bluuebunny/crossref_metadata_2025_split huggingface dataset:
CIRC_0033530 KNOCKDOWN ALLEVIATES LIPOPOLYSACCHARIDE-INDUCED ACUTE LUNG INJURY MODEL OF HUMAN LUNG FIBROBLASTS BY MIR-1184/TLR4 AXIS
Authors: Xia Rui , Shan Yanhua , Luo Songyuan , Li Jiancheng , Liu Yongping 
Published: November 2023

ABSTRACT

Background: Circular RNAs have been reported to be involved in regulating the progression of sepsis and sepsis-associated damage. Herein, this work investigated whether circ_0033530 had roles in the process of septic acute lung injury (sepsis-ALI) and its associated mechanism. Methods: Lipopolysaccharide (LPS)–stimulated human lung fibroblasts MRC-5 were used to mimic the cell model of sepsis-ALI in vitro. Levels of genes and proteins were detected by quantitative real-time polymerase chain reaction and Western blotting. Functional experiments were conducted using 5-ethynyl-2′-deoxyuridine assay, Cell Counting Kit-8 assay, flow cytometry, and enzyme-linked immunosorbent assay. The interaction between miR-1184 and circ_0033530 or toll-like receptor 4 (TLR4) was confirmed by dual-luciferase reporter and RNA immunoprecipitation assays. Results: Circ_0033530 expression was lower in sepsis patients and LPS-induced fibroblasts than those in healthy control and untreated cells. Functionally, knockdown of circ_0033530 protected fibroblasts against LPS-induced proliferation arrest, apoptosis, and inflammatory response. Mechanistically, circ_0033530 acted as a sponge for miR-1184, and TLR4 RNA was targeted by miR-1184, indicating the circ_0033530/miR-1184/TLR4 axis. Further rescue experiments showed that circ_0033530 silencing–mediated growth inhibition and inflammation on fibroblasts were attenuated by miR-1184 downregulation or TLR4 upregulation. Conclusion: Circ_0033530 knockdown alleviated LPS-induced proliferation arrest, apoptosis, and inflammation in lung fibroblasts by miR-1184/TLR4 axis, and provided molecular theoretical basis for circ_0033530 on the pathogenesis of sepsis-ALI.
Equol, a soybean metabolite with estrogen-like functions, decreases lipopolysaccharide-induced human neutrophil extracellular traps in vitro
Authors: Murakami Hiromoto , Ishikawa Michiko , Higashi Hideki , Kohama Keisuke , Inoue Taketo , Fujisaki Noritomo , Hirata Jun-ichi 
Published: November 2023

ABSTRACT

Objective
Neutrophil extracellular traps (NETs) defend against acute infections. However, their overexpression causes organ failure during sepsis. Control of NET formation may improve the outcomes of patients with sepsis. Equol, a soybean isoflavone, is a female hormone analog, which prevents inflammation. We evaluated the effects of equol on NET formation in human neutrophils during inflammatory stimulation in vitro.

Methods
Healthy volunteers provided blood samples. An enzyme-linked immunosorbent assay (ELISA) assessed serum equol concentrations. NET formation in neutrophils was induced by lipopolysaccharide (LPS) treatment. ELISA quantified DNA-binding elastase, and immunostaining assessed NET formation. Reverse-transcription quantitative PCR and western blotting detected G-protein-coupled receptor 30 (GPR30) or peptidyl arginine deiminase 4 (PAD4) expression. Flow cytometry assessed neutrophil phagocytic ability with inactivated Escherichia coli.

Results
In neutrophils derived from males with low-serum equol levels (low-serum equol group), equol significantly decreased DNA-binding elastase levels and NET formation. Equol did not decrease NETs in neutrophils from males with high-serum equol levels. GPR30 expression of neutrophils was higher in the low-serum than in the high-serum equol group. PAD4 mRNA levels and nuclear PAD4 protein expression also decreased than the vehicle control in the low-serum equol group. Equol did not alter the phagocytic ability of neutrophils. In neutrophils from young females, equol had no inhibitory effect on NET formation.

