bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validation of a method evaluating T cell metabolic potential in compliance with ICH Q2 (R1)
Authors: Mercier-Letondal Patricia , Marton Chrystel , Godet Yann , Galaine Jeanne 
Published: January 2021

AbstractBackgroundMetabolic cell features are able to give reliable information on cell functional state. Thus, metabolic potential assessment of T cells in malignancy setting represents a promising area, especially in adoptive cell therapy procedures. Easy to set up and convenient Seahorse technology have recently been proposed by Agilent Technologies and it could be used to monitor T cells metabolic potential. However, this method demonstrates an inter-assay variability and lacks practices standardization.ResultsWe aimed to overcome these shortcomings thanks to a lymphoblastic derived JURKAT cell line seeding in each experiment to standardize the Seahorse process. We used an adapted XF Cell MitoStress Kit protocol, consisting in the evaluation of basal, stressed and maximal glycolysis and oxidative phosphorylation related parameters, through sequential addition of oligomycin and carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (FCCP) to a glucose containing medium. Data were acquired and analyzed through Agilent Seahorse XFe96 analyzer. Indeed, we validated this method in the light of ICH Q2 (R1) guidelines. We were able to confirm the specificity and accuracy of the method. We also demonstrated the precision, linearity and range of the method in our experimental conditions.ConclusionThe validation of the method consisting in a JURKAT cell line experimental incorporation as a control material contributes to improve the Seahorse technology’s robustness. These results lay the groundwork for the implementation of this technology to optimize T cell based cellular therapy products production process and monitoring.
Development of nomogram based on immune-related gene FGFR4 for advanced non-small cell lung cancer patients with sensitivity to immune checkpoint inhibitors
Authors: Wang Li , Ren Zhixuan , Yu Bentong , Tang Jian 
Published: January 2021

Abstract
Introduction
Immune checkpoint inhibitors (ICIs) have become a frontier in the field of clinical technology for advanced non-small cell lung cancer (NSCLC). Currently, the predictive biomarker of ICIs mainly including the expression of PD-L1, TMB, TIICs, MMR and MSI-H. However, there are no official biomarkers to guide the treatment of ICIs and to determine the prognosis. Therefore, it is essential to explore a systematic nomogram to predict the prognosis of ICIs treatment in NSCLC

Methods
In this work, we obtained gene expression and clinical data of NSCLC patients from the TCGA database. Immune-related genes (IRGs) were downloaded from the ImmPort database. The detailed clinical annotation and response data of 240 advanced NSCLC patients who received ICIs treatment were obtained from the cBioPortal for Cancer Genomics. Kaplan–Meier survival analysis was used to perform survival analyses, and selected clinical variables to develop a novel nomogram. The prognostic significance of FGFR4 was validated by another cohort in cBioPortal for Cancer Genomics.

Results
3% of the NSCLC patients harbored FGFR4 mutations. The mutation of FGFR4 were confirmed to be associated with PD-L1, and TMB. Patients harbored FGFR4 mutations were found to have a better prolonged progression-free survival (PFS) to ICIs treatment (FGFR4: P = 0.0209). Here, we built and verified a novel nomogram to predict the prognosis of ICIs treatment for NSCLC patients.

Conclusion
Our results showed that FGFR4 could serve as novel biomarkers to predict the prognosis of ICIs treatment of advanced NSCLC. Our systematic prognostic nomogram showed a great potential to predict the prognosis of ICIs for advanced NSCLC patients.
Anti-migraine agents from an immunological point of view
Authors: Assas Mushref Bakri 
Published: January 2021

AbstractThe new wave of anti-migraine agents is nothing less than a milestone in our battle to manage this devastating disease. However, concerns have recently increased regarding the safety of these drugs. CGRP, while known as a potent vasodilator, is also a key neural and immune modulator. The roles of CGRP in immune determination, have been studied in depth, with particular focus on its functional significance with respect to common immune challenges i.e., bacterial, viral, fungal and parasitic infections. This review discusses many potential areas of concern in regard to blocking CGRP function and its potential influence on immune milieus during infection, and the risk of adverse effects. Finally, this review recommends specific measures to be taken into consideration when administering anti-CGRP/CGRPR agents.
An analytical method for the identification of cell type-specific disease gene modules
Authors: Guan Jinting , Lin Yiping , Wang Yang , Gao Junchao , Ji Guoli 
Published: January 2021

