bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrating transcriptomics, eQTL, and Mendelian randomization to dissect monocyte roles in severe COVID-19 and gout flare
Authors: Li Jiajia , Yang Guixian , Liu Junnan , Li Guofeng , Zhou Huiling , He Yuan , Fei Xinru , Zhao Dongkai 
Published: September 2024

IntroductionThere are considerable similarities between the pathophysiology of gout flare and the dysregulated inflammatory response in severe COVID-19 infection. Monocytes are the key immune cells involved in the pathogenesis of both diseases. Therefore, it is critical to elucidate the molecular basis of the function of monocytes in gout and COVID-19 in order to develop more effective therapeutic approaches.MethodsThe single-cell RNA sequencing (scRNA-seq), large-scale genome-wide association studies (GWAS), and expression quantitative trait loci (eQTL) data of gout and severe COVID-19 were comprehensively analyzed. Cellular heterogeneity and intercellular communication were identified using the scRNA-seq datasets, and the monocyte-specific differentially expressed genes (DEGs) between COVID-19, gout and normal subjects were screened. In addition, the correlation of the DEGs with severe COVID-19 and gout flare was analyzed through GWAS statistics and eQTL data.ResultsThe scRNA-seq analysis exhibited that the proportion of classical monocytes was increased in both severe COVID-19 and gout patient groups compared to healthy controls. Differential expression analysis and MR analysis showed that NLRP3 was positively associated with the risk of severe COVID-19 and involved 11 SNPs, of which rs4925547 was not significantly co-localized. In contrast, IER3 was positively associated with the risk of gout and involved 9 SNPs, of which rs1264372 was significantly co-localized.DiscussionMonocytes have a complex role in gout flare and severe COVID-19, which underscores the potential mechanisms and clinical significance of the interaction between the two diseases.
Higher frequency of peripheral blood CD103+CD8+ T cells with lower levels of PD-1 and TIGIT expression related to favorable outcomes in leukemia patients
Authors: Liu Lian , Lai Wenpu , Zhuo Xiaoling , Chen Sihui , Luo Xiaodan , Tan Huo 
Published: September 2024

BackgroundLeukemia is a prevalent pediatric life-threatening hematologic malignancy with a poor prognosis. Targeting immune checkpoints (ICs) to reverse T cell exhaustion is a potentially effective treatment for leukemia. Tissue resident memory T (TRM) cells have been found to predict the efficacy of programmed death receptor-1 inhibitor (anti-PD-1) therapy in solid tumors. However, the IC characteristics of TRM cells in leukemia and their relationship with prognosis remain unclear.MethodsWe employed multi-color flow cytometry to evaluate the frequencies of CD103+CD4+ and CD103+CD8+ T cells in the peripheral blood (PB) of patients with acute myeloid leukemia and B-cell acute lymphoblastic leukemia compared to healthy individuals. We examined the expression patterns of PD-1 and T cell immunoreceptor with immunoglobulin and ITIM domain (TIGIT) within the circulating CD103+ T cell subsets affected by leukemia. To further elucidate the immunological landscape, we assessed the differentiation status of CD103+ T cells across various disease states in patients with leukemia.ResultsOur findings showed a significant increase in the frequency of CD103+CD8+ T cells in the PB of patients with leukemia who had achieved complete remission (CR) compared to those in the de novo (DN) and relapsed/refractory (RR) stages. This increase was accompanied by a notable decrease in the expression levels of PD-1 and TIGIT in CD103+CD8+ T cells in the CR stage. Additionally, our analysis revealed a higher proportion of CD103+CD8+ T cells in the central memory (TCM) and effector memory (TEM) subsets of the immune profile. Notably, the proportions of CD103+ naïve T cells, CD103+ TEM, and CD103+ terminally differentiated T cells within the CD8+ T cell population were significantly elevated in patients with CR compared to those in the DN/RR stages.ConclusionThe data indicate that circulating higher frequency of CD103+CD8+ T cells with lower expression of PD-1 and TIGIT are associated with favorable outcomes in patients with leukemia. This suggests a potential role of TRM cells in leukemia prognosis and provides a foundation for developing targeted immunotherapies.
Differential expression of HIV target cells CCR5 and α4β7 in tissue resident memory CD4 T cells in endocervix during the menstrual cycle of HIV seronegative women
Authors: Govindaraj Sakthivel , Tyree Staple , Herring Gina Bailey , Rahman Sadia J. , Babu Hemalatha , Ibegbu Chris , Young Marisa R. , Mehta C. Christina , Haddad Lisa B. , Smith Alicia K. , Velu Vijayakumar 
Published: September 2024

