bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti-CD49d Antibody Treatment Improves Survival and Attenuates Neurocognitive Deficits after Traumatic Brain Injury in Aged Mice
Authors: Chen Zhangying , Ford Kacie , Islam Mecca , Iamsawat Supinya , Davis Booker , Weiss Craig , Schwulst Steven 
Published: November 2023

Abstract
Patients aged 65 and older account for an increasing proportion of traumatic brain injury (TBI) patients. Aged TBI patients suffer increased morbidity and mortality compared to young TBI patients. We previously demonstrated a marked accumulation of CD8 + T-cells within the brains of aged TBI mice compared to young TBI mice. Therefore, we hypothesized that blocking peripheral T-cell infiltration into the injured brain would improve neurocognitive outcomes in aged mice after TBI. Young and aged male C57BL/6 mice underwent TBI via controlled cortical impact vs. sham injury. Two hours-post injuries, mice received an anti-CD49d antibody (aCD49d Ab) to block peripheral lymphocyte infiltration or its isotype control. Dosing was repeated every two weeks. Mortality was tracked. Neurocognitive testing for anxiety, associative learning, and memory was assessed. Motor function was evaluated. Plasma was collected for cytokine analysis. Flow cytometry was employed to phenotype different immune cells within the brains. Consequently, aCD49d Ab treatment significantly improved post-TBI survival, anxiety level, associative learning, memory, and motor function in aged mice two months post-TBI compared to isotype control treated mice. aCD49d Ab treatment augmented Th2 response in the plasma of aged mice two months post-TBI compared to isotype control-treated mice. Notably, aCD49d Ab treatment significantly reduced activated CD8+ cytotoxic T-cells within aged mouse brains after TBI. Contrastingly, no difference was detected in young mice after aCD49d Ab treatment. Collectively, aCD49 Ab treatment reduced T-cells in the injured brain, improved survival, and attenuated neurocognitive and gait deficits. Hence, aCD49d Ab may be a promising therapeutic intervention in aged TBI subjects—a population often excluded in TBI clinical trials.
CIRC_0003907 MODULATES SEPSIS-INDUCED MYOCARDIAL INJURY VIA ENHANCING MYD88/NLRP3/NF-ΚB AXIS BY SPONGING MIR-944
Authors: Lv Wei , Liu Hui , Wang Xin , Hao Rui 
Published: November 2023

ABSTRACT

Background: Sepsis-induced cardiomyopathy (SIC) is a common complication of sepsis with high morbidity and mortality but lacks specific therapy. The purpose of this study was to investigate the role of circularRNA_0003907 (circ_0003907) in myocardium injury induced by sepsis. Methods: In this experiment, human AC16 cells were treated with lipopolysaccharide (LPS) to induce an in vitro cardiomyocyte injury model. Expression of circ_0003907, microRNA-944 (miR-944), and MYD88 was detected using quantitative real-time polymerase chain reaction. Cell proliferation and apoptosis were assessed using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide, thymidine analog 5-ethynyl-2′-deoxyuridine, and flow cytometry assays. Secretions of proinflammatory cytokines IL-6 and TNF-α were detected using ELISA kits. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) level were detected using special kits. Protein levels of cyclin D1, cleaved caspase-3, MYD88, NLRP3, P65, and IκBα were determined using western blot assay. After being predicted using Circineractome and starBase, the interaction between miR-944 and circ_0003907 or MYD88 was confirmed using dual-luciferase reporter and RNA immunoprecipitation assays. Results: Circ_0003907 expression was increased in serum from SIC patients and in LPS-treated AC16 cells. Circ_0003907 knockdown might abolish LPS-triggered proliferation inhibition, and the promotion of apoptosis, inflammatory response, and oxidative stress in AC16 cells. In mechanism, circ_0003907 acted as a sponge for miR-944 to increase MYD88 expression. Meanwhile, the absence of circ_0003907 induced miR-944 expression and suppressed MYD88/NLRP3/NF-κB levels. Conclusion: Circ_0003907 sponged miR-944 to aggravate LPS-induced AC16 cell dysfunction via activating the MYD88/NLRP3/NF-κB axis during sepsis, which might provide a new direction for the treatment of SIC.
DIFFERENCES IN MANAGEMENT AND PROGNOSTICATION OF CARDIOGENIC SHOCK PATIENTS IN THE PRESENCE AND ABSENCE OF OUT-OF-HOSPITAL CARDIAC ARREST
Authors: Mieritz Hanne Beck , Povlsen Amalie Ling , Linde Louise , Beske Rasmus Paulin , Helgestad Ole Kristian Lerche , Josiassen Jakob , Hassager Christian , Schmidt Henrik , Jensen Lisette Okkels , Holmvang Lene , Møller Jacob Eifer , Ravn Hanne Berg 
Published: November 2023

