bluuebunny/crossref_metadata_2025_split huggingface dataset:
A comprehensive preimplantation genetic testing approach for SEA-type α-thalassemia by fluorescent gap-polymerase chain reaction combined with haplotype analysis
Authors: Wang Jing , Ma Yuanlin , Guo Jing , Li Rong , Zhou Canquan , Xu Yanwen 
Published: November 2023

Introduction: This study aimed to evaluate the feasibility and necessity of using fluorescence Gap-polymerase chain reaction combined with haplotype analysis in preimplantation genetic testing for SEA-type α-thalassemia.Methods: A total of 26 preimplantation genetic testing biopsy cycles were performed in 25 families from June 2021 to February 2022. All couples were carriers of SEA-type α-thalassemia. Fluorescent Gap-polymerase chain reaction was used for detecting fragment deletion. Subsequently, according to the results of polymerase chain reaction, reference embryos were identified to establish haplotype using single nucleotide polymorphism array, and aneuploidy was screened simultaneously. In cases wherein the polymerase chain reaction results were inconsistent with the haplotype results, the reasons were investigated, either by retest of the biopsied samples or rebiopsy of the embryo.Results: Among the 172 embryos, 162 had consistent results when tested using both methods, resulting in a consistency rate of 94.2%. Conversely, 10 embryos had inconsistent results, mainly due to chromosome 16 aneuploidy (n = 7), allele dropout in Gap-polymerase chain reaction (n = 2), or incorrect haplotype due to poor sample amplification quality (n = 1). The clinical pregnancy rate of each frozen-thawed embryo transfer was 57.7% (15/26). Six families underwent prenatal diagnosis, which confirmed the results of preimplantation genetic testing.Conclusion: Fluorescent Gap-polymerase chain reaction combined with haplotype analysis is feasible and necessary for SEA-type α-thalassemia preimplantation genetic testing.
A two-sample Mendelian randomization analysis: causal association between chemokines and pan-carcinoma
Authors: Cui Kai , Song Na , Fan Yanwu , Zeng Liqun , Shi Pingyu , Wang Ziwei , Su Wei , Wang Haijun 
Published: November 2023

Objective: According to the 2020 data from the World Health Organization (WHO), cancers stand as one of the foremost contributors to global mortality. Revealing novel cancer risk factors and protective factors is of paramount importance in the prevention of disease occurrence. Studies on the relationship between chemokines and cancer are ongoing; however, due to the coordination of multiple potential mechanisms, the specific causal association remains unclear.Methods: We performed a bidirectional Mendelian randomization analysis to explore the causal association between serum chemokines and pan-carcinoma. All data is from the GWAS catalog and IEU Open GWAS database. The inverse-variance weighted (IVW) method is primarily employed for assessing the statistical significance of the findings. In addition, the significance threshold after the multiple hypothesis test (Bonferroni) was 0.0013, and the evidence of a potential association was considered if the p-value &lt; 0.05, but remained greater than Bonferroni’s threshold.Results: The results indicate that CCL1 (odds ratio, OR = 1.18), CCL2 (OR = 1.04), CCL8 (OR = 1.36), CCL14 (Colorectal, OR = 1.08, Small intestine, OR = 0.77, Lung, OR = 1.11), CCL15 (OR = 0.85), CCL18 (Breast, OR = 0.95, Prostate, OR = 0.96), CCL19 (Lung, OR = 0.66, Prostate, OR = 0.92), CCL20 (Lung, OR = 0.53, Thyroid, OR = 0.76), CCL21 (OR = 0.62), CCL22 (OR = 2.05), CCL23 (OR = 1.31), CCL24 (OR = 1.06), CCL27 (OR = 1.49), CCL28 (OR = 0.74), CXCL5 (OR = 0.95), CXCL9 (OR = 3.60), CXCL12 (Breast, OR = 0.87, Small intestine, OR = 0.58), CXCL13 (Breast, OR = 0.93, Lung, OR = 1.29), CXCL14 (Colon, OR = 1.40) and CXCL17 (OR = 1.07) are potential risk factors for cancers. In addition, there was a reverse causal association between CCL1 (OR = 0.94) and CCL18 (OR = 0.94) and breast cancer. Sensitivity analysis results were similar. The results of the other four MR Methods were consistent with the main results, and the leave-one-out method showed that the results were not driven by a Single nucleotide polymorphism (SNP). Moreover, there was no heterogeneity and pleiotropy in our analysis.Conclusion: Based on the two-sample MR Analysis method, we found that chemokines might be upstream factors of cancer pathogenesis. These results might provide new insights into the future use of chemokines as potential targets for cancer prevention and treatment. Our results also provide important clues for tumor prevention, and changes of serum chemokine concentration may be recognized as one of the features of precancerous lesions in future clinical trials.
More rapid blood interferon α2 decline in fatal versus surviving COVID-19 patients
Authors: Joly Candie , Desjardins Delphine , Porcher Raphael , Péré Hélène , Bruneau Thomas , Zhang Qian , Bastard Paul , Cobat Aurélie , Resmini Léa , Lenoir Olivia , Savale Laurent , Lécuroux Camille , Verstuyft Céline , Roque-Afonso Anne-Marie , Veyer David , Baron Gabriel , Resche-Rigon Matthieu , Ravaud Philippe , Casanova Jean-Laurent , Le Grand Roger , Hermine Olivier , Tharaux Pierre-Louis , Mariette Xavier 
Published: November 2023