Conclusions
Equol decreases LPS-induced NET formation in neutrophils from males via inhibition of PAD4 expression. Our findings provide a rationale for investigating a new therapeutic approach using equol to control neutrophil activity during sepsis.
Impact of Standard Versus Low Pneumoperitoneum Pressure on Peritoneal Environment in Laparoscopic Cholecystectomy. Randomized Clinical Trial
Authors: Serrano Ana Belén , Díaz-Cambronero Óscar , Montiel María , Molina José , Núñez Mónica , Mendía Elena , Mané María Nuria , Lisa Eduardo , Martínez-Botas Javier , Gómez-Coronado Diego , Gaetano Andrea , Casarejos María José , Gómez Ana , Sanjuanbenito Alfonso 
Published: November 2023

Background:
High CO2 pneumoperitoneum pressure during laparoscopy adversely affects the peritoneal environment. This study hypothesized that low pneumoperitoneum pressure may be linked to less peritoneal damage and possibly to better clinical outcomes.

Materials and Methods:
One hundred patients undergoing scheduled laparoscopic cholecystectomy were randomized 1:1 to low or to standard pneumoperitoneum pressure. Peritoneal biopsies were performed at baseline time and 1 hour after peritoneum insufflation in all patients. The primary outcome was peritoneal remodeling biomarkers and apoptotic index. Secondary outcomes included biomarker differences at the studied times and some clinical variables such as length of hospital stay, and quality and safety issues related to the procedure.

Results:
Peritoneal IL6 after 1 hour of surgery was significantly higher in the standard than in the low-pressure group (4.26±1.34 vs. 3.24±1.21; P=0.001). On the contrary, levels of connective tissue growth factor and plasminogen activator inhibitor-I were higher in the low-pressure group (0.89±0.61 vs. 0.61±0.84; P=0.025, and 0.74±0.89 vs. 0.24±1.15; P=0.028, respectively). Regarding apoptotic index, similar levels were found in both groups and were 44.0±10.9 and 42.5±17.8 in low and standard pressure groups, respectively. None of the secondary outcomes showed differences between the 2 groups.

Conclusions:
Peritoneal inflammation after laparoscopic cholecystectomy is higher when surgery is performed under standard pressure. Adhesion formation seems to be less in this group. The majority of patients undergoing surgery under low pressure were operated under optimal workspace conditions, regardless of the surgeon’s expertise.
Acute pain management after trauma: What you need to know
Authors: Klugh James M. , Harvin John A. 
Published: November 2023

ABSTRACT
Effective acute pain control is mandatory after injury. Opioids continue to be a pillar acute pain management of strategies despite not being as effective as some nonnarcotic alternatives. An acute pain management strategy after trauma should be thoughtful, effective, and responsible. A thoughtful approach includes managing a patient's expectations for acute pain control and ensuring that interventions purposefully and rationally affect the domain of pain that is uncontrolled. An effective pain management strategy includes a multimodal approach using acetaminophen, nonsteroidal anti-inflammatory drugs, and regional anesthesia. A responsible acute pain management approach includes knowing the relative strengths of the opioids prescribed and standardized approach to opioid prescribing at discharge to minimize diversion. Acute pain management is quite understudied, and future considerations include a reliable objective measurement of pain and the evaluation of nonmedication acute pain interventions.
Feasibility and safety of intraoperative bile duct clearance by antegrade transcystic balloon sphincteroplasty: A prospective observational pilot study
Authors: Prevost Gian Andrea , Huber Chantal , Schnell Bianca , Candinas Daniel , Wiest Reiner , Schnüriger Beat 
Published: November 2023

BACKGROUND
Concomitant cholecystolithiasis and choledocholithiasis are common. Standard treatments are endoscopic retrograde cholangiography (ERC) followed by cholecystectomy or laparoendoscopic rendezvous. Endoscopic retrograde cholangiography has drawbacks, such as post-ERC pancreatitis or bleeding, and potentially more than one intervention is required to address common bile duct (CBD) stones. Safety and feasibility of an intraoperative antegrade transcystic single-stage approach during cholecystectomy with balloon sphincteroplasty and pushing of stones to the duodenum has not been evaluated prospectively. The aim of this pilot study was to evaluate this procedure regarding safety, feasibility, and stone clearance rate.

METHODS
Prospective single-center intervention study (SUPER Reporting-Guideline). Main inclusion criterion was confirmed choledocholithiasis (stones ≤6 mm) at intraoperative cholangiography. Success of the procedure was defined as CBD stone clearance at intraoperative control cholangiography, absence of symptoms and no elevated cholestasis parameters at 6 weeks follow-up. Simon’s two-stage design was used to determine sample size.

