bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tranexamic acid is not associated with a higher rate of thrombotic-related reintervention after major vascular injury repair
Authors: Asaadi Sina , Mukherjee Kaushik , Abou-Zamzam Ahmed M. , Ji Liang , Luo-Owen Xian , Tabrizi Maryam B. , Catalano Richard D. , Dubose Joseph J. , Rosenthal Martin G. ,   AAST PROOVIT Study Group
Published: December 2023

BACKGROUND
Tranexamic acid (TXA) is associated with lower mortality and transfusion requirements in trauma patients, but its role in thrombotic complications associated with vascular repairs remains unclear. We investigated whether TXA increases the risk of thrombosis-related technical failure (TRTF) in major vascular injuries (MVI).

METHODS
The PROspective Observational Vascular Injury Treatment (PROOVIT) registry was queried from 2013 to 2022 for MVI repaired with an open or endovascular intervention. The relationship between TXA administration and TRTF was examined.

RESULTS
The TXA group (n = 297) had higher rates of hypotension at admission (33.6% vs. 11.5%, p < 0.001), need for continuous vasopressors (41.4% vs. 18.4%, p < 0.001), and packed red blood cell transfusion (3.2 vs. 2.0 units, p < 0.001) during the first 24 hours compared with the non-TXA group (n = 1941), although demographics, injury pattern, and interventions were similar. Cryoprecipitate (9.1% vs. 2%, p < 0.001), and anticoagulant administration during the intervention (32.7% vs. 43.8%, p < 0.001) were higher in the TXA group; there was no difference in the rate of factor VII use between groups (1% vs. 0.7%, p = 0.485). Thrombosis-related technical failure was not different between the groups (6.3% vs. 3.8 p = 0.141) while the rate of immediate need for reoperation (10.1% vs. 5.7%, p = 0.006) and overall reoperation (11.4% vs. 7%, p = 0.009) was significantly higher in the TXA group on univariate analysis. There was no significant association between TXA and a higher rate of immediate need for reintervention (odds ratio [OR], 1.19; 95% confidence interval [CI], 0.75–1.88; p = 0.465), overall reoperation rate (OR, 1.33; 95% CI, 0.82–2.17; p = 0.249) and thrombotic events in a repaired vessel (OR, 1.07; 95% CI, 0.60–1.92; p = 0.806) after adjusting for type of injury, vasopressor infusions, blood product and anticoagulant administration, and hemodynamics.

CONCLUSION
Tranexamic acid is not associated with a higher risk of thrombosis-related technical failure in traumatic injuries requiring major vascular repairs. Further prospective studies to examine dose-dependent or time-dependent associations between TXA and thrombotic events in MVIs are needed.

LEVEL OF EVIDENCE
Therapeutic/Care Management; Level IV.
Analysis of lipid metabolites derived from gut microbiota in ischemia-reperfusion model
Authors: Nakatsutsumi Keita , Morishita Koji , Costantini Todd W. , Adachi Tomohiro , Suekane Akira , Suzuki Keisuke , Kojima Mitsuaki , Arita Makoto , Otomo Yasuhiro 
Published: December 2023

BACKGROUND
Disruption of intestinal barrier caused by intestinal ischemia due to hemorrhagic shock is associated with the pathogenesis of multiple organ dysfunction (MOD) after severe trauma. Mesenteric lymph (ML) plays an important role as a route for transporting inflammatory mediators, including lipids. Postbiotics, such as 10-hydroxy-cis-12-octadecenoic acid (HYA), have received much attention as a treatment option. However, the relationship between postbiotics and MOD has yet to be clarified. The aim of the present study was to analyze lipid metabolites derived from gut microbiota in the intestinal ischemia-reperfusion (IR) rat model.

METHODS
Male Sprague-Dawley rats underwent laparotomy, and their ML duct and superior mesenteric artery were exposed. The superior mesenteric artery was clamped for 60 minutes, followed by 120 minutes of reperfusion. The ML and the plasma were collected before and after intestinal IR. Lipids were extracted from plasma and ML, and liquid chromatography–tandem mass spectrometry was performed.