BackgroundThe clinical outcome of COVID-19 pneumonia is highly variable. Few biological predictive factors have been identified. Genetic and immunological studies suggest that type 1 interferons (IFN) are essential to control SARS-CoV-2 infection.ObjectiveTo study the link between change in blood IFN-α2 level and plasma SARS-Cov2 viral load over time and subsequent death in patients with severe and critical COVID-19.MethodsOne hundred and forty patients from the CORIMUNO-19 cohort hospitalized with severe or critical COVID-19 pneumonia, all requiring oxygen or ventilation, were prospectively studied. Blood IFN-α2 was evaluated using the Single Molecule Array technology. Anti-IFN-α2 auto-Abs were determined with a reporter luciferase activity. Plasma SARS-Cov2 viral load was measured using droplet digital PCR targeting the Nucleocapsid gene of the SARS-CoV-2 positive-strand RNA genome.ResultsAlthough the percentage of plasmacytoid dendritic cells was low, the blood IFN-α2 level was higher in patients than in healthy controls and was correlated to SARS-CoV-2 plasma viral load at entry. Neutralizing anti-IFN-α2 auto-antibodies were detected in 5% of patients, associated with a lower baseline level of blood IFN-α2. A longitudinal analysis found that a more rapid decline of blood IFN-α2 was observed in fatal versus surviving patients: mortality HR=3.15 (95% CI 1.14–8.66) in rapid versus slow decliners. Likewise, a high level of plasma SARS-CoV-2 RNA was associated with death risk in patients with severe COVID-19.ConclusionThese findings could suggest an interest in evaluating type 1 IFN treatment in patients with severe COVID-19 and type 1 IFN decline, eventually combined with anti-inflammatory drugs.Clinical trial registrationhttps://clinicaltrials.gov, identifiers NCT04324073, NCT04331808, NCT04341584.
Construction of an acute myeloid leukemia prognostic model based on m6A-related efferocytosis-related genes
Authors: Wang Ying , Bin Ting , Tang Jing , Xu Xiao-Jun , Lin Chao , Lu Bo , Sun Tian-Tian 
Published: November 2023

