bluuebunny/crossref_metadata_2025 huggingface dataset:
5% Dextrose in Ringer’s Lactate versus 5% Dextrose Normal Saline as maintenance intravenous fluid therapy in Children - A Randomised Controlled Trial
Authors: Kaviti Hemanth , John Joseph , Gulla Krishna Mohan , Sahu Suchanda
Published: October 2023

Rationale:
Our study compares the effects of 5% Dextrose in Ringer’s Lactate versus 5% Dextrose Normal Saline as maintenance fluid therapy to nullify iatrogenic hyperchloremia, hyperchloremic metabolic acidosis (HCMA) caused by NS.
Objectives
To estimate the difference in serum chloride levels between the children receiving 5% Dextrose in Ringer’s Lactate versus 5% Dextrose Normal Saline and to estimate the incidence of dyselectrolytemia, HCMA, acute kidney injury and all-cause mortality in both groups.
Methods
A randomised controlled trial was conducted on children aged 6 months to 14 years admitted to AIIMS, Bhubaneswar, between August 2021 and July 2022, with controls receiving 5% Dextrose Normal Saline and the Intervention group receiving 5% Dextrose in Ringer’s Lactate.
Results:
A total of 142 children (71 in each group) were enrolled. The mean chloride difference between the two groups at 24 hours and 48 hours was 1.67 (p-value − 0.03) and 2.78 (p-value – 0.01), respectively. At 24h, 1.4% of children had AKI in the RLD5 group, and no one had AKI in the DNS group. At 48h, 2.8% in the RLD5 group and 1.4% in the DNS group had AKI. At 24h, 2.8% of children had HCMA in the RLD5 group, and 14% of children had HCMA in the DNS group (p-value − 0.02). At 48h, 2.8% of children had HCMA in the RLD5 group, and 4.2% had HCMA in the DNS group. There was no mortality in either group.
Conclusion
Though clinically insignificant, there was a statistically significant difference in the serum chloride levels between the groups.
Ethical approval and CTRI Registration: IEC/AIIMS BBSR/PG Thesis/2020-21/97 dated December 21, 2020; Clinical Trial Registry India (CTRI) (www.ctri.nic.in) vide registration number CTRI/2021/08/035924 dated 25/08/2021.
Causal relationships between psychological disorders and functional gastrointestinal disorders: a bidirectional two-sample Mendelian randomization study
Authors: Liu Tangyi , Wang Zeyu , Kang Xiaoyu , Wang Xiangping , Ren Gui , Lv Yong , Li Jing , Liu Yaling , Liang Shuhui , Nie Yongzhan , Luo Hui , Pan Yanglin
Published: October 2023

Background and Aims: Observational studies have shown bidirectional associations between phycological disorders (e.g., depression and anxiety) and functional gastrointestinal disorders. However, whether the relationships are causal is uncertain. Here we used a bidirectional two-sample Mendelian randomization (MR) method to investigate the association between phycological disorders and functional gastrointestinal disorders (FGIDs).
Methods: We obtained genome-wide association study (GWAS) summary statistics for two common phycological disorders (depression and anxiety) and three common FGIDs (functional dyspepsia (FD), constipation and irritable bowel syndrome (IBS)) from several publicly available GWAS databases. The inverse variance weighted (IVW) method was used as the main MR method.
Results: IVW MR analyses showed statistically significant associations between genetically predicted depression and risk of FD (OR 1.40, 95%CI 1.08-1.82), constipation (OR 1.28, 95%CI 1.13-1.44) and IBS (OR 1.51, 95%CI 1.37-1.67). Genetically predicted anxiety was associated with higher risk of IBS (OR 1.13, 95%CI 1.10-1.17) instead of FD and constipation. Additionally, genetically predicted IBS instead of FD and constipation was associated with higher risk of depression (OR 1.33, 95%CI 1.12-1.57) and anxiety (OR 2.05, 95%CI 1.05-4.03).
Conclusions: Depression is a causal risk factor for three common FGIDs. A bidirectional causal relationship between IBS and anxiety or depression was also identified.
Causal associations between autoimmune disease and sepsis: a two-sample Mendelian randomization study
Authors: Bai Xueyang , Zhuo Chengui , Tong Renyang , Dao Ling , Yu Lu , Xu Longwei , Li Ling
Published: October 2023

Background
Recent observational studies have revealed an inconclusive correlation between autoimmune disease (AID) and sepsis, accompanied by an uncertain understanding of the causal relationship between the two. The objective of this study was to investigate the causality between AID and sepsis by employing a two-sample Mendelian randomization (MR) approach.
Methods
A genome-wide significant threshold (P < 5×10− 8) was achieved in order to identify single nucleotide polymorphisms (SNPs) as instrumental variables (IVs) for various common types of AID, such as Crohn's disease (CD), ulcerative colitis (UC), systemic lupus erythematosus (SLE), multiple sclerosis (MS), rheumatoid arthritis (RA), and ankylosing spondylitis (AS). Subsequently, the selected SNPs were assessed in relation to three categories of sepsis, namely sepsis, sepsis (critical care), and sepsis (28-day death in critical care). An inverse-variance weighted (IVW) estimation of MR was conducted, followed by sensitivity analysis on multiple dimensions.
Results
In the context of the study, a significant causal correlation was observed between genetic susceptibility and sepsis (28-day death in critical care) in patients with CD (OR, 1.246; 95% CI, 1.090–1.423; P = 0.0012). On the other hand, UC patients showed a slightly higher risk for sepsis, although this difference was not statistically significant (OR, 1.031; 95% CI, 0.988–1.064; P = 0.064). Additionally, there was evidence of a suggestive significant association between genetic liability to SLE (OR, 1.025; 95% CI, 1.009–1.043; P = 0.0029) and MS (OR, 1.038; 95% CI, 1.002–1.076; P = 0.041) with sepsis, but not specifically with sepsis (critical care) and sepsis (28-day death in critical care). However, there was no significant association of the genetic vulnerability to RA or AS with any of three types of sepsis.
Conclusion
Our study offers genetic evidence that supports a substantial causal relationship between CD and sepsis (28-day death in critical care), as well as a suggestive significant association between SLE/MS and sepsis. To enhance the specificity and objectivity of future research findings, it is recommended to specify the types of AID and the severity of sepsis. Furthermore, the identified genetic risk loci may serve as promising targets for drug development.
Investigations of the dynamical behaviors of a millimeter-scale cavitation bubble near the rigid wall
Authors: Zi Dan , He DongQiao , Yao Zhifeng , Wang Fujun , Zhong Qiang , Pin Lyu
Published: October 2023