RESULTS
The concentration of linoleic acid in plasma samples was not different before and after IR; however, the linoleic acid concentration in the ML samples increased after intestinal IR. Eicosapentaenoic acids and docosahexaenoic related to linoleic acids showed similar changes with IR-induced increase in the ML. The concentration of HYA, a linoleic acid–derived bioactive metabolite produced by gut bacteria, was high in ML samples, while that in plasma samples was low. The relative increase rate of HYA in ML samples after IR was higher than that of the plasma samples (the ML samples: relative increase, 3.23 ± 1.36; the plasma samples: relative increase, 0.95 ± 0.35; n = 3, p = 0.048).

CONCLUSION
The present study demonstrated increased linoleic acids and high concentrations of HYA, lipid metabolites derived from gut bacteria in the ML after intestinal IR. These findings may contribute to clarifying the relation between gut microbiota and MOD after severe trauma.
Long wavelength light exposure reduces systemic inflammation coagulopathy and acute organ injury following multiple injuries in mice
Authors: Zarisfi Mohammadreza , Younes Reem , Alsaadi Nijmeh , Liu Zeyu , Loughran Patricia , Williamson Kelly , Spinella Philip C. , Shea Susan M. , Rosengart Matthew R. , Andraska Elizabeth A. , Neal Matthew D. 
Published: December 2023

BACKGROUNDEvidence suggests that variation in light exposure strongly influences the dynamic of inflammation, coagulation, and the immune system. Multiple injuries induce systemic inflammation that can lead to end-organ injury. Here, we hypothesize that alterations in light exposure influence posttrauma inflammation, coagulopathy, and end-organ injury.METHODSC57BL/6 mice underwent a validated multiple-injury and hemorrhage model performed following 72 hours of exposure to red (617 nm, 1,700 lux), blue (321 nm, 1,700 lux), and fluorescent white light (300 lux) (n = 6–8/group). The animals were sacrificed at 6 hours posttrauma. Plasma samples were evaluated and compared for proinflammatory cytokine expression levels, coagulation parameters, markers of liver and renal injury, and histological changes (Carstairs staining). One-way analysis of variance statistical tests were applied to compare study groups.RESULTSPreexposure to long-wavelength red light significantly reduced the inflammatory response at 6 hours after multiple injuries compared with blue and ambient light, as evidenced by decreased levels of interleukin 6, monocyte chemoattractant protein-1 (bothp< 0.001), liver injury markers (alanine transaminase,p< 0.05), and kidney injury markers (cystatin C,p< 0.01). In addition, Carstairs staining of organ tissues revealed milder histological changes in the red light–exposed group, indicating reduced end-organ damage. Furthermore, prothrombin time was significantly lower (p< 0.001), and fibrinogen levels were better maintained (p< 0.01) in the red light–exposed mice compared with those exposed to blue and ambient light.CONCLUSIONProphylactic light exposure can be optimized to reduce systemic inflammation and coagulopathy and minimize acute organ injury following multiple injuries. Understanding the mechanisms by which light exposure attenuates inflammation may provide a novel strategy to reducing trauma-related morbidity.
IL-4 shaping glutamatergic synapse like structures for more mature iPSC derived neuron phenotypes
Authors: Zimmermann David , Schöpf Clemens L. , Kern Georg , Kalpachidou Theodora , Zeidler Maximilian , Kress Michaela 
Published: December 2023

AbstractThe prototypical pleiotropic anti-inflammatory cytokine IL-4 not only acts on immune cells but also has important roles in the nervous system mediating antinociception and neuroregeneration. Therefore, we explored the expression of IL-4, its receptors IL4RA and IL13RA1 and downstream signaling components together with morphological and functional assays as well as transcriptomic profiling in human nociceptors differentiating from induced pluripotent stem cells (iNocs).IL-4 induced de novo formation of synaptic boutons immunoreactive for vesicular glutamate transporter vGLUT1 in iNocs which express both, components of the IL-4 receptor complex (IL-4RA and IL-13RA1) and signaling machinery (Jak1/2, STAT6, PKC isoforms, translation factor EiF4E) during differentiation. Pharmacological inhibition of these translational or cellular signaling components reduced the synaptogenic effect. IL-4 induced distinct transcriptomic changes associated with biological process ontologies for “neuron projection development”, “axonogenesis” and “synapse”, “cellular process involved in reproduction in multicellular organism”, “regulation of membrane potential” and “calcium ion transmembrane transport”. This partially reflected injury-induced transcriptional changes of mouse nerve injury models which contribute to regenerative processes in peripheral nerve but possibly also to reconnecting primary afferent neurons to their projections in the spinal dorsal horn and indicates a critical role for IL-4 in the control of developing and established neuronal networks.
Exploring the prokaryote-eukaryote interplay in microbial mats from an Andean athalassohaline wetland
Authors: Cubillos Carolina F. , Aguilar Pablo , Moreira David , Bertolino Paola , Iniesto Miguel , Dorador Cristina , López-García Purificación 
Published: December 2023