BackgroundOne of the most prevalent hematological system cancers is acute myeloid leukemia (AML). Efferocytosis-related genes (ERGs) and N6-methyladenosine (m6A) have an important significance in the progression of cancer, and the metastasis of tumors.MethodsThe AML-related data were collected from The Cancer Genome Atlas (TCGA; TCGA-AML) database and Gene Expression Omnibus (GEO; GSE9476, GSE71014, and GSE13159) database. The “limma” R package and Venn diagram were adopted to identify differentially expressed ERGs (DE-ERGs). The m6A related-DE-ERGs were obtained by Spearman analysis. Subsequently, univariate Cox and Least Absolute Shrinkage and Selection Operator (LASSO) were used to construct an m6A related-ERGs risk signature for AML patients. The possibility of immunotherapy for AML was explored. The pRRophetic package was adopted to calculate the IC50 of drugs for the treatment of AML. Finally, the expression of characterized genes was validated by quantitative reverse transcription-PCR (qRT-PCR).ResultsBased on m6A related-DE-ERGs, a prognostic model with four characteristic genes (UCP2, DOCK1, SLC14A1, and SLC25A1) was constructed. The risk score of model was significantly associated with the immune microenvironment of AML, with four immune cell types, 14 immune checkpoints, 20 HLA family genes and, immunophenoscore (IPS) all showing differences between the high- and low-risk groups. A total of 56 drugs were predicted to differ between the two groups, of which Erlotinib, Dasatinib, BI.2536, and bortezomib have been reported to be associated with AML treatment. The qRT-PCR results showed that the expression trends of DOCK1, SLC14A1 and SLC25A1 were consistent with the bioinformatics analysis.ConclusionIn summary, 4 m6A related- ERGs were identified and the corresponding prognostic model was constructed for AML patients. This prognostic model effectively stratified the risk of AML patients.
A2A adenosine receptor-driven cAMP signaling in olfactory bulb astrocytes is unaffected in experimental autoimmune encephalomyelitis
Authors: Wendlandt Marina , Kürten Alina J. , Beiersdorfer Antonia , Schubert Charlotte , Samad-Yazdtchi Kiana , Sauer Jessica , Pinto M. Carolina , Schulz Kristina , Friese Manuel A. , Gee Christine E. , Hirnet Daniela , Lohr Christian 
Published: November 2023

IntroductionThe cyclic nucleotide cyclic adenosine monophosphate (cAMP) is a ubiquitous second messenger, which is known to play an important anti-inflammatory role. Astrocytes in the central nervous system (CNS) can modulate inflammation but little is known about the significance of cAMP in their function.MethodsWe investigated cAMP dynamics in mouse olfactory bulb astrocytes in brain slices prepared from healthy and experimental autoimmune encephalomyelitis (EAE) mice.ResultsThe purinergic receptor ligands adenosine and adenosine triphosphate (ATP) both induced transient increases in cAMP in astrocytes expressing the genetically encoded cAMP sensor Flamindo2. The A2A receptor antagonist ZM241385 inhibited the responses. Similar transient increases in astrocytic cAMP occurred when olfactory receptor neurons were stimulated electrically, resulting in ATP release from the stimulated axons that increased cAMP, again via A2A receptors. Notably, A2A-mediated responses to ATP and adenosine were not different in EAE mice as compared to healthy mice.DiscussionOur results indicate that ATP, synaptically released by afferent axons in the olfactory bulb, is degraded to adenosine that acts on A2A receptors in astrocytes, thereby increasing the cytosolic cAMP concentration. However, this pathway is not altered in the olfactory bulb of EAE mice.
Molecular and functional changes in neutrophilic granulocytes induced by nicotine: a systematic review and critical evaluation
Authors: Brembach Theresa-Charlotte , Sabat Robert , Witte Katrin , Schwerdtle Tanja , Wolk Kerstin 
Published: November 2023