The collapse of the cavitation bubble near the rigid wall emits shock waves and creates micro-jet, causing cavitation damage and operation instability of the hydraulic machinery. In this paper, the millimeter-scale bubble near the rigid wall was investigated experimentally and numerically with the help of a laser photogrammetry system with nanosecond-micron space-time resolution and the open source package OpenFOAM-2212. The morphological characteristics of the bubble during its growth phase, collapse phase and rebound phase were observed by experiment and numerical simulation, and characteristics of the accompanying phenomena including the shock wave propagation and micro-jet evolution were well elucidated. The numerical results agree well with the experimental data. The bubble starts from a tiny small size with high internal pressure and expands into a sphere with a radius of 1.07mm for γ=d/Rmax=1.78. The bubble collapses into a heart shape and moves towards to the rigid wall during its collapse phase, resulting in a higher pressure load for the rigid wall in the second collapse. The maximum pressure of the shock wave of the first bubble collapse phase reaches 5.4MPa, and the velocity of the micro-jet reaches approximately 100m/s. This study enriches the existing experimental and numerical results of the dynamics of the near-wall cavitation bubble.
Patient factors associated with prolonged length of stay after traumatic brain injury
Authors: Taylor Shameeke , Loo George T. , Richardson Lynne , Legome Eric
Published: October 2023

Background
For traumatic brain injury (TBI) survivors, recovery can lead to significant time spent in the inpatient/rehabilitation settings. Hospital length of stay (LOS) after TBI is a crucial metric of resource utilization and treatment costs. Risk factors for prolonged LOS (PLOS) after TBI require further characterization.
Methods
We conducted a retrospective analysis of patients with diagnosed TBI at an urban trauma center. PLOS was defined as the 95th percentile of the LOS of the cohort. Patients with and without PLOS were compared using clinical/injury factors. Analyses included descriptive statistics, non-parametric analyses and multivariable logistic regression for PLOS status.
Results
The threshold for PLOS was ≥ 24 days. In the cohort of 1343 patients, 77 had PLOS. PLOS was significantly associated with longer mean intensive care unit (ICU) stays (16.4 vs. 1.5 days), higher mean injury severity scores (18.6 vs. 13.8), lower mean Glasgow coma scale score (11.3 vs. 13.7) and greater mean complication burden (0.7 vs 0.1). PLOS patients were more likely to have moderate/severe TBI, Medicaid insurance and were less likely to be discharged home. In the regression model, PLOS was associated with ICU stay, inpatient disposition, ventilator use, unplanned intubation and inpatient alcohol withdrawal.
Conclusions
TBI patients with PLOS were more likely to have severe injuries, in-hospital complications and Medicaid insurance. PLOS was predicted by ICU stay, intubation, alcohol withdrawal and disposition to inpatient/post-acute care facilities. Efforts to reduce in-hospital complications and expedite discharge may reduce LOS and accompanying costs. Further validation of these results is needed from larger multicenter studies.
Wearable Chemical Gas Sensors with Color Changeable Functional Dyes Detecting Organophosphorus Nerve Agents
Authors: Lee Junheon , Kim Taekyeong
Published: October 2023

Wearable military chemical gas sensors were realized using 19 kinds of color changeable functional dyes having great aggregative characteristics and the optimal wearable sensor with the best detection performance was selected. The wearable sensor was designed to exhibit color change properties that are sensitive to low concentration of chemical warfare agent (CWA) vapors at room temperature. The dyes were applied to cotton fabrics as a substrate of the wearable chemical gas sensors and examined their sensing properties, performance, and mechanisms for an organophosphorus simulant of nerve agents, dimethyl-methyl-phosphonate (DMMP). The color difference of almost 5 was obtained even at as low concentration as 3 ppm within 10 min and the spectrum was exhibited hypsochromic and hyperchromic shift. The sensing mechanism was considered to depend on solvatochromism, aggregative characteristics of the dye molecules and adsorption amounts of DMMP vapors on textile substrates on which the dyes were applied. In addition, the reusability of the wearable sensor was tested for 10 repeat cycles.
Investigation of Magneto-Convection Characteristics in A Sudden Expanding Channel with Convex Surface Geometry Under Thermally Developing Flow Conditions
Authors: Gürsoy Emrehan , Pazarlıoğlu Hayati Kadir , Gürdal Mehmet , Arslan Kamil , Gedik Engin , Dağdeviren Abdullah
Published: October 2023