ABSTRACTMicrobial community assembly results from the interaction between biotic and abiotic factors. However, environmental selection is thought to predominantly shape communities in extreme ecosystems. Salar de Huasco, situated in the high altitude Andean Altiplano, represents a poly-extreme ecosystem displaying spatial gradients of physicochemical conditions. To disentangle the influence of abiotic and biotic factors, we studied prokaryotic and eukaryotic communities from microbial mats and underlying sediments across contrasting areas of this athalassohaline ecosystem. The prokaryotic communities were primarily composed of bacteria, notably including a significant proportion of photosynthetic organisms like Cyanobacteria and anoxygenic photosynthetic members of Alpha- and Gammaproteobacteria and Chloroflexi. Additionally, Bacteroidetes, Verrucomicrobia, and Deltaproteobacteria were abundantly represented. Among eukaryotes, photosynthetic organisms (Ochrophyta, Archaeplastida) were predominant, alongside relatively abundant ciliates, cercozoans, and flagellated fungi. Salinity emerged as a key driver for the assembly of prokaryotic communities. Collectively, abiotic factors influenced both prokaryotic and eukaryotic communities, particularly those of algae. However, prokaryotic communities strongly correlated with photosynthetic eukaryotes, suggesting a pivotal role of biotic interactions in shaping these communities. Co-occurrence networks suggested potential interactions between different organisms, such as diatoms with specific photosynthetic and heterotrophic bacteria or with protist predators, indicating influences beyond environmental selection. While some associations may be explained by environmental preferences, the robust biotic correlations, alongside insights from other ecosystems and experimental studies, suggest that symbiotic and trophic interactions significantly shape microbial mat and sediment microbial communities in this athalassohaline ecosystem.
A niche-adapted brain microbiome in salmonids at homeostasis
Authors: Mani Amir , Henn Cory , Couch Claire , Patel Sonal , Korytar Tomas , Salinas Irene 
Published: December 2023

AbstractEctotherms have long been known to have peculiar relationships with microorganisms. For instance, bacteria can be recovered from blood and internal organs of healthy teleost fish. However, until now, the presence of a microbial community in the healthy teleost brain has not been proposed. Here we report a living bacterial community in the brain of healthy salmonids. Brain bacterial loads in salmonids are comparable to those found in the spleen and 1000-fold lower than in the gut. Brain bacterial communities share >50% of their diversity with gut and blood bacterial communities. Using culturomics, we obtained 54 bacterial isolates from the brain of healthy rainbow trout. Comparative genomics uncovered unique niche adaptations associated with brain colonization and polyamine biosynthesis. In a natural system, salmonid brain microbiomes shift with the host life cycle, becoming dysbiotic in reproductively mature Chinook salmon, a species that undergoes reproductive death. Our study redefines the relationship between the teleost brain and bacterial microbiomes under physiological conditions. We posit that this symbiosis may endow salmonids with a direct mechanism to sense and respond to environmental microbes.One-Sentence SummarySalmonids have a brain-adapted, resident bacterial community
Effect of Genetic and Dietary Perturbation of Glycine Metabolism on Atherosclerosis in Humans and Mice
Authors: Biswas Subarna , Hilser James R. , Woodward Nicholas C. , Wang Zeneng , Gukasyan Janet , Nemet Ina , Schwartzman William S. , Huang Pin , Han Yi , Fouladian Zachary , Charugundla Sarada , Spencer Neal J. , Pan Calvin , Tang W.H. Wilson , Lusis Aldons J. , Hazen Stanley L. , Hartiala Jaana A. , Allayee Hooman 
Published: December 2023

