bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasma ceramides are associated with MRI-based liver fat content but not with noninvasive scores of liver fibrosis in patients with type 2 diabetes
Authors: Denimal Damien , Béland-Bonenfant Sarah , Pais-de-Barros Jean-Paul , Rouland Alexia , Bouillet Benjamin , Duvillard Laurence , Vergès Bruno , Petit Jean-Michel 
Published: November 2023

Abstract
Background
There is growing evidence that ceramides play a significant role in the onset and progression of non-alcoholic fatty liver disease (NAFLD), a highly prevalent condition in patients with type 2 diabetes associated with hepatic and cardiovascular events. However, the relationship between plasma ceramide levels and NAFLD severity in type 2 diabetes remains unclear. The main purpose of the present study was to investigate whether circulating levels of ceramides in patients with type 2 diabetes are associated with liver steatosis assessed by the highly accurate magnetic resonance imaging proton density fat fraction (MRI-PDFF). The secondary objective was to assess the relationship between plasma ceramides and noninvasive scores of liver fibrosis.

Methods
In this cross-sectional single-center study, plasma concentrations of 7 ceramides were measured by liquid chromatography-mass spectrometry in 255 patients with type 2 diabetes (GEPSAD cohort). Liver fat content was assessed by MRI-PDFF, and noninvasive scores of liver fibrosis (i.e. Fibrosis-4 index, NAFLD Fibrosis Score, FibroTest® and Fibrotic NASH Index) were calculated. A validation cohort of 80 patients with type 2 diabetes was also studied (LIRA-NAFLD cohort).

Results
Liver steatosis, defined as a liver fat content > 5.56%, was found in 62.4 and 82.5% of individuals with type 2 diabetes in the GEPSAD and LIRA-NAFLD cohorts, respectively. In GEPSAD, MRI-PDFF-measured liver fat content was positively associated with plasma levels of total ceramides (r = 0.232, p = 0.0002), and 18:0, 20:0, 22:0 and 24:0 ceramides in univariate analysis (p ≤ 0.0003 for all). In multivariate analysis, liver fat content remained significantly associated with total ceramides (p = 0.001), 18:0 (p = 0.006), 22:0 (p = 0.0009) and 24:0 ceramides (p = 0.0001) in GEPSAD, independently of age, diabetes duration, body mass index and dyslipidemia. Overall, similar relationship between plasma ceramides and liver fat content was observed in the LIRA-NAFLD validation cohort. No significant association was found between plasma ceramides and noninvasive scores of fibrosis after adjustment for age in both cohorts.

Conclusions
Plasma ceramide levels are associated with liver steatosis in patients with type 2 diabetes, independently of traditional risk factors for NAFLD. The independent association between plasma ceramides and liver steatosis adds new insights regarding the relationship between ceramides and NAFLD in type 2 diabetes.
VISTA and its ligands: the next generation of promising therapeutic targets in immunotherapy
Authors: Shekari Najibeh , Shanehbandi Dariush , Kazemi Tohid , Zarredar Habib , Baradaran Behzad , Jalali Seyed Amir 
Published: November 2023

AbstractV-domain immunoglobulin suppressor of T cell activation (VISTA) is a novel negative checkpoint receptor (NCR) primarily involved in maintaining immune tolerance. It has a role in the pathogenesis of autoimmune disorders and cancer and has shown promising results as a therapeutic target. However, there is still some ambiguity regarding the ligands of VISTA and their interactions with each other. While V-Set and Immunoglobulin domain containing 3 (VSIG-3) and P-selectin glycoprotein ligand-1(PSGL-1) have been extensively studied as ligands for VISTA, the others have received less attention. It seems that investigating VISTA ligands, reviewing their functions and roles, as well as outcomes related to their interactions, may allow an understanding of their full functionality and effects within the cell or the microenvironment. It could also help discover alternative approaches to target the VISTA pathway without causing related side effects. In this regard, we summarize current evidence about VISTA, its related ligands, their interactions and effects, as well as their preclinical and clinical targeting agents.
Unveiling the etiology of peritonsillar abscess using next generation sequencing
Authors: Saar Merili , Vaikjärv Risto , Parm Ülle , Kasenõmm Priit , Kõljalg Siiri , Sepp Epp , Jaagura Madis , Salumets Andres , Štšepetova Jelena , Mändar Reet 
Published: November 2023

Abstract
Background
Peritonsillar abscess (PTA) is a severe deep neck space infection with an insufficiently characterized bacterial etiology. We aimed to reveal the bacteria associated with PTA applying next generation sequencing (NGS). Tonsil biopsies and pus samples of 91 PTA patients were analysed applying NGS method.