BackgroundOver 1.1 billion people smoke worldwide. The alkaloid nicotine is a prominent and addictive component of tobacco. In addition to tumors and cardiovascular disorders, tobacco consumption is associated with a variety of chronic-inflammatory diseases. Although neutrophilic granulocytes (neutrophils) play a role in the pathogenesis of many of these diseases, the impact of nicotine on neutrophils has not been systematically reviewed so far.ObjectivesThe aim of this systematic review was to evaluate the direct influence of nicotine on human neutrophil functions, specifically on cell death/damage, apoptosis, chemotaxis, general motility, adhesion molecule expression, eicosanoid synthesis, cytokine/chemokine expression, formation of neutrophil extracellular traps (NETs), phagocytosis, generation of reactive oxygen species (ROS), net antimicrobial activity, and enzyme release.Material and methodsThis review was conducted according to the PRISMA guidelines. A literature search was performed in the databases NCBI Pubmed® and Web of Science™ in February 2023. Inclusion criteria comprised English written research articles, showing in vitro studies on the direct impact of nicotine on specified human neutrophil functions.ResultsOf the 532 originally identified articles, data from 34 articles were finally compiled after several evaluation steps. The considered studies highly varied in methodological aspects. While at high concentrations (&gt;3 mmol/l) nicotine started to be cytotoxic to neutrophils, concentrations typically achieved in blood of smokers (in the nmol/l range) applied for long exposure times (24-72h) supported the survival of neutrophils. Smoking-relevant nicotine concentrations also increased the chemotaxis of neutrophils towards several chemoattractants, elevated their production of elastase, lipocalin-2, CXCL8, leukotriene B4 and prostaglandin E2, and reduced their integrin expression. Moreover, while nicotine impaired the neutrophil phagocytotic and anti-microbial activity, a range of studies demonstrated increased NET formation. However, conflicting effects were found on ROS generation, selectin expression and release of β-glucuronidase and myeloperoxidase.ConclusionNicotine seems to support the presence in the tissue and the inflammatory and selected tissue-damaging activity of neutrophils and reduces their antimicrobial functions, suggesting a direct contribution of nicotine to the pathogenesis of chronic-inflammatory diseases via influencing the neutrophil biology.
Role of the co-stimulatory molecule inducible T-cell co-stimulator ligand (ICOSL) in the progression of experimental metabolic dysfunction-associated steatohepatitis
Authors: Provera Alessia , Ramavath Naresh Naik , Gadipudi Laila Lavanya , Gigliotti Casimiro Luca , Boggio Elena , Vecchio Cristina , Stoppa Ian , Rolla Roberta , Boldorini Renzo , Pirisi Mario , Smirne Carlo , Albano Emanuele , Dianzani Umberto , Sutti Salvatore 
Published: November 2023

Background and aimsInducible T-cell Co-Stimulator (ICOS) present on T-lymphocytes and its ligand ICOSL expressed by myeloid cells play multiple roles in regulating T-cell functions. However, recent evidence indicates that reverse signalling involving ICOSL is also important in directing the differentiation of monocyte-derived cells. In this study, we investigated the involvement of ICOS/ICOSL dyad in modulating macrophage functions during the evolution of metabolic dysfunction-associated steatohepatitis (MASH).ResultsIn animal models of MASH, ICOS was selectively up-regulated on CD8+ T-cells in parallel with an expansion of ICOSL-expressing macrophages. An increase in circulating soluble ICOSL was also evident in patients with MASH as compared to healthy individuals. ICOSL knockout (ICOSL-/-) mice receiving choline/methionine deficient (MCD) diet for 6 weeks had milder steatohepatitis than wild type mice. MASH improvement was confirmed in mice fed with cholesterol-enriched Western diet for 24 weeks in which ICOSL deficiency greatly reduced liver fibrosis along with the formation of crown-like macrophage aggregates producing the pro-fibrogenic mediators osteopontin (OPN) and galectin-3 (Gal-3). These effects associated with a selective shewing of F4-80+/CD11bhigh monocyte-derived macrophages (MoMFs) expressing the Triggering Receptor Expressed on Myeloid cells 2 (TREM2) to CD11blow/F4-80+ cells positive for the Kupffer cell marker C-type lectin-like type 2 receptor (CLEC-2), thus indicating an increased MoMF maturation toward monocyte-derived Kupffer cells.ConclusionsThese results suggest that CD8+ T-cells interaction with monocyte-derived macrophages through ICOS/ICOSL critically supports a specific subset of TREM2+-expressing cells contributing to the evolution of steatohepatitis. The data also point ICOS/ICOSL dyad as a possible target for therapeutic interventions in MASH.
Expansion of CD4+ cytotoxic T lymphocytes with specific gene expression patterns may contribute to suppression of tumor immunity in oral squamous cell carcinoma: single-cell analysis and in vitro experiments
Authors: Chen Hu , Sameshima Junsei , Yokomizo Shiho , Sueyoshi Tomoki , Nagano Haruki , Miyahara Yuka , Sakamoto Taiki , Fujii Shinsuke , Kiyoshima Tamotsu , Guy Thomas , Nakamura Seiji , Moriyama Masafumi , Kaneko Naoki , Kawano Shintaro 
Published: November 2023

