bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prehospital tranexamic acid is associated with a dose-dependent decrease in syndecan-1 after trauma: A secondary analysis of a prospective randomized trial
Authors: Gruen Danielle S. , Brown Joshua B. , Guyette Francis X. , Johansson Pär I. , Stensballe Jakob , Li Shimena R. , Leeper Christine M. , Eastridge Brian J. , Nirula Raminder , Vercruysse Gary A. , O’Keeffe Terence , Joseph Bellal , Neal Matthew D. , Sperry Jason L. 
Published: May 2023

BACKGROUND
In the Study of Tranexamic Acid During Air and Ground Prehospital Transport (STAAMP) Trial, prehospital tranexamic acid (TXA) was associated with lower mortality in specific patient subgroups. The underlying mechanisms responsible for a TXA benefit remain incompletely characterized. We hypothesized that TXA may mitigate endothelial injury and sought to assess whether TXA was associated with decreased endothelial or tissue damage markers among all patients enrolled in the STAAMP Trial.

METHODS
We collected blood samples from STAAMP Trial patients and measured markers of endothelial function and tissue damage including syndecan-1, soluble thrombomodulin (sTM), and platelet endothelial cell adhesion molecule-1 at hospital admission (0 hours) and 12 hours, 24 hours, and 72 hours after admission. We compared these marker values for patients in each treatment group during the first 72 hours, and modeled the relationship between TXA and marker concentration using regression analysis to control for potential confounding factors.

RESULTS
We analyzed samples from 766 patients: 383 placebo, 130 abbreviated dosing, 119 standard dosing, and 130 repeat dosing. Lower levels of syndecan-1, TM, and platelet endothelial cell adhesion molecule measured within the first 72 hours of hospital admission were associated with survival at 30 days (p < 0.001). At hospital admission, syndecan-1 was lower in the TXA group (28.30 [20.05, 42.75] vs. 33.50 [23.00, 54.00] p = 0.001) even after controlling for patient, injury, and prehospital factors (p = 0.001). For every 1 g increase in TXA administered over the first 8 hours of prehospital transport and hospital admission, there was a 4-ng/mL decrease in syndecan-1 at 12 hours controlling for patient, injury, and treatment factors (p = 0.03).

CONCLUSION
Prehospital TXA was associated with decreased syndecan-1 at hospital admission. Syndecan-1 measured 12 hours after admission was inversely related to the dose of TXA received. Early prehospital and in-hospital TXA may decrease endothelial glycocalyx damage or upregulate vascular repair mechanisms in a dose-dependent fashion.

LEVEL OF EVIDENCE
Therapeutic/Care Management; Level III.
Financial toxicity after trauma and acute care surgery: From understanding to action
Authors: Scott John W. , Knowlton Lisa Marie , Murphy Patrick , Neiman Pooja U. , Martin R. Shayn , Staudenmayer Kristan ,   on behalf of the AAST Health Economics Committee
Published: May 2023

ABSTRACT
Gains in inpatient survival over the last five decades have shifted the burden of major injuries and surgical emergencies from the acute phase to their long-term sequelae. More attention has been placed on evaluation and optimization of long-term physical and mental health; however, the impact of major injuries and surgical emergencies on long-term financial well-being remains a critical blind spot for clinicians and researchers. The concept of financial toxicity encompasses both the objective financial consequences of illness and medical care as well as patients' subjective financial concerns. In this review, representatives of the Healthcare Economics Committee from the American Association for the Surgery of Trauma (1) provide a conceptual overview of financial toxicity after trauma or emergency surgery, (2) outline what is known regarding long-term economic outcomes among trauma and emergency surgery patients, (3) explore the bidirectional relationship between financial toxicity and long-term physical and mental health outcomes, (4) highlight policies and programs that may mitigate financial toxicity, and (5) identify the current knowledge gaps and critical next steps for clinicians and researchers engaged in this work.
Catastrophic health expenditure in nonneurological injury due to motor vehicle crash
Authors: Nishtala Madhuri V. , Reed Madeline , Schumacher Jessica , Hanlon Bret , Venkatesh Manasa , Collins Michael , Zarzaur Ben L. 
Published: May 2023

BACKGROUND
Motor vehicle crashes (MVCs) are a leading cause of nonfatal injury in the United States and impose a high financial cost to the patient and the economy. For many patients, this cost may be financially devastating and contribute to worsening health outcomes after injury. We aimed to describe the population level risk of catastrophic health expenditure (CHE) and determine factors associated with risk of CHE.

