bluuebunny/crossref_metadata_2025_split huggingface dataset:
Polymorphism Pro64His within galectin-3 has functional consequences at proteome level in thyroid cells
Authors: Silvestri Roberto , Zallocco Lorenzo , Corrado Alda , Ronci Maurizio , Aceto Romina , Ricci Benedetta , Cipollini Monica , Dell’Anno Irene , De Simone Chiara , De Marco Giuseppina , Ferrarini Eleonora , Beghelli Daniela , Mazzoni Maria Rosa , Lucacchini Antonio , Gemignani Federica , Giusti Laura , Landi Stefano 
Published: June 2024

IntroductionThe single nucleotide polymorphism (SNP) rs4644 at codon 64 of galectin-3 (gal-3, gene name: LGALS3), specifying the variant proline (P64) to histidine (H64), is known to affect the protein’s functions and has been associated with the risk of several types of cancer, including differentiated thyroid carcinoma (DTC).Materials and methodsTo deepen our understanding of the biological effects of this SNP, we analyzed the proteome of two isogenic cell lines (NC-P64 vs. NA-H64) derived from the immortalized non-malignant thyrocyte cell line Nthy-Ori, generated through the CRISPR-Cas9 technique to differ by rs4644 genotype. We compared the proteome of these cells to detect differentially expressed proteins and studied their proteome in relation to their transcriptome.ResultsFirstly, we found, consistently with previous studies, that gal-3-H64 could be detected as a monomer, homodimer, and heterodimer composed of one cleaved and one uncleaved monomer, whereas gal-3-P64 could be found only as a monomer or uncleaved homodimer. Moreover, results indicate that rs4644 influences the expression of several proteins, predominantly upregulated in NA-H64 cells. Overall, the differential protein expression could be attributed to the altered mRNA expression, suggesting that rs4644 shapes the function of gal-3 as a transcriptional co-regulator. However, this SNP also appeared to affect post-transcriptional regulatory mechanisms for proteins whose expression was oppositely regulated compared to mRNA expression. It is conceivable that the rs4644-dependent activities of gal-3 could be ascribed to the different modalities of self-dimerization.ConclusionOur study provided further evidence that rs4644 could affect the gal-3 functions through several routes, which could be at the base of differential susceptibility to diseases, as reported in case-control association studies.
A novel host restriction factor MRPS6 mediates the inhibition of PDCoV infection in HIEC-6 cells
Authors: Jiang Yuhang , Zhang Guoqing , Li Letian , Chen Jing , Hao Pengfei , Gao Zihan , Hao Jiayi , Xu Zhiqiang , Wang Maopeng , Li Chang , Jin Ningyi 
Published: June 2024

IntroductionPorcine deltacoronavirus (PDCoV) is a zoonotic pathogen with a global distribution, capable of infecting both pigs and humans. To mitigate the risk of cross-species transmission and potential outbreaks, it is crucial to characterize novel antiviral genes, particularly those from human hosts.MethodsThis research used HIEC-6 to investigate PDCoV infection. HIEC-6 cells were infected with PDCoV. Samples were collected 48 h postinfection for proteomic analysis.ResultsWe discovered differential expression of MRPS6 gene at 48 h postinfection with PDCoV in HIEC-6 cells. The gene expression initially increased but then decreased. To further explore the role of MRPS6 in PDCoV infection, we conducted experiments involving the overexpression and knockdown of this gene in HIEC-6 and Caco2 cells, respectively. Our findings revealed that overexpression of MRPS6 significantly inhibited PDCoV infection in HIEC-6 cells, while knockdown of MRPS6 in Caco2 cells led to a significant increase of virus titer. Furthermore, we investigated the correlation between PDCoV infection and the expression of MRPS6. Subsequent investigations demonstrated that MRPS6 exerted an augmentative effect on the production of IFN-β through interferon pathway activation, consequently impeding the progression of PDCoV infection in cellular systems. In conclusion, this study utilized proteomic analysis to investigate the differential protein expression in PDCoV-infected HIEC-6 cells, providing evidence for the first time that the MRPS6 gene plays a restrictive role in PDCoV virus infection.DiscussionOur findings initially provide the validation of MRPS6 as an upstream component of IFN-β pathway, in the promotion of IRF3, IRF7, STAT1, STAT2 and IFN-β production of HIEC-6 via dual-activation from interferon pathway.
Plasma metabolites as mediators in immune cell-pancreatic cancer risk: insights from Mendelian randomization
Authors: Zhang Ke , Zhu Jie , Wang Peng , Chen Yuan , Wang Zhengwang , Ge Xinyu , Wu Junqing , Chen Long , Lu Yipin , Xu Peng , Yao Jie 
Published: June 2024