BackgroundOvarian hormones are known to modulate the immune system in the female genital tract (FGT). We sought to define the impact of the menstrual cycle on the mucosal HIV target cell levels, and tissue-resident CD4 T cells.Materials and methodsHere, we characterized the distribution, phenotype, and function of CD4 T cells with special emphasis on HIV target cells (CCR5+ and α4β7+) as well as tissue-resident memory (TRM; CD69+ and CD103+) CD4 T cells in FGT of cycling women. Peripheral blood and Endocervical cells (EC-collected from cytobrush) were collected from 105 healthy women and performed multicolor flow cytometry to characterize the various subsets of CD4 T cells. Cervicovaginal lavage (CVL) were collected for cytokine analysis and plasma were collected for hormonal analysis. All parameters were compared between follicular and luteal phase of menstrual cycle.ResultsOur findings revealed no significant difference in the blood CD4 T cell subsets between the follicular and luteal phase. However, in EC, the proportion of several cell types was higher in the follicular phase compared to the luteal phase of menstrual cycle, including CCR5+α4β7-cells (p=0.01), CD69+CD103+ TRM (p=0.02), CCR5+CD69+CD103+ TRM (p=0.001) and FoxP3+ CD4 T cells (p=0.0005). In contrast, α4β7+ CCR5- cells were higher in the luteal phase (p=0.0004) compared to the follicular phase. In addition, we also found that hormonal levels (P4/E2 ratio) and cytokines (IL-5 and IL-6) were correlated with CCR5+ CD4 T cells subsets during the follicular phase of the menstrual cycleConclusionOverall, these findings suggest the difference in the expression of CCR5 and α4β7 in TRM CD4 T cell subsets in endocervix of HIV seronegative women between the follicular and luteal phase. Increase in the CCR5+ expression on TRM subsets could increase susceptibility to HIV infection during follicular phase of the menstrual cycle.
Prostate-specific membrane antigen PET versus [99mTc]Tc-MDP bone scan for diagnosing bone metastasis in prostate cancer: a head-to-head comparative meta-analysis
Authors: Wang Yiming , Qiu Yiran , Yan Xingjian 
Published: September 2024

PurposeTo evaluate the diagnostic performance of PSMA PET/CT, including [68Ga]Ga-PSMA-11 and [18F]DCFPyL, in comparison with the [99mTc]Tc-MDP bone scan (BS) in identifying bone metastases among prostate cancer patients.MethodsA search was performed in the PubMed and Embase databases to locate pertinent publications from inception to February 12, 2024. The studies included were those that examined the diagnostic effectiveness of PSMA PET/CT (covering [68Ga]Ga-PSMA-11 and [18F]DCFPyL) compared to [99mTc]Tc-MDP BS in identifying bone metastases among prostate cancer patients. The quality of the selected studies was evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) checklist.ResultsThe meta-analysis included nine articles involving 702 patients. The sensitivity of PSMA PET/CT was higher compared to [99mTc]Tc-MDP BS (0.98 vs. 0.85, P &lt; 0.01), while the specificity of PSMA PET/CT was also higher than [99mTc]Tc-MDP BS (0.97 vs. 0.70,P &lt; 0.01). In subgroup analysis, the sensitivity of [68Ga]Ga-PSMA-11 PET/CT was higher compared to [99mTc]Tc-MDP BS (0.98 vs. 0.86), while the specificity of [68Ga]Ga-PSMA-11 PET/CT was also higher than [99mTc]Tc-MDP BS (0.98 vs. 0.65).ConclusionOur meta-analysis demonstrates that PSMA PET/CT exhibits superior sensitivity and specificity in comparison with [99mTc]Tc-MDP BS for identifying bone metastases in prostate cancer patients. Further research with head-to-head design is necessary to validate these results and evaluate the clinical effectiveness of these imaging methods.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier PROSPERO CRD42024545112.
The response of microbiome assembly within different niches across four stages to the cultivation of glyphosate-tolerant and conventional soybean varieties
Authors: Chao Shengqian , Sun Yu , Zhang Yin , Chen Yifan , Song Lili , Li Peng , Tang Xueming , Liang Jingang , Lv Beibei 
Published: September 2024