METHODS
We performed a retrospective review using the 2014–2017 Nationwide Inpatient Sample. The study population consisted of uninsured and privately insured adults aged 26 to 64 years who were hospitalized for nonneurologic traumatic injury due to MVCs. Our measure of financial hardship was CHE, which was defined as hospital charges ≥40% of postsubsistence income. Income estimates were derived from zip-code level data using Γ distribution modeling.

RESULTS
Our sample included 189,000 patients, of which 149,705 had private insurance and 39,375 were uninsured. The median estimated income for the study cohort was $66,118 (interquartile range, $65,353–$66,884). The median cost of hospitalization was $53,467 (interquartile range, $29,854–$99,914). In addition, 91.5% of uninsured patients suffering from MVC are at risk for CHE, and 10.1% of privately insured patients are at risk for CHE. Among the insured, Black, Hispanic, and low income were associated with CHE.

CONCLUSION
Nine of 10 uninsured patients are at risk for CHE after hospitalization for MVC. Despite having insurance, 10% of patients are still at risk of CHE. Black, Hispanic, and low-income communities are at highest risk of having private insurance and still experiencing CHE. This is the first population level analysis after the implementation of the Affordable Care Act that assesses the financial burden of no insurance and underinsurance. These data are important to understand the effectiveness of insurance coverage and guide hospital and policy level interventions to prevent CHE.

LEVEL OF EVIDENCE
Prognostic and Epidemiological; Level III.
The American Association for the Surgery of Trauma–European Society of Trauma and Emergency Surgery Emergency Surgery Course: Initial experience in Japan
Authors: Morishita Koji , Coimbra Raul , Ito Kaori , Otomo Yasuhiro 
Published: May 2023

BACKGROUND
Acute care surgery has recently been recognized as a field of surgery in Japan, but no well-organized nontrauma emergency surgery education system exists. The American Association for the Surgery of Trauma–European Society of Trauma and Emergency Surgery Emergency Surgery Course (AAST-ESTES ESC) course gives surgeons the knowledge and skills to make daily decisions about nontrauma emergency surgery. We held an AAST-ESTES ESC course in Japan from October 2 to 3, 2022.

METHODS
Thirty-two Japanese participants were asked to rate the following items using a 5-point Likert scale from 1 to 5: overall assessment, program subjects, content, instructional style, and activity. In addition, we also inquired about topics that participants intended to change as a result of what they had learned in the course.

RESULTS
All items were rated highly (4.1–4.7) by the participants. Participants reported intending to implement changes concerning mesenteric ischemia, colorectal crises, and acute pancreatitis after taking the course.

CONCLUSION
Japanese surgeons gave the AAST-ESTES ESC course excellent ratings, suggesting its crucial role in Japan, where there has been no development of nontrauma emergency surgery education courses.
Prehospital and emergency department pediatric readiness for injured children: A statement from the American College of Surgeons Committee on Trauma Emergency Medical Services Committee
Authors: Ross Samuel Wade , Campion Eric , Jensen Aaron R. , Gray Lisa , Gross Toni , Namias Nicholas , Goodloe Jeffrey M. , Bulger Eileen M. , Fischer Peter E. , Fallat Mary E. 
Published: May 2023