AbstractObjectiveEpidemiological and genetic studies have reported inverse associations between circulating glycine levels and risk of coronary artery disease (CAD). However, these findings have not been consistently observed in all studies. We sought to evaluate the causal relationship between circulating glycine levels and atherosclerosis using large-scale genetic analyses in humans and dietary supplementation experiments in mice.MethodsSerum glycine levels were evaluated for association with prevalent and incident CAD in the UK Biobank. A multi-ancestry genome-wide association study (GWAS) meta-analysis was carried out to identify genetic determinants for circulating glycine levels, which were then used to evaluate the causal relationship between glycine and risk of CAD by Mendelian randomization (MR). A glycine feeding study was carried out with atherosclerosis-prone apolipoprotein E deficient (ApoE−/−) mice to determine the effects of increased circulating glycine levels on amino acid metabolism, metabolic traits, and aortic lesion formation.ResultsAmong 105,718 subjects from the UK Biobank, elevated serum glycine levels were associated with significantly reduced risk of prevalent CAD (Quintile 5 vs. Quintile 1 OR=0.76, 95% CI 0.67-0.87; P<0.0001) and incident CAD (Quintile 5 vs. Quintile 1 HR=0.70, 95% CI 0.65-0.77; P<0.0001) in models adjusted for age, sex, ethnicity, anti-hypertensive and lipid-lowering medications, blood pressure, kidney function, and diabetes. A meta-analysis of 13 GWAS datasets (total n=230,947) identified 61 loci for circulating glycine levels, of which 26 were novel. MR analyses provided modest evidence that genetically elevated glycine levels were causally associated with reduced systolic blood pressure and risk of type 2 diabetes, but did provide evidence for an association with risk of CAD. Furthermore, glycine-supplementation inApoE−/−mice did not alter cardiometabolic traits, inflammatory biomarkers, or development of atherosclerotic lesions.ConclusionsCirculating glycine levels were inversely associated with risk of prevalent and incident CAD in a large population-based cohort. While substantially expanding the genetic architecture of circulating glycine levels, MR analyses andin vivofeeding studies in humans and mice, respectively, did not provide evidence that the clinical association of this amino acid with CAD represents a causal relationship, despite being associated with two correlated risk factors.
A Pose-Informed De-Noising Diffusion Model for Adult Naturalistic EEG Signals
Authors: Dutta Angshuk , Hirt Marcel , Santamaria Lorena , Georgieva Stanimira , Gerloff Christian , Li Boyang , Leong Victoria 
Published: December 2023

AbstractArtifact contamination in EEG (electroencephalogram) signals is a significant problem, especially in naturalistic settings where participants can move freely. This contamination stems from various sources like eye movements, muscle activity, sweat, and electrical interference, whose effects differ greatly from each other. Traditional denoising methods, such as Independent Component Analysis, are limited because they assume a linear relationship between the source of the artifacts and the EEG signals, and often require the dominance of one noise source over others. Moreover, these methods need expert knowledge in EEG analysis and lack an objective standard for evaluation.To overcome these challenges, we propose two innovations: Firstly, we introduce the use of “video-estimated” pose coordinates – the x and y positions of different body points (like wrists, eyes, and ankles) – to assist in the EEG denoising process. Secondly, we present a denoising diffusion model, EEG-DDM, that utilizes both the contaminated EEG signals and these pose coordinates to effectively denoise the EEG. Our findings show that incorporating keypoints (pose coordinates) improves denoising performance and helps maintain cross-spatial dependencies in the data. Additionally, we enhance human interpretability of the process by displaying saliency maps generated by our model, which explain the contributions of these keypoints in the denoising process.
Coevolution with toxic prey produces functional trade-offs in sodium channels of predatory snakes
Authors: del Carlo Robert E. , Reimche Jessica S. , Moniz Haley A. , Hague Michael T.J. , Agarwal Shailesh R. , Brodie Edmund D. , Brodie Edmund D. , Leblanc Normand , Feldman Chris R. 
Published: December 2023