IntroductionPlants are inherently connected with the microbiome, which plays a crucial role in regulating various host plant biological processes, including immunity, nutrient acquisition, and resistance against abiotic and biotic stresses. Many factors affect the interaction between plants and microbiome.Methods and resultsIn this study, microbiome samples were collected from five niches (bulk soil, rhizoplane, root endosphere, phylloplane, and leaf endosphere) across four developmental stages (seedling, flowering, podding, and maturity) of various soybean varieties. Composition and structure of bacterial and fungal communities were analyzed using 16S rRNA gene and ITS (Internally Transcribed Spacer) region amplicon sequencing. It was observed that both niches and developmental stages significantly impact on the assembly and composition of soybean microbiome. However, variety, presence of a transgene, and glyphosate application had minimal effects on microbial communities. The dominant microbiome varied across the five niches, with most containing beneficial microbial communities capable of promoting plant growth or increasing disease resistance. Types and abundance of the dominant microbes affected network stability, potentially resulting in functional changes in different ecological niches.ConclusionThis study provides theoretical evidence for microbial protection of plants against diseases and demonstrates that systematic analysis of the composition and diversity of soybean microbiomes can contribute to the development of biological control technologies.
Antimicrobial mechanisms and antifungal activity of compounds generated by banana rhizosphere Pseudomonas aeruginosa Gxun-2 against fusarium oxysporum f. sp. cubense
Authors: Lu Junming , Huang Yanbing , Liu Rui , Liang Ying , Zhang Hongyan , Shen Naikun , Yang Dengfeng , Jiang Mingguo 
Published: September 2024

IntroductionFusarium wilt of banana, also recognized as Panama disease, is caused by the soil-borne fungus Fusarium oxysporum f. sp. cubense tropical race 4 (FOC TR4). In recent years, strategies utilizing biocontrol agents, comprising antifungal microorganisms and their associated bioactive compounds from various environments, have been implemented to control this destructive disease. Our previous study showed that Pseudomonas aeruginosa Gxun-2 had significant antifungal effects against FOC TR4. However, there has been little scientific investigation of the antibacterial or antifungal activity. The aim of this study was to isolate, identify and evaluate the inhibition strength of active compounds in P. aeruginosa Gxun-2, so as to explain the mechanism of the strain inhibition on FOC TR4 from the perspective of compounds.MethodsThe main antibacterial compounds of strain Gxun-2 were isolated, purified and identified using by fermentation extraction, silica gel column chromatography, thin-layer chromatography (TLC), high-performance liquid chromatography (HPLC), and nuclear magnetic resonance (NMR) techniques. The effect of the compounds on the mycelial growth, morphology and spore germination of strain FOC TR4 was observed by 96-well plate method and AGAR diffusion method.ResultsAmong the metabolites produced by the strain, four antifungal compounds which were identified phenazine (C12H8N2), phenazine-1-carboxylic acid (PCA) (C13H8N2O2), 2-acetamidophenol (C8H9NO2) and aeruginaldehyde (C10H7NO2S) were identified through HPLC and NMR. Of these compounds, phenazine and PCA exhibited the most pronounced inhibitory effects on the spore germination and mycelial growth of FOC TR4. Phenazine demonstrated potent antifungal activity against FOC TR4 with a minimum inhibitory concentration (MIC) of 6.25 mg/L. The half-maximal effective concentration (EC50) was calculated to be 26.24 mg/L using the toxicity regression equation. PCA exhibited antifungal activity against FOC TR4 with an MIC of 25 mg/L and an EC50 of 89.63 mg/L. Furthermore, phenazine and PCA triggered substantial morphological transformations in the mycelia of FOC TR4, encompassing folding, bending, fracturing, and diminished spore formation.DiscussionThese findings indicate that strain Gxun-2 plays a crucial role in controlling FOC TR4 pathogenesis, predominantly through producing the antifungal compounds phenazine and PCA, and possesses potential as a cost-efficient and sustainable biocontrol agent against Fusarium wilt of banana in forthcoming times.
Effect of fentanyl on HIV expression in peripheral blood mononuclear cells
Authors: Krishnan Janani Madhuravasal , Roskin Krishna M. , Meeds Heidi L. , Blackard Jason T. 
Published: September 2024

