bluuebunny/crossref_metadata_2025_split huggingface dataset:
pREBOA versus ER-REBOA impact on blood utilization and resuscitation requirements: A pilot analysis
Authors: Meyer Courtney H. , Beckett Andrew , Dennis Bradley M. , Duchesne Juan , Kundi Rishi , Pandya Urmil , Lawless Ryan , Moore Ernest , Spalding Chance , Vassy William M. , Nguyen Jonathan ,   The AAST AORTA Study Group
Published: May 2024

BACKGROUND
Partial occlusion of the aorta is a resuscitation technique designed to maximize proximal perfusion while allowing a graduated amount of distal flow to reduce the ischemic sequelae associated with complete aortic occlusion. The pREBOA-PRO catheter affords the ability to titrate perfusion as hemodynamics allows; however, the impact of this new technology for resuscitative endovascular balloon occlusion of the aorta (REBOA) on blood use and other resuscitative requirements is currently unknown. We hypothesize that patients undergoing REBOA with the pREBOA-PRO catheter will utilize partial occlusion, when appropriate, and decrease overall resuscitative requirements when compared to patients undergoing REBOA with the ER-REBOA catheter.

METHODS
The entire American Association for the Surgery of Trauma Aortic Occlusion for Resuscitation in Trauma and Acute Care Surgery registry was used to compare resuscitation requirements between all ER-REBOA and pREBOA. Unpaired t tests were used to compare resuscitation strategies including packed red blood cells (PRBCs), fresh frozen plasma (FFP), platelets, cryoprecipitate, crystalloids, and need for pressors.

RESULTS
When comparing ER-REBOA (n = 800) use to pREBOA (n = 155), initial patient presentations were similar except for age (44 years vs. 40 years, p = 0.026) and rates of blunt injury (78.4% vs. 78.7% p < 0.010). Zone 1 occlusion was used less often in ER-REBOA (65.8 vs. 71.7, p = 0.046). Partial occlusion was performed in 85% of pREBOA compared with 11% in ER-REBOA (p < 0.050). Vitals at the time of REBOA were worse in ER-REBOA and received significantly more units of PRBCs, FFP, platelets, and liters of crystalloids than pREBOA (p < 0.05). Rates of ARDS and septic shock were lower in pREBOA (p < 0.05).

CONCLUSION
When comparing pREBOA to ER-REBOA, there has been a rise in Zone 1 and partial occlusion. In our pilot analysis of the Aortic Occlusion for Resuscitation in Trauma and Acute Care Surgery registry, there was a reduction in administration of PRBCs, FFP, platelets, and crystalloids. Although further prospective studies are required, this is the first to demonstrate an association between pREBOA, partial occlusion, and reduced blood use and resuscitative requirements.

LEVEL OF EVIDENCE
Therapeutic/Care Management; Level IV.
Analysis of ECMO Outcomes in Patients with Known Adrenal Insufficiency: Insights from the National Inpatient Sample Database
Authors: Randhawa Aastha , Jana Kundan , Sattar Moin 
Published: May 2024

AbstractAdrenal crises occur due to either a complete lack or an insufficient amount of cortisol and are usually triggered by stressors like infections, trauma, surgical interventions, and dental procedures. The physiological changes associated with major surgery are well-studied stressors linked to adrenal crisis. Extracorporeal membrane oxygenation (ECMO), a strategy employed to assist with circulatory support and gas exchange, is also a significant physiologically demanding stressor to the human body. In this study, we retrospectively assess the incidence and outcomes of patients with adrenal insufficiency who were cannulated for extracorporeal membrane oxygenation (ECMO) using the National Inpatient Sample (NIS) database. Patients who were cannulated for ECMO from 2016 to 2020 were identified and divided into two cohorts depending on the presence or absence of adrenal insufficiency. The two groups were compared for the primary outcome of inpatient mortality and secondary outcomes including rates of LVAD, heart transplant, lung transplantation, stroke, GI bleed, and renal failure.In our study, we found that mortality rates between the two groups were similar. All-cause inpatient mortality was 45% in both groups (p>0.9). We found no differences in the rates of heart transplantation, lung transplantation, or LVAD implantation between patients with and without adrenal insufficiency. We additionally find that mortality rates in our study mirror those from dedicated ECMO registries, further lending credence to our findings. Our study discusses important findings from a relatively understudied disease process, based on a large and representative population from multiple centers across the country.
Multiomics reveals gut dysbiosis links to fatty acid dysmetabolism in early phase of acute myocardial infarction
Authors: Ying Jiajun , Fan Yong , Huangfu Ning , He Kewan , Hu Teng , Su Pengpeng , Hu Xintao , He Hequn , Liang Wei , Liu Junsong , Cheng Jinsong , Wang Shiqi , Zhao Ruochi , Mao Hengyi , He Fuwei , Su Jia , Zhou Honglin , Li Zhenwei , Fei Xiaohong , Sun Xiafei , Wang Peipei , Guan Minfang , Du Weiping , Lin Shaoyi , Wang Yong , Yang Fangkun , Fang Renyuan , Kong Ziqing , Chen Xiaomin , Cui Hanbin ,   Jiajun Ying and Yong Fan contributed equally to this work
Published: May 2024