RESULTS
From January 2021 to April 2022, a total of 57 patients fulfilled the final inclusion criteria and were included. Mild pancreatitis or cholangitis were present upon admission in 15 (26%) and 15 (26%) patients, respectively. Median number of CBD-stones was 1 (1–6). Median stone diameter was 4 mm (0.1–6 mm). Common bile duct stone clearance was achieved in 54 patients (94%). The main reason for failed CBD clearance was the inability to push the guidewire along the biliary stone into the duodenum. Median intervention time was 28 minutes (14–129 minutes). While there was no postoperative pancreatitis, two patients (3.5%) had asymptomatic hyperlipasemia 4 hours postoperatively.

CONCLUSION
Intraoperative CBD stone clearance by antegrade balloon sphincteroplasty appears to be safe and highly feasible. Its overall superiority to the current standards warrants evaluation by a randomized controlled trial.

LEVEL OF EVIDENCE
Therapeutic/Care Management, Level V.
Association between transfusion volume and survival outcome following trauma: Insight into the limit of transfusion from an analysis of nationwide trauma registry in Japan
Authors: Shibahashi Keita , Aoki Makoto , Hikone Mayu , Sugiyama Kazuhiro 
Published: November 2023

BACKGROUND
Whether and how the transfusion volume should be limited in resuscitation after trauma remains unclear. We investigated the association between transfusion volume and survival outcome following trauma.

METHODS
Using the Japan Trauma Data Bank (2019–2021), we identified patients 18 years or older who received balanced blood transfusion within the first 24 hours of injury. We evaluated the association between the total number of red blood cell (RBC) units transfused and survival at discharge using logistic regression analysis and generalized additive model. Subgroup analyses based on patient characteristics were performed.

RESULTS
Overall, 5,123 patients from 165 hospitals were eligible for analysis. The transfusion volume was significantly associated with survival rate. Compared with that of patients receiving 4 to 9 RBC units, the within-hospital odds ratios (95% confidence interval) for survival at discharge were 0.62 (0.55–0.75), 0.32 (0.25–0.40), and 0.15 (0.12–0.20) for those receiving 10 to 19, 20 to 29, and ≥30 U, respectively. The probability of survival decreased consistently without any discernible threshold; however, the survival rates remained >40% and >20% even in patients receiving 50 and 80 RBC units, respectively. Significant interactions were observed between the number of RBC units transfused and each subgroup for survival at discharge.

CONCLUSION
The probability of survival consistently diminished as the transfusion volume increased. The absence of a threshold and lack of exceedingly low probability of survival support massive transfusion when clinicians perceive ongoing transfusion as beneficial. The unique context of each clinical situation must be considered in decision making.

LEVEL OF EVIDENCE
Therapeutic/Care Management; Level III.
Intramuscular Administration of Tranexamic Acid in a Large Swine Model of Hemorrhage with Hyperfibrinolysis
Authors: Haberkorn Christopher J. , Severance Carter C. , Wetmore Nathan C. , West Walker G. , Ng Patrick C. , Cendali Francesca , Pitotti Christopher , Schauer Steven G. , Maddry Joseph K. , Bebarta Vikhyat S. , Hendry-Hofer Tara B. 
Published: November 2023

ABSTRACT

Background
Traumatic injury with subsequent hemorrhage is one of the leading causes of mortality among military personnel and civilians alike. Post traumatic hemorrhage accounts for 40-50% of deaths in severe trauma patients occurring secondary to direct vessel injury or the development of trauma induced coagulopathy (TIC). Hyperfibrinolysis plays a major role in TIC and its presence increases a patient’s risk of mortality. Early therapeutic intervention with intravenous (IV) tranexamic acid (TXA) prevents development of hyperfibrinolysis and subsequent TIC leading to decreased mortality. However, obtaining IV access in an austere environment can be challenging. In this study, we evaluated the efficacy of intramuscular (IM) versus IV TXA at preventing hyperfibrinolysis in a hemorrhaged swine.

Methods
Yorkshire cross swine were randomized on the day of study to receive IM or IV TXA or no treatment. Swine were sedated, intubated, and determined to be hemodynamically stable prior to experimentation. Controlled hemorrhaged was induced by the removal of 30% total blood volume. After hemorrhage, swine were treated with 1000 mg of IM or IV TXA. Control animals received no treatment. Thirty minutes post TXA treatment, fibrinolysis was induced with a 50 mg bolus of tissue plasminogen activator (tPA). Blood samples were collected to evaluate blood TXA concentrations, blood gases, blood chemistry, and fibrinolysis.

