Shifting the limits in wheat research and breeding using a fully annotated reference genome

Introduction: Wheat (Triticum aestivum L.) is the most widely cultivated crop on Earth, contributing about a fifth of the total calories consumed by humans. Consequently, wheat yields and production affect the global economy, and failed harvests can lead to social unrest. Breeders continuously strive to develop improved varieties by fine-tuning genetically complex yield and end-use quality parameters while maintaining stable yields and adapting the crop to regionally specific biotic and abiotic stresses. Rationale: Breeding efforts are limited by insufficient knowledge and understanding of wheat biology and the molecular basis of central agronomic traits. To meet the demands of human population growth, there is an urgent need for wheat research and breeding to accelerate genetic gain as well as to increase and protect wheat yield and quality traits. In other plant and animal species, access to a fully annotated and ordered genome sequence, including regulatory sequences and genome-diversity information, has promoted the development of systematic and more time-efficient approaches for the selection and understanding of important traits. Wheat has lagged behind, primarily owing to the challenges of assembling a genome that is more than five times as large as the human genome, polyploid, and complex, containing more than 85% repetitive DNA. To provide a foundation for improvement through molecular breeding, in 2005, the International Wheat Genome Sequencing Consortium set out to deliver a high-quality annotated reference genome sequence of bread wheat. Results: An annotated reference sequence representing the hexaploid bread wheat genome in the form of 21 chromosome-like sequence assemblies has now been delivered, giving access to 107,891 high-confidence genes, including their genomic context of regulatory sequences. This assembly enabled the discovery of tissue- and developmental stage–related gene coexpression networks using a transcriptome atlas representing all stages of wheat development. The dynamics of change in complex gene families involved in environmental adaptation and end-use quality were revealed at subgenome resolution and contextualized to known agronomic single-gene or quantitative trait loci. Aspects of the future value of the annotated assembly for molecular breeding and research were exemplarily illustrated by resolving the genetic basis of a quantitative trait locus conferring resistance to abiotic stress and insect damage as well as by serving as the basis for genome editing of the flowering-time trait. Conclusion: This annotated reference sequence of wheat is a resource that can now drive disruptive innovation in wheat improvement, as this community resource establishes the foundation for accelerating wheat research and application through improved understanding of wheat biology and genomics-assisted breeding. Importantly, the bioinformatics capacity developed for model-organism genomes will facilitate a better understanding of the wheat genome as a result of the high-quality chromosome-based genome assembly. By necessity, breeders work with the genome at the whole chromosome level, as each new cross involves the modification of genome-wide gene networks that control the expression of complex traits such as yield. With the annotated and ordered reference genome sequence in place, researchers and breeders can now easily access sequence-level information to precisely define the necessary changes in the genomes for breeding programs. This will be realized through the implementation of new DNA marker platforms and targeted breeding technologies, including genome editing

Characteristics and comparison between e-scooters and bicycle-related trauma: a multicentre cross-sectional analysis of data from a road collision registry

Urban mobility has drastically evolved over the last decade and micromobility rapidly became an expanding segment of contemporary daily transportation routines. E-scooter riders and bicyclists may share similar trauma characteristics, but this has been little explored. The objective was to describe and compare the characteristics of e-scooter and bicycle-related trauma

Additional file 1 of Characteristics and comparison between e-scooters and bicycle-related trauma: a multicentre cross-sectional analysis of data from a road collision registry

Additional file 1. STROBE Statement—Checklist of items that should be included in reports of cross-sectional studies

Road traffic accident-related thoracic trauma: Epidemiology, injury pattern, outcome, and impact on mortality?A multicenter observational study

Background Thoracic trauma is a major cause of death in trauma patients and road traffic accident (RTA)-related thoracic injuries have different characteristics than those with non-RTA related thoracic traumas, but this have been poorly described. The main objective was to investigate the epidemiology, injury pattern and outcome of patients suffering a significant RTA-related thoracic injury. Secondary objective was to investigate the influence of serious thoracic injuries on mortality, compared to other serious injuries. Methods We performed a multicenter observational study including patients of the Rhône RTA registry between 1997 and 2016 sustaining a moderate to lethal (Abbreviated Injury Scale, AIS?2) injury in any body region. A subgroup (AISThorax?2 group) included those with one or more AIS?2 thoracic injury. Descriptive statistics were performed for the main outcome and a multivariate logistic regression was computed for our secondary outcome. Results A total of 176,346 patients were included in the registry and 6,382 (3.6%) sustained a thoracic injury. Among those, median age [IQR] was 41 [25-58] years, and 68.9% were male. The highest incidence of thoracic injuries in female patients was in the 70-79 years age group, while this was observed in the 20-29 years age group among males. Most patients were car occupants (52.3%). Chest wall injuries were the most frequent thoracic injuries (62.1%), 52.4% of which were multiple rib fractures. Trauma brain injuries (TBI) were the most frequent concomitant injuries (29.1%). The frequency of MAISThorax = 2 injuries increased with age while that of MAISThorax = 3 injuries decreased. A total of 16.2% patients died. Serious (AIS?3) thoracic injuries (OR = 12.4, 95%CI [8.6;18.0]) were strongly associated with mortality but less than were TBI (OR = 27.9, 95%CI [21.3;36.7]). Conclusion Moderate to lethal RTA-related thoracic injuries were rare. Multiple ribs fractures, pulmonary contusions, and sternal fractures were the most frequent anatomical injuries. The incidence, injury pattern and mechanisms greatly vary across age groups