ABSTRACT
Injury is the leading cause of death in children older than 1 year, and children make up 22% of the population. Pediatric readiness (PR) of the nation's emergency departments and state trauma and emergency medical services (EMS) systems is conceptually important and vital to mitigate mortality and morbidity in this population. The extension of PR to the trauma community has become a focused area for training, staffing, education, and equipment at all levels of trauma center designation, and there is evidence that a higher level of emergency department PR is independently associated with long-term survival among injured children. Although less well studied, there is an associated need for EMS PR, which is relevant to the injured child who needs assessment, treatment, triage, and transport to a trauma center. We outline a blueprint along with recommendations for incorporating PR into trauma system development in this opinion from the EMS Committee of the American College of Surgeons Committee on Trauma. These recommendations are particularly pertinent in the rural and underserved areas of the United States but are directed toward all levels of professionals who care for an injured child along the trauma continuum of care.
Silvio Weidmann: laying the foundations for unravelling the mechanism of heart rhythm
Authors: DiFrancesco Dario , Noble Denis 
Published: May 2023

Silvio Weidmann laid the basis of cardiac electrophysiology and was the forerunner in the search for mechanisms governing the electrical activity of the heart in his legendary first studies of Purkinje fibres in the 1950s. His work was the cornerstone of research in this field for many generations, and countless cardiologists and electrophysiologists have based their studies on the knowledge generated by Weidmann's pioneering data. This review summarizes his key contributions from the first intracellular recordings of cardiac membrane potentials in 1949 to the publication of his monograph in 1956. That summary is followed by an imagined dialogue between the authors and Silvio Weidmann himself, in the format of a one-act play. Both of us have such good recollections of our real-life conversations with Silvio Weidmann that we decided we could achieve a better feel for the history and issues by using a dialogue format. We hope that, in that way, we may transmit the character of Silvio Weidmann better for those readers who will not have known him personally. Silvio Weidmann was an extraordinarily sensitive and conversational person as well as a great scientist, and we feel it is worth the effort to convey that fact here.
This article is part of the theme issue ‘The heartbeat: its molecular basis and physiological mechanisms’.
FKBP12 binds to the cardiac ryanodine receptor with negative cooperativity: implications for heart muscle physiology in health and disease
Authors: Richardson S. J. , Thekkedam C. G. , Casarotto M. G. , Beard N. A. , Dulhunty A. F. 
Published: May 2023

Cardiac ryanodine receptors (RyR2) release the Ca2+from intracellular stores that is essential for cardiac myocyte contraction. The ion channel opening is tightly regulated by intracellular factors, including the FK506 binding proteins, FKBP12 and FKBP12.6. The impact of these proteins on RyR2 activity and cardiac contraction is debated, with often apparently contradictory experimental results, particularly for FKBP12. The isoform that regulates RyR2 has generally been considered to be FKBP12.6, despite the fact that FKBP12 is the major isoform associated with RyR2 in some species and is bound in similar proportions to FKBP12.6 in others, including sheep and humans. Here, we show time- and concentration-dependent effects of adding FKBP12 to RyR2 channels that were partly depleted of FKBP12/12.6 during isolation. The added FKBP12 displaced most remaining endogenous FKBP12/12.6. The results suggest that FKBP12 activates RyR2 with high affinity and inhibits RyR2 with lower affinity, consistent with a model of negative cooperativity in FKBP12 binding to each of the four subunits in the RyR tetramer. The easy dissociation of some FKBP12/12.6 could dynamically alter RyR2 activity in response to changes inin vivoregulatory factors, indicating a significant role for FKBP12/12.6 in Ca2+signalling and cardiac function in healthy and diseased hearts.This article is part of the theme issue ‘The heartbeat: its molecular basis and physiological mechanisms’.
Advances in basic and translational research in atrial fibrillation
Authors: Hu Dan , Barajas-Martinez Hector , Zhang Zhong-He , Duan Hong-Yi , Zhao Qing-Yan , Bao Ming-Wei , Du Yi-Mei , Burashnikov Alexander , Monasky Michelle M. , Pappone Carlo , Huang Cong-Xin , Antzelevitch Charles , Jiang Hong 
Published: May 2023