Results
Blood TXA concentrations were significantly different between administration routes at the early timepoints, but were equivalent by 20 minutes after injection, remaining consistently elevated for up to three hours post administration. Induction of fibrinolysis resulted in 87.18 ± 4.63% lysis in control animals, compared to swine treated with IM TXA 1.96 ± 2.66 % and 1.5 ± 0.42% lysis in the IV TXA group.

Conclusion
In the large swine model of hemorrhage with hyperfibrinolysis, IM TXA is bioequivalent and equally efficacious in preventing hyperfibrinolysis as IV TXA administration.
Setting an agenda for a national pediatric trauma system: Operationalization of the Pediatric Trauma State Assessment Score
Authors: Stephens Caroline Q. , Fallat Mary E. 
Published: November 2023

ABSTRACT
Pediatric trauma system development is essential to public health infrastructure and pediatric health systems. Currently, trauma systems are managed at the state level, with significant variation in consideration of pediatric needs. A recently developed Pediatric Trauma System Assessment Score (PTSAS) demonstrated that states with lower PTSAS have increased pediatric mortality from trauma. Critical gaps are identified within six PTSAS domains: Legislation and Funding, Access to Care, Injury Prevention and Recognition, Disaster, Quality Improvement and Trauma Registry, and Pediatric Readiness. For each gap, a recommendation is provided regarding the necessary steps to address these challenges. Existing national organizations, including governmental, professional, and advocacy, highlight the potential partnerships that could be fostered to support efforts to address existing gaps. The organizations created under the US administration are described to highlight the ongoing efforts to support the development of pediatric emergency health systems.
It is no longer sufficient to describe the disparities in pediatric trauma outcomes without taking action to ensure that the health system is equipped to manage injured children. By capitalizing on organizations that intersect with trauma and emergency systems to address known gaps, we can reduce the impact of injury on all children across the United States.
A Method for Analyzing AFM Force Mapping Data Obtained from Soft Tissue Cryosections
Authors: Wong Cydney A. , Fraticelli Guzmán Nina Sara , Read A. Thomas , Hedberg-Buenz Adam , Anderson Michael G. , Feola Andrew J. , Sulchek Todd , Ethier C. Ross 
Published: November 2023

AbstractAtomic force microscopy (AFM) is a valuable tool for assessing mechanical properties of biological samples, but interpretations of measurements on whole tissues can be difficult due to the tissue’s highly heterogeneous nature. To overcome such difficulties and obtain more robust estimates of tissue mechanical properties, we describe an AFM force mapping and data analysis pipeline to characterize the mechanical properties of cryosectioned soft tissues. We assessed this approach on mouse optic nerve head and rat trabecular meshwork, cornea, and sclera. Our data show that the use of repeated measurements, outlier exclusion, and log-normal data transformation increases confidence in AFM mechanical measurements, and we propose that this methodology can be broadly applied to measuring soft tissue properties from cryosections.
Utility of T1 mapping and T2 mapping for non-invasive assessment of liver fibrosis: preclinical results
Authors: Rong Jing , Zhu Yujie , Zhu Kun , Shao Min , Yin Xiujuan , Liu Tongtong , Wang Xiao 
Published: November 2023

AbstractObjectiveTo explore the potential of T1 and T2 mappings in assessing liver fibrosis (LF) and investigate the relationships between MRI and liver fibrogenesis markers.Materials and methods A total of 39 male C57BL/6 mice were divided into the control group (n = 9) and the model group (n = 10 per subgroup) with carbon tetrachloride (CCl4) administration for 2, 4, and 6 weeks. The METAVIR system (F0-4) was performed to stage fibrosis. MRI T1 and T2 mappings were performed and T1, and T2 values were calculated. One-way analysis of variance (ANOVA), Spearman’s rank correlation analysis, and receiver operating characteristic (ROC) curves were performed.ResultsT1 and T2 values increased with progressing severity of fibrosis induction (P< 0.01). T1 and T2 were significantly correlated with LF stages (ρ = 0.854, 0.697,P< 0.001). The area under the curves (AUCs) range of T1 and T2 for predicting ≥F1, ≥F2, ≥F3, and F4 were 0.842-0.994 and 0.808-0.883, respectively. T1 and T2 showed moderate to strong correlations with collagen-associated protein and inflammatory factors.DiscussionT1 and T2 mappings can evaluate and differentiate LF stages in the CCl4-induced model. T1 is better correlated with collagen deposition and inflammation of LF than T2.
Modification of the antibiotic, colistin, with dextrin causes enhanced cytotoxicity and triggers apoptosis in myeloid leukemia
Authors: Rizzo Siân , Varache Mathieu , Sayers Edward J. , Jones Arwyn T. , Tonks Alex , Thomas David W. , Ferguson Elaine L. 
Published: November 2023