AbstractBackgroundAcute myocardial infarction (AMI) remains a major cause of death, with limited understanding of its early risk stratification. While gut microbiome disturbances has been associated with late-stage AMI, the connection to early-stage AMI (eAMI) is less explored.MethodsUsing metabolomics and metagenomics, we analyzed 56 samples, comprising 30 eAMI patients (within 12 hours of onset) and 26 age- and gender-matched healthy controls, to discern the influence of gut microbes and their metabolites.ResultsWe found the eAMI plasma is dominated by increased long-chain fatty acids (LCFAs), 14 of which provide differentiating power of eAMI patients from HCs. Multiomics analysis reveals up to 70% of the variance in LCFAs of eAMI patients can be explained by altered gut microbiome. Higher-resolution profiling of gut bacterial species demonstrated that bacterial structural variations are mechanistically linked to LCFAs dysregulation. Byin silicomolecular docking andin vitrothrombogenic assay in isolated human platelets, we highlighted that eAMI-associated LCFAs contribute to platelet aggregation, a driving factor for AMI initiation.ConclusionsLCFAs hold significant potential as early biomarkers of AMI and gut microbiome contributes to altered LCFAs in eAMI. Further studies are imperative to expand upon these observations to better leverage LCFAs as a potential biomarker for eAMI and as a therapeutic target for inhibition of platelet aggregation in eAMI.
Characterizing interactions of ER resident proteins in situ through the YST-PPI method
Authors: Fan Xian , He Huahua , Wang Ting , Xu Pan , Zhang Faying , Hu Shantong , Yun Yueli , Mei Meng , Zhang Guimin , Yi Li 
Published: May 2024

ABSTRACTThe mutual interactions of ER resident proteins in the ER maintain its functions, prompting the protein folding, modification, and transportation. Here, a new method, named YST-PPI (YESS-based Split fast TEV protease System for Protein-protein Interaction) was developed, targeting the characterization of protein interactions in ER. YST-PPI method integrated the YESS system, split-TEV technology and endoplasmic reticulum retention signal peptide (ERS) to provide an effective strategy for studying ER in situ PPIs in a fast and quantitative manner. The interactions among 15 ER resident proteins ofS. cerevisiaewere explored using the YST-PPI system, and their interaction network map was constructed, in which more than 74 interacting resident protein pairs were identified. Our studies also showed that Lhs1p plays a critical role in regulating the interactions of most of the ER resident proteins, expect the Sil1p, indicating its potential role in controlling the ER molecular chaperones. Moreover, the mutual interaction revealed by our studies further confirmed that the ER resident proteins perform their functions in a synergetic way and multimer complex might be formed during the process.
Hemoglobin as a peroxidase and drug target for oxidative stress-related diseases
Authors: Won Woojin , Lee Elijah Hwejin , Gotina Lizaveta , Chun Heejung , Lee Jae-Hun , Park Uiyeol , Kim Daeun , Kim Tai Young , Choi Jiwon , Kim Yoowon , Park Sun Jun , Bhalla Mridula , Lim Jiwoon , Park Jong-Hyun , Oh Soo-Jin , Ryu Hoon , Pae Ae Nim , Park Ki Duk , Lee C. Justin 
Published: May 2024

