bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Comparative Analysis of Tranexamic Acid Dosing Strategies in Traumatic Major Hemorrhage
Authors: Gunn Finn , Stevenson Rheanna , Almuwallad Ateeq , Rossetto Andrea , Vulliamy Paul , Brohi Karim , Davenport Ross ,   London, United Kingdom
Published: October 2023

Abstract

Introduction
Tranexamic acid (TXA) is a life-saving treatment for traumatic hemorrhage, but the optimal dosing regimen remains unknown. Different doses and treatment strategies have been proposed, including single bolus, repeated bolus or bolus plus infusion. The aim of this study was to determine the effect of different TXA dosing strategies on clinical outcomes in bleeding trauma patients.

Methods
Secondary analysis of a perpetual cohort study from a UK Level 1 trauma center. Adult patients who activated the local major hemorrhage protocol and received TXA were included. The primary outcome was 28-day mortality. Secondary outcomes were 24-hour mortality, multiple organ dysfunction syndrome (MODS), venous thromboembolism (VTE) and ROTEM fibrinolysis.

Results
Over an 11-year period, 525 patients were included. Three dosing groups were identified: 1 g bolus only (n = 317), 1 g bolus +1 g infusion over 8 hours (n = 80), and 2 g bolus (n = 128). Demographics and admission physiology were similar, but there were differences in injury severity (median ISS: 25, 29 & 25); and admission systolic blood pressure (median SBP: 99, 108, 99 mmHg) across the 1 g, 1 g + 1 g and 2 g groups. 28-day mortality was 21% in each treatment group. The incidence of MODS was significantly higher in the bolus plus infusion group (84%) vs 1 g bolus (64%) and 2 g bolus (62%) group, p = 0.002, but on multivariable analysis was non-significant. VTE rates were similar in the 1 g bolus (4%), 2 g bolus (8%) and bolus plus infusion groups (7%). There was no difference in ROTEM Maximum Lysis at 24 hours: 5% in both the 1 g and 2 g bolus groups vs 4% in bolus plus infusion group.

Conclusion
Clinical outcomes and 24-hour fibrinolysis state were equivalent across three different dosing strategies of TXA. Single bolus administration is likely preferable to a bolus plus infusion regimen.

Level of Evidence
Level IV, Therapeutic/Care Management
Persistent Long-Term Opioid Use After Trauma: Incidence and Risk Factors
Authors: Benns Matthew V. , Gaskins Jeremy T. , Miller Keith R. , Nash Nicholas A. , Bozeman Matthew C. , Pera Samuel J. , Marshall G. Ryne , Coleman Jamie J. , Harbrecht Brian G. 
Published: October 2023

Abstract

Background
The opioid epidemic in the United States continues to lead to a substantial number of preventable deaths and disability. The development of opioid dependence has been strongly linked to previous opioid exposure. Trauma patients are at particular risk since opioids are frequently required to control pain after injury. The purpose to this study was to examine the prevalence of opioid use before and after injury and to identify risk factors for persistent long-term opioid use after trauma.

Methods
Records for all patients admitted to a Level 1 trauma center over a one-year period were analyzed. Demographics, injury characteristics, and hospital course were recorded. A multi-state Prescription Controlled Drug Monitoring Program (PDMP) database was queried to obtain records of all controlled substances prescribed from 6 months prior to the date of injury to 12 months after hospital discharge. Patients still receiving narcotics at 1 year were defined as persistent long-term users and were compared against those who were not.

Results
2992 patients were analyzed. 20.4% of patients had filled a narcotic prescription within the 6 months prior to injury. 53.5% of patients received opioids at hospital discharge. 12.5% of patients had persistent long-term use after trauma with the majority demonstrating pre-injury use. Univariate risk factors for long term use included female sex, longer length of stay, higher injury severity score, anxiety, depression, orthopedic surgeries, spine injuries, multiple surgical locations, discharge to acute inpatient rehab, and pre-injury opioid use. On multi-variate analysis, the only significant predictors of persistent long-term prescription opioid use were pre-injury use, as well as a much smaller effect associated with use at discharge.

Conclusion
During a sustained opioid epidemic, concerns and caution are warranted in the use of prescription narcotics for trauma patients. However, persistent long-term opioid use among opioid naïve patients is rare and difficult to predict after trauma.

