bluuebunny/crossref_metadata_2025_split huggingface dataset:
Promoting patient engagement in cancer genomics research programs: An environmental scan
Authors: Schuster Anne L. R. , Crossnohere Norah L. , Paskett Jonathan , Thomas Neena , Hampel Heather , Ma Qin , Tiner Jessica C. , Paskett Electra D. , Bridges John F. P. 
Published: January 2023

Background:A national priority in the United States is to promote patient engagement in cancer genomics research, especially among diverse and understudied populations. Several cancer genomics research programs have emerged to accomplish this priority, yet questions remain about the meaning and methods of patient engagement. This study explored how cancer genomics research programs define engagement and what strategies they use to engage patients across stages in the conduct of research.Methods:An environmental scan was conducted of cancer genomics research programs focused on patient engagement. Research programs were identified and characterized using materials identified from publicly available sources (e.g., websites), a targeted literature review, and interviews with key informants. Descriptive information about the programs and their definitions of engagement, were synthesized using thematic analysis. The engagement strategies were synthesized and mapped to different stages in the conduct of research, including recruitment, consent, data collection, sharing results, and retention.Results:Ten research programs were identified, examples of which include the Cancer Moonshot Biobank, the MyPART Network, NCI-CONNECT, and the Participant Engagement and Cancer Genome Sequencing (PE-CGS) Network. All programs aimed to include understudied or underrepresented populations. Based on publicly available information, four programs explicitly defined engagement. These definitions similarly characterized engagement as being interpersonal, reciprocal, and continuous. Five general strategies of engagement were identified across the programs: 1) digital (such as websites) and 2) non-digital communications (such as radio broadcasts, or printed brochures); 3) partnering with community organizations; 4) providing incentives; and 5) affiliating with non-academic medical centers. Digital communications were the only strategy used across all stages of the conduct of research. Programs tailored these strategies to their study goals, including overcoming barriers to research participation among diverse populations.Conclusion:Programs studying cancer genomics are deeply committed to increasing research participation among diverse populations through patient engagement. Yet, the field needs to reach a consensus on the meaning of patient engagement, develop a taxonomy of patient engagement measures in cancer genomics research, and identify optimal strategies to engage patients in cancer genomics. Addressing these needs could enable patient engagement to fulfill its potential and accelerate the pace of cancer genomic discoveries.
Nr4a1-dependent non-classical monocytes are important for macrophage-mediated wound healing in the large intestine
Authors: Heidbreder Karin , Sommer Katrin , Wiendl Maximilian , Müller Tanja M. , Atreya Imke , Hildner Kai , Neurath Markus F. , Zundler Sebastian 
Published: January 2023

IntroductionMacrophages play an important role in intestinal wound healing. However, the trajectories from circulating monocytes to gut macrophages are incompletely understood.MethodsTaking advantage of mice depleted for non-classical monocytes due to deficiency for the transcription factor Nr4a1, we addressed the relevance of non-classical monocytes for large intestinal wound healing using flow cytometry, in vivo wound healing assays and immunofluorescence.ResultsWe show that wound healing in Nr4a1-deficient mice is substantially delayed and associated with reduced peri-lesional presence of macrophages with a wound healing phenotype.DiscussionOur data suggest that non-classical monocytes are biased towards wound healing macrophages. These insights might help to understand, how targeting monocyte recruitment to the intestine can be used to modulate intestinal macrophage functions.
Single-cell atlas reveals different immune environments between stable and vulnerable atherosclerotic plaques
Authors: Ge Peicong , Li Hao , Ya Xiaolong , Xu Yiqiao , Ma Long , He Qiheng , Wang Rong , Liu Zechen , Zhang Qian , Zhang Yan , Wang Wenjing , Zhang Dong , Zhao Jizong 
Published: January 2023

IntroductionRegardless of the degree of stenosis, vulnerable plaque is an important cause of ischemic stroke and thrombotic complications. The changes of the immune microenvironment within plaques seem to be an important factor affecting the characteristics of the plaque. However, the differences of immune microenvironment between stable and vulnerable plaques were remained unknown.MethodsIn this study, RNA-sequencing was performed on superficial temporal arteries from 5 traumatic patients and plaques from 3 atherosclerotic patients to preliminary identify the key immune response processes in plaques. Mass cytometry (CyTOF) technology was used to explore differences in immune composition between 9 vulnerable plaques and 12 stable plaques. Finally, immunofluorescence technique was used to validate our findings in the previous analysis.ResultsOur results showed that more CD86+CD68+ M1 pro-inflammatory macrophages were found in vulnerable plaques, while CD4+T memory cells were mainly found in stable plaques. In addition, a CD11c+ subset of CD4+T cells with higher IFN-r secretion was found within the vulnerable plaque. In two subsets of B cells, CD19+CD20-B cells in vulnerable plaques secreted more TNF-a and IL-6, while CD19-CD20+B cells expressed more PD-1 molecules.ConclusionIn conclusion, our study suggested that M1-like macrophages are the major cell subset affecting plaque stability, while functional B cells may also contribute to plaque stability.
Protective effects of blocking PD-1 pathway on retinal ganglion cells in a mouse model of chronic ocular hypertension
Authors: Sheng Siqi , Ma Yixian , Zou Yue , Hu Fangyuan , Chen Ling 
Published: January 2023