Summary paragraphHemoglobin (Hb) is well-known for transporting oxygen in red blood cells within blood vessels1. Although Hb is also present in the brain2, its role remains poorly understood. Here, we show that Hb, found in astrocytes of neurodegenerative animal models and patients, displays significant antioxidant effects through its H2O2-decomposing peroxidase activity, and a small molecule enhancer boosts this activity, reducing aberrant H2O2and mitigating H2O2-induced neurodegeneration. To counteract the harmful effects of aberrant H2O2-production in Alzheimer’s disease (AD), we developed KDS12025, a blood-brain barrier (BBB)-permeable small molecule that effectively enhances the peroxidase activity of Hb by a hundredfold, especially at a low level of Hb. KDS12025 and its analogs achieve this enhancement through its electron-donating amine group. KDS12025 reduces H2O2levels in astrocytes, exhibits neuroprotective effects, and reverses memory impairment in AD models. Gene-silencing of Hbβ abrogates KDS12025’s impact in both culture and animal models of AD. Moreover, KDS12025 prevented the death of dopaminergic neurons in a Parkinson’s disease (PD) model without altering the oxygen-transporting function of Hb. KDS12025 extended survival and improved motor function even in the severe amyotrophic lateral sclerosis (ALS) mouse model. Our findings propose Hb as a new therapeutic target for neurodegenerative diseases, with KDS12025 emerging as a first-in-class drug candidate that enhances Hb’s peroxidase activity to reduce H2O2. Boosting Hb’s peroxidase activity with KDS12025 mitigates oxidative stress and alleviates neurodegeneration in AD, PD, and ALS with broad applicability for numerous oxidative-stress-driven diseases.
Leukemia inhibitory factor (LIF) receptor amplifies pathogenic activation of fibroblasts in lung fibrosis
Authors: Nguyen Hung N. , Jeong Yunju , Kim Yunhye , Kim Yaunghyun H. , Athar Humra , Castaldi Peter J. , Hersh Craig P. , Padera Robert F. , Sholl Lynette M. , Vivero Marina , Sharma Nirmal S. , Yun Jeong , Merriam Louis T. , Yuan Ke , Kim Edy Y. , Brenner Michael B. 
Published: May 2024

AbstractFibrosis drives end-organ damage in many diseases. However, clinical trials targeting individual upstream activators of fibroblasts, such as TGFβ, have largely failed. Here, we target the leukemia inhibitory factor receptor (LIFR) as a “master amplifier” of multiple upstream activators of lung fibroblasts. In idiopathic pulmonary fibrosis (IPF), the most common fibrotic lung disease, we found that lung myofibroblasts had high LIF expression. Further, TGFβ1, one of the key drivers of fibrosis, upregulated LIF expression in IPF fibroblasts. In vitro anti-LIFR antibody blocking on human IPF lung fibroblasts reduced induction of profibrotic genes downstream of TGFβ1, IL-4 and IL-13. Further, siRNA silencing of LIFR in IPF precision cut lung slices reduced expression of fibrotic proteins. Together, we find that LIFR drives an autocrine positive feedback loop that amplifies and sustains pathogenic activation of IPF fibroblasts downstream of multiple external stimuli, implicating LIFR as a therapeutic target in fibrosis.Significance StatementFibroblasts have a central role in the pathogenesis of fibrotic diseases. However, due to in part to multiple profibrotic stimuli, targeting a single activator of fibroblasts, like TGFβ, has not yielded successful clinical treatments. We hypothesized that a more effective therapeutic strategy is identifying a downstream “master amplifier” of a range of upstream profibrotic stimuli. This study identifies the leukemia inhibitory factor receptor (LIFR) on fibrotic lung fibroblasts amplifies multiple profibrotic stimuli, such as IL-13 and TGFβ. Blocking LIFR reduced fibrosis in ex vivo lung tissue from patients with idiopathic pulmonary fibrosis (IPF). LIFR, acting as a master amplifier downstream of fibroblast activation, offers an alternative therapeutic strategy for fibrotic diseases.
Inferring Single-Cell RNA Kinetics from Various Biological Priors
Authors: Chen Yanshuo , Hu Zhengmian , Ni Ke , Feng Site , Chen Wei , Huang Heng 
Published: May 2024

AbstractIn the context of transcriptional dynamics modeled by ordinary differential equations (ODEs), the RNA level in a single cell is controlled by specific RNA kinetics parameters, which include transcription rate, splicing rate, and degradation rate. Investigating these single-cell RNA kinetics rates is pivotal for understanding RNA metabolism and the heterogeneity of complex tissues. Although metabolic labeling is an effective method to estimate these kinetics rates experimentally, it is not suitable for current large-scale conventional single-cell RNA sequencing (scRNA-seq) data. Moreover, existing methods for scRNA-seq often either neglect certain specific kinetics parameters or use inappropriate ways to fit the parameters. To address these issues, we introduce scRNAkinetics, a parallelized method that fits the kinetics parameters of the ODE for each cell using pseudo-time derived from various biological priors (e.g. cell lineage tree and differentiation potential). This approach allows for the estimation of the relative kinetics of each cell and gene in a scRNA-seq dataset. Validated on simulated datasets, scRNAkinetics can accurately infer the kinetics rates of transcription boosting, multi-branch, and time-dependent RNA degradation systems. Nevertheless, the inferred kinetics trends are concordant with previous studies on metabolic labeling and conventional scRNA-seq datasets. Furthermore, we show that scRNAkinetics can provide valuable insights into different regulatory schemes and validate the coupling between transcription and splicing in RNA metabolism. The open-source implementation of scRNAkinetics is available athttps://github.com/poseidonchan/scRNAkinetics.
Morphological, physiological and metabolic responses of diverse barley inbreds to dry down and moderate drought stress
Authors: Shrestha Asis , König Tobias , Meikle Lena Adler , Westhoff Philipp , Erban Alexander , Stich Benjamin 
Published: May 2024