Level of Evidence
III, Prognostic/Epidemiological
Facemask wearing in COVID-19 pandemic: Correlates and prevalence; A survey after COVID-19 second wave in Uganda
Authors: Alema Nelson Onira , Okot Christopher , Olal Emmanuel , Ikoona Eric Nzirakaindi , Oyat Freddy Wathum Drinkwater , Baguma Steven , Ochula Denish Omoya , Olwedo Patrick Odong , Oloya Johnson Nyeko , Pebolo Francis Pebalo , Atim Pamela Okot , Okot Godfrey Smart , Nantale Ritah , Aloyo Judith , Kitara David Lagoro 
Published: October 2023

AbstractBackgroundThe WHO and the US. CDC documented that facemask-wearing in public situations is one of the most important prevention measures that can limit the acquisition and spread of COVID-19. Considering this, WHO and US. CDC developed guidelines for using facemasks in public settings. This study aimed to determine correlates and prevalence of facemask wearing during COVID-19 pandemic among adult population of Northern Uganda.MethodsWe conducted a cross-sectional study on five hundred and eighty-seven adult population of northern Uganda. A single stage stratified, and systematic sampling methods were used to select respondents from twenty-four Acholi subregion’s health facilities. Data was collected in a face-to-face questionnaire interview with an internal validity of Cronbach’s α=0.72. A local IRB approved the study, and Stata 18 was used for data analysis at multivariable Poisson regression with a p-value set at ≤0.05.ResultsThe most substantial findings from this study were the high prevalence of face mask-wearing in public among respondents [88.7%,95%CI:86%-91%]. At a multivariable Poisson regression analysis, we found that obese respondents were 1.12 times more likely to wear facemasks than those who were not, [adjusted Interval Rates Ratios, aIRR=1.12,95%CI:1.04-1.19;p<0.01], and respondent who agreed to the lockdown measures were 1.23 times more likely to wear facemasks during COVID-19 pandemic than those who did not, [aIRR=1.23, 95%CI:1.07-1.41;p<0.01]. Other sociodemographic characteristics such as sex, age, occupation, level of education, religion, tribes, marital status, nationality, race, and comorbidities were not statistically significant at 95% Confidence Intervals.ConclusionThe most significant findings from this study were the high prevalence of face mask-wearing among adult community members in northern Uganda. The correlates of facemask wearing in public were the obese and respondents who agreed with the presidential directives on the lockdown measures. Although this was within acceptable prevalence rates, the strict enforcement of face mask-wearing by security forces raised concerns among many community members and human rights advocates. We recommend more studies on communities’ perspectives on the challenges and benefits of facemask-wearing during the COVID-19 pandemic.
Systematic assessment of early brain injury severity at admission with aneurysmal subarachnoid hemorrhage
Authors: Tuzi Sheri , Kranawetter Beate , Mielke Dorothee , Rohde Veit , Malinova Vesna 
Published: October 2023

AbstractBackgroundEarly brain injury (EBI) after aneurysmal subarachnoid hemorrhage (aSAH) has been increasingly recognized as a risk factor for delayed cerebral ischemia (DCI). While several clinical and radiological EBI biomarkers have been identified, no tool for systematic assessment of EBI severity has been established so far. This study aimed to develop an EBI grading system based on clinical signs and neuroimaging for estimation of EBI severity at admission.MethodsThis is a retrospective observational study assessing imaging parameters (intracranial blood amount, global cerebral edema (GCE)), and clinical signs (persistent loss of consciousness [LOC]) representative for EBI. The intracranial blood amount was semi-quantitatively assessed. One point was added for GCE and LOC, respectively. All points were summed up resulting in an EBI grading ranging from 1-5. The estimated EBI severity was correlated with progressive GCE requiring decompressive hemicraniectomy (DHC), DCI-associated infarction, and outcome according to the modified Rankin scale (mRS) at 3-month-follow up.ResultsA consecutive cohort including 324 aSAH-patients with a mean age of 55.9 years, was analyzed. The probability of developing progressive GCE was 9% for EBI grade 1, 28% for EBI grade 2, 43% for EBI grade 3, 61% for EBI grade 4, and 89% for EBI grade 5. The EBI grading correlated significantly with the need for DHC (r=0.25,p<0.0001), delayed infarction (r=0.30,p<0.0001), and outcome (r=0.31,p<0.0001).ConclusionsAn EBI grading based on clinical and imaging parameters allowed an early systematic estimation of EBI severity with a higher EBI grade associated not only with a progressive GCE but also with DCI and poor outcome.
Parental awareness and attitudes towards prevention of respiratory syncytial virus in infants and young children in Australia
Authors: Holland Charlie , Baker Megan , Bates Amber , Hughes Catherine , Richmond Peter C , Carlson Samantha , Moore Hannah C 
Published: October 2023