IntroductionIllicit drug use, particularly the synthetic opioid fentanyl, presents a significant global health challenge. Previous studies have shown that fentanyl enhances viral replication; yet, the mechanisms by which it affects HIV pathogenesis remain unclear. This study investigated the impact of fentanyl on HIV replication in CD4+ T lymphocytes.MethodsCD4+ T lymphocytes from HIV-negative donors were activated, infected with HIVNL4-3, and treated with fentanyl. HIV proviral DNA and p24 antigen expression were quantified using real-time PCR and ELISA, respectively. Single-cell RNA libraries were analyzed to identify differentially expressed genes.ResultsResults indicated that fentanyl treatment increased HIV p24 expression and proviral DNA levels, and naltrexone mitigated these effects. Single-cell RNAseq analysis identified significantly altered gene expression in CD4+ T lymphocytes.DiscussionThe results of our findings suggest that fentanyl promotes HIV replication ex vivo, emphasizing the need for a deeper understanding of opioid-virus interactions to develop better treatment strategies for individuals with HIV and opioid use disorder.
An effective screening model for subjective cognitive decline in community-dwelling older adults based on gait analysis and eye tracking
Authors: Hao Chenxi , Zhang Xiaonan , An Junpin , Bao Wenjing , Yang Fan , Chen Jinyu , Hou Sijia , Wang Zhigang , Du Shuning , Zhao Yarong , Wang Qiuyan , Min Guowen , Li Yang 
Published: September 2024

ObjectiveTo evaluate the effectiveness of multimodal features based on gait analysis and eye tracking for elderly people screening with subjective cognitive decline in the community.MethodsIn the study, 412 cognitively normal older adults aged over 65 years were included. Among them, 230 individuals were diagnosed with non-subjective cognitive decline and 182 with subjective cognitive decline. All participants underwent assessments using three screening tools: the traditional SCD9 scale, gait analysis, and eye tracking. The gait analysis involved three tasks: the single task, the counting backwards dual task, and the naming animals dual task. Eye tracking included six paradigms: smooth pursuit, median fixation, lateral fixation, overlap saccade, gap saccade, and anti-saccade tasks. Using the XGBoost machine learning algorithm, several models were developed based on gait analysis and eye tracking to classify subjective cognitive decline.ResultsA total of 161 gait and eye-tracking features were measured. 22 parameters, including 9 gait and 13 eye-tracking features, showed significant differences between the two groups (p &lt; 0.05). The top three eye-tracking paradigms were anti-saccade, gap saccade, and median fixation, with AUCs of 0.911, 0.904, and 0.891, respectively. The gait analysis features had an AUC of 0.862, indicating better discriminatory efficacy compared to the SCD9 scale, which had an AUC of 0.762. The model based on single and dual task gait, anti-saccade, gap saccade, and median fixation achieved the best efficacy in SCD screening (AUC = 0.969).ConclusionThe gait analysis, eye-tracking multimodal assessment tool is an objective and accurate screening method that showed better detection of subjective cognitive decline. This finding provides another option for early identification of subjective cognitive decline in the community.
Barriers of the CNS transfer rate dynamics in patients with vascular cognitive impairment and dementia
Authors: Taheri Saeid , Prestopnik Jill , Rosenberg Gary A. 
Published: September 2024

BackgroundAdvances in in vivo MRI techniques enable cerebral barrier transfer rates (Ktrans) measurement in patients with vascular cognitive impairment and dementia (VCID). However, a consensus has not been reached on the dynamic contribution and importance of cerebral barrier abnormalities to the differential diagnosis of dementia subtypes. Our goal was to investigate the dynamics of blood-brain barrier (BBB) and blood-CSF barrier (BCSFB) Ktrans in patients with VCID longitudinally and determine the effect of aging.MethodsWe studied subjects at two time points over two years; they were 65.5 years of age (SD = 15.94, M/F = 24/14) at the first visit. We studied 38 patients, 18 of whom had two visits. We calculated the BBB and BCSFB Ktrans with dynamic contrast-enhanced T1 MR, and we used 1H-MR spectroscopy to measure N-acetylaspartate (NAA) levels in the white matter as a marker of injury. In addition, we measured CSF levels of active-matrix metalloproteinase-3 (MMP3) as an inflammatory biomarker to aid in patient clustering.ResultsLongitudinal BBB measurements revealed variable dynamic behavior: after two years, the BBB Ktrans increased in 55% of patients and decreased in the remaining 45% unpredictably. We did not find a significant linear model of BBB Ktrans versus age for VCID. For healthy controls, the model was Ktrans = 0.0014 + 0.0002 × age, which was significant (p = 0.046). VCID patients showed a reduction in BCSFB Ktrans compared to healthy controls (p = 0.01). Combining NAA, CSF MMP3, and Ktrans in a clustering analysis separated patients into groups.ConclusionThese results suggest that BBB Ktrans in VCID is dynamic and BCSFB Ktrans reduced by age. By combining inflammatory biomarkers with BBB Ktrans data, it is possible to separate VCID patients into distinct groups with different underlying pathologies.
Subjective visual sensitivity in neurotypical adults: insights from a magnetic resonance spectroscopy study
Authors: Jurkovičová Lenka , Páleník Julie , Kudlička Petr , Pezlar Lenka , Ružičková Alexandra , Juřík Vojtěch , Mareček Radek , Roman Robert , Braithwaite Jason J. , Sandberg Kristian , Near Jamie , Brázdil Milan 
Published: September 2024