AbstractAcute myeloid leukemia (AML) remains difficult to treat due to its heterogeneity in molecular landscape, epigenetics and cell signaling alterations. Precision medicine is a major goal in AML therapy towards developing agents that can be used to treat patients with different ‘subtypes’ in combination with current chemotherapies. We have previously developed dextrin-colistin conjugates to combat the rise in multi-drug resistant bacterial infections and overcome dose-limiting nephrotoxicity. Recent evidence of colistin’s anticancer activity, mediated through inhibition of intracellular lysine-specific histone demethylase 1 (LSD1/KDM1A), suggests that dextrin-colistin conjugates could be used to treat cancer cells, including AML. This study aimed to evaluate whether dextrin conjugation (which reducesin vivotoxicity and prolongs plasma half-life) could enhance colistin’s cytotoxic effects in myeloid leukemia cell lines and compare the intracellular uptake and localization of the free and conjugated antibiotic. Our results identified a conjugate (containing 8,000 g/mol dextrin with 1 mol% succinoylation) that caused significantly increased toxicity in myeloid leukemia cells, compared to free colistin. Dextrin conjugation altered the mechanism of cell death by colistin, from necrosis to caspase 3/7-dependent apoptosis. In contrast, conjugation via a reversible ester linker, instead of an amide, had no effect on the mechanism of the colistin-induced cell death. Live cell confocal microscopy of fluorescently-labelled compounds showed both free and dextrin-conjugated colistin were endocytosed and co-localized in lysosomes and increasing the degree of modification by succinoylation of dextrin significantly reduced colistin internalization. Whilst clinical translation of dextrin-colistin conjugates for the treatment of AML is unlikely due to the potential to promote AMR and the relatively high colistin concentrations required for anticancer activity, the ability to potentiate the effectiveness of an anticancer drug by polymer conjugation, while reducing side effects and improving biodistribution of the drug, is very attractive, and this approach warrants further investigation.Graphical abstract
Genome folding principles revealed in condensin-depleted mitotic chromosomes
Authors: Zhao Han , Lin Yinzhi , Lin En , Liu Fuhai , Shu Lirong , Jing Dannan , Wang Baiyue , Wang Manzhu , Shan Fengnian , Zhang Lin , Lam Jessica C. , Midla Susannah C. , Giardine Belinda M. , Keller Cheryl A. , Hardison Ross C. , Blobel Gerd A. , Zhang Haoyue 
Published: November 2023

ABSTRACTDuring mitosis, condensin activity interferes with interphase chromatin structures. Here, we generated condensin-free mitotic chromosomes to investigate genome folding principles. Co- depletion of condensin I and II, but neither alone, triggered mitotic chromosome compartmentalization in ways that differ from interphase. Two distinct euchromatic compartments, indistinguishable in interphase, rapidly emerged upon condensin loss with different interaction preferences and dependence on H3K27ac. Constitutive heterochromatin gradually self-aggregated and co-compartmentalized with the facultative heterochromatin, contrasting with their separation during interphase. While topologically associating domains (TADs) and CTCF/cohesin mediated structural loops remained undetectable, cis-regulatory element contacts became apparent, providing an explanation for their quick re-establishment during mitotic exit. HP1 proteins, which are thought to partition constitutive heterochromatin, were absent from mitotic chromosomes, suggesting, surprisingly, that constitutive heterochromatin can self-aggregate without HP1. Indeed, in cells traversing from M- to G1-phase in the combined absence of HP1α, HP1Π and HP1γ, re-established constitutive heterochromatin compartments normally. In sum, “clean-slate” condensin-deficient mitotic chromosomes illuminate mechanisms of genome compartmentalization not revealed in interphase cells.