BackgroundCancer immunotherapy targeting CD8+ T cells has made remarkable progress, even for oral squamous cell carcinoma (OSCC), a heterogeneous epithelial tumor without a substantial increase in the overall survival rate over the past decade. However, the therapeutic effects remain limited due to therapy resistance. Thus, a more comprehensive understanding of the roles of CD4+ T cells and B cells is crucial for more robust development of cancer immunotherapy.MethodsIn this study, we examined immune responses and effector functions of CD4+ T cells, CD8+ T cells and B cells infiltrating in OSCC lesions using single-cell RNA sequencing analysis, T cell receptor (TCR) and B cell receptor (BCR) repertoire sequencing analysis, and multi-color immunofluorescence staining. Finally, two Kaplan-Meier curves and several Cox proportional hazards models were constructed for the survival analysis.ResultsWe observed expansion of CD4+ cytotoxic T lymphocytes (CTLs) expressing granzymes, which are reported to induce cell apoptosis, with a unique gene expression patterns. CD4+ CTLs also expressed CXCL13, which is a B cell chemoattractant. Cell–cell communication analysis and multi-color immunofluorescence staining demonstrated potential interactions between CD4+ CTLs and B cells, particularly IgD- CD27- double negative (DN) B cells. Expansion of CD4+ CTLs, DN B cells, and their contacts has been reported in T and B cell-activated diseases, including IgG4-related disease and COVID-19. Notably, we observed upregulation of several inhibitory receptor genes including CTLA-4 in CD4+ CTLs, which possibly dampened T and B cell activity. We next demonstrated comprehensive delineation of the potential for CD8+ T cell differentiation towards dysfunctional states. Furthermore, prognostic analysis revealed unfavorable outcomes of patients with a high proportion of CD4+ CTLs in OSCC lesions.ConclusionOur study provides a dynamic landscape of lymphocytes and demonstrates a systemic investigation of CD4+ CTL effects infiltrating into OSCC lesions, which may share some pathogenesis reported in severe T and B cell-activated diseases such as autoimmune and infectious diseases.
A non-coding variant in SLC15A4 modulates enhancer activity and lysosomal deacidification linked to lupus susceptibility
Authors: Singh Manish Kumar , Maiti Guru Prashad , Rallabandi Harikrishna Reddy , Fazel-Najafabadi Mehdi , Looger Loren L. , Nath Swapan K. 
Published: November 2023

BackgroundSystemic lupus erythematosus (SLE) is a complex autoimmune disease with a strong genetic basis. Despite the identification of several single nucleotide polymorphisms (SNPs) near the SLC15A4 gene that are significantly associated with SLE across multiple populations, specific causal SNP(s) and molecular mechanisms responsible for disease susceptibility are unknown.MethodsTo address this gap, we employed bioinformatics, expression quantitative trait loci (eQTLs), and 3D chromatin interaction analysis to nominate a likely functional variant, rs35907548, in an active intronic enhancer of SLC15A4.ResultsThrough luciferase reporter assays followed by chromatin immunoprecipitation (ChIP)-qPCR, we observed significant allele-specific enhancer effects of rs35907548 in diverse cell lines. The rs35907548 risk allele T is associated with increased regulatory activity and target gene expression, as shown by eQTLs and chromosome conformation capture (3C)-qPCR. The latter revealed long-range chromatin interactions between the rs35907548 enhancer and the promoters of SLC15A4, GLTLD1, and an uncharacterized lncRNA. The enhancer-promoter interactions and expression effects were validated by CRISPR/Cas9 knock-out (KO) of the locus in HL60 promyeloblast cells. KO cells also displayed dramatically dysregulated endolysosomal pH regulation.ConclusionsTogether, our data show that the rs35907548 risk allele affects multiple aspects of cellular physiology and may directly contribute to SLE.
Chitosan- hypothalamic hormonal analogue nanoconjugates enhanced the reproductive performance in Indian major carp, Labeo rohita
Authors: Malik Mohd Ashraf , Gupta Subodh , Varghese Tincy , Jahageerdar Shrinivas , Nayak Sunil Kumar , Reang Dhalongsaih , Bhat Irfan Ahmad , Mahadevaswamy Chandan Gowramma , Chuphal Nisha , Dar Showkat Ahmad , Prabhakaran Arya 
Published: November 2023

