducted a secondary analysis of the Interventions for Postoperative Delirium-Biomarker 2 (IPOD-B2, NCT02926417) study, a prospective observational cohort study. We included 24 patients aged >21 yr undergoing aortic aneurysm repair. CSF samples were obtained before (n=24) and after surgery (n=13), with some participants having multiple postoperative samples. Our primary outcome was the perioperative change in CSF fibrinogen. Delirium was assessed using the Delirium Rating Scale-Revised-98. Results: CSF fibrinogen increased after surgery (P

Abstract Exposure to acute, damaging radiation may occur through a variety of events from cancer therapy and industrial accidents to terrorist attacks and military actions. Our understanding of how to protect individuals and mitigate the effects of radiation injury or Acute Radiation Syndrome (ARS) is still limited. There are only a few Food and Drug Administration-approved therapies for ARS; whereas, amifostine is limited to treating low dose (0.7–6 Gy) radiation poisoning arising from cancer radiotherapy. An early intervention is critical to treat ARS, which necessitates identifying diagnostic biomarkers to quickly characterize radiation exposure. Towards this end, a multiplatform metabolomics study was performed to comprehensively characterize the temporal changes in metabolite levels from mice and non-human primate serum samples following γ-irradiation. The metabolomic signature of amifostine was also evaluated in mice as a model for radioprotection. The NMR and mass spectrometry metabolomics analysis identified 23 dysregulated pathways resulting from the radiation exposure. These metabolomic alterations exhibited distinct trajectories within glucose metabolism, phospholipid biosynthesis, and nucleotide metabolism. A return to baseline levels with amifostine treatment occurred for these pathways within a week of radiation exposure. Together, our data suggests a unique physiological change that is independent of radiation dose or species. Furthermore, a metabolic signature of radioprotection was observed through the use of amifostine prophylaxis of ARS.

Abstract Wheat grain yield (GY) improvement using genomic tools is important for achieving yield breakthroughs. To dissect the genetic architecture of wheat GY potential and stress-resilience, we have designed this large-scale genome-wide association study using 100 datasets, comprising 105,000 GY observations from 55,568 wheat lines evaluated between 2003 and 2019 by the International Maize and Wheat Improvement Center and national partners. We report 801 GY-associated genotyping-by-sequencing markers significant in more than one dataset and the highest number of them were on chromosomes 2A, 6B, 6A, 5B, 1B and 7B. We then used the linkage disequilibrium (LD) between the consistently significant markers to designate 214 GY-associated LD-blocks and observed that 84.5% of the 58 GY-associated LD-blocks in severe-drought, 100% of the 48 GY-associated LD-blocks in early-heat and 85.9% of the 71 GY-associated LD-blocks in late-heat, overlapped with the GY-associated LD-blocks in the irrigated-bed planting environment, substantiating that simultaneous improvement for GY potential and stress-resilience is feasible. Furthermore, we generated the GY-associated marker profiles and analyzed the GY favorable allele frequencies for a large panel of 73,142 wheat lines, resulting in 44.5 million datapoints. Overall, the extensive resources presented in this study provide great opportunities to accelerate breeding for high-yielding and stress-resilient wheat varieties.

BackgroundElectronic consultations (eConsults) are an increasingly used form of telemedicine that allows a nonspecialist clinician to seek specialist advice remotely without direct patient-specialist communication. Surgical clinics may see benefits from such forms of communication but face challenges with the need for intervention planning. ObjectiveWe aimed to use the Quadruple Aim Framework to integrate published knowledge of surgical outpatient eConsults with regard to efficacy, safety, limitations, and evolving use in the era of COVID-19. MethodsWe systematically searched for relevant studies across four databases (Ovid MEDLINE, Embase, Scopus, and Web of Science) on November 4, 2021, with the following inclusion criteria: English language, published in the past 10 years, and data on the outcomes of outpatient surgical eConsults. ResultsA total of 363 studies were screened for eligibility, of which 33 (9.1%) were included. Most of the included studies were from the United States (23/33, 70%) and Canada (7/33, 21%), with a predominant multidisciplinary focus (9/33, 27%). Most were retrospective audits (16/33, 48%), with 15% (5/33) of the studies having a prospective component. ConclusionsThe surgical eConsult studies indicated a possible benefit for population health, promising safety results, enhanced patient and clinician experience, and cost savings compared with the traditional face-to-face surgical referral pathway. Their use appeared to be more favorable in some surgical subspecialties, and the overall efficacy was similar to that of medical subspecialties. Limited data on their long-term safety and use during the COVID-19 pandemic were identified, and this should be the focus of future research.