BackgroundImmune cells play a crucial role in the development and progression of pancreatic cancer, yet the causal relationship remains uncertain due to complex immune microenvironments and conflicting research findings. Mendelian randomization (MR), this study aims to delineate the causal relationships between immune cells and pancreatic cancer while identifying intermediary factors.MethodsThe genome-wide association study (GWAS) data on immune cells, pancreatic cancer, and plasma metabolites are derived from public databases. In this investigation, inverse variance weighting (IVW) as the primary analytical approach to investigate the causal relationship between exposure and outcome. Furthermore, this study incorporates MR-Egger, simple mode, weighted median, and weighted mode as supplementary analytical approaches. To ensure the reliability of our findings, we further assessed horizontal pleiotropy and heterogeneity and evaluated the stability of MR results using the Leave-one-out method. In conclusion, this study employed mediation analysis to elucidate the potential mediating effects of plasma metabolites.ResultsOur investigation revealed a causal relationship between immune cells and pancreatic cancer, highlighting the pivotal roles of CD11c+ monocytes (odds ratio, ORIVW=1.105; 95% confidence interval, 95%CI: 1.002–1.218; P=0.045), HLA DR+ CD4+ antigen-presenting cells (ORIVW=0.920; 95%CI: 0.873–0.968; P=0.001), and HLA DR+ CD8br T cells (ORIVW=1.058; 95%CI: 1.002–1.117; P=0.041) in pancreatic cancer progression. Further mediation analysis indicated that oxalate (proportion of mediation effect in total effect: -11.6%, 95% CI: -89.7%, 66.6%) and the mannose to trans-4-hydroxyproline ratio (-19.4, 95% CI: -136%, 96.8%) partially mediate the relationship between HLA DR+ CD8br T cells and pancreatic cancer in nature. In addition, our analysis indicates that adrenate (-8.39%, 95% CI: -18.3%, 1.54%) plays a partial mediating role in the association between CD11c+ monocyte and pancreatic cancer, while cortisone (-26.6%, 95% CI: 138%, -84.8%) acts as a partial mediator between HLA DR+ CD4+ AC and pancreatic cancer.ConclusionThis MR investigation provides evidence supporting the causal relationship between immune cell and pancreatic cancer, with plasma metabolites serving as mediators. Identifying immune cell phenotypes with potential causal effects on pancreatic cancer sheds light on its underlying mechanisms and suggests novel therapeutic targets.
PD-L1 has a heterogeneous and dynamic expression in gastric cancer with implications for immunoPET
Authors: Ibrahim Dina , Simó Cristina , Brown Emma L. , Shmuel Shayla , Panikar Sandeep Surendra , Benton Alex , DeWeerd Rachel , Dehdashti Farrokh , Park Haeseong , Pereira Patrícia M. R. 
Published: June 2024

IntroductionThis study aimed to investigate the dynamics of programmed death-ligand 1 (PD-L1) expression, spatial heterogeneity, and binding affinity of FDA-approved anti-PD-L1 antibodies (avelumab and atezolizumab) in gastric cancer. Additionally, we determined how PD-L1 glycosylation impacts antibody accumulation in gastric cancer cells.MethodsDynamic PD-L1 expression was examined in NCIN87 gastric cancer cells. Comparative binding studies of avelumab and atezolizumab were conducted in gastric cancer models, both in vitro and in vivo. Antibody uptake in tumors was visualized through positron emission tomography (PET) imaging. PD-L1 glycosylation status was determined via Western blot analyses before and after PNGase F treatment. ResultsConsistent findings revealed time-dependent PD-L1 induction in NCIN87 gastric cancer cells and spatial heterogeneity in tumors, as shown by PET imaging and immunofluorescence. Avelumab displayed superior binding affinity to NCIN87 cells compared to atezolizumab, confirmed by in vivo PET imaging and ex vivo biodistribution analyses. Notably, PD-L1 glycosylation at approximately 50 kDa was observed, with PNGase F treatment inducing a shift to 35 kDa in molecular weight. Tissue samples from patient-derived xenografts (PDXs) validated the presence of both glycosylated and deglycosylated PD-L1 (degPD-L1) forms in gastric cancer. Immunofluorescence microscopy and binding assays demonstrated enhanced avelumab binding post-deglycosylation. DiscussionThis study provides an understanding of dynamic and spatially heterogeneous PD-L1 expression in gastric cancer. Anti-PD-L1 immunoPET was able to visualize gastric tumors, and PD-L1 glycosylation has significant implications for antibody recognition. These insights contribute to demonstrating the complexities of PD-L1 in gastric cancer, holding relevance for refining PD-L1 imaging-based approaches.
T cell-related ubiquitination genes as prognostic indicators in hepatocellular carcinoma
Authors: Chen Chaobo , Chen Zheng , Zhou Zheyu , Ye Hui , Xiong Shaohui , Hu Weidong , Xu Zipeng , Ge Chen , Zhao Chunlong , Yu Decai , Shen Jiapei 
Published: June 2024