The current study reports the potential of chitosan nanoparticles for the efficient delivery of hypothalamic hormonal analogue in Labeo rohita, aiming to improve reproductive performance. Here salmon gonadotropin-releasing hormone analogue (sGnRH-a) was conjugated with chitosan nanoparticles (ChN-sGnRH-a) to evaluate its efficiency in enhancing the reproductive gene expression, hormones as well as the overall reproductive output in L. rohita. A total of 54 pairs of brooders were selected and divided into six treatments viz; C0: Negative Control (fish injected with bare chitosan nanoparticles), C: Positive Control (fish injected with Gonopro-FH®, a commercially available inducing hormone, at a dose of 0.2 ml/kg body weight of fish), T1: fish injected with ChN-sGnRH-a at a dose of 0.2 ml/kg, T2: T1 + 10 mg/ml domperidone, T3: fish injected with ChN-sGnRH-a at a dose of 0.1 ml/kg, T4: T3 + 10 mg/ml domperidone. In T2 and T4 treatments, serum hormones, Testosterone (T); Estradiol (E2); Vitellogenin (Vtg); and 17α, 20β-dihydroxyprogesterone (17α, 20β-DHP) showed the sustained elevation. The means of reproductive traits like fecundity, fertilization rate, pseudo-gonadosomatic index and spawning rate were significantly (P&lt;0.05) higher in T2 treatment, while no significant difference was found between C and T4 treatment. The mRNA expression level of follicle-stimulating hormone (fshβ), luteinizing hormone (lhβ) and their cognate receptors was significantly better in T2 treatment, while no significant difference was found between T4 and C treatments. Further, the histological analysis of ovaries showed increased post-ovulatory follicles in C, T2 and T4 treatments. The results indicate that ChN-sGnRH-a could help in reducing the recommended dose of sGnRH-a without affecting the reproductive performance in L. rohita females. The sustained releasing mechanism of this formulation may be used as an induced breeding strategy in female L. rohita broodstock.
Design and performance evaluation of a novel broadband THz modulator based on graphene metamaterial for emerging applications
Authors: Tiang Jun Jiat , Soliman Naglaa F. , Khan Imran , Choi Jaeyoung , Chung Hee Chan , Madsen Dag Øivind 
Published: November 2023

Introduction: Metamaterials consist of periodic arrangements of artificial subwavelength units that possess electromagnetic properties not present in natural media. It has attracted more interest due to its ability to alter electromagnetic radiation in a flexible manner, which has resulted in the development of multiple radio frequency devices based on metamaterials. Metamaterials with the required frequency band for electric or magnetic resonance can be made using unit cell structure. The incident electromagnetic wave will enter the metamaterials and be kept there in the absence of reflection.Methods: This paper proposes a novel broadband THz absorber filter based on graphene for emerging applications. The proposed structure comprised of three parts. The top layer consists of graphene, the middle layer consists of dielectric and the bottom layer is made up of gold.Results: The proposed structure is experimentally designed and validated using the COMSOL simulator.Discussion: Simulation results show that the proposed absorber has better performance as compared with existing methods.