Genebanks hold comprehensive collections of wild species, wild relatives, and landraces that are useful for genetic improvement. Here, the authors report the genotype of nearly 80,000 wheat accessions using DArTseq technology to show the less explored genetic diversity.

Introduction There are no disease-modifying treatments for Parkinson’s disease (PD). We undertook the first drug screen in PD patient tissue and idntified ursodeoxycholic acid (UDCA) as a promising mitochondrial rescue agent. The aims of this trial are to determine safety and tolerability of UDCA in PD at 30 mg/kg, confirm the target engagement of UDCA, apply a novel motion sensor-based approach to quantify disease progression objectively, and estimate the mean effect size and its variance on the change in motor severity.Methods and analysis This is a phase II, two-centre, double-blind, randomised, placebo-controlled trial of UDCA at a dose of 30 mg/kg in 30 participants with early PD. Treatment duration is 48 weeks, followed by an 8-week washout phase. Randomisation is 2:1, drug to placebo. Assessments are performed at baseline, week 12, 24, 36, 48 and 56. The primary outcome is safety and tolerability. Secondary outcomes will compare the change between baseline and week 48 using the following three approaches: the Movement Disorders Society Unified Parkinson’s Disease Rating Scale Part 3 in the practically defined ‘OFF’ medication state; confirmation of target engagement, applying 31Phosphorus MR Spectroscopy to assess the levels of ATP and relevant metabolites in the brain; and objective quantification of motor impairment, using a validated, motion sensor-based approach. The primary outcome will be reported using descriptive statistics and comparisons between treatment groups. For each secondary outcome, the change from baseline will be summarised within treatment groups using summary statistics and appropriate statistical tests assessing for significant differences. All outcomes will use an intention-to-treat analysis population.Ethics and dissemination This trial has been approved by the East of England – Cambridgeshire and Hertfordshire Research Ethics committee. Results will be disseminated in peer-reviewed journals, presentations at scientific meetings and to patients in a lay-summary format.Trial registration number NCT03840005.

Breeding for grain yield (GY) in bread wheat at the International Maize and Wheat Improvement Center (CIMMYT) involves three-stage testing at Obregon, Mexico in different selection environments (SEs). To understand the efficiency of selection in the SEs, we performed a large retrospective quantitative genetics study using CIMMYT’s yield trials evaluated in the SEs (2013–2014 to 2017–2018), the South Asia Bread Wheat Genomic Prediction Yield Trials (SABWGPYTs) evaluated in India, Pakistan, and Bangladesh (2014–2015 to 2017–2018), and the Elite Spring Wheat Yield Trials (ESWYTs) evaluated in several sites globally (2003–2004 to 2016–2017). First, we compared the narrow-sense heritabilities in the Obregon SEs and target sites and observed that the mean heritability in the SEs was 44.2 and 92.3% higher than the mean heritabilities in the SABWGPYT and ESWYT sites, respectively. Second, we observed significant genetic correlations between a SE in Obregon and all the five SABWGPYT sites and 65.1% of the ESWYT sites. Third, we observed high ratios of response to indirect selection in the SEs of Obregon with a mean of 0.80 ± 0.21 and 2.6 ± 5.4 in the SABWGPYT and ESWYT sites, respectively. Furthermore, our results also indicated that for all the SABWGPYT sites and 82% of the ESWYT sites, a response greater than 0.5 can be achieved by indirect selection for GY in Obregon. We also performed genomic prediction for GY in the target sites using the performance of the same lines in the SEs of Obregon and observed moderate mean prediction accuracies of 0.24 ± 0.08 and 0.28 ± 0.08 in the SABWGPYT and ESWYT sites, respectively using the genotype x environment (GxE) model. However, we observed similar accuracies using the baseline model with environment and line effects and no advantage of modeling GxE interactions. Overall, this study provides important insights into the suitability of the Obregon SEs in breeding for GY, while the variable genomic predictabilities of GY and the high year-to-year GY fluctuations reported, highlight the importance of multi-environment testing across time and space to stave off GxE induced uncertainties in varietal yields.