BackgroundT lymphocytes, integral to the adaptive immune system, wield pivotal influence in bolstering anti-tumor responses, and are strictly regulated by ubiquitination modification. The objective of this investigation was to devise a novel prognostic and immunotherapeutic efficacy predictor for hepatocellular carcinoma patients utilizing T cell-related ubiquitination genes (TCRUG).MethodThe single-cell RNA sequencing (scRNA-seq) data and bulk RNA data of HCC patients are derived from the GEO database and TCGA database. Based on the processing of scRNA-seq, T cell marker genes are obtained and TCRUG is obtained. Further combined with WGCNA, differential analysis, univariate Cox regression analysis, LASSO analysis, and multivariate Cox regression analysis to filter and screen TCRUG. Finally construct a riskscore for predicting the prognosis of HCC patients, the predictive effect of which is validated in the GEO dataset. In addition, we also studied the correlation between riskscore and immunotherapy efficacy. Finally, the oncogenic role of UBE2E1 in HCC was explored through various in vitro experiments.ResultBased on patients’ scRNA-seq data, we finally obtained 3050 T cell marker genes. Combined with bulk RNA data and clinical data from the TCGA database, we constructed a riskscore that accurately predicts the prognosis of HCC patients. This riskscore is an independent prognostic factor for HCC and is used to construct a convenient column chart. In addition, we found that the high-risk group is more suitable for immunotherapy. Finally, the proliferation, migration, and invasion abilities of HCC cells significantly decreased after UBE2E1 expression reduction.ConclusionThis study developed a riskscore based on TCRUG that can accurately and stably predict the prognosis of HCC patients. This riskscore is also effective in predicting the immune therapy response of HCC patients.
Numerical modeling of bamboo fences with various infill porosities deployed for mangrove restoration
Authors: Shu Anping , Zhang Ziru , Cui Baoshan , Zhuo Yiyuan , Zhang Xin , Pi Chengling , Zhu Fuyang , Christian Huarez 
Published: June 2024

As part of mangrove restoration initiatives eco-friendly fence has been implemented in eroded coastal areas in recent years. These fences provide the capacity to mitigate incoming wave energy and facilitate sediment deposition, thereby promoting the establishment and maintenance of mangrove habitats. Nevertheless, it is crucial to investigate the influence of the infill porosity on the wave dissipation performance of these fences, as the infill porosity can vary considerably across different restoration projects. The aim of this research is to explore the relationship between the infill porosity and wave dissipation effectiveness to identify more efficient designs for these eco-friendly restoration measures. The experiments involving wave interactions with fence models were conducted in a wave flume measuring 0.8 m in width and 25 m in length. Four wooden fences with distinct infill porosities ranging from 0.60 to 0.90 were strategically positioned to assess wave transmission, reflection, and dissipation phenomena under 18 distinct wave conditions. Additionally, the simulating waves till shore (SWASH)model was employed to calibrate critical bulk drag coefficient parameters and simulate the flow velocity distribution surrounding the fences under the experimental wave conditions. The findings indicated that a fence with a reduced infill porosity exhibits a higher wave transmission coefficient. However, this is accompanied by a higher reflection coefficient and lower wave energy dissipation within the fence. Both the infill porosity and incident wave conditions influence the flow velocity distribution characteristics in the vicinity of the fences. The area where the interaction between waves and fences is the most prominent is concentrated in the upper water layer immediately adjacent to the frontal section of the fences. Understanding the velocity distribution and hydrodynamic characteristics of the fence area aids in better determining the suitable porosity of fill materials for engineering applications.
Acute-on-chronic: using magnetic resonance imaging to disentangle the haemodynamic responses to acute and chronic fetal hypoxaemia
Authors: Darby Jack R. T. , Saini Brahmdeep S. , Holman Stacey L. , Hammond Sarah J. , Perumal Sunthara Rajan , Macgowan Christopher K. , Seed Mike , Morrison Janna L. 
Published: June 2024