Results
Over 400 genera and 800 species belonging to 34 phyla were revealed. The most abundant species in both sample types were Streptococcus pyogenes, Fusobacterium necrophorum and Fusobacterium nucleatum. When present, S. pyogenes was normally a predominant species, although it was recovered as a minor population in some samples dominated by F. nucleatum and occasionally F. necrophorum. S. pyogenes and F. necrophorum were the predominant species (> 10% in a community) in 28 (31%) pus samples, while F. nucleatum in 21 (23%) and S. anginosus in 8 (9%) pus samples. We observed no substantial differences between the microbial findings in pus and tonsil biopsies.

Conclusions
The most probable causative agents of PTA according to our NGS-study include Streptococcus pyogenes, Fusobacterium necrophorum and Fusobacterium nucleatum. Some other streptococci (S. anginosus) and anaerobes (Prevotella, Porphyromonas) may contribute to the infection as well. Pus of the peritonsillar abscess is more representative specimen for microbiological examination than the tonsillar tissue. Our results are important in the context of optimizing the handling of the PTA patients.
ITGB1 alleviates osteoarthritis by inhibiting cartilage inflammation and apoptosis via activating cAMP pathway
Authors: Xie Lifeng , Li Zhengnan , Chen Zhijun , Li Mingzhang , Tao Jun 
Published: November 2023

Abstract
Objective
We aimed to screen novel biomarkers for osteoarthritis (OA) using bioinformatic methods and explore its regulatory mechanism in OA development.

Methods
Differentially expressed genes were screened out from GSE98918 and GSE82107 datasets. Protein–protein interaction network and enrichment analysis were employed to search for hub gene and regulatory pathway. Hematoxylin–eosin, Safranin O-Fast green staining, and immunohistochemistry were performed to assess pathological damage. TNF-α, IL-1β, and IL-6 concentrations were determined by enzyme-linked immunosorbent assay. Real-time quantitative PCR was applied to verify expression of hub genes in OA model. The expression of key protein and pathway proteins was determined by western blot. Furthermore, Cell Counting Kit-8 and flow cytometry were conducted to explore the role of hub gene in chondrocytes.

Results
We identified 6 hub genes of OA, including ITGB1, COL5A1, COL1A1, THBS2, LAMA1, and COL12A1, with high prediction value. ITGB1 was screened as a pivotal regulator of OA and cAMP pathway was selected as the key regulatory pathway. ITGB1 was down-regulated in OA model. ITGB1 overexpression attenuated pathological damage and apoptosis in OA rats with the reduced levels of TNF-α, IL-1β and IL-6. ITGB1 overexpression activated cAMP pathway in vivo and vitro models. In vitro model, ITGB1 overexpression promoted cell viability, while inhibited apoptosis. ITGB1 overexpression also caused a decrease of TNF-α, IL-1β, and IL-6 concentrations. cAMP pathway inhibitor reversed the positive effect of ITGB1 on OA cell model.

Conclusion
ITGB1 is a novel biomarker for OA, which inhibits OA development by activating the cAMP pathway.
Baicalein improves the chemoresistance of ovarian cancer through regulation of CirSLC7A6
Authors: Li Shuqing , Yi Zhihui , Li Mingqing , Zhu Zhiling 
Published: November 2023

Abstract
Purpose
The present study aimed to investigate whether baicalein improves the sensitivity of resistant ovarian cancer cells to cisplatin.

Methods
Transcriptomic sequencing and bioinformatics analysis were used to screen differentially expressed CirSLC7A6 in A2780 and A2780/CDDP cells. RT-qPCR was performed to examine the expression levels of CirSLC7A6, miR-2682-5p, and SLC7A6. Cell proliferation and apoptosis were examined using a Cell Counting Kit-8 assay and flow cytometry, and cell migration and invasion were analyzed using wound healing and Transwell assays. Cell suspensions were inoculated into the subcutaneous tissues of the bilateral interscapular region of nude mice. Saline, cisplatin, baicalein and cisplatin plus baicalein were intraperitoneally injected to observe the effects on tumor growth. Toxicity analyses in the liver and kidney were performed using H&E staining. RT-qPCR and immunohistochemistry were used to detect the expression of CirSLC7A6, miR-2682-5p, and SLC7A6 in tumor tissues, and western blot analysis was carried out to measure protein expression levels.