The current study presents a novelty with focusing on the magnetic field effect on a sudden expansion tube with expansion ratio, total length, and pitch length of the dimpled fin is 2.5, 1500 mm, and 3.0, respectively. The magnetizable Fe3O4/H2O Ferrofluid with different nanoparticle volumetric concentrations (φ = 1.0% and 2.0%) were used as a heat transfer fluid, and magnetohydrodynamic effects were elaborately investigated in this study. The numerical analysis was conducted under laminar flow regime and the DC magnetic field (B0 = 0.03T, 0.05T, 0.3T, and 0.5T). The present study provided a comprehensive investigation, which presented the thermo-hydraulic performance of difference dimpled fins, Fe3O4/H2O Ferrofluid, and magnetic field. According to the results, dimple fins showed the best increment within heat transfer enhancement techniques. The heat transfer enhancement rate of the dimple tube and Fe3O4/H2O Ferrofluid were respectively acquired as 22.62% and 5.43%-6.28% (φ = 1.0% and 2.0%). When dimpled fin and Fe3O4/H2O Ferrofluid were used, the increment in Performance Evaluation Criteria was calculated as 21.31% and 4.85%-9.79% (φ = 1.0% and 2.0%). Although the highest average Nusselt number was obtained at B0 = 0.5T, the highest performance evaluation criteria were detected at B0 = 0.3T due to the friction factor showing an increment.
Expansion of endogenous T cells in CSF of pediatric CNS tumor patients undergoing locoregional delivery of IL13R⍺2-targeting CAR T cells: an interim analysis
Authors: Wang Leo , Oill Angela Taravella , Blanchard M. , Wu Melody , Hibbard Jonathan , Sepulveda Sean , Peter Lance , Kilpatrick Julie , Munoz Margarita , Stiller Tracey , Shulkin Noah , Wagner Jamie , Dolatabadi Ally , Nisis Monica , Shepphird Jennifer , Sanchez Gabriela , Lingaraju Chetan , Manchanda Mishika , Natri Heini , Kouakanou Léonce , Sun Grace , Oliver-Cervantes Cheryl , Georges Joseph , Aftabizadeh Maryam , Forman Stephen , Priceman Saul , Ressler Julie , Arvanitis Leonidas , Cotter Jennifer , D'Apuzzo Massimo , Tamrazi Benita , Badie Behnam , Davidson Tom , Banovich Nicholas , Brown Christine
Published: October 2023

Outcomes for pediatric brain tumor patients remain poor, and there is optimism that chimeric antigen receptor (CAR) T cell therapy can improve prognosis. Here, we present interim results from the first six pediatric patients treated on an ongoing phase I clinical trial (NCT04510051) of IL13BBζ-CAR T cells delivered weekly into the lateral cerebral ventricles, identifying clonal expansion of endogenous CAR-negative CD8+ T cells in the cerebrospinal fluid (CSF) over time. Additionally, of the five patients evaluable for disease response, three experienced transient radiographic and/or clinical benefit not meeting protocol criteria for response. The first three patients received CAR T cells alone; later patients received lymphodepletion before the first infusion. There were no dose limiting toxicities (DLTs). Aside from expected cytopenias in patients receiving lymphodepletion, serious adverse events possibly attributed to CAR T cell infusion were limited to one episode of headache and one of liver enzyme elevation. One patient withdrew from treatment during the DLT period due to a Grade 3 catheter-related infection and was not evaluable for disease response, although this was not attributed to CAR T cell infusion. Importantly, scRNA- and scTCR-sequence analyses provided insights into CAR T cell interaction with the endogenous immune system. In particular, clonally expanded endogenous CAR− T cells were recovered from the CSF, but not the peripheral blood, of patients who received intraventricular IL13BBζ-CAR T cell therapy. Additionally, although immune infiltrates in CSF and post-therapy tumor did not generally correlate, a fraction of expanded T cell receptors (TCRs) was seen to overlap between CSF and tumor. This has important implications for what samples are collected on these trials and how they are analyzed. These initial findings provide support for continued investigation into locoregionally-delivered IL13BBζ-CAR T cells for children with brain tumors.
Changes in fractional exhaled nitric oxide, forced expiratory volume in one second, and forced oscillation technique parameters over three years in adults with bronchial asthma managed under Yokohama Seibu Hospital’s coordinated care system
Authors: Tsuburai Takahiro , Tanaka Satoshi , Komase Yuko , Oyama Baku , Muraoka Hiromi , Shinozaki Yusuke , Nishiyama Kazuhiro , Ueno Junko , Nishi Yoshihiro , Numata Yu , Hida Naoya , Mineshita Masamichi , Inoue Takeo
Published: October 2023