IntroductionThe fetal haemodynamic response to acute episodes of hypoxaemia are well characterised. However, how these responses change when the hypoxaemia becomes more chronic in nature such as that associated with fetal growth restriction (FGR), is less well understood. Herein, we utilised a combination of clinically relevant MRI techniques to comprehensively characterize and differentiate the haemodynamic responses occurring during acute and chronic periods of fetal hypoxaemia.MethodsPrior to conception, carunclectomy surgery was performed on non-pregnant ewes to induce FGR. At 108–110 days (d) gestational age (GA), pregnant ewes bearing control (n = 12) and FGR (n = 9) fetuses underwent fetal catheterisation surgery. At 117–119 days GA, ewes underwent MRI sessions where phase-contrast (PC) and T2 oximetry were used to measure blood flow and oxygenation, respectively, throughout the fetal circulation during a normoxia and then an acute hypoxia state.ResultsFetal oxygen delivery (DO2) was lower in FGR fetuses than controls during the normoxia state but cerebral DO2 remained similar between fetal groups. Acute hypoxia reduced both overall fetal and cerebral DO2. FGR increased ductus venosus (DV) and foramen ovale (FO) blood flow during both the normoxia and acute hypoxia states. Pulmonary blood flow (PBF) was lower in FGR fetuses during the normoxia state but similar to controls during the acute hypoxia state when PBF in controls was decreased.ConclusionDespite a prevailing level of chronic hypoxaemia, the FGR fetus upregulates the preferential streaming of oxygen-rich blood via the DV-FO pathway to maintain cerebral DO2. However, this upregulation is unable to maintain cerebral DO2 during further exposure to an acute episode of hypoxaemia. The haemodynamic alterations required at the level of the liver and lung to allow the DV-FO pathway to maintain cerebral DO2, may have lasting consequences on hepatic function and pulmonary vascular regulation after birth.
Designing and implementing a training program on surgical hand scrubbing, wearing surgical cap and surgical mask, gowning, and gloving using HMD-based virtual reality technologies for nursing students: an exploration of student perceptions
Authors: Güngör Songül , Yava Ayla , Koyuncu Aynur 
Published: June 2024

ObjectiveThe aim of this study is to determine the steps of a training program utilizing Head-Mounted Display (HMD) based Virtual Reality Technology to enhance nursing students’ skills in surgical hand scrubbing, wearing surgical cap and surgical mask, gowning and gloving, and to evaluate students’ perceptions toward the program.MethodsThe study aimed to investigate the potential applications of HMD-Based Virtual Reality Technology in Surgical Hand Scrubbing, Wearing Surgical Cap and Surgical Mask, Gowning and Gloving Program for nursing students, as well as students’ perceptions toward this technology. The research was conducted with a focus group consisting of second-year nursing students in Osmaniye/Turkey, between January and June 2022, and the training program was implemented in five stages: Analysis, Design, Development, Implementation, and Evaluation. The program was evaluated with a focus group of nursing students. Focus group discussions were conducted to provide insights into students’ experiences, feedback, and perceptions of the program.ResultsA vast majority of participants (92.5%) reported feeling fully immersed in the operating room environment during the virtual reality (VR) experience. Notably, all students acknowledged the potential of HMD-Based Virtual Reality Technology to enrich their understanding of surgical hand scrubbing, wearing surgical cap and surgical mask, gowning and gloving procedures, surpassing conventional instructional models. While many participants found the experience exhilarating (85.1%), a considerable portion reported a decline in engagement after repeated exposures (88.8%). Overall, participants welcomed the integration of VR technology into education, expressing optimism about its capacity to facilitate additional instructional modules (74.4%). Moreover, they conveyed satisfaction with the opportunity to engage with the VR application, emphasizing its significant educational value (81.4%).ConclusionBased on these findings, we can suggest that virtual reality technology has the potential to have an impact on nursing students’ education. The majority of students expressing a sense of presence in the operating room highlights the value of this method in education. However, the reported boredom after repeated experiences by most participants underscores the importance of diversifying the program and introducing innovative approaches to keep students engaged.
Association between volume of lung damage and endoplasmic reticulum stress expression among severe COVID-19 ICU patients
Authors: Renard Domitille , Verdalle-Cazes Mikael , Leprêtre Perrine , Bellien Jérémy , Brunel Valery , Renet Sylvanie , Tamion Fabienne , Besnier Emmanuel , Clavier Thomas 
Published: June 2024