AbstractBackgroundGenome-wide association studies have identified genetic variants associated with the risk of brain-related diseases, such as neurological and psychiatric disorders, while the causal variants and the specific vulnerable cell types are often needed to be studied. Many disease-associated genes are expressed in multiple cell types of human brains, while the pathologic variants affect primarily specific cell types. We hypothesize a model in which what determines the manifestation of a disease in a cell type is the presence of disease module comprised of disease-associated genes, instead of individual genes. Therefore, it is essential to identify the presence/absence of disease gene modules in cells.MethodsTo characterize the cell type-specificity of brain-related diseases, we construct human brain cell type-specific gene interaction networks integrating human brain nucleus gene expression data with a referenced tissue-specific gene interaction network. Then from the cell type-specific gene interaction networks, we identify significant cell type-specific disease gene modules by performing statistical tests.ResultsBetween neurons and glia cells, the constructed cell type-specific gene networks and their gene functions are distinct. Then we identify cell type-specific disease gene modules associated with autism spectrum disorder and find that different gene modules are formed and distinct gene functions may be dysregulated in different cells. We also study the similarity and dissimilarity in cell type-specific disease gene modules among autism spectrum disorder, schizophrenia and bipolar disorder. The functions of neurons-specific disease gene modules are associated with synapse for all three diseases, while those in glia cells are different. To facilitate the use of our method, we develop an R package, CtsDGM, for the identification of cell type-specific disease gene modules.ConclusionsThe results support our hypothesis that a disease manifests itself in a cell type through forming a statistically significant disease gene module. The identification of cell type-specific disease gene modules can promote the development of more targeted biomarkers and treatments for the disease. Our method can be applied for depicting the cell type heterogeneity of a given disease, and also for studying the similarity and dissimilarity between different disorders, providing new insights into the molecular mechanisms underlying the pathogenesis and progression of diseases.
Model based on five tumour immune microenvironment-related genes for predicting hepatocellular carcinoma immunotherapy outcomes
Authors: Gu Xinyu , Guan Jun , Xu Jia , Zheng Qiuxian , Chen Chao , Yang Qin , Huang Chunhong , Wang Gang , Zhou Haibo , Chen Zhi , Zhu Haihong 
Published: January 2021

Abstract
Background
Although the tumour immune microenvironment is known to significantly influence immunotherapy outcomes, its association with changes in gene expression patterns in hepatocellular carcinoma (HCC) during immunotherapy and its effect on prognosis have not been clarified.

Methods
A total of 365 HCC samples from The Cancer Genome Atlas liver hepatocellular carcinoma (TCGA-LIHC) dataset were stratified into training datasets and verification datasets. In the training datasets, immune-related genes were analysed through univariate Cox regression analyses and least absolute shrinkage and selection operator (LASSO)-Cox analyses to build a prognostic model. The TCGA-LIHC, GSE14520, and Imvigor210 cohorts were subjected to time-dependent receiver operating characteristic (ROC) and Kaplan–Meier survival curve analyses to verify the reliability of the developed model. Finally, single-sample gene set enrichment analysis (ssGSEA) was used to study the underlying molecular mechanisms.

Results
Five immune-related genes (LDHA, PPAT, BFSP1, NR0B1, and PFKFB4) were identified and used to establish the prognostic model for patient response to HCC treatment. ROC curve analysis of the TCGA (training and validation sets) and GSE14520 cohorts confirmed the predictive ability of the five-gene-based model (AUC > 0.6). In addition, ROC and Kaplan–Meier analyses indicated that the model could stratify patients into a low-risk and a high-risk group, wherein the high-risk group exhibited worse prognosis and was less sensitive to immunotherapy than the low-risk group. Functional enrichment analysis predicted potential associations of the five genes with several metabolic processes and oncological signatures.