Accuracy of a Prehospital Triage Protocol in Predicting In-Hospital Mortality and Severe Trauma Cases among Older Adults

Background: Prehospital trauma triage tools are not tailored to identify severely injured older adults. Our trauma triage protocol based on a three-tier trauma severity grading system (A, B, and C) has never been studied in this population. The objective was to assess its accuracy in predicting in-hospital mortality among older adults (≥65 years) and to compare it to younger patients. Methods: A retrospective multicenter cohort study, from 2011 to 2021. Consecutive adult trauma patients managed by a mobile medical team were prospectively graded A, B, or C according to the initial seriousness of their injuries. Accuracy was evaluated using sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios. Results: 8888 patients were included (14.1% were ≥65 years). Overall, 10.1% were labeled Grade A (15.2% vs. 9.3% among older and younger adults, respectively), 21.9% Grade B (27.9% vs. 20.9%), and 68.0% Grade C (56.9% vs. 69.8%). In-hospital mortality was 7.1% and was significantly higher among older adults regardless of severity grade. Grade A showed lower sensitivity (50.5 (43.7; 57.2) vs. 74.6 (69.8; 79.1), p < 0.0001) for predicting mortality among older adults compared to their younger counterparts. Similarly, Grade B was associated with lower sensitivity (89.5 (84.7; 93.3) vs. 97.2 (94.8; 98.60), p = 0.0003) and specificity (69.4 (66.3; 72.4) vs. 74.6 (73.6; 75.7], p = 0.001) among older adults. Conclusions: Our prehospital trauma triage protocol offers high sensitivity for predicting in-hospital mortality including older adults

Effect of the Implementation of a Local Care Pathway on the Transient Ischemic Attack Management in Emergency Departments

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Data_Sheet_1_Clinical assessment to identify pelvic injuries in the prehospital setting: a prospective cohort study.docx

ObjectivesPelvic injuries can be life-threatening and are challenging to identify in the prehospital phase. This study aimed to assess how pelvic examination is performed by paramedics and to determine the accuracy of their clinical examination when identifying pelvic fractures.MethodsThis was a prospective cohort study of prehospital interventions including both real and simulated trauma patients between July and August 2022. Data collection for the injured patient was made by an observer who was paired with teams of two consenting paramedics. Data pertaining to the clinical assessment for potential pelvic injuries during all interventions with a trauma patient were collected. Additionally, data were collected during four simulated scenarios of patients with an open-book type pelvic fracture following high-energy trauma mechanisms.ResultsA total of 29 trauma-related clinical interventions were assessed. Most patients were female (n = 22, 75.9%) with a mean age of 69.8 (SD 22.2) years. Fall from standing was the main trauma mechanism (n = 21, 72.4%). During 72.4% (n = 21) of all trauma-related interventions, an assessment for pelvic injuries was performed, mostly by pelvic palpation (n = 19, 65.5%), inquiring about the presence of pain (n = 12, 41.4%), searching for deformation (n = 7, 24.1%), and/or assessing leg length (n = 8, 27.6%). No pelvic injury was suspected by the paramedics, but two patients (6.9%) had a pelvic fracture and two (6.9%) had a hip fracture. Simulated cases of high-velocity mechanisms with an open-book pelvic fracture were completed by 11 pairs of paramedics. Most did a clinical pelvic assessment (n = 8, 72.7%) using palpation. When asked after the simulation, nine pairs (81.8%) suspected a pelvic fracture.ConclusionPelvic injuries are challenging to identify, and pelvic assessment on the field is not standardized among paramedics. Training is needed to increase awareness relative to pelvic injuries and to improve detection.</p

Risk factors and mortality associated with undertriage after major trauma in a physician-led prehospital system: a retrospective multicentre cohort study