Background: In western Yokohama, our hospital and primary care clinics manage adult asthmatics via a coordinated care system. We investigated the changes in the fractional expired nitric oxide (FeNO), forced expiratory volume in 1 second (FEV1), and forced oscillation technique (FOT) parameters over 3 years in a cohort of patients in our collaborative system.
Methods: From 288 adults with stable asthma managed under the Yokohama Seibu Hospital coordinated care system between January 2009 and May 2018, we selected 99 subjects to undergo spirometry, FeNO and FOT testing over 3 years and analyzed the changes in these parameters.
Results: Of the 99 patients enrolled, 35 (35.3%) experienced exacerbations during the 3-year study period. There were no differences in FeNO, FEV1, or FOT parameters at baseline between patients with and without exacerbations. The FeNO decreased significantly over 3 years in all patients regardless of exacerbation status. The FEV1 levels decreased gradually, whereas the percent predicted FEV1 levels significantly increased. We also observed significant improvement in FOT parameters; specifically reactance at 5 Hz (R5), resonant frequency (Fres), and integral of reactance up to the resonant frequency (AX). The stable group (without exacerbations) demonstrated significant relationships between the change in FeNO and the change in FEV1 and between the change in FEV1 and the change in FOT parameters. No significant correlations emerged in the exacerbation group.
Conclusion: The decrease in FeNO and increase in the percent predicted FEV1 we observed in all study participants suggest that the coordinated care system model benefits patients with bronchial asthma. Although predicting which patients will experience an exacerbation at baseline may be difficult, monitoring changes in FeNO and FEV1 is useful in managing adults with stable asthma. Furthermore, monitoring changes in R5, Fres, and AX via forced oscillation technique testing is useful for detecting airflow limitation.
An epicutaneous therapeutic pollen-allergen extract delivery system in the allergic rhinitis mouse model: based on allergen loading on DC-specific aptamers conjugated nanogolds
Authors: Pordel Safoora , Haghnavaz Navideh , Rezaee MohammadAli , Shobeiri Saeideh Sadat , Ansari Bahareh , Dashti Mohammadreza , Moghadam Malihe , Khorrami Motahare , Sankian Mojtaba
Published: October 2023

Background: We investigated whether gold nanoparticles (GNPs) and dendritic cells (DC)-specific aptamer-modified GNPs (Apts-GNP) could be effective for epicutaneous immunotherapy (EPIT) in the case of pollen allergen extracts containing a variety of allergenic and nonallergenic components.
Methods: BALB/c mice were sensitized to total protein extract of Platanus orientalis pollen and then epicutaneously treated in different groups either with free P. orientalis total pollen extract, naked GNPs, the total extract loaded GNPs, and the total extract loaded Apts-GNPs with and without skin-penetrating peptides (SPPs). We then examined the specific IgE level (sIgE), total IgE concentration (tIgE) in the serum sample, IL-4, IL-17a, IFN-γ, and IL-10 cytokine concentrations in re-stimulated splenocytes with the total extract and the mixture of its recombinant allergens, nasopharyngeal lavage fluid (NALF) analysis, and histopathological analysis of lung tissue.
Results: The current study showed that the total extract-loaded GNPs, especially Pla. ext (50 μg)-GNPs, significantly decreased sIgE, tIgE, IL-17a, and IL-4 concentrations, immune cells and eosinophils infiltration in NALF, and increased IL-10 and IFN-γ concentrations compared with the PBS-treated group. In addition, histopathological analysis of lung tissue showed that it also led to a remarkable decrease in allergic rhinitis (AR)-associated inflammation and histopathological damage. The DC-targeted group showed greatest improvement in AR-related immune factors and had no histopathological damage compared with the same dose without aptamer.
Conclusion: Consequently, it seems that loading total protein extract on the GNPs and the Apt-modified GNPs could be an effective approach to improve EPIT efficacy in pollen-induced AR.
Identification of Novel COPD Susceptibility Genes: A Genome-wide Interaction Study
Authors: Kim Chi Young , Park Boram , Jung Ji Ye , Kim Je Hyeong , Nam Chung Mo , Won Sungho , Kim Young Sam
Published: October 2023

Background: Variants of some genes are associated with chronic obstructive pulmonary disease (COPD). However, genetic susceptibility for lung function decline in the general population remains unclear. Here, we investigated the genetic susceptibility associated with lung function decline with or without COPD by analyzing a community.
Methods: A genome-wide interaction study was performed to identify the association between genetic variants and pulmonary function and examine their impact on lung impairment in terms of smoking status. We analyzed the association between genetic variants and lung function using a linear mixed model for association and interaction-to-time effects.
Results: We observed 8,554 participants for 12 years. The annual mean FEV1 declines were 41.7 mL (in men) and 33.4 mL (in women); the annual rate of FEV1 decline was the fastest for current smokers. A locus upstream of FAM13 on chromosome 4, which harbored the most significant single-nucleotide polymorphisms (SNPs), was previously identified from two likelihood ratio tests for FEV1/FVC; these SNPs had similar minor allele frequencies. Additionally, certain SNPs showed lower FEV1/FVC values. The rs75679995 SNP on chromosome 7 showed the highest association with lung function decline; the SNPs located within the DNAH11 region TAD and rs9991425 eQTL were associated with higher MFAP3L and AADAT expression.
Conclusion: This is the first gene-time interaction study of lung function decline as a risk factor for COPD in a community-based population. We replicated previously known signals for FAM13A and identified two novel genomic regions (DNAH11 and AADAT) involved in these gene-environment interactions.
Pan-cancer analysis reveals IL32 is a potential prognostic and immunotherapeutic biomarker in cancer
Authors: Han Feng , ma jianxin
Published: October 2023