Atrial fibrillation (AF) is a very common cardiac arrhythmia with an estimated prevalence of 33.5 million patients globally. It is associated with an increased risk of death, stroke and peripheral embolism. Although genetic studies have identified a growing number of genes associated with AF, the definitive impact of these genetic findings is yet to be established. Several mechanisms, including electrical, structural and neural remodelling of atrial tissue, have been proposed to contribute to the development of AF. Despite over a century of exploration, the molecular and cellular mechanisms underlying AF have not been fully established. Current antiarrhythmic drugs are associated with a significant rate of adverse events and management of AF using ablation is not optimal, especially in cases of persistent AF. This review discusses recent advances in our understanding and management of AF, including new concepts of epidemiology, genetics and pathophysiological mechanisms. We review the current status of antiarrhythmic drug therapy for AF, new potential agents, as well as mechanism-based AF ablation.This article is part of the theme issue ‘The heartbeat: its molecular basis and physiological mechanisms’.
Cultivation ofMelilotus officinalisas a source of bioactive compounds in association with soil recovery practices
Authors: Nogues Isabel , Passatore Laura , Bustamante María Ángeles , Pallozzi Emanuele , Luz João , Traquete Francisco , Ferreira António E.N. , Silva Marta Sousa , Cordeiro Carlos 
Published: May 2023

AbstractMelilotus officinalisis a Leguminosae with relevant applications in medicine and soil recovery. This study reports the application ofMelilotus officinalisplants in soil recovery and as a source of bioactive compounds. Plants were cultivated in semiarid soil under four different fertilizer treatments, urban waste compost at 10 t/ha and 20 t/ha, inorganic fertilizer and a control (no fertilizer). Agronomic properties of soil (pH, EC, soil respiration, C content, macro- and micro-elements) were analyzed before and after treatment. Also, germination, biomass, element contents, and physiological response were evaluated. Results showed a significant enhancement of the soil microbial activity in planted soils amended with compost, though there were no other clear effects on the soil physicochemical and chemical characteristics during the short experimental period. An improvement inM. officinalisgermination and growth was observed in soils with compost amendment. Metabolite composition of plants was analyzed through Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR MS). Principal Component and Agglomerative Hierarchical Clustering models suggest that there is a clear separation of the metabolome of four groups of plants grown under different soil treatments. The five most important discriminative metabolites (annotated) were oleamide, palmitic acid, stearic acid, 3-hydroxy-cis-5-octenoylcarnitine, and 6-hydroxynon-7-enoylcarnitine. This study provides information on how the metabolome ofMelilotusmight be altered by fertilizer application in poor soil regions. These metabolome changes might have repercussions for the application of this plant in medicine and pharmacology. The results support the profitability ofMelilotus officinaliscultivation for bioactive compounds production in association with soil recovery practices.
Orchid seed germination through auto-activation of mycorrhizal symbiosis signaling regulated by gibberellin
Authors: Miura Chihiro , Furui Yuki , Yamamoto Tatsuki , Kanno Yuri , Honjo Masaya , Yamaguchi Katsushi , Suetsugu Kenji , Yagame Takahiro , Seo Mitsunori , Shigenobu Shuji , Yamato Masahide , Kaminaka Hironori 
Published: May 2023

AbstractOrchids parasitically depend on external nutrients from mycorrhizal fungi for seed germination. Previous findings suggest that orchids utilize a genetic system of mutualistic arbuscular mycorrhizal (AM) symbiosis to establish parasitic symbiosis. In AM symbiosis, recent studies have revealed that the plant hormone gibberellin (GA) negatively affects fungal colonization and development. Although previous studies imply that GA is important for orchid mycorrhizal symbiosis, the molecular mechanism of seed germination in which mycorrhizal symbiosis co-occurs remains unclear because, in AM plants, GA regulates seed germination and symbiosis positively and negatively, respectively. To elucidate this conflict, we investigated the effect of GA onBletilla striataseed germination and mycorrhizal symbiosis using asymbiotic and symbiotic germination methods. Additionally, we compared the transcriptome profiles between asymbiotically and symbiotically germinated seeds. Exogenous GA negatively affected seed germination and fungal colonization, and endogenous bioactive GA was actively converted to the inactive form during seed germination. Transcriptome analysis showed thatB. striatashared many of the induced genes between asymbiotically and symbiotically germinated seeds, including GA metabolism- and signaling-related genes and AM-specific marker homologs. Our study suggests that orchids have evolved in a manner that they do not use bioactive GA as a positive regulator of seed germination and instead, auto-activate the mycorrhizal symbiosis pathway through GA inactivation to accept the fungal partner immediately during seed germination.
The transcription factor NF-YA10 determines the area explored byArabidopsis thalianaroots through direct regulation ofLAZYandTACgenes
Authors: Barrios Andana , Gaggion Nicolas , Mansilla Natanael , Lucero Leandro , Blein Thomas , Sorin Céline , Ferrante Enzo , Crespi Martin , Ariel Federico 
Published: May 2023