Conclusions
We established a novel five-gene-based prognostic model based on the tumour immune microenvironment that can predict immunotherapy efficacy in HCC patients.
Do geography and ethnicity play a role in juvenile Spondyloarthritis? A multi-center binational retrospective study
Authors: Ghantous Nassem , Heshin-Bekenstein Merav , Dequattro Kimberly , Lakovsky Yaniv , Hendel Amir Moshe , Rappoport Nadav , Aviel Yonatan Butbul , Tirosh Irit , Harel Liora , Weiss Pamela F. , Gensler Lianne , Mackenzie John , Amarilyo Gil 
Published: January 2021

Abstract
Background
Observations among Israeli pediatric rheumatologists reveal that pediatric Juvenile Spondyloarthritis (JSpA) may present differently compared to patients from the United States (US). This study is aimed to compare the demographic and clinical variables of Israeli and US JSpA patients upon presentation.

Methods
We performed a retrospective, cross-sectional, multicenter comparison of JSpA patients among 3 large Israeli pediatric rheumatology centers and a large US pediatric rheumatology center. Patients with diagnosis of Juvenile Ankylosing Spondylitis (JAS) and/or Enthesitis-related Arthritis (ERA) were included. The demographic, clinical and radiologic features were compared.

Results
Overall 87 patients were included (39 Israeli, 48 US patients). Upon presentation, inflammatory back pain, sacroiliac joint tenderness and abnormal modified Schober test, were significantly more prevalent among Israeli patients (59% vs. 35.4, 48.7% vs. 16.7, and 41.2% vs. 21.5%, respectively, all p < 0.05), whereas peripheral arthritis and enthesitis were significantly more prevalent among US patients (43.6% vs. 91.7 and 7.7% vs. 39.6% in Israeli patients vs. US patients, p < 0.05). In addition, 96.7% of the Israeli patients versus 29.7% of the US patients demonstrated sacroiliitis on MRI (p < 0.001, N = 67). Less than one-third of the Israeli patients (32%) were HLA-B27 positive vs. 66.7% of US patients (p = 0.007).

Conclusion
Israeli children with JSpA presented almost exclusively with axial disease compared to US patients who were more likely to present with peripheral symptoms. HLA B27 prevalence was significantly lower in the Israeli cohort compared to the US cohort. Further studies are needed to unravel the genetic and possibly environmental factors associated with these findings.
Microglial inflammation after chronic spinal cord injury is enhanced by reactive astrocytes via the fibronectin/β1 integrin pathway
Authors: Yoshizaki Shingo , Tamaru Tetsuya , Hara Masamitsu , Kijima Ken , Tanaka Masatake , Konno Dai-jiro , Matsumoto Yoshihiro , Nakashima Yasuharu , Okada Seiji 
Published: January 2021

AbstractBackgroundAfter spinal cord injury (SCI), glial scarring is mainly formed around the lesion and inhibits axon regeneration. Recently, we reported that anti-β1 integrin antibody (β1Ab) had a therapeutic effect on astrocytes by preventing the induction of glial scar formation. However, the cellular components within the glial scar are not only astrocytes but also microglia, and whether or not β1Ab treatment has any influence on microglia within the glial scar remains unclear.MethodsTo evaluate the effects of β1Ab treatment on microglia within the glial scar after SCI, we applied thoracic contusion SCI to C57BL/6N mice, administered β1Ab in the sub-acute phase, and analyzed the injured spinal cords with immunohistochemistry in the chronic phase. To examine the gene expression in microglia and glial scars, we selectively collected microglia with fluorescence-activated cell sorting and isolated the glial scars using laser-captured microdissection (LMD). To examine the interaction between microglia and astrocytes within the glial scar, we stimulated BV-2 microglia with conditioned medium of reactive astrocytes (RACM) in vitro, and the gene expression of TNFα (pro-inflammatory M1 marker) was analyzed via quantitative polymerase chain reaction. We also isolated both naïve astrocytes (NAs) and reactive astrocytes (RAs) with LMD and examined their expression of the ligands for β1 integrin receptors. Statistical analyses were performed using Wilcoxon’s rank-sum test.ResultsAfter performing β1Ab treatment, the microglia were scattered within the glial scar and the expression of TNFα in both the microglia and the glial scar were significantly suppressed after SCI. This in vivo alteration was attributed to fibronectin, a ligand of β1 integrin receptors. Furthermore, the microglial expression of TNFα was shown to be regulated by RACM as well as fibronectin in vitro. We also confirmed that fibronectin was secreted by RAs both in vitro and in vivo. These results highlighted the interaction mediated by fibronectin between RAs and microglia within the glial scar.ConclusionMicroglial inflammation was enhanced by RAs via the fibronectin/β1 integrin pathway within the glial scar after SCI. Our results suggested that β1Ab administration had therapeutic potential for ameliorating both glial scar formation and persistent neuroinflammation in the chronic phase after SCI.
Statistical field theory of the transmission of nerve impulses
Authors: Zangari del Balzo Gianluigi 
Published: January 2021