IntroductionLinks have been established between SARS-CoV-2 and endoplasmic reticulum stress (ERS). However, the relationships between inflammation, ERS, and the volume of organ damage are not well known in humans. The aim of this study was to explore whether ERS explains lung damage volume (LDV) among COVID-19 patients admitted to the intensive care unit (ICU).Materials and methodsWe conducted a single-center retrospective study (ancillary analysis of a prospective cohort) including severe COVID-19 ICU patients who had a chest computed tomography (CT) scan 24 h before/after admission to assess LDV. We performed two multivariate linear regression models to identify factors associated with plasma levels of 78 kDa-Glucose-Regulated Protein (GRP78; ERS marker) and Interleukin-6 (IL-6; inflammation marker) at admission.ResultsAmong 63 patients analyzed, GRP78 plasma level was associated with LDV in both multivariate models (β = 22.23 [4.08;40.38]; p = 0.0179, β = 20.47 [0.74;40.20]; p = 0.0423) but not with organ failure (Sequential Organ Failure Assessment (SOFA) score) at admission (r = 0.03 [−0.22;0.28]; p = 0.2559). GRP78 plasma level was lower among ICU survivors (1539.4 [1139.2;1941.1] vs. 1714.2 [1555.2;2579.1] pg./mL. respectively; p = 0.0297). IL-6 plasma level was associated with SOFA score at admission in both multivariate models (β = 136.60 [65.50;207.70]; p = 0.0003, β = 193.70 [116.60;270.90]; p &lt; 0.0001) but not with LDV (r = 0.13 [−0.14;0.39]; p = 0.3219). IL-6 plasma level was not different between ICU survivors and non-survivors (12.2 [6.0;43.7] vs. 30.4 [12.9;69.7] pg./mL. respectively; p = 0.1857). There was no correlation between GRP78 and IL-6 plasma levels (r = 0.13 [−0.13;0.37]; p = 0.3106).ConclusionAmong severe COVID-19 patients, ERS was associated with LDV but not with systemic inflammation, while systemic inflammation was associated with organ failure but not with LDV.
Protection from prior natural infection vs. vaccination against SARS-CoV-2—a statistical note to avoid biased interpretation
Authors: Weber Susanne , Hedberg Pontus , Naucler Pontus , Wolkewitz Martin 
Published: June 2024

IntroductionThe fight against SARS-CoV-2 has been a major task worldwide since it was first identified in December 2019. An imperative preventive measure is the availability of efficacious vaccines while there is also a significant interest in the protective effect of a previous SARS-CoV-2 infection on a subsequent infection (natural protection rate).MethodsIn order to compare protection rates after infection and vaccination, researchers consider different effect measures such as 1 minus hazard ratio, 1 minus odds ratio, or 1 minus risk ratio. These measures differ in a setting with competing risks. Nevertheless, as there is no unique definition, these metrics are frequently used in studies examining protection rate. Comparison of protection rates via vaccination and natural infection poses several challenges. For instance many publications consider the epidemiological definition, that a reinfection after a SARS-CoV-2 infection is only possible after 90 days, whereas there is no such constraint after vaccination. Furthermore, death is more prominent as a competing event during the first 90 days after infection compared to vaccination. In this work we discuss the statistical issues that arise when investigating protection rates comparing vaccination with infection. We explore different aspects of effect measures and provide insights drawn from different analyses, distinguishing between the first and the second 90 days post-infection or vaccination.ResultsIn this study, we have access to real-world data of almost two million people from Stockholm County, Sweden. For the main analysis, data of over 52.000 people is considered. The infected group is younger, includes more men, and is less morbid compared to the vaccinated group. After the first 90 days, these differences increased. Analysis of the second 90 days shows differences between analysis approaches and between age groups. There are age-related differences in mortality. Considering the outcome SARS-CoV-2 infection, the effect of vaccination versus infection varies by age, showing a disadvantage for the vaccinated in the younger population, while no significant difference was found in the elderly.DiscussionTo compare the effects of immunization through infection or vaccination, we emphasize consideration of several investigations. It is crucial to examine two observation periods: The first and second 90-day intervals following infection or vaccination. Additionally, methods to address imbalances are essential and need to be used. This approach supports fair comparisons, allows for more comprehensive conclusions and helps prevent biased interpretations.