ABSTRACTRoot developmental plasticity relies on transcriptional reprogramming, which largely depends on the activity of transcription factors (TFs). NF-YA2 and NF-YA10 (Nuclear Factor A2 and A10) are down-regulated by the specific miRNA isoform miR169defg, in contrast to miR169a. Here, we analyzed the role of theArabidopsis thalianaTF NF-YA10 in the regulation of lateral root development. Plants expressing a version ofNF-YA10resistant to miR169 cleavage showed a perturbation in the lateral root gravitropic response. By extracting novel features of root architecture using the ChronoRoot deep-learning-based phenotyping system, we uncovered a differential emergence angle of lateral roots over time when compared to Col-0. Detailed phenotyping of root growth dynamics revealed that NF-YA10 activity modulates the area explored by Arabidopsis roots. Furthermore, we found that NF-YA10 directly regulatesTAC1andLAZYgenes by targeting their promoter regions, genes previously linked to gravitropism. Hence, the TF NF-YA10 is a new element in the control of LR gravitropism and root system architecture.
Preferred left ventricular lead position for upgrade from right ventricular pacing to cardiac resynchronization therapy
Authors: Ogano Michio , Iwasaki Yu-ki , Okada Taiji , Tanabe Jun , Shimizu Wataru , Asai Kuniya 
Published: May 2023

AbstractBackgroundCardiac resynchronization therapy (CRT) is a well-established treatment for symptomatic heart failure with electrical dyssynchrony. The left ventricle (LV) lead position is recommended at LV posterolateral to lateral sites in patients with left bundle branch block; however, its preferred region remains unclear in patients upgrading from conventional right ventricular (RV) apical pacing to CRT. We aimed to identify the preferred LV lead position for upgrading conventional RV apical pacing to CRT.MethodsThis study used electrode catheters positioned at the RV apex and LV anterolateral and posterolateral sites via the coronary sinus (CS) branches to measure the ratio of activation time to QRS duration from the RV apex to the LV anterolateral and LV posterolateral sites during RV apical pacing. We performed simultaneous biventricular pacing at the RV apex and each LV site and measured the differences in QRS duration and LV dP/dtmaxfrom those of RV apical pacing.ResultsThis study included 37 patients with anterolateral and posterolateral LV CS branches. During RV apical pacing, the average ratio of activation time to QRS duration was higher at the LV anterolateral site than at the LV posterolateral site (0.90±0.06 vs. 0.71±0.11, p<0.001). The decreasing ratio of QRS duration and the increasing ratio of LV dP/dtmaxwere higher at the LV anterolateral site than at the LV posterolateral site (45.7±18.0% vs. 32.0±17.6%, p<0.001 and 12.7±2.9% vs. 3.7±8.2%, p<0.001, respectively) during biventricular pacing compared with those during RV apical pacing.ConclusionsThe LV lead position is preferred at the LV anterolateral site in patients upgrading from conventional RV apical pacing to CRT.Condensed abstractPacing at the latest electrical activation site is crucial to improve electrical dyssynchrony in cardiac resynchronization therapy (CRT). However, the preferred location of the left ventricle (LV) lead position in patients upgrading from conventional right ventricular apical pacing to CRT is unclear. This study aimed to investigate proper strategies for CRT and identify an approach for patients upgrading to CRT. We showed that the preferred location is the LV anterolateral site. Our findings will help cardiologists and clinicians develop better strategies for treating patients with heart failure complicated with atrioventricular block.