AbstractBackgroundStochastic processes leading voltage-gated ion channel dynamics on the nerve cell membrane are a sufficient condition to describe membrane conductance through statistical mechanics of disordered and complex systems.ResultsVoltage-gated ion channels in the nerve cell membrane are described by the Ising model. Stochastic circuit elements called “Ising Neural Machines” are introduced. Action potentials are described as quasi-particles of a statistical field theory for the Ising system.ConclusionsThe particle description of action potentials is a new point of view and a powerful tool to describe the generation and propagation of nerve impulses, especially when classical electrophysiological models break down.The particle description of action potentials allows us to develop a new generation of devices to study neurodegenerative and demyelinating diseases as Multiple Sclerosis and Alzheimer’s disease, even integrated by connectomes. It is also suitable for the study of complex networks, quantum computing, artificial intelligence, machine and deep learning, cryptography, ultra-fast lines for entanglement experiments and many other applications of medical, physical and engineering interest.
A numerical simulation of air flow in the human respiratory system for various environmental conditions
Authors: Issakhov Alibek , Zhandaulet Yeldos , Abylkassymova Aizhan , Issakhov Assylbek 
Published: January 2021

AbstractThe functions of the nasal cavity are very important for maintaining the internal environment of the lungs since the inner walls of the nasal cavity control the temperature and saturation of the inhaled air with water vapor until the nasopharynx is reached. In this paper, three-dimensional computational studies of airflow transport in the models of the nasal cavity were carried out for the usual inspiratory velocity in various environmental conditions. Three-dimensional numerical results are compared with experimental data and calculations of other authors. Numerical results show that during normal breathing, the human nose copes with heat and relative moisture metabolism in order to balance the intra-alveolar conditions. It is also shown in this paper that a normal nose can maintain balance even in extreme conditions, for example, in cold and hot weather. The nasal cavity accelerates heat transfer by narrowing the air passages and swirls from the nasal concha walls of the inner cavity.
Potential challenges to sustained viral load suppression in the HIV treatment programme in South Africa: a narrative overview
Authors: Bessong Pascal O. , Matume Nontokozo D. , Tebit Denis M. 
Published: January 2021

AbstractBackgroundSouth Africa, with one of the highest HIV prevalences in the world, introduced the universal test and treat (UTT) programme in September 2016. Barriers to sustained viral suppression may include drug resistance in the pre-treated population, non-adherence, acquired resistance; pharmacokinetics and pharmacodynamics, and concurrent use of alternative treatments.ObjectiveThe purpose of this review is to highlight potential challenges to achieving sustained viral load suppression in South Africa (SA), a major expectation of the UTT initiative.MethodologyThrough the PRISMA approach, published articles from South Africa on transmitted drug resistance; adherence to ARV; host genetic factors in drug pharmacokinetics and pharmacodynamics, and interactions between ARV and herbal medicine were searched and reviewed.ResultsThe level of drug resistance in the pre-treated population in South Africa has increased over the years, although it is heterogeneous across and within Provinces. At least one study has documented a pre-treated population with moderate (> 5%) or high (> 15%) levels of drug resistance in eight of the nine Provinces. The concurrent use of ARV and medicinal herbal preparation is fairly common in SA, and may be impacting negatively on adherence to ARV. Only few studies have investigated the association between the genetically diverse South African population and pharmacokinetics and pharmacodynamics of ARVs.ConclusionThe increasing levels of drug resistant viruses in the pre-treated population poses a threat to viral load suppression and the sustainability of first line regimens. Drug resistance surveillance systems to track the emergence of resistant viruses, study the burden of prior exposure to ARV and the parallel use of alternative medicines, with the goal of minimizing resistance development and virologic failure are proposed for all the Provinces of South Africa. Optimal management of the different drivers of drug resistance in the pre-treated population, non-adherence, and acquired drug resistance will be beneficial in ensuring sustained viral suppression in at least 90% of those on treatment, a key component of the 90-90-90 strategy.
Combined Lycium barbarum polysaccharides and C-phycocyanin increase gastric Bifidobacterium relative abundance and protect against gastric ulcer caused by aspirin in rats
Authors: Hsieh Shu-Yu , Lian Yu Zhi , Lin I-Hsuan , Yang Yu-Chen , Tinkov Alexey A. , Skalny Anatoly V. , Chao Jane C.-J. 
Published: January 2021