ABSTRACT

Background: The clinical spectrum of acute myocardial infarction complicated by cardiogenic shock (AMICS) varies. Out-of-hospital cardiac arrest (OHCA) can be the first sign of cardiac failure, whereas others present with various degrees of hemodynamic instability (non-OHCA). The aim of the present study was to explore differences in prehospital management and characteristics of survivors and nonsurvivors in AMICS patients with OHCA or non-OHCA. Methods: Data analysis was based on patient data from the RETROSHOCK cohort comprising consecutive AMICS patients admitted to two tertiary cardiac centers between 2010 and 2017. Results: 1,716 AMICS patients were included and 42% presented with OHCA. Mortality in OHCA patients was 47% versus 57% in the non-OHCA group. Almost all OHCA patients were intubated before admission (96%). In the non-OHCA group, prehospital intubation (25%) was associated with a better survival (P < 0.001). Lactate level on admission demonstrated a linear relationship with mortality in OHCA patients. In non-OHCA, probability of death was higher for any given lactate level <12 mmol/L compared with OHCA. However, a lactate level >7 mmol/L in non-OHCA did not increase mortality odds any further. Conclusion: Mortality was almost doubled for any admission lactate level up to 7 mmol/L in non-OHCA patients. Above this level, mortality remained unchanged in non-OHCA patients but continued to increase in OHCA patients. Prehospital intubation was performed in almost all OHCA patients but only in one of four patients without OHCA. Early intubation in non-OHCA patients was associated with a better outcome.
Impact of high-dose vasopressor during endotoxic shock on the cerebral, lingual, hepatic, and renal microcirculation evaluated by near-infrared spectroscopy in swine
Authors: Kurita Tadayoshi , Kawashima Shingo , Khaleelullah Mohamed Mathar Sahib Ibrahim , Nakajima Yoshiki 
Published: November 2023

Abstract

Background
High-dose vasopressors maintain blood pressure during septic shock but may adversely reduce microcirculation in vital organs. We assessed the effect of high-dose norepinephrine and vasopressin on the microcirculation of the brain, tongue, liver, and kidney during endotoxic shock using near-infrared spectroscopy (NIRS).

Methods
Thirteen pigs (24.5 ± 1.8 kg) were anesthetized, and an NIRS probe was attached directly to each organ. Approximately 0.2, 0.5, 1, and 2 μg/kg/min of norepinephrine were administered in a stepwise manner, followed by 0.5, 1, 2, and 5 μg/kg/min of sodium nitroprusside in normal condition. Moreover, 1 μg/kg/h of lipopolysaccharide was administered continuously after 100 μg bolus to create endotoxic shock, and after 1000 mL of crystalloid infusion, high-dose norepinephrine (2, 5, 10, and 20 μg/kg/min) and vasopressin (0.6, 1.5, 3, and 6 U/min) were administered in a stepwise manner. The relationship between the mean arterial pressure (MAP) and each tissue oxygenation index (TOI) during vasopressor infusion was evaluated.

Results
Three pigs died after receiving lipopolysaccharides, and 10 were analyzed. An increase of >20% from the baseline MAP induced by high-dose norepinephrine during endotoxic shock reduced the TOI in all organs except the liver. The elevation of MAP to baseline with vasopressin alone increased the kidney and liver TOIs and decreased the tongue TOI.