Background:Interleukin 32 (IL32) is a pro-inflammatory cytokine that plays a key role in promoting sterile inflammation by modulating immune responses. However, the role of IL32 in various cancers remains unclear. This research aimed to investigate the correlation between IL32 expression and immunity and visualize its prognostic landscape in pan-cancer.
Methods: We investigated gene expression, genomic alterations, and survival analysis of IL32 in pan-cancer in numerous databases including TCGA, GTEx, cBioPortal, and GDC databases. Tumor immune cell infiltration was assessed using the CIBERSORT computational method as well as the ESTIMATE method to analyze the correlation of IL32 expression with stromal and immune components. Protein-protein interaction analysis was performed in the STRING and GeneMANIA databases, and gene function enrichment was performed by GO set enrichment analysis.
Results: Tumor tissues had higher IL32 expression levels than normal tissues. Elevated IL32 expression was associated with poor OS and prognosis. In addition, tumor stemness, TMB, MSI, and immune checkpoint genes were also associated with IL32 expression. Correlations were observed between IL32 expression and B cell, CD4T cell, CD8T cell, neutrophil, macrophage, and DC infiltration in multiple cancers. GO enrichment analysis showed that IL32 expression was associated with cancer pathways, cytokine-receptor interactions, and NOD-like receptor signaling pathways.
Conclusion: These findings suggest that IL32 may serve as a biomarker of cancer immune infiltration and poor prognosis, providing new therapeutic targets for cancer treatment.
Neutrophilia with damage to the blood-brain barrier and neurovascular unit following acute lung injury
Authors: Li Herman , Le Linh , Marrero Mariah , David-Bercholz Jennifer , Caceres Anabel Isabel , Lim Claire , Chiang Wesley , Majewska Ania , Terrando Niccolo , Gelbard Harris
Published: October 2023

Background: Links between acute lung injury (ALI), infectious disease, and neurological outcomes have been frequently discussed over the past few years, especially due to the COVID-19 pandemic. Yet, much of the cross-communication between organs, particularly the lung and the brain, has been understudied. Here, we have focused on the role of neutrophils in driving changes to the brain endothelium with ensuing microglial activation and neuronal loss in a model of ALI.
Methods: We have applied a three-dose paradigm of 10μg/40μl intranasal lipopolysaccharide (LPS) to induce neutrophilia accompanied by proteinaceous exudate in bronchoalveolar lavage fluid (BALF) in adult C57BL/6 mice. Brain endothelial markers, microglial activation, and neuronal cytoarchitecture were evaluated 24hr after the last intranasal dose of LPS or saline. C57BL/6-Ly6g(tm2621(Cre-tdTomato)Arte (Catchup mice) were used to measure neutrophil and blood-brain barrier permeability following LPS exposure with intravital 2-photon imaging.
Results: Three doses of intranasal LPS induced robust neutrophilia accompanied by proteinaceous exudate in BALF. ALI triggered central nervous system pathology as highlighted by robust activation of the cerebrovascular endothelium (VCAM1, CD31), accumulation of plasma protein (fibrinogen), microglial activation (IBA1, CD68), and decreased expression of proteins associated with postsynaptic terminals (PSD-95) in the hippocampal stratum lacunosum moleculare, a relay station between the entorhinal cortex and CA1 of the hippocampus. 2-photon imaging of Catchup mice revealed neutrophil homing to the cerebral endothelium in the blood-brain barrier and neutrophil extravasation from cerebral vasculature 24hr after the last intranasal treatment.
Conclusions: Overall, these data demonstrate ensuing brain pathology resulting from ALI, highlighting a key role for neutrophils in driving brain endothelial changes and subsequent neuroinflammation. This paradigm may have a considerable translational impact on understanding how infectious disease with ALI can lead to neurodegeneration, particularly in the elderly.
The NADase CD38 is a central regulator in gouty inflammation and a novel druggable therapeutic target
Authors: Alabarse Paulo Gil , Oliveira Patricia , Qin Huaping , Yan Tiffany , Migaud Marie , Terkeltaub Robert , Liu-Bryan Ru
Published: October 2023

Objectives: Cellular NAD+ declines in inflammatory states associated with increased activity of the leukocyte-expressed NADase CD38. In this study, we tested the potential role of therapeutically targeting CD38 and NAD+ in gout.
Methods: We studied cultured mouse wild type and CD38 knockout (KO) murine bone marrow derived macrophages (BMDMs) stimulated by monosodium urate (MSU) crystals and used the air pouch gout synovitis model.
Results: MSU crystals induced CD38 in BMDMs in vitro, associated with NAD+ depletion, and IL-1b and CXCL1 release, effects reversed by pharmacologic CD38 inhibitors (apigenin, 78c). Mouse air pouch inflammatory responses to MSU crystals were blunted by CD38 KO and apigenin. Pharmacologic CD38 inhibition suppressed MSU crystal-induced NLRP3 inflammasome activation and increased anti-inflammatory SIRT3-SOD2 activity in macrophages. BMDM RNA-seq analysis of differentially expressed genes (DEGs) revealed CD38 to control multiple MSU crystal-modulated inflammation pathways. Top DEGs included the circadian rhythm modulator GRP176, and the metalloreductase STEAP4 that mediates iron homeostasis, and promotes oxidative stress and NF-kB activation when it is overexpressed.
Conclusions: CD38 and NAD+ depletion are druggable targets controlling the MSU crystal- induced inflammation program. Targeting CD38 and NAD+ are potentially novel selective molecular approaches to limit gouty arthritis.
RETRACTED: Spatial Distribution of Soil Grain Size and its Associated Deposition Environment in the Surrounding Areas of the Badain Jaran Desert
Authors: WANG MENG , FU Peng
Published: October 2023

The authors have requested that this preprint be removed from Research Square.
Butyric acid is potent protective agent that targets RhoA/ROCK2/MLCK signaling pathway in LPS-induced intestinal mucosal barrier damage
Authors: Liu Luqiong , Chen Tong , Xie Zhenrong , Zhang Yongjin , He Chenglu , Huang Yongkun
Published: October 2023