Abstract
Background
Non-steroidal anti-inflammatory drugs such as aspirin are used for the treatment of cardiovascular disease. Chronic use of low-dose aspirin is associated with the occurrence of gastric ulcer. The aim of this study was to investigate the healing potential of Lycium barbarum polysaccharides (LBP) from Chinese Goji berry and C-phycocyanin (CPC) from Spirulina platensis on gastric ulcer in rats.

Methods
Male Sprague–Dawley rats were divided into five groups: normal, aspirin (700 mg/kg bw), LBP (aspirin + 100 mg/kg bw/d LBP), CPC (aspirin + 50 mg/kg bw/d CPC), and MIX (aspirin + 50 mg/kg bw/d LBP + 25 mg/kg bw/d CPC) groups. Gastric ulcer was developed by daily oral feeding of aspirin for 8 weeks. Treatments were given orally a week before ulcer induction for 9 weeks.

Results
The MIX group elevated gastric cyclooxygenase-1, prostaglandin E2, and total nitrite and nitrate levels by 139%, 86%, and 66%, respectively, compared with the aspirin group (p < 0.05). Moreover, the MIX group reduced lipid peroxides malondialdehyde levels by 78% (p < 0.05). The treatment of LBP and/or CPC increased gastric Bifidobacterium relative abundance by 2.5–4.0 times compared with the aspirin group (p < 0.05).

Conclusions
We conclude that combined LBP and CPC enhance gastroprotective factors, inhibit lipid peroxidation, and increase gastric Bifidobacterium relative abundance. Combined LBP and CPC have protective potential against gastric ulcer caused by aspirin in rats.
New field wind manipulation methodology reveals adaptive responses of steppe plants to increased and reduced wind speed
Authors: Zhang Shudong , Liu Guofang , Cui Qingguo , Huang Zhenying , Ye Xuehua , Cornelissen Johannes H. C. 
Published: January 2021

Abstract
Background
Wind strongly impacts plant growth, leaf traits, biomass allocation, and stem mechanical properties. However, whether there are common whole-plant wind responses among different plant species is still unclear. We tested this null hypothesis by exposing four eudicot steppe species to three different wind treatments in a field experiment: reduced wind velocity using windbreaks, ambient wind velocity, and enhanced wind velocity through a novel methodology using wind-funneling baffles.

Results
Across the four species, wind generally decreased plant height, projected crown area, and stepwise bifurcation ratio, and increased root length and stem base diameter. In contrast, the response patterns of shoot traits, especially mechanical properties, to wind velocity were idiosyncratic among species. There was no significant difference in total biomass among different treatments; this might be because the negative effects on heat dissipation and photosynthesis of low wind speed during hot periods, could counteract positive effects during favorable cooler periods.

Conclusions
There are common wind response patterns in plant-size-related traits across different steppe species, while the response patterns in shoot traits vary among species. This indicates the species-specific ways by which plants balance growth and mechanical support facing wind stress. Our new field wind manipulation methodology was effective in altering wind speed with the intended magnitude. Especially, our field wind-funneling baffle system showed a great potential for use in future field wind velocity enhancement. Further experiments are needed to reveal how negative and positive effects play out on whole-plant performance in response to different wind regimes, which is important as ongoing global climatic changes involve big changes in wind regimes.