Results
CirSLC7A6 was markedly upregulated in A2780/CDDP cells compared with the A2780 cells. CirSLC7A6 knockdown notably increased the expression of miR-2682-5p and decreased SLC7A6 expression. The rates of inhibition and apoptosis in the group treated with a combination of cisplatin and baicalein were significantly higher than those of the cisplatin and baicalein groups of A2780/CDDP shCirSLC7A6 cells. In A2780/CDDP shCirSLC7A6 cells, migration and invasion were significantly higher in the cisplatin and baicalein groups, compared with the combined treatment group. In the A2780/CDDP shCirSLC7A6 cell xenograft, the tumor weight of the combined treatment group was significantly lower than that of the cisplatin and baicalein groups. In addition, the combination of cisplatin and baicalein did not induce higher levels of toxicity in the liver or kidney. Baicalein alone and in combination with cisplatin notably reduced the expression of CirSLC7A6 and SLC7A6, and increased the expression of miR-2682-5p in the A2780/CDDP shCirSLC7A6 cell xenograft. In A2780/CDDP shCirSLC7A6 cells, the expression levels of P-Akt, P-mTOR, P-Erk, Bcl-2 and MMP2 were lower in the combined treatment group than in the control group.

Conclusions
Treatment with baicalein improved the sensitivity of ovarian cancer cells to cisplatin and inhibited cell proliferation, metastasis and tumor growth.
Reliability of pulse pressure and stroke volume variation in assessing fluid responsiveness in the operating room: a metanalysis and a metaregression
Authors: Messina Antonio , Caporale Mariagiovanna , Calabrò Lorenzo , Lionetti Giulia , Bono Daniele , Matronola Guia Margherita , Brunati Andrea , Frassanito Luciano , Morenghi Emanuela , Antonelli Massimo , Chew Michelle S. , Cecconi Maurizio 
Published: November 2023

Abstract
Background
Pulse pressure and stroke volume variation (PPV and SVV) have been widely used in surgical patients as predictors of fluid challenge (FC) response. Several factors may affect the reliability of these indices in predicting fluid responsiveness, such as the position of the patient, the use of laparoscopy and the opening of the abdomen or the chest, combined FC characteristics, the tidal volume (Vt) and the type of anesthesia.

Methods
Systematic review and metanalysis of PPV and SVV use in surgical adult patients. The QUADAS-2 scale was used to assess the risk of bias of included studies. We adopted a metanalysis pooling of aggregate data from 5 subgroups of studies with random effects models using the common-effect inverse variance model. The area under the curve (AUC) of pooled receiving operating characteristics (ROC) curves was reported. A metaregression was performed using FC type, volume, and rate as independent variables.

Results
We selected 59 studies enrolling 2,947 patients, with a median of fluid responders of 55% (46–63). The pooled AUC for the PPV was 0.77 (0.73–0.80), with a mean threshold of 10.8 (10.6–11.0). The pooled AUC for the SVV was 0.76 (0.72–0.80), with a mean threshold of 12.1 (11.6–12.7); 19 studies (32.2%) reported the grey zone of PPV or SVV, with a median of 56% (40–62) and 57% (46–83) of patients included, respectively. In the different subgroups, the AUC and the best thresholds ranged from 0.69 and 0.81 and from 6.9 to 11.5% for the PPV, and from 0.73 to 0.79 and 9.9 to 10.8% for the SVV. A high Vt and the choice of colloids positively impacted on PPV performance, especially among patients with closed chest and abdomen, or in prone position.

Conclusion
The overall performance of PPV and SVV in operating room in predicting fluid responsiveness is moderate, ranging close to an AUC of 0.80 only some subgroups of surgical patients. The grey zone of these dynamic indices is wide and should be carefully considered during the assessment of fluid responsiveness. A high Vt and the choice of colloids for the FC are factors potentially influencing PPV reliability.
Trial Registration: PROSPERO (CRD42022379120), December 2022. https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=379120
Bayesian methods: a potential path forward for sepsis trials
Authors: Tomlinson George , Al-Khafaji Ali , Conrad Steven A. , Factora Faith N. F. , Foster Debra M. , Galphin Claude , Gunnerson Kyle J. , Khan Sobia , Kohli-Seth Roopa , McCarthy Paul , Meena Nikhil K. , Pearl Ronald G. , Rachoin Jean-Sebastien , Rains Ronald , Seneff Michael , Tidswell Mark , Walker Paul M. , Kellum John A. 
Published: November 2023

Abstract
Background
Given the success of recent platform trials for COVID-19, Bayesian statistical methods have become an option for complex, heterogenous syndromes like sepsis. However, study design will require careful consideration of how statistical power varies using Bayesian methods across different choices for how historical data are incorporated through a prior distribution and how the analysis is ultimately conducted. Our objective with the current analysis is to assess how different uses of historical data through a prior distribution, and type of analysis influence results of a proposed trial that will be analyzed using Bayesian statistical methods.