IntroductionAltered subjective visual sensitivity manifests as feelings of discomfort or overload elicited by intense and irritative visual stimuli. This can result in a host of visual aberrations including visual distortions, elementary visual hallucinations and visceral responses like dizziness and nausea, collectively referred to as “pattern glare.” Current knowledge of the underlying neural mechanisms has focused on overall excitability of the visual cortex, but the individual contribution of excitatory and inhibitory systems has not yet been quantified.MethodsIn this study, we focus on the role of glutamate and γ-aminobutyric acid (GABA) as potential mediators of individual differences in subjective visual sensitivity, measured by a computerized Pattern Glare Test—a series of monochromatic square-wave gratings with three different spatial frequencies, while controlling for psychological variables related to sensory sensitivity with multiple questionnaires. Resting neurotransmitter concentrations in primary visual cortex (V1) and right anterior insula were studied in 160 healthy participants using magnetic resonance spectroscopy.ResultsData showed significant differences in the perception of visual distortions (VD) and comfort scores between men and women, with women generally reporting more VD, and therefore the modulatory effect of sex was considered in a further examination. A general linear model analysis showed a negative effect of occipital glutamate on a number of reported visual distortions, but also a significant role of several background psychological traits. When assessing comfort scores in women, an important intervening variable was the menstrual cycle.DiscussionOur findings do not support that baseline neurotransmitter levels have a significant role in overreactivity to aversive stimuli in neurotypical population. However, we demonstrated that biological sex can have a significant impact on subjective responses. Based on this additional finding, we suggest that future studies investigate aversive visual stimuli while examining the role of biological sex.
Further validation of the association between MAPT haplotype-tagging polymorphisms and Alzheimer’s disease: neuropsychological tests, cerebrospinal fluid biomarkers, and APOE genotype
Authors: Babić Leko Mirjana , Španić Popovački Ena , Willumsen Nanet , Nikolac Perković Matea , Pleić Nikolina , Zubčić Klara , Langer Horvat Lea , Vogrinc Željka , Boban Marina , Borovečki Fran , Zemunik Tatijana , de Silva Rohan , Šimić Goran 
Published: September 2024

IntroductionGenetic studies have shown that variants in the microtubule-associated protein tau (MAPT) gene, which encodes tau protein, can increase the risk for Alzheimer’s disease (AD). Additionally, two haplotypes of the MAPT gene (H1 and H2) are associated with various neurodegenerative disorders, including AD. This study aimed to test the association of MAPT haplotypes (H1 and H2) and MAPT haplotype-tagging polymorphisms (rs1467967, rs242557, rs3785883, rs2471738, del–In9, rs7521) with AD.MethodsThe study included 964 individuals: 113 with AD, 53 with mild cognitive impairment (MCI), 54 with other dementias, and 744 healthy controls.ResultsThe results showed that individuals carrying the A allele in the MAPT rs1467967 polymorphism, the GG genotype in the MAPT rs7521 polymorphism, and the G allele in the MAPT rs242557 polymorphism had worse performance on various neuropsychological tests. Carriers of the C allele in MAPT rs2471738 polymorphism and CC homozygotes also showed worse performance on neuropsychological tests and pathological levels of several cerebrospinal fluid (CSF) biomarkers. However, T allele carriers in the MAPT rs2471738 polymorphism were more represented among patients with dementia and apolipoprotein E (APOE) ɛ4 carriers. Carriers of the H2 MAPT haplotype had worse performance on various neuropsychological tests, consistent with our previous study, which associated the H2 MAPT haplotype with pathological levels of CSF AD biomarkers. Regarding the MAPT rs3785883 polymorphism, further research is needed since both the AA and GG genotypes were associated with pathological levels of CSF and plasma AD biomarkers.DiscussionIn conclusion, further genetic studies are needed to elucidate the role of MAPT haplotypes and MAPT haplotype-tagging polymorphisms in the development of AD.