Butyric acid (BA) could improve intestinal barrier function, meanwhile RhoA/ROCK2/MLCK signaling pathway has been confirmed vital in the maintenance of intestinal epithelial permeability. However, the specific mechanism by which BA protects intestine mucosal barrier still needs to be clarified. Here, the optimal time and concentration were explored. Then, cell growth status, TEER and FD-4 permeability, the mRNA expression of ZO-1 and Occludin, RhoA, ROCK2 and MLCK, and the expression and distribution of them in Caco2 were detected. After that, RhoA/ROCK2/MLCK pathway inhibitor Y-27632 was adopted. The final concentration of 0.2mM BA and 5ug/ml LPS treatment for 24 h was confirmed. Compared with LPS alone, BA improved the growth state of Caco2 cells, restored the declined TEER, reduced FD-4 permeability, improved the mRNA expression of ZO-1, Occludin and restored their distrbution, as well as inhibited the mRNA expression of RhoA, ROCK2 and MLCK, and the reversed their location. After treatment of Y-276432, the cell growth state and mucosal barrier function, the mRNA expression of ZO-1 and Occludin and their location were further improved, while the pathway was inhibitied. This study provided complementary data for BA as a potential target for attenuating LPS-induced intestinal barrier injury through inhibiting the RhoA/ROCK2/MLCKpathway.
Factors Influencing Open Science Participation Through Research Data Sharing and Reuse Among Researchers:
A Systematic Literature Review
Authors: Ahmed Mahfooz , Othman Roslina , Noordin Mohamad Fauzan
Published: October 2023

This systematic literature review investigates the influential factors guiding researchers' active engagement in open science through research data sharing and subsequent reuse, spanning various scientific disciplines. The review addresses key objectives and questions, including identifying distinct sample types, data collection methods, critical factors, and existing gaps within the body of literature concerning data sharing and reuse in open science. The methodology employed in the review was detailed, outlining a series of systematic steps. These steps encompass the systematic search and selection of relevant studies, rigorous data extraction and analysis, comprehensive evaluation of selected studies, and transparent reporting of the resulting findings. The review's evaluation process was governed by well-defined inclusion and exclusion criteria, encompassing publication dates, language, study design, and research outcomes. Furthermore, it adheres to the PRISMA 2020 flow diagram, effectively illustrating the progression of records through the review stages, highlighting the number of records identified, screened, included, and excluded. The findings include a concise tabular representation summarising data extracted from the 51 carefully selected studies incorporated within the review. The table provides essential details, including study citations, sample sizes, data collection methodologies, and key factors influencing open science data sharing and reuse. Additionally, common themes and categories among these influential factors are identified, shedding light on overarching trends in the field. In conclusion, this systematic literature review offers valuable insights into the multifaceted landscape of open science participation, emphasising the critical role of research data sharing and reuse. It is a comprehensive resource for researchers and practitioners interested in further understanding the dynamics and factors shaping the open science ecosystem.
Rationally-defined microbial consortia suppress multidrug-resistant proinflammatory Enterobacteriaceae via ecological control
Authors: Honda Kenya , Furuichi Munehiro , Kawaguchi Takaaki , Pust Marie-Madlen , Yasuma-Mitobe Keiko , Plichta Damian , Hasegawa Naomi , Ohya Takashi , Bhattarai Shakti , Sasajima Satoshi , Yoshimasa Aoto , Tuganbaev Timur , Yaginuma Mizuki , Ueda Masahiro , Okahashi Nobuyuki , Amafuji Kimiko , Kiridooshi Yuuko , Sugita Kayoko , Stražar Martin , Skelly Ashwin , Suda Wataru , Hattori Masahira , Nakamoto Nobuhiro , Caballero Silvia , Norman Jason , Olle Bernat , Tanoue Takeshi , Arita Makoto , Bucci Vanni , Atarashi Koji , Xavier Ramnik
Published: October 2023

Persistent colonization and outgrowth of pathogenic organisms in the intestine may occur due to long-term antibiotic usage or inflammatory conditions, which perpetuate dysregulated immunity and tissue damage1,2. Gram-negative Enterobacteriaceae gut pathobionts are particularly recalcitrant to conventional antibiotic treatment3,4, though an emerging body of evidence suggests that manipulation of the commensal microbiota may be a practical alternative therapeutic strategy5-7. In this study, we rationally isolated and down-selected commensal bacterial consortia from healthy human stool samples capable of strongly and specifically suppressing intestinal Enterobacteriaceae. One of the elaborated consortia, consisting of 18 commensal strains, effectively controlled ecological niches by regulating gluconate availability, thereby reestablishing colonization resistance and alleviating antibiotic-resistant Klebsiella-driven intestinal inflammation in mice. Harnessing these microbial activities in the form of live bacterial therapeutics may represent a promising solution to combat the growing threat of proinflammatory, antimicrobial-resistant bacterial infection.
microRNAs modulate immunological and inflammatory responses in Holstein cattle naturally infected with Mycobacterium avium subsp. paratuberculosis
Authors: Badia-Bringué Gerard , Canive Maria , Blanco-Vázquez Cristina , Torremocha Rosana , Ovalle Susana , Ramos Ricardo , Casais Rosa , Alonso-Hearn Marta
Published: October 2023