Methods
We conducted a simulation study incorporating historical data from a published multicenter, randomized clinical trial in the US and Canada of polymyxin B hemadsorption for treatment of endotoxemic septic shock. Historical data come from a 179-patient subgroup of the previous trial of adult critically ill patients with septic shock, multiple organ failure and an endotoxin activity of 0.60–0.89. The trial intervention consisted of two polymyxin B hemoadsorption treatments (2 h each) completed within 24 h of enrollment.

Results
In our simulations for a new trial of 150 patients, a range of hypothetical results were observed. Across a range of baseline risks and treatment effects and four ways of including historical data, we demonstrate an increase in power with the use of clinically defensible incorporation of historical data. In one possible trial result, for example, with an observed reduction in risk of mortality from 44 to 37%, the probability of benefit is 96% with a fixed weight of 75% on prior data and 90% with a commensurate (adaptive-weighting) prior; the same data give an 80% probability of benefit if historical data are ignored.

Conclusions
Using Bayesian methods and a biologically justifiable use of historical data in a prior distribution yields a study design with higher power than a conventional design that ignores relevant historical data. Bayesian methods may be a viable option for trials in critical care medicine where beneficial treatments have been elusive.

Graphical abstract
Green chromatographic methods for determination of co-formulated lidocaine hydrochloride and miconazole nitrate along with an endocrine disruptor preservative and potential impurity
Authors: Ashour Esraa S. , Hegazy Maha A. , Al-Alamein Amal M. Abou , El-Sayed Ghada M. , Ghoniem Nermine S. 
Published: November 2023

AbstractRecently, green analytical chemistry (GAC) is a key issue towards the idea of sustainability, the analytical community is focused on developing analytical methods that incorporate green chemistry principles to minimize adverse impacts on the environment and humans. Herein, we present 2 sustainable, selective, and validated chromatographic methods. Initially, lidocaine hydrochloride (LDC) and miconazole nitrate (MIC) with two preservatives; methyl paraben (MTP) and saccharin sodium (SAC) were chromatographed via TLC–densitometric method which employed ethyl acetate: methanol: formic acid (9:1:0.1, by volume) as the mobile phase with UV detection at 220.0 nm, good correlation was obtained in the range of 0.3–3.0 µg/band for MIC and LDC. Following that, RP-HPLC was successfully applied for separating quinary mixture of LDC, MIC, MTP, SAC along with LDC impurity; dimethyl aniline (DMA) using C18 column, and a gradient green mobile phase composed of methanol and phosphate buffer (pH 6.0) in different ratios with a flow rate 1.5 mL/min and UV detection at 210.0 nm, linearity ranges from 1.00 to 100.00 µg/mL for MIC, 2.00–100.00 µg/mL for LDC and 1.00–-20.00 µg/mL for MTP and DMA. No records to date regarding the determination of the two drugs, besides MTP and DMA. The proposed methods were validated according to the ICH guidelines and applied successfully to the analysis of the compounds. The methods' results were statistically compared to those obtained by applying the reported one, indicating no significant difference regarding both accuracy and precision. The methods' greenness profiles have been assessed and compared with those of the reported method using different assessment tools.
Graphical Abstract
Developing an analytical method for quantification of trientine based on modified silver nanoparticles
Authors: Khodadadi Mahsa , Shayanfar Ali 
Published: November 2023