AbstractAimsTo assess parental awareness of respiratory syncytial virus (RSV) and the level of acceptance of future RSV prevention strategies.MethodsA cross-sectional online survey was implemented targeting “future” and “current” parents of children aged ≤5 years in Australia.ResultsFrom 1,992 eligible participants, two non-mutually exclusive subgroups were formed; “current” parents (N=1931) and “pregnant/planning” parents (N=464; 403 also “current” parents; 61 “future” parents). Participants were predominantly (86.6%) aged 25-39 years and 68.5% with university education. The majority (89.6% current; 78.7% future) had heard of RSV. Of those, 64.2% (current) and 50.0% (future) were aware that pneumonia is associated with RSV; 71.8% (current) and 52.1% (future) were aware that bronchiolitis is associated. In multivariable logistic regression analyses, Australian-born parents (aOR=2.47 [95%CI:1.48-4.12]), living in the Eastern States (e.g., New South Wales: aOR=6.15 [95%CI:2.10-18.04]), with a university level education (aOR=2.61 [95%CI:1.38-4.94]) and being a current parent (aOR=12.26 [95%CI:2.82-53.28]) were associated with higher RSV awareness. There was a high level of acceptance for maternal vaccines (future: 79.3%) and infant immunisation (all: 81.7%).ConclusionWhile RSV awareness and immunisation acceptance was high, there was limited knowledge of severity of RSV, especially in future parents. Education campaigns need to be developed to increase RSV knowledge.Key notesThe success of RSV immunisation programs is dependent on the community having sufficient disease awareness and acceptance of new immunisation strategies. Majority of parents in the study had heard of RSV, however lacked awareness on associated conditions and disease severity, particularly future parents. Education and awareness campaigns are required to inform parents about RSV and future immunisations; there is a critical opportunity to increase awareness prior to immunisation arrival.
Low-flow in aortic valve stenosis patients with reduced ejection fraction does not depend on left ventricular function
Authors: Gersch Svante , Lange Torben , Beuthner Bo Eric , Elkenani Manar , Paul Niels , Schnelle Moritz , Zeisberg Elisabeth , Puls Miriam , Hasenfuß Gerd , Schuster Andreas , Toischer Karl 
Published: October 2023

AbstractBackgroundPatients with severe aortic stenosis (AS) and reduced left ventricular ejection fraction (LVEF) can be distinguished into high-(HG) and low-gradient (LG) subgroups. However, less is known about their characteristics and underlying (pathophysiological) hemodynamic mechanisms.Methods98 AS patients with reduced LVEF were included. Subgroup characteristics were analyzed by a multimodal approach using clinical and histological data, next-generation sequencing (NGS) and applying echocardiography as well as cardiovascular magnetic resonance (CMR) imaging. Biopsy samples were analyzed with respect to fibrosis and mRNA expression profiles.Results40 patients were classified as HG-AS and 58 patients as LG-AS. Severity of AS was comparable between the subgroups. Comparison of both subgroups revealed no differences in LVEF (p=0.1), LV mass (p=0.6) or end-diastolic LV diameter (p=0.12). Neither histological (HG: 23.2% vs. LG: 25.6%, p=0.73) and circulating biomarker-based assessment (HG: 2.6 ± 2.2 % vs. LG: 3.2 ± 3.1 %; p= 0.46) of myocardial fibrosis nor global gene expression patterns differed between subgroups. Mitral regurgitation (MR), atrial fibrillation (AF) and impaired right ventricular function (MR: HG: 8% vs. LG: 24%; p<0.001; AF: HG: 30% vs. LG: 51.7%; p=0.03; RVSVi: HG 36.7 vs. LG 31.1 ml/m2, p=0.045; TAPSE: HG 20.2 vs. LG 17.3 mm, p=0.002) were more frequent in LG-AS patients compared to HG-AS. These pathologies could explain the higher mortality of LG vs. HG-AS patients.ConclusionIn patients with low-flow severe aortic stenosis, low transaortic gradient and cardiac output are not primarily due to LV dysfunction or global changes in gene expression, but may be attributed to other additional cardiac pathologies like mitral regurgitation, atrial fibrillation or right ventricular dysfunction. These factors should also be considered during planning of aortic valve replacement.
Kynurenic acid promotes activity-dependent synaptic pruning in schizophrenia
Authors: Orhan Funda , Malwade Susmita , Khanlarkhani Neda , Gkoga Asimenia , Jungholm Oscar , Koskuvi Marja , Lehtonen Šárka , Schwieler Lilly , Jardemark Kent , Tiihonen Jari , Koistinaho Jari , Erhardt Sophie , Engberg Göran , Samudyata Samudyata , Sellgren Carl M. 
Published: October 2023