Conclusions
Forced blood pressure elevation with high-dose norepinephrine during endotoxic shock decreased the microcirculation of vital organs, especially the kidney. Cerebral TOI may be useful for identifying the upper limit of blood pressure, at which norepinephrine impairs microcirculation.
Pilot study of frozen platelet extracellular vesicles as a therapeutic agent in hemorrhagic shock in rats
Authors: Durbin Samantha , Loss Lindsey , Buzzard Lydia , Minoza Karen , Beiling Marissa , Karsonovich Carmen , Liu Moqing , Garay Joseph , Fields Alexander , Mathews Michael , Kuhn Benjamin , Moskowitz Keith , Miyazawa Byron , Trivedi Alpa , Kornblith Lucy , Fitzpatrick Michael , Pati Shibani , Schreiber Martin 
Published: November 2023

BACKGROUND
Hemorrhage accounts for the most preventable deaths after trauma. Resuscitation is guided by studies that demonstrate improved outcomes in patients receiving whole blood or balanced administration of blood products. Platelets present a logistical challenge due to short shelf life and need for refrigeration. Platelet-derived extracellular vesicles (PEVs) are a possible platelet alternative. Platelet-derived extracellular vesicles are secreted from platelets, have hemostatic effects and mitigate inflammation and vascular injury, similar to platelets. This pilot study aimed to elucidate the therapeutic effects of PEVs in a rat model of uncontrolled hemorrhage.

METHODS
Male rats were anesthetized and femoral vessels cannulated. Vital signs (MAP, HR, and RR) were monitored. Electrolytes, lactate and ABG were obtained at baseline, 1-hour and 3-hours post injury. Laparotomy was performed, 50% of the middle hepatic lobe excised and the abdomen packed with gauze. Rats received 2 mL PEVs or lactated Ringers (LR) over 6 minutes immediately after injury. Peritoneal blood loss was quantified using preweighed gauze at 5 minutes, 15 minutes, 30 minutes, 45 minutes, and 60 minutes. Laparotomy was closed 1-hour postinjury. Animals were monitored for 3 hours postinjury then euthanized. Generalized Linear Mixed Effects models were performed to assess effects of treatment and time on lactate and MAP.

RESULTS
Twenty-one rats were included (11 LR, 10 PEV). Overall blood loss was between 6 mL and 10 mL and not significantly different between groups. There was a 36% mortality rate in the LR group and 0% mortality in the PEV group (p = 0.03). The LR group had significantly higher lactates at 1 hour (p = 0.025). At 15 minutes, 45 minutes, 60 minutes, and 180 minutes, the MAP of the PEV group was significantly higher than the LR group.

CONCLUSION
Early studies are encouraging regarding the potential use of PEVs in uncontrolled hemorrhagic shock based on improved survival and hemodynamics.
Effects of Buprenorphine, Methadone and Substance-Use on COVID-19 Morbidity and Mortality
Authors: Christian Nicholaus , Zhou Xin , Radhakrishnan Rajiv 
Published: November 2023

ABSTRACTObjectivesSubstance use disorder has been associated with increased morbidity in COVID-19 infection. However, less is known about the impact of active substance use and medications for opioid use disorder (MOUD) on COVID-19 outcomes. We conducted a retrospective cohort study to evaluate the impact of substance use, namely cannabis, cocaine, alcohol, sedative and opioid use as well as buprenorphine or methadone = on COVID-19 morbidity and mortality.MethodsUsing electronic-health record data at a large urban hospital system, patients who tested positive for COVID-19 between January 1, 2020 to December 31, 2021 were included. Substance use was identified from urine toxicology and MOUD prescriptions within 90 days prior to admission. COVID-19 outcomes included mortality, ICU admission, need for ventilatory support, number and duration of hospitalizations. Multivariable logistic regression was performed controlling for variables such as age, sex, medical comorbidity, tobacco use, and social disadvantage.ResultsAmong COVID-19 positive patients (n=17,423), sedative, cannabis, cocaine, and opioid use was associated with statistically significant increases in need for ICU care, need for ventilatory support, number of hospitalizations and duration of hospitalization. Substance use was not associated with an increase in all-cause mortality. There were no statistically significant differences between methadone, buprenorphine and other opioids on COVID-19 outcomes.ConclusionsActive substance use were associated with increased morbidity in COVID-19 infection. MOUD was not associated with worse COVID-19 outcomes compared to OUD. Future studies focused on MOUD treatments that reduce morbidity may help improve clinical outcomes in COVID-19.
Genomic selection for herbage yield in forage oats (Avena sp.)
Authors: Rocha Dediel A. , Cordova Ulisses A. , Flaresso Jefferson , Stradiotto Joseli 
Published: November 2023