International audiencePurpose: To assess the incidence of undertriage in major trauma, its determinant, and association with mortality.Methods: A multicentre retrospective cohort study was conducted using data from a French regional trauma registry (2011-2017). All major trauma (Injury Severity Score ≥ 16) cases aged ≥ 18 years and managed by a physician-led mobile medical team were included. Those transported to a level-II/III trauma centre were considered as undertriaged. Multivariable logistic regression was used to identify factors associated with undertriage.Results: A total of 7110 trauma patients were screened; 2591 had an ISS ≥ 16 and 320 (12.4%) of these were undertriaged. Older patients had higher risk for undertriage (51-65 years: OR = 1.60, 95% CI [1.11; 2.26], p = 0.01). Conversely, injury mechanism (fall from height: 0.62 [0.45; 0.86], p = 0.01; gunshot/stab injuries: 0.45 [0.22; 0.90], p = 0.02), on-scene time (> 60 min: 0.62 [0.40; 0.95], p = 0.03), prehospital endotracheal intubation (0.53 [0.39; 0.71], p < 0.001), and prehospital focussed assessment with sonography [FAST] (0.15 [0.08; 0.29], p < 0.001) were associated with a lower risk for undertriage. After adjusting for severity, undertriage was not associated with a higher risk of mortality (1.22 [0.80; 1.89], p = 0.36).Conclusions: In our physician-led prehospital EMS system, undertriage was higher than recommended. Advanced aged was identified as a risk factor highlighting the urgent need for tailored triage protocol in this population. Conversely, the potential benefit of prehospital FAST on triage performance should be furthered explored as it may reduce undertriage. Fall from height and penetrating trauma were associated with a lower risk for undertriage suggesting that healthcare providers should remain vigilant of the potential seriousness of trauma associated with low-energy mechanisms

Arabidopsis ATRX Modulates H3.3 Occupancy and Fine-Tunes Gene Expression.

International audienceHistones are essential components of the nucleosome, the major chromatin subunit that structures linear DNA molecules and regulates access of other proteins to DNA. Specific histone chaperone complexes control the correct deposition of canonical histones and their variants to modulate nucleosome structure and stability. In this study, we characterize the Arabidopsis thaliana Alpha Thalassemia-mental Retardation X-linked (ATRX) ortholog and show that ATRX is involved in histone H3 deposition. Arabidopsis ATRX mutant alleles are viable, but show developmental defects and reduced fertility. Their combination with mutants of the histone H3.3 chaperone HIRA (Histone Regulator A) results in impaired plant survival, suggesting that HIRA and ATRX function in complementary histone deposition pathways. Indeed, ATRX loss of function alters cellular histone H3.3 pools and in consequence modulates the H3.1/H3.3 balance in the cell. H3.3 levels are affected especially at genes characterized by elevated H3.3 occupancy, including the 45S ribosomal DNA (45S rDNA) loci, where loss of ATRX results in altered expression of specific 45S rDNA sequence variants. At the genome-wide scale, our data indicate that ATRX modifies gene expression concomitantly to H3.3 deposition at a set of genes characterized both by elevated H3.3 occupancy and high expression. Together, our results show that ATRX is involved in H3.3 deposition and emphasize the role of histone chaperones in adjusting genome expression

Prehospital Tranexamic Acid in Major Pediatric Trauma Within a Physician-Led Emergency Medical Services System: A Multicenter Retrospective Study

International audienceObjectives: Describe prehospital tranexamic acid (TXA) use and appropriateness within a major trauma pediatric population, and identify the factors associated with its use.Design: Multicenter, retrospective study, 2014-2020.Setting: Data were extracted from a multicenter French trauma registry including nine trauma centers within a physician-led prehospital emergency medical services (EMS) system.Patients: Patients less than 18 years old were included. Those who did not receive prehospital intervention by a mobile medical team and those with missing data on TXA administration were excluded.Interventions: None.Measurements and main results: Nine-hundred thirty-four patients (median [interquartile range] age: 14 yr [9-16 yr]) were included, and 68.6% n = 639) were male. Most patients were involved in a road collision (70.2%, n = 656) and suffered a blunt trauma (96.5%; n = 900). Patients receiving TXA (36.6%; n = 342) were older (15 [13-17] vs 12 yr [6-16 yr]) compared with those who did not. Patient severity was higher in the TXA group (Injury Severity Score 14 [9-25] vs 6 [2-13]; p < 0.001). The median dosage was 16 mg/kg (13-19 mg/kg). TXA administration was found in 51.8% cases (n = 256) among patients with criteria for appropriate use. Conversely, 32.4% of patients (n = 11) with an isolated severe traumatic brain injury (TBI) also received TXA. Age (odds ratio [OR], 1.2; 95% CI, 1.1-1.2), A and B prehospital severity grade (OR, 7.1; 95% CI, 4.1-12.3 and OR, 4.5; 95% CI, 2.9-6.9 respectively), and year of inclusion (OR, 1.2; 95% CI, 1.1-1.3) were associated with prehospital TXA administration.Conclusions: In our physician-led prehospital EMS system, TXA is used in a third of severely injured children despite the lack of high-level of evidence. Only half of the population with greater than or equal to one criteria for appropriate TXA use received it. Conversely, TXA was administered in a third of isolated severe TBI. Further research is warranted to clarify TXA indications and to evaluate its impact on mortality and its safety profile to oversee its prescription