Breeding wheat with enhanced levels of grain zinc (Zn) and iron (Fe) is a cost-effective, sustainable solution to malnutrition problems. Modern wheat varieties have limited variation in grain Zn and Fe, but large-scale screening has identified high levels of Zn and Fe in wild relatives and progenitors of cultivated wheat. The most promising sources of high Zn and Fe are einkorn (Triticum monococcum), wild emmer (T. dicoccoides), diploid progenitors of hexaploid wheat (such as Aegilops tauschii), T. spelta, T. polonicum, and landraces of T. aestivum. This study evaluate the effects of translocations from rye and different Aegilops species in a “Pavon-76” wheat genetic background and utilized in the wheat biofortification breeding program at CIMMYT that uses diverse genetic resources, including landraces, recreated synthetic hexaploids, T. spelta and pre-breeding lines. Four translocations were identified that resulted significantly higher Zn content in “Pavon 76” genetic background than the check varieties, and they had increased levels of grain Fe as well-compared to “Pavon 76.” These lines were also included in the breeding program aimed to develop advanced high Zn breeding lines. Advanced lines derived from diverse crosses were screened under Zn-enriched soil conditions in Mexico during the 2017 and 2018 seasons. The Zn content of the grain was ranging from 35 to 69 mg/kg during 2017 and 38 to 72 mg/kg during 2018. Meanwhile grain Fe ranged from 30 to 43 mg/kg during 2017 and 32 to 52 mg/kg during 2018. A highly significant positive correlation was found between Zn and Fe (r = 0.54; P < 0.001) content of the breeding lines, therefore it was possible to breed for both properties in parallel. Yield testing of the advanced lines showed that 15% (2017) and 24% (2018) of the lines achieved 95–110% yield potential of the commercial checks and also had 12 mg/kg advantage in the Zn content suggesting that greater genetic gains and farmer-preferred wheat varieties were developed and deployed. A decade of research and breeding efforts led to the selection of “best-bet” breeding lines and the release of eight biofortified wheat varieties in target regions of South Asia and in Mexico.

Bread wheat can be used to make different products thanks to the presence of gluten, a protein network that confers unique visco-elastic properties to wheat doughs. Gluten is composed by gliadins and glutenins. The glutenins can be further divided into high and low-molecular-weight glutenins (HMWGs and LMWGs, respectively) and are encoded by Glu-1 and Glu-3 loci. The variability of these genes is associated with differences in quality. Because of this, the identification of novel glutenin alleles is still an important target. In this study, 57 haplotypes or glutenin combinations were registered among a set of 158 Iranian landraces and five novel HMWGs alleles were identified. The landraces were also characterized for several quality traits, including gluten quality, which allowed to associate the different glutenin alleles with low or high quality. Other quality traits examined were iron, zinc, and phytate contents, which are intimately related with the nutritional quality. Important variation for these components was found as well as for the phytate:iron/zinc molar ratios (related to the potential bioavailability of these important micronutrients). The landraces identified in the present study (some of them combining high gluten quality with low phytate:zinc values) could be a useful resource for breeders who aim to improve the wheat end-use quality and especially the content of zinc and its relative bioavailability.

This study examines genomic prediction within 8416 Mexican landrace accessions and 2403 Iranian landrace accessions stored in gene banks. The Mexican and Iranian collections were evaluated in separate field trials, including an optimum environment for several traits, and in two separate environments (drought, D and heat, H) for the highly heritable traits, days to heading (DTH), and days to maturity (DTM). Analyses accounting and not accounting for population structure were performed. Genomic prediction models include genotype × environment interaction (G × E). Two alternative prediction strategies were studied: (1) random cross-validation of the data in 20% training (TRN) and 80% testing (TST) (TRN20-TST80) sets, and (2) two types of core sets, “diversity” and “prediction”, including 10% and 20%, respectively, of the total collections. Accounting for population structure decreased prediction accuracy by 15–20% as compared to prediction accuracy obtained when not accounting for population structure. Accounting for population structure gave prediction accuracies for traits evaluated in one environment for TRN20-TST80 that ranged from 0.407 to 0.677 for Mexican landraces, and from 0.166 to 0.662 for Iranian landraces. Prediction accuracy of the 20% diversity core set was similar to accuracies obtained for TRN20-TST80, ranging from 0.412 to 0.654 for Mexican landraces, and from 0.182 to 0.647 for Iranian landraces. The predictive core set gave similar prediction accuracy as the diversity core set for Mexican collections, but slightly lower for Iranian collections. Prediction accuracy when incorporating G × E for DTH and DTM for Mexican landraces for TRN20-TST80 was around 0.60, which is greater than without the G × E term. For Iranian landraces, accuracies were 0.55 for the G × E model with TRN20-TST80. Results show promising prediction accuracies for potential use in germplasm enhancement and rapid introgression of exotic germplasm into elite materials.