AbstractThe study investigated the potential of genomic selection (GS) to accelerate genetic improvement in forage oats (Avena sp.) by predicting herbage yield. The results showed that GS can be an effective tool for predicting herbage yield in forage oats, with prediction accuracies ranging from 0.91 to 0.97. The use of SNP markers for GS in forage oats has several advantages over traditional marker-assisted selection (MAS), including the ability to capture more of the genetic variation for the trait of interest. The accuracy of GS predictions can be further improved by using trait-specific relationship matrices (TGRMs) and genomic information from multiple generations.Key FindingsGS can be an effective tool for predicting herbage yield in forage oats, with prediction accuracies ranging from 0.91 to 0.97.The use of SNP markers for GS in forage oats has several advantages over traditional MAS, including the ability to capture more of the genetic variation for the trait of interest.The accuracy of GS predictions can be further improved by using TGRMs and genomic information from multiple generations.ImplicationsGS can be used to accelerate the development of new forage oat varieties with improved herbage yield.GS has the potential to significantly improve the agronomic performance and quality of forage oat varieties.Future ResearchDevelop a more structured training population to improve the accuracy of GS predictions.Identify trait-specific relationship matrices (TGRMs) to further improve the accuracy of GS predictions.Investigate the use of genomic information from multiple generations to improve the accuracy of GS predictions.
Origin of evolutionary bifurcation in an enzyme
Authors: Miton Charlotte M. , Campbell Eleanor C. , Kaczmarski Joe A. , Feixas Ferran , Romero-Rivera Adrian , Sandhu Mahakaran , Anderson Dave W. , Shatani Naoya , Osuna Sílvia , Jackson Colin J. , Tokuriki Nobuhiko 
Published: November 2023

SummaryEvolution can lead to significantly distinct outcomes depending on the mutational path taken. Evolutionary bifurcation, in which two mutational trajectories segregate, becoming non-interchangeable over time, is the basis of diversification in all kingdoms of life. Here, we present a detailed molecular description of a bifurcation event that rapidly led to the emergence of two distinct enzymes from a common ancestor. When initiated from two starting points that differed by a single amino acid, the laboratory evolution of a phosphotriesterase (PTE) toward arylester hydrolysis resulted in different genetic and phenotypic outcomes. One trajectory led to a >35,000-fold increase in activityviathe reorganization of its active site to achieve exquisite enzyme-substrate complementarity. The second trajectory gave rise to an evolved variant with a ∼500-fold increase in activity, but exhibiting an alternative substrate binding mode resulting from the destabilization of an active site loop. While initial mutations tend to dictate mutational accessibility, we rather observed the gradual divergence and specialisation of each trajectory, following the emergence of distinct molecular interaction networks. Intramolecular epistasis underlay pathway bifurcation by promoting unique synergistic interactions within each trajectory, while restricting the fixation of mutation across pathways. Our results illustrate how distinct molecular outcomes can radiate from a common protein ancestor and give rise to phenotypic diversity.
Machine learning analysis of lung adenocarcinoma and squamous cell carcinoma microbiome datasets reveals biomarkers for early diagnosis
Authors: Kashyap Pragya , Raj Kalbhavi Vadhi , Dutt Naveen , Yadav Pankaj 
Published: November 2023

AbstractIntroductionLung cancer (LC) is the second most frequent cancer worldwide with high incidences and mortality rates and non-small-cell-lung cancer (NSCLC) accounts for 80-85% cases of LC. It is further majorly sub-classified into adenocarcinoma (AC), and squamous-cell carcinoma (SCC). A late diagnosis at an advanced stage, a high rate of metastasis, and the development of therapy resistance are responsible for approximately 95% of mortality. Owing to high heterogeneity and variances in subtypes, it is important to precisely classify them for treatment. However, it poses a challenge in clinical practices, as it requires accurate quantification of each proportion subtype which is time-consuming and sometimes erroneous. The lower airways are home to a dynamic bacterial population sustained by the immigration, elimination, and migration of microbes from the gastrointestinal tract and upper airway tracts. The disruption in the homeostasis of microbiome compositions was found to be correlated with the increased risk of LC. Artificial intelligence (AI) techniques are used extensively in the early screening, and treatment of NSCLC have made significant strides in recent years. Recently, the use of CT/MRI scan image data in prediction models also results in false-positive rates and requires subsequent tests for further exploration which delays the prognostication. Therefore, early diagnosis, prevention, and treatment are critical to enhance survival and reduce death. Here, we aim for the classification of AC and SCC using the lung microbiome of lung tissue samples, implementing AI-based algorithms.MethodsWe have obtained raw sequencing data from the NCBI online database, and 149 AC samples and 145 SCC samples in patients were analyzed for their lung microbiome present in the lung tissue samples. The metadata such as patient age, sex, smoking history, and environmental material (malignant or not) were also analyzed. Using these data, machine learning algorithms were applied to select the best microbiome features for the classification of subtypes.ResultsA supervised ML and DL based model was developed that can discriminate NSCLC subtypes based on their microbial information, exploring the microbiome as predictive information for early screening. Consequently, 17 features were identified as a biomarker, and they showed good performance in distinguishing AC from SCC with an accuracy of 81% in KNN and 71% in DNN when demonstrated on the validation dataset.ConclusionThis study proposed a supervised machine learning framework where we can rely on taxonomic features and AI techniques to classify overlapped AC and SCC metagenomic data providing lung microbiome as a predictive and diagnostic biomarker in LC. Moreover, our framework will also be very helpful to other researchers to obtain further biomarkers and perform analysis in overlapped subtypes in different diseases.
Tracking the misallocation and reallocation of spatial attention towards auditory stimuli
Authors: Mandal Ananya , Liesefeld Anna M. , Liesefeld Heinrich R. 
Published: November 2023