MicroRNAs (miRNAs) regulate the post-transcriptional expression of genes by binding to their target mRNAs. In this study, whole miRNA sequencing was used to compare the expression of miRNAs in ileocecal valve (ICV) and peripheral blood (PB) samples of cows with focal or diffuse paratuberculosis (PTB)-associated lesions in gut tissuesversus(vs) control cows without lesions. Among the eight miRNAs differentially expressed in the PB samples from cows with diffuse lesionsvscontrols, three (miR-19a, miR-144, miR32) were also down-regulated in cows with diffusevsfocal lesions. In the ICV samples, we identified a total of 4, 5, and 18 miRNAs differentially expressed in cows with focal lesionsvscontrols, diffuse lesionsvscontrols, and diffusevsfocal lesions, respectively. The expression changes observed in five of the differentially expressed microRNAs (miR-19a, miR-144, miR-2425-3p, miR-139, miR-101) were validated using RT-qPCR. Next, mRNA target prediction was performed for each differentially expressed miRNA. A functional analysis using the predicted gene targets revealed a significant enrichment of the RNA polymerase and MAPK signaling pathways in the comparison of cows with focalvsno lesions and with diffusevsfocal lesions, respectively. The identified miRNAs could be used for the development of novel diagnostic and therapeutical tools for PTB control.
A Distributed Approach to Meteorological Predictions: Addressing Data Imbalance in Precipitation Prediction Models through Federated Learning and GANs
Authors: Jafarigol Elaheh , Trafalis Theodore
Published: October 2023

The classification of weather data involves categorizing meteorological phenomena into classes, thereby facilitating nuanced analyses and precise predictions for various sectors such as agriculture, aviation, and disaster management. This involves utilizing machine learning models to analyze large, multidimensional weather datasets for patterns and trends. These datasets may include variables such as temperature, humidity, wind speed, and pressure, contributing to meteorological conditions. Furthermore, it’s imperative that classification algorithms proficiently navigate challenges such as data imbalances, where certain weather events (e.g., storms or extreme temperatures) might be underrepresented. This empirical study explores data augmentation methods to address imbalanced classes in tabular weather data in centralized and federated settings. Employing data augmentation techniques such as the Synthetic Minority Over-sampling Technique or Generative Adversarial Networks can improve the model's accuracy in classifying rare but critical weather events. Moreover, with advancements in federated learning, machine learning models can be trained across decentralized databases, ensuring privacy and data integrity while mitigating the need for centralized data storage and processing. Thus, the classification of weather data stands as a critical bridge, linking raw meteorological data to actionable insights, enhancing our capacity to anticipate and prepare for diverse weather conditions.
Comparison of the long-term efficacy of ROI-C and conventional cage-plate in treatment of spinal cord injury without fracture or dislocation: a retrospective study
Authors: Lu Hui , Li Renjie , Wang Cailin , Fang Mei , Qian Jianxue , Qian Bin , Song Yi , Jiang Xinchao , Chen Jie
Published: October 2023

Background
The self-locking cage (ROI-C, LDR, Troyes, France) has been clinically applied in treating cervical degenerative disc disease (CDDD). However, only a few long-term clinical and radiographic studies have been performed in the treatment of spinal cord injury without fracture or dislocation (SCIWFD) so far. A comparison between ACDF with either ROI-C or CCP was performed to determine the better treatment for SCIWFD.
Methods
A total of 83 patients who underwent ACDF using either ROI-C or CCP were reviewed for radiological and clinical outcomes. There are 60 males and 23 females, aged between 32 and 88 years old, with an average age of 58.23 years. All patients had symptoms of nerve injury, including limb numbness, muscle weakness, hypoesthesia or urinary dysfunction. Preoperative ASIA classification of spinal nerve function: 7 cases of grade A, 23 cases of grade B, 34 cases of grade C and 19 cases of grade D were included in the study.
Results
48 patients underwent ACDF with ROI-C and 35 patients with conventional cage-plate. They were studied with a follow-up of 28.63 ± 17.41 months and 29.48 ± 15.43 months respectively. No significant difference was found in blood loss, JOA and ASIA between the two groups. No significant difference was found in cervical lordosis (CL) (P > 0.05). Statistical difference was found in disc height of fused segment and T1 slope between the two groups (P < 0.05). No statistical difference was in the incidence of cage subsidence (P > 0.05). There was significant difference in the incidence of dysphagia. Both of two groups achieved bony fusion at final follow-up.
Conclusion
Our study demonstrated that ROI-C has the same efficacy as CCP in improving the cervical stability in treatment of SCIWFD. The migration of cage didn’t occur in ROI-C group at final follow-up, showing steadily fixed in cervical column. Moreover, the ROI-C does have the advantages of good therapeutic effect, mis-invasive, shorter operation time and fewer complications.
15-Year Analysis of Surgical Approaches and Outcomes for Coarctation in 132 Neonates and Infants
Authors: Jacobs Jeffrey P. , Sharaf Omar M. , Peek Giles J. , Pitkin Andrew D. , Beltran Susana C. Cruz , Lopez-Colon Dalia , Nixon Connie S. , Bleiweis Mark S. , Stukov Yuriy
Published: October 2023