AbstractSchizophrenia is a neurodevelopmental disorder characterized by an excessive loss of synapses. Recent data suggest that this is due to increased microglia-mediated synaptic pruning. Here, we utilize human induced pluripotent stem cell-derived models to show that kynurenic acid (KYNA), an endogenous NMDA-receptor antagonist observed to be increased in the brains of individuals with schizophrenia, reduces neuronal activity and promote microglial uptake of synapses. In a human brain organoid model, we confirm reduced microglia-mediated synaptic pruning upon inhibiting the endogenous KYNA production. To verify our experimental data in a clinical context, we integrate large-scale transcriptomic and genetic datasets and show that KYNA-producing kynurenine aminotransferases (KATs) enrich for genes governing synaptic activity and genetic risk variants for schizophrenia. Together, these results link genetic risk variants for schizophrenia to elevated production of KYNA and excessive activity-dependent synaptic pruning, while implicating pharmacological inhibition of KATs as a strategy to avoid synapse loss in schizophrenia.
A High-Fat and Fructose Diet in Dogs Mirrors Insulin Resistance and β-cell Dysfunction Characteristic of Impaired Glucose Tolerance in Humans
Authors: Gregory Justin M. , Kraft Guillaume , Man Chiara Dalla , Slaughter James C , Scott Melanie F. , Hastings Jon R. , Edgerton Dale S. , Moore Mary C. , Cherrington Alan D. 
Published: October 2023

ABSTRACTThis study examined the impact of a hypercaloric high-fat high-fructose diet (HFFD) in dogs as a potential model for human impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM). The HFFD not only led to weight gain but also triggered metabolic alterations akin to the precursors of human T2DM, notably insulin resistance and β-cell dysfunction. Following the HFFD intervention, the dogs exhibited a 50% decrease in insulin sensitivity within the first four weeks, paralleling observations in the progression from normal to IGT in humans. Calculations of the insulinogenic index using both insulin and C-peptide revealed a significant and sustained decrease in early-phase insulin release, with partial compensation in the later phase, predominantly stemming from reduced hepatic insulin clearance. In addition, the Disposition Index, representing the β-cell’s capacity to compensate for diminished insulin sensitivity, fell dramatically. These results confirm that a HFFD can instigate metabolic changes in dogs akin to the early stages of progression to T2DM in humans. The study underscores the potential of using dogs subjected to a HFFD as a model organism for studying human IGT and T2DM.
Visual impairment cell non-autonomously dysregulates brain-wide proteostasis
Authors: Shekhar Shashank , Wert Katherine J , Krämer Helmut 
Published: October 2023

AbstractLoss of hearing or vision has been identified as a significant risk factor for dementia but underlying molecular mechanisms are unknown. In different Drosophila models of blindness, we observe non-autonomous induction of stress granules in the brain and their reversal upon restoration of vision. Stress granules include cytosolic condensates of p62, ATF4 and XRP1. This cytosolic restraint of the ATF4 and XRP1 transcription factors dampens expression of their downstream targets during cellular stress. Cytosolic condensates of p62 and ATF4 were also evident in the thalamus and hippocampus of mouse models of congenital or degenerative blindness. These data indicate conservation of the link between loss of sensory input and dysregulation of stress responses critical for protein quality control in the brain.One-sentence summaryDrosophila and mouse models link loss of visual input to dysregulated stress responses of neurons and glia in the brain.
Endothelial Cell Serum and Glucocorticoid Regulated Kinase 1 (SGK1) Mediates Vascular Stiffening
Authors: Zhang Liping , Sun Zhe , Yang Yan , Mack Austin , Rodgers Mackenna , Aroor Annayya , Jia Guanghong , Sowers James R. , Hill Michael A. 
Published: October 2023