AbstractCompletely ignoring a salient distractor presented concurrently with a target is difficult and sometimes attention is involuntarily attracted to the distractor’s location (attentional capture). Employing the N2ac component as a marker of attention allocation towards sounds, in this study we investigate the spatio-temporal dynamics of auditory attention across two experiments. Human participants (male and female) performed an auditory search task, where the target was accompanied by a distractor in 2/3rd of the trials. For a distractor more salient than target (Exp. 1), we observe not only a distractor N2ac (indicating attentional capture), but the full chain of attentional dynamics implied by the notion of attentional capture, namely: (a) the distractor captures attention before the target is attended, (b) allocation of attention to the target is delayed by distractor presence, and (c) the target is attended after the distractor. Conversely, for a distractor less salient than the target (Exp. 2), although behavioral interference was present, no attentional capture was observed. Together, these findings reveal two types of spatial-attentional dynamics in the auditory modality (distraction with and without attentional capture).Significance StatementOftentimes, we find it hard to ignore the location of a salient sound that distracts us from our current tasks. Although, a common everyday experience, little is known about how spatial distraction unfolds at the neural level in the auditory modality. Using electrophysiological markers of attention allocations, we report comprehensive evidence of spatial attentional capture by a salient auditory distractor, indicating that attention is first misallocated to the distractor and only afterwards reallocated towards the target. Similar patterns were observed earlier only in vision and their discovery in the auditory modality indicates towards the existence of domain-general spatial attentional dynamics consistent across sensory modalities. Finally, we demonstrate that only a distractor more salient than the target reliably captures attention.
Increased offspring size and reduced gestation length in an ectothermic vertebrate under a worst-case climate change scenario
Authors: Hubert David L , Bentz Ehren J , Mason Robert T 
Published: November 2023

ABSTRACTAs global temperatures continue to increase, understanding the impacts of warming environments is increasingly relevant. Temperature is especially relevant for ectothermic organisms which depend upon consistent and predictable annual temperature cycles for reproduction and development. However, additional research is required in this area to elucidate the potential impacts of climate change on future generations. To understand how projected increases in environmental temperatures may impact reproductive outcomes within natural populations of ectothermic vertebrates, we manipulated minimum ambient temperatures during gestation in Red-sided garter snakes (Thamnophis sirtalis parietalis). Wild snakes were collected in the Interlake region of Manitoba, Canada during their spring mating season and allowed to mate in controlled conditions. For the duration of gestation, mated females were placed into one of two ambient thermal conditions: temperatures emulating those found in the species’ natural habitat or temperatures with a consistent 5 °C increase to match end-of-century climate change projections. We recorded observations for each litter and all neonates resulting from controlled mating trials. We observed no difference in litter sizes or birth rates between thermal conditions. However, we observed a significant reduction in gestation length and significant increase to neonate body mass and body condition associated with increased ambient temperatures. These results suggest that increased minimum temperatures during gestation may confer reproductive benefits for the northern populations of this species even under the most extreme current modeled warming predictions. We discuss the broader implications of this effect, including possible negative ecological outcomes.