AbstractDrought stress alters the metabolic activity, physiological processes, and plant growth and such responses might differ with the intensity of stress. We evaluated the genotypic diversity on plant morphology, photosynthetic responses, metabolite shift and their relationship in diverse barley inbreds under dry down (DD) and moderate drought (MD) stress using 23 genetically diverse parental inbreds of genetic mapping population of barley. MD stress caused a strong growth reduction, while DD stress triggered inhibition of photosynthetic health. We observed that the induced changes occurred in a genotype-dependent manner. Compared to control conditions, the metabolism of simple sugars and polyhydroxy acids increased in MD and DD, while the maximum accumulation of amino acid, lipids and phosphates occurred in DD stress. Accumulation of hexose and metabolites with unknown classification was the metabolic signature of drought tolerant inbreds. The inbreds tolerant to MD originated from the temperate regions while those tolerant to both MD and DD came from semi-arid regions. Low stomata density, reduced water loss and retarded growth under drought stress were the key features of inbreds with better survival capacity under severe dehydration. We identified drought tolerant barley inbreds and our study offers resources for future genetic research on various drought tolerance strategies.
Sex differences in olfactory behavior and neurophysiology in Long Evans Rats
Authors: Maheshwar Kruthika V , Stuart Abigail E. , Kay Leslie M. 
Published: May 2024

AbstractIn many species, olfactory abilities in females are more sensitive than those in males. Studies in humans show that women have lower olfactory thresholds and are better able to discriminate and identify odors than men. In mice, odorants elicit faster activation from a larger number of olfactory sensory neurons in females than males. Our study explores sex differences in olfaction in Long Evans rats from a behavioral and electrophysiological perspective. Local field potentials (LFPs) in the olfactory bulb (OB) represent the coordinated activity of bulbar neurons. Olfactory gamma (65-120 Hz) and beta (15-30 Hz) oscillations have been functionally linked to odor perception. Spontaneous and odor-evoked OB LFPs were recorded from awake rats at the same time for 12 days. Odors used included urine of both sexes and monomolecular odorants characterized previously for correlation of volatility with behavior and OB oscillations. Sampling duration, baseline gamma and beta power, and odor-elicited beta and gamma power were analyzed. We find that females sample odorants for a shorter duration than males (close to 1s difference). While baseline gamma and beta power do not show significant differences between the two sexes, odor-elicited gamma and beta power in females is significantly lower than in males. Neither sampling duration nor beta and gamma power in females varied systematically with day of estrus. We further verify that variance of these behavioral and physiological measures is not different across sexes, adding to growing evidence that researchers need not be concerned about often- claimed additional variance in female subjects.New and NoteworthyOlfaction plays a large role in evolutionary processes. However, we know little about sex differences in olfactory bulb neurophysiology, and many scientists believe that females are more variable due to estrus. We show that female rats sniff odors for shorter durations than males and have lower power in neural oscillations related to cognition. Estrus was not related to variance in any measures. Finally, males and females show equal variance on these behavioral and physiological processes.
Clearing truncated tau protein restores neuronal function and prevents microglia activation in tauopathy mice
Authors: Martín-Ávila Alejandro , Modak Swananda R. , Rajamohamedsait Hameetha B. , Dodge Andie , Shamir Dov B. , Krishnaswamy Senthilkumar , Sandusky-Beltran Leslie A. , Walker Marilyn , Lin Yan , Congdon Erin E. , Sigurdsson Einar M. 
Published: May 2024