AbstractBackgroundExcess dietary salt increases vascular stiffness in humans, especially in salt- sensitive populations. While we recently suggested that the endothelial sodium channel (EnNaC) contributes to salt-sensitivity related endothelial cell (EC) and arterial stiffening, mechanistic understanding is incomplete. This study thus aimed to explore the role of EC-serum and glucocorticoid regulated kinase 1 (SGK1), as a regulator of sodium channels, in EC and arterial stiffening.Methods and ResultsA mouse model of salt sensitivity-associated vascular stiffening was produced by subcutaneous implantation of slow-release deoxycorticosterone acetate (DOCA) pellets, with salt (1% NaCl, 0.2% KCl) administered via drinking water. Preliminary data showed that global SGK1 deletion caused significantly decreased blood pressure, EnNaC activity and aortic endothelium stiffness as compared to control mice following DOCA-salt treatment. To probe EC signaling pathways, selective deletion of EC-SGK1 was performed by cross-breeding cadherin 5-Cre mice with sgk1flox/floxmice. DOCA-salt treated control mice had significantly increased blood pressure, EC and aortic stiffness in vivo and ex vivo, which were attenuated by EC-SGK1 deficiency. To demonstrate relevance to humans, human aortic ECs were cultured in the absence or presence of aldosterone and high salt with or without the SGK1 inhibitor, EMD638683 (10uM or 25uM). Treatment with aldosterone and high salt increased intrinsic stiffness of ECs, which was prevented by SGK1 inhibition. Further, the SGK1 inhibitor prevented aldosterone and high salt induced actin polymerization, a key mechanism in cellular stiffening.ConclusionEC-SGK1 mediates salt-sensitivity related EC and aortic stiffening by mechanisms appearing to involve regulation actin polymerization.Graphical Abstract
Variational Bayesian Phylogenies through Matrix Representation of Tree Space
Authors: Bouckaert Remco R. 
Published: October 2023

ABSTRACTIn this paper, we study the distance matrix as a representation of a phylogeny by way of hierarchical clustering. By defining a multivariate normal distribution on (a subset of) the entries in a matrix, this allows us to represent a distribution over rooted time trees. Here, we demonstrate tree distributions can be represented accurately this way for a number of published tree distributions. Though such a representation does not map to unique trees, restriction to a subspace, in particular one we call a “cube”, makes the representation bijective at the cost of not being able to represent all possible trees. We introduce an algorithm “cubeVB” specifically for cubes and show through well calibrated simulation study that it is possible to recover parameters of interest like tree height and length. Although a cube cannot represent all of tree space, it is a great improvement over a single summary tree, and it opens up exciting new opportunities for scaling up Bayesian phylogenetic inference. We also demonstrate how to use a matrix representation of a tree distribution to get better summary trees than commonly used maximum clade credibility trees. An open source implementation of the cubeVB algorithm is available fromhttps://github.com/rbouckaert/cubevbas thecubevbpackage for BEAST 2.
Selective Cancellation of Reactive and Anticipated Movement: Differences in Speed of Action Reprogramming, but not Stopping
Authors: Weber Simon , Salomoni Sauro E. , Hinder Mark R. 
Published: October 2023

AbstractThe ability to inhibit movements is an essential component of a healthy executive control system. Two distinct but commonly used tasks to assess motor inhibition are the stop signal task (SST) and the anticipated response inhibition (ARI) task. The SST and ARI tasks are similar in that they both require cancelation of a prepotent movement; however, the SST involves cancelation of a speeded reaction to a temporally unpredictable signal, while the ARI task involves cancelation of an anticipated response that the participant has prepared to enact at a wholly predictable time.33 participants (mean age = 33.3 years, range = 18-55 years) completed variants of the SST and ARI task. In each task, the majority of trials required bimanual button presses, while on a subset of trials a stop signal indicated that one of the presses should be cancelled (i.e., motor selective inhibition). Additional variants of the tasks also included trials featuring signals which were to be ignored, allowing for insights into the attentional component of the inhibitory response. Electromyographic (EMG) recordings allowed detailed comparison of the characteristics of voluntary action and cancellation.The speed of the inhibitory process was not influenced by whether the enacted movement was reactive (SST) or anticipated (ARI task). However, the ongoing (non-cancelled) component of anticipated movements was more efficient than reactive movements, as a result of faster action reprogramming (i.e., faster ongoing actions following successful selective inhibition). Older age was associated with both slower inhibition and slower action reprogramming across all reactive and anticipated tasks.