The international collections of plant genetic resources for food and agriculture (PGRFA) hosted by 11 CGIAR Centers are important components of the United Nations Food and Agriculture Organization’s global system of conservation and use of PGRFA. They also play an important supportive role in realizing Target 2.5 of the Sustainable Development Goals. This paper analyzes CGIAR genebanks’ trends in acquiring and distributing PGRFA over the last 35 years, with a particular focus on the last decade. The paper highlights a number of factors influencing the Centers’ acquisition of new PGRFA to include in the international collections, including increased capacity to analyze gaps in those collections and precisely target new collecting missions, availability of financial resources, and the state of international and national access and benefit-sharing laws and phytosanitary regulations. Factors contributing to Centers’ distributions of PGRFA included the extent of accession-level information, users’ capacity to identify the materials they want, and policies. The genebanks’ rates of both acquisition and distribution increased over the last decade. The paper ends on a cautionary note concerning the potential of unresolved tensions regarding access and benefit sharing and digital genomic sequence information to undermine international cooperation to conserve and use PGRFA.

Background To examine the prevalence and patterns of recent electronic cigarette (e‐cigarette) use in a nationally representative sample of US adults and adolescents. Methods and Results Using tobacco information from NHANES (National Health and Nutrition Examination Survey) 2013–2014, 5423 adults and 895 adolescents (aged 13–17 years) were included in this analysis. Demographic, tobacco use, and drug use information were self‐reported. Recent e‐cigarette use (within the previous 5 days) was stratified by smoking status. Of 125 e‐cigarette users, 116 participants were aged ≥18 years, corresponding to 2.6% (95% confidence interval [CI], 2.0–3.1) and 1.21% (95% CI, 0.3–2.1) prevalence of e‐cigarette use among US adults and adolescents, respectively. E‐cigarette adult users were current smokers (68.1%), former smokers (23.7%), and never smokers (8.2%). The highest prevalence of e‐cigarette use was among current smokers (8.2%; 95% CI, 6.3–10.1), followed by former smokers (2.7%; 95% CI, 1.4–4.1), and then never smokers (0.4%; 95% CI, 0.2–0.6). After adjusting for age, sex, and ethnicity, e‐cigarette users had higher odds of being exposed to secondhand smoke (odds ratio: 6.3; 95% CI, 3.6–11.1) and drinking alcohol (odds ratio: 4.2; 95% CI, 1.8–10.0) and lower odds of having at least a college education or a higher income, compared with tobacco nonusers. Conclusions Between 2013 and 2014, e‐cigarette use in the United States was more common among younger people, those with low socioeconomic status, and current and former smokers. These findings will help inform future research as well as public policy and regulatory actions.

This qualitative study investigates the uses of be in Contemporary English. Based on this study, one easy claim and one more difficult claim are proposed. The easy claim is that the traditional distinction between be as a lexical verb and be as an auxiliary is faulty. In particular, 'copular-be', traditionally considered to be a lexical verb, is in fact a prototypical auxiliary. The harder claim is that there is a syntactic distinction between lexical-be and auxiliary-be, but that distinction does not coincide with the copular vs. non-copular usages. Rather, the syntactic distinction between lexical and auxiliary be has an entirely different, semantic motivation based on stativity vs. activity. In the process of providing evidence for these claims, the paper challenges a major assumption of traditional grammar â namely that every English sentence requires a lexical verb. This assumption is replaced by the notion that every English sentence requires Inflection. The proposals in this paper bridge the gap between theoretical and applied linguistics and have the potential to simplify significantly the conceptualization, teaching and learning of English grammar.

Identifying and mobilizing useful genetic variation from germplasm banks to breeding programs is an important strategy for sustaining crop genetic improvement. The molecular diversity of 1,423 spring bread wheat accessions representing major global production environments was investigated using high quality genotyping-by-sequencing (GBS) loci, and gene-based markers for various adaptive and quality traits. Mean diversity index (DI) estimates revealed synthetic hexaploids to be genetically more diverse (DI= 0.284) than elites (DI = 0.267) and landraces (DI = 0.245). GBS markers discovered thousands of new SNP variations in the landraces which were well known to be adapted to drought (1273 novel GBS SNPs) and heat (4473 novel GBS SNPs) stress environments. This may open new avenues for pre-breeding by enriching the elite germplasm with novel alleles for drought and heat tolerance. Furthermore, new allelic variation for vernalization and glutenin genes was also identified from 47 landraces originating from Iraq, Iran, India, Afghanistan, Pakistan, Uzbekistan and Turkmenistan. The information generated in the study has been utilized to select 200 diverse gene bank accessions to harness their potential in pre-breeding and for allele mining of candidate genes for drought and heat stress tolerance, thus channeling novel variation into breeding pipelines. This research is part of CIMMYT's ongoing 'Seeds of Discovery' project visioning towards the development of high yielding wheat varieties that address future challenges from climate change.