AbstractSeemingly unrelated traits often share the same underlying molecular mechanisms, potentially generating a pleiotropic relationship whereby selection shaping one trait can simultaneously compromise another. While such functional trade-offs are expected to influence evolutionary outcomes, their actual relevance in nature is masked by obscure links between genotype, phenotype, and fitness. Here, we describe functional trade-offs that likely govern a key adaptation and coevolutionary dynamics in a predator-prey system. Several garter snake (Thamnophisspp.) populations have evolved resistance to tetrodotoxin (TTX), a potent chemical defense in their prey, toxic newts (Tarichaspp.). Snakes achieve TTX resistance through mutations occurring at toxin-binding sites in the pore of snake skeletal muscle voltage-gated sodium channels (NaV1.4). We hypothesized that these mutations impair basic NaVfunctions, producing molecular trade-offs that should ultimately scale up to compromised organismal performance. We investigate biophysical costs in two snake species with unique and independently evolved mutations that confer TTX resistance. We show electrophysiological evidence that skeletal muscle sodium channels encoded by toxin-resistant alleles are functionally compromised. Furthermore, skeletal muscles from snakes with resistance genotypes exhibit reduced mechanical performance. Lastly, modeling the molecular stability of these sodium channel variants partially explains the electrophysiological and muscle impairments. Ultimately, adaptive genetic changes favoring toxin resistance appear to negatively impact sodium channel function, skeletal muscle strength, and organismal performance. These functional trade-offs at the cellular and organ levels appear to underpin locomotor deficits observed in resistant snakes and may explain variation in the population-level success of toxin-resistant alleles across the landscape, ultimately shaping the trajectory of snake-newt coevolution.
Modeling the synergistic interplay between malaria dynamics and economic growth
Authors: Ngonghala Calistus N. , Enright Hope , Prosper Olivia , Zhao Ruijun 
Published: December 2023

AbstractThe mosquito-borne disease (malaria) imposes significant challenges on human health, healthcare systems, and economic growth/productivity in many countries. This study develops and analyzes a model to understand the interplay between malaria dynamics, economic growth, and transient events. It uncovers varied effects of malaria and economic parameters on model outcomes, highlighting the interdependence of the reproduction number (R0) on both malaria and economic factors, and a reciprocal relationship where malaria diminishes economic productivity, while higher economic output is associated with reduced malaria prevalence. This emphasizes the intricate interplay between malaria dynamics and socio-economic factors. The study offers insights into malaria control and underscores the significance of optimizing external aid allocation, especially favoring an even distribution strategy, with the most significant reduction observed in an equal monthly distribution strategy compared to longer distribution intervals. Furthermore, the study shows that controlling malaria in high mosquito biting areas with limited aid, low technology, inadequate treatment, or low economic investment is challenging. The model exhibits a backward bifurcation implying that sustainability of control and mitigation measures is essential even whenR0is slightly less than one. Additionally, there is a parameter regime for which long transients are feasible. Long transients are critical for predicting the behavior of dynamic systems and identifying factors influencing transitions; they reveal reservoirs of infection, vital for disease control. Policy recommendations for effective malaria control from the study include prioritizing sustained control measures, optimizing external aid allocation, and reducing mosquito biting.
Synthesized Economic Evidence on the Cost-effectiveness of Screening Familial Hypercholesterolemia: A meta-analytic review and Aggregate Distributional Cost-Effectiveness Analysis
Authors: Wang Mengying , Jiang Shan , Lu Jiao , Tan Kai , Gu Yuanyuan , Li Shunping 
Published: December 2023

ABSTRACTBackgroundFamilial hypercholesterolemia (FH) is a prevalent genetic disorder with global implications for severe cardiovascular diseases. Amid ongoing advancements in genetic disease screening and treatment, the economic evaluation of FH is increasingly vital. Despite numerous studies, international disparities persist, necessitating a comprehensive analysis of the economic assessments of FH screening to provide valuable insights. This study aims to globally examine economic assessments of FH, synthesize evidence, and present economic insights into the impact of FH screening on population equity.MethodsSystematic literature analysis was used to systematically evaluate 19 FH screening economic evaluation studies and synthesize the evidence. Meta-analysis was used to comprehensively explore the total cost-effectiveness and total net health benefit of different FH screening methods. The aggregate Distributional Cost-Effectiveness Analysis (DCEA) was utilized to assess the impact of FH screening on population equity.ResultsThe study results reveal significant differences in the economic evaluations of FH across different countries, and we provide detailed descriptions of unique characteristics. The comprehensive results of cost-effectiveness analysis indicate that FH screening is cost-effective in the majority of countries. The meta-analysis synthesizes the economic impacts of Cascade Screening and Universal Screening across various health outcomes. Additionally, our aggregate Distributional Cost-Effectiveness Analysis (DCEA) suggests that FH screening strategies have the potential to alleviate health inequalities.ConclusionThis study provides a global perspective on FH economic evaluation. Despite international differences, findings suggest that, in the majority of cases, FH screening is cost-effective, improving health equity and overall population health. The study offers a positive outlook for future health decisions.