Background: A variety of surgical approaches exist to treat aortic coarctation in neonates and infants. Our institutional approach is designed to match the surgical approach to the individual anatomy of the patient. The objective of this study is to evaluate operative characteristics and outcomes of all neonates and infants undergoing surgical repair of aortic coarctation or hypoplastic aortic arch.
Methods: Retrospective review of 132 patients aged 0-1 year who underwent surgical repair of coarctation or hypoplastic aortic arch between 2006 and 2021, inclusive, either in isolation or with concomitant repair of atrial septal defect (ASD) and/or ventricular septal defect (VSD). Patients were divided into two groups based on the surgical approach: Group 1 = Median Sternotomy and Group 2 = Left Lateral Thoracotomy. Continuous variables are presented as median (minimum-maximum); categorical variables are presented as N (%).
Results: The most common operative technique in Group 1 was end-to-side reconstruction with ligation of the aortic isthmus. The most common operative technique in Group 2 was extended end-to-end repair. Operative Mortality was one patient (1/132 = 0.76%). Transcatheter intervention for recurrent coarctation was performed in seven patients (7/132 = 5.3%). Surgical re-intervention for recurrent coarctation was performed in three patients (3/132 = 2.3%).
Conclusions: A strategy of matching the surgical approach to the anatomy for neonates and infants undergoing surgical repair of coarctation or hypoplastic aortic arch, either in isolation or with concomitant repair of ASD and/or VSD, is associated with <1% Operative Mortality and <3% recurrent coarctation requiring reoperation.
Estrogen-related receptor alpha promotes thyroid tumor cell survival via a tumor subtype-specific regulation of target gene networks
Authors: Chen* Wenjing , Song* Young Shin , Lee Han Sai , Lin Chien-Wei , Lee Junguee , Kang Yea Eun , Kim Seon-Kyu , Kim Seon-Young , Park Young Joo , Park Jong-In
Published: October 2023

Mortalin (encoded by HSPA9) is a mitochondrial chaperone often overexpressed in cancer through as-yet-unknown mechanisms. By searching different RNA-sequencing datasets, we found that ESRRA is a transcription factor highly correlated with HSPA9 in thyroid cancer, especially in follicular, but not C cell-originated, tumors. Consistent with this correlation, ESRRA depletion decreased mortalin expression only in follicular thyroid tumor cells. Further, ESRRA expression and activity were relatively high in thyroid tumors with oncocytic characteristics, wherein ESRRA and mortalin exhibited relatively high functional overlap. Mechanistically, ESRRA directly regulated HSPA9 transcription through a novel ESRRA-responsive element located upstream of the HSPA9 promoter. Physiologically, ESRRA depletion suppressed thyroid tumor cell survival via caspase-dependent apoptosis, which ectopic mortalin expression substantially abrogated. ESRRA depletion also effectively suppressed tumor growth and mortalin expression in the xenografts of oncocytic or ESRRA-overexpressing human thyroid tumor cells in mice. Notably, our Bioinformatics analyses of patient data revealed two ESRRA target gene clusters that contrast oncocytic-like and anaplastic features of follicular thyroid tumors. These findings suggest that ESRRA is a tumor-specific regulator of mortalin expression, the ESRRA-mortalin axis has higher significance in tumors with oncocytic characteristics, and ESRRA target gene networks can refine molecular classification of thyroid cancer.

*The authors would like to note that Wenjing Chen and Young Shin Song contributed equally to this work.
An electric kickscooter multibody model: equations of motion and linear stability analysis
Authors: Blanco Alfonso García-Agúndez , Vallejo Daniel García , Freire Emilio
Published: October 2023

In this work, a detailed multibody model of an electric kickscooter is presented. The model includes toroidal wheels as well as rear and front suspensions. The equations of motion are derived and linearized along the steady forward motion of the vehicle. The use of an efficient linearization approach, suitable for complex multibody systems with holonomic and nonholonomic constraints, allows for obtaining the reduced linearized equations of motion as a function of the geometric, dynamic, wheels’ and suspensions’ parameters. The proposed electric kickscooter multibody model is validated with the stability results of a previously presented electric kickscooter benchmark. Since the resulting eigenvalues are parameterized in terms of the design parameters, a detailed linear stability analysis of the system is performed. In particular, the influence on stability of the toroidal geometry of the wheels, the elliptic cross section of the toroidal wheels, the rider model, the steering axis inclination angle, the inertia tensor of the front frame, and the rear and front suspensions is analyzed. The model presented, together with the linearized equations of motion obtained in this work, enables a systematic analysis of the stability of these vehicles, which helps at designing new electric kickscooters with improved vehicle safety conditions and oriented to a wider range of potential users.
Evaluation of ELF-MF Exposure Levels for Elementary School Students in Indoor and Outdoor Environments
Authors: S.D.N.A.M. Amila Madhushanka Weerasinghe , Hong Seung-Cheol
Published: October 2023

This research investigation is focused on evaluating the possible health concerns that may arise for elementary school students due to their proximity to transmission and underground lines near their school. The primary goal of this research is to measure extremely low-frequency magnetic field (ELF-MF) levels during school hours and various other times of the day to ensure that these levels are in accordance with established safety standards, thereby safeguarding the well-being of both students and the school community. A total of 32 personal exposure measurements were collected from elementary students in the Gyeonggi-do region. These measurements encompassed a continuous 24-hour period, covering time spent at school, at home, during extracurricular activities, and in daily life. Some students displayed noticeable spikes in ELF-MF values, particularly during non-school hours, with levels reaching as high as 13.96 µT. This study underscores the significance of acknowledging the possible health risks associated with ELF-MF exposure stemming from common household devices. It emphasizes the importance of consistently maintaining and responsibly using microwave ovens and other electronic appliances to mitigate such risks. Furthermore, the research underscores the necessity for proactive measures aimed at minimizing children's exposure to ELF-MF within the school environment.