AbstractTau protein truncated at aspartate 421 (Asp421) is a characteristic feature of Alzheimer’s disease (AD) and other tauopathies. It is likely to have a role in their pathogenesis by promoting tau aggregation. Here, using two tauopathy mouse models, we show that a monoclonal antibody against Asp421, 5G2, led to a) a 59-74% clearance of insoluble tau protein in the brains of JNPL3 tauopathy mice following a thirteen-week treatment period, b) a 46% decrease of tau levels in brain interstitial fluid immediately following a single dose of 5G2 as examined by brain microdialysis in awake JNPL3 mice, c) improved neuronal function and d) reduced microglial activation as determined by two-photon imaging in awake PS19 tauopathy mice, where we also found tau accumulation earlier than signs of microglial activation. For mechanistic insight using culture models, 5G2 prevented toxicity of AD brain-derived pathological tau protein, cleared intracellular tau, and prevented microgliosis. We also knocked down the intracellular Fc receptor and ubiquitin E3 ligase, TRIM21, and found a reduction in cellular retention of tau antibodies, which appeared to reduce the acute efficacy (24 h) of tau antibodies but not their longer-term efficacy (5 days). Overall, these findings strongly support the feasibility of targeting Asp421 truncated tau protein to treat tauopathies, indicate that tau-associated abnormalities of neuronal activity precede microglial activation and that antibody-mediated tau clearance via the TRIM21 pathway is mostly transient.
Assessing different next-generation sequencing technologies for wastewater-based epidemiology
Authors: John Anika , Dreifuss David , Kang Seju , Bratus-Neuenschwander Anna , Zajac Natalia , Topolsky Ivan , Dondi Arthur , Aquino Catharine , Julian Timothy R. , Beerenwinkel Niko 
Published: May 2024

AbstractWastewater-based epidemiology has proven to be an important public health asset during the COVID-19 pandemic. It can provide less biassed and more cost-effective population-level monitoring of the disease burden as compared to clinical testing. An essential component of SARS-CoV-2 wastewater monitoring is next-generation sequencing, providing genomic data to identify and quantify circulating viral strains rapidly. However, the specific choice of sequencing method influences the quality and timeliness of generated data and hence its usefulness for wastewater-based pathogen surveillance. Here, we systematically benchmarked Illumina Novaseq 6000, Element Aviti, ONT R9.4.1 MinION flow cell, and ONT R9.4.1 Flongle flow cell sequencing data to facilitate the selection of sequencing technology. Using a time series of wastewater samples from influent of six wastewater treatment plants throughout Switzerland, along with spike-in experiments, we show that higher sequencing error rates of ONT Nanopore sequencing reduce the accuracy of estimates of the relative abundance of viral variants, but the overall trend is in good concordance among all technologies. We find that the sequencing runtime for ONT Nanopore flow cells can be reduced to as little as five hours without significant impact on the quality of variant estimates. Our findings suggest that SARS-CoV-2 variant tracking is readily achievable with all tested technologies, albeit with different tradeoffs in terms of cost, timeliness and accuracy.
Impact of heat on respiratory hospitalizations among older adults living in 120 large US urban areas
Authors: O’Lenick Cassandra R. , Cleland Stephanie E. , Neas Lucas M. , Turner Mallory W. , Mcinroe E. Melissa , Hill K. Lloyd , Ghio Andrew J. , Rebuli Meghan E. , Jaspers Ilona , Rappold Ana G. 
Published: May 2024

ABSTRACTObjectivesA nationwide study of the impact of high temperature on respiratory disease hospitalizations among older adults (65+) living in large urban centers.MethodsDaily rates of short-stay, inpatient respiratory hospitalizations were examined with respect to variations in ZIP-code-level daily mean temperature in the 120 largest US cities between 2000-2017. For each city, we estimated cumulative associations (lag-days 0-6) between warm-season temperatures (June-September) and cause-specific respiratory hospitalizations using time-stratified conditional quasi-Poisson regression with distributed lag non-linear models. We estimated nationwide associations using meta-regression and updated city-specific associations via best linear unbiased prediction. With stratified models, we explored effect modification by age, sex, and race (Black/white). Results were reported as percent change in hospitalizations at high temperatures (95th percentile) compared to median temperatures for each outcome, demographic-group, and metropolitan area. Excess hospitalization rates were estimated for days above median temperatures.ResultsAt high temperatures, we observed increases in the percent of all-cause respiratory hospitalizations [1.2 (0.4, 2.0)], primarily driven by an increase in respiratory tract infections [1.8 (0.6, 3.0)], and chronic respiratory diseases/respiratory failure [1.2 (0.0, 2.4)]. East North Central, New England, Mid-Atlantic, and Pacific cities accounted for 98.5% of the excess burden. By demographic group, we observed disproportionate burdens of heat-related respiratory hospitalizations among the oldest beneficiaries (85+ years), and among Black beneficiaries living in South Atlantic cities.ConclusionThis study found robust impacts of high temperature on respiratory failure and chronic inflammatory and fibrotic diseases among older adults. The geographic variation suggests that contextual factors account for disproportionate burdens.