AbstractTrientine or (N,N´-bis(2-aminoethyl)-1,2-ethanediamine (TETA) is a copper chelator and used in Wilson’s disease, is aliphatic amine that does not have UV absorbing groups. In this study, the modified silver nanoparticles (AgNPs) by sodium lauryl sulfate have been used to develop an analytical method for quantification of TETA. Different concentrations of TETA were added into a particular concentration of AgNPs and absorbance of each sample was measured at 397 nm under the optimal conditions which include pH, time, salt and AgNPs volume. It was optimized by a design of experiments using response surface methodology. Then, the calibration curve was obtained based on the concentrations of TETA solution versus decrease in the absorbance of AgNPs. Selectivity of the developed method was performed in plasma and presence of common cations i.e. copper, zinc and ferrous. Under optimum conditions, linear range of this method was between 10 and 40 ng.mL− 1 with correlation coefficient (R2) of 0.996 with limit of detection and quantification of 3 ng.mL− 1 and 10 ng.mL− 1, respectively. Selectivity of established method in presence of cations eliminated by diluting because of high sensitivity of the established analytical techniques based on AgNPs. This method is suitable and low costing for quantification of TETA and does not require high equipment.
Integrating properties and conditions to predict spray performance of alternative aviation fuel by ANN model
Authors: Liu Ziyu , Tang Zimu , Yang Xiaoyi 
Published: November 2023

AbstractAlternative aviation fuel has been confirmed benefits for GHGs reduction and energy saving. Alternative fuel use should meet drop-in fuel requirement, and one of the important factors to ensure combustion completeness is to achieve spray requirement in the whole envelop of flight. Alternative fuels are characterized different fuel properties at low temperature comparison with traditional jet fuel. For understanding fuel properties and spray-related processes under different conditions, alternative aviation fuel, including Fischer Tropsch (FT), cellulose hydrotreating jet fuel (CHJ) and traditional jet fuel (RP-3), were investigated spray performance. According to empirical equation deduced from experiment data (283 K-343 K), deviations to RP-3 enhanced significantly on surface tension and viscosity at low temperature aera (243 K-273 K). As the complex and discontinuous interaction between nozzle structure and fuel properties with temperature, and thus it is difficult to obtain appropriate empirical equation or simulation results at low temperature. Moreover, non-drop-in fuel like pure FT fuel cannot comply with the same spray mechanism as drop-in fuel. The artificial neural network (ANN) approaches have been involved to solve the complex relationship of properties with spray performance. ANN-spray model coupling with ANN-mass flow can predict not only cone angle and liquid length but also SMD and velocity in liquid zone and droplet zone with above 0.99 total correlation coefficient. Coupling simulation results of mass flow and spray performance, FT and CHJ as well as blend fuels present more obvious difference to RP-3 in droplet size distribution and velocity distribution at low temperature.
Spatial transferability of an agent-based model to simulate Taenia solium control interventions
Authors: Pizzitutti Francesco , Bonnet Gabrielle , Gonzales-Gustavson Eloy , Gabriël Sarah , Pan William K. , Gonzalez Armando E. , Garcia Hector H. , O’Neal Seth E. ,   for the Cysticercosis Working Group in Peru
Published: November 2023

Abstract
Background
Models can be used to study and predict the impact of interventions aimed at controlling the spread of infectious agents, such as Taenia solium, a zoonotic parasite whose larval stage causes epilepsy and economic loss in many rural areas of the developing nations. To enhance the credibility of model estimates, calibration against observed data is necessary. However, this process may lead to a paradoxical dependence of model parameters on location-specific data, thus limiting the model’s geographic transferability.

Methods
In this study, we adopted a non-local model calibration approach to assess whether it can improve the spatial transferability of CystiAgent, our agent-based model of local-scale T. solium transmission. The calibration dataset for CystiAgent consisted of cross-sectional data on human taeniasis, pig cysticercosis and pig serology collected in eight villages in Northwest Peru. After calibration, the model was transferred to a second group of 21 destination villages in the same area without recalibrating its parameters. Model outputs were compared to pig serology data collected over a period of 2 years in the destination villages during a trial of T. solium control interventions, based on mass and spatially targeted human and pig treatments.

Results
Considering the uncertainties associated with empirical data, the model produced simulated pre-intervention pig seroprevalences that were successfully validated against data collected in 81% of destination villages. Furthermore, the model outputs were able to reproduce validated pig seroincidence values in 76% of destination villages when compared to the data obtained after the interventions. The results demonstrate that the CystiAgent model, when calibrated using a non-local approach, can be successfully transferred without requiring additional calibration.

Conclusions
This feature allows the model to simulate both baseline pre-intervention transmission conditions and the outcomes of control interventions across villages that form geographically homogeneous regions, providing a basis for developing large-scale models representing T. solium transmission at a regional level.

Graphical Abstract