PurposeIn this study, we aimed to investigate whether Programmed cell death 1 ligand 1/programmed cell death 1 ligand 2 (PD-L1/PD-L2) double knockout (dKO) has a protective effect on RGCs in a mouse model of chronic ocular hypertension (COHT).MethodsWe used superparamagnetic iron oxide to induce COHT in mice. Apoptosis of retinal ganglion cells (RGCs) and activation of microglia were evaluated using western blotting (WB) and immunofluorescence staining of the mouse retina. In addition, we also conducted transcriptome sequencing and further gene expression analyses using the gene ontology (GO) and Kyoto Encyclopedia of Genes (KEGG) database.ResultsIn the mouse model of COHT, PD-L1/PD-L2 prevented the apoptosis of RGCs to some extent. Blocking the programmed cell death 1 (PD-1) pathway also increased the number of anti-inflammatory M2-activated microglia and enhanced the phosphorylation of its related pathway signal transducer and activator of transcription (STAT)6. Sequencing results showed that this protective effect may have been achieved by regulating the NF−B, tumour necrosis factor (TNF), PI3K/Akt and toll-like receptor signaling pathway etc.ConclusionBlocking the PD-1 pathway has a protective effect on RGCs in the mouse model of COHT induced by superparamagnetic iron oxide.
CD8+ T-cell immunity orchestrated by iNKT cells
Authors: Qin Yingyu , Bao Xueyang , Zheng Mingzhu 
Published: January 2023

CD8+ T cells belonging to the adaptive immune system play key roles in defending against viral infections and cancers. The current CD8+ T cell-based immunotherapy has emerged as a superior therapeutic avenue for the eradication of tumor cells and long-term prevention of their recurrence in hematologic malignancies. It is believed that an effective adaptive immune response critically relies on the help of the innate compartment. Invariant natural killer T (iNKT) cells are innate-like T lymphocytes that have been considered some of the first cells to respond to infections and can secrete a large amount of diverse cytokines and chemokines to widely modulate the innate and adaptive immune responders. Like CD8+ T cells, iNKT cells also play an important role in defense against intracellular pathogenic infections and cancers. In this review, we will discuss the CD8+ T-cell immunity contributed by iNKT cells, including iNKT cell-mediated cross-priming and memory formation, and discuss recent advances in our understanding of the mechanisms underlying memory CD8+ T-cell differentiation, as well as aging-induced impairment of T-cell immunity.
Knowledge landscape of tumor-associated macrophage research: A bibliometric and visual analysis
Authors: Zhou Feng , Liu Yang , Liu Cong , Wang Fangfei , Peng Jianxiang , Xie Yong , Zhou Xiaojiang 
Published: January 2023

Background and aimsTumor-associated macrophage (TAM) is a highly abundant immune population in tumor microenvironment, which plays an important role in tumor growth and progression. The aim of our study was to explore the development trends and research hotspots of TAM by bibliometric method.MethodsThe publications related to TAM were obtained from the Web of Science Core Collection database. Bibliometric analysis and visualization were conducted using VOSviewer, CiteSpace and R software.ResultsA total of 6,405 articles published between 2001 and 2021 were included. The United States and China received the most citations, whereas the University of Milan, the university of California San Francisco and Sun Yat-sen University were the main research institutions. Mantovani, Alberto from Humanitas University was the most productive authors with the most citations. Cancer Research published the most articles and received the most co-citations. Activation, angiogenesis, breast cancer, NF-κB and endothelial growth factor were important keywords in TAM research. Among them, PD-1/L1, nanoparticle, PI3Kγ, resistance and immune microenvironment have become the focus of attention in more recent research.ConclusionsThe research on TAM is rapidly evolving with active cooperation worldwide. Anticancer therapy targeting TAM is emerging and promising area of future research, especially in translational application. This may provide guidance and new insights for further research in the field of TAM.
Exploration of the shared pathways and common biomarker PAN3 in ankylosing spondylitis and ulcerative colitis using integrated bioinformatics analysis
Authors: Zhang Minna , Zhou Junyi , Wang Honggang , He Le , Wang Jingyi , Yang Xiaozhong , Zhong Xiaomin 
Published: January 2023

BackgroundUlcerative colitis (UC) is a chronic autoimmune-related disease that causes inflammation of the intestine. Ankylosing spondylitis (AS) is a common extraintestinal complication of UC involving the sacroiliac joint. However, the pathogenesis of AS secondary to UC has not been studied. This study aimed to investigate the shared pathways and potential common biomarkers of UC and AS.MethodsMicroarray data downloaded from the Gene Expression Omnibus (GEO) database were used to screen differentially expressed genes (DEGs) in the UC and AS datasets. Weighted gene co-expression network analysis (WGCNA) was performed to identify co-expression modules related to UC and AS. Shared genes were then further analyzed for functional pathway enrichment. Next, the optimal common biomarker was selected using SVM-RFF and further validated using two independent GEO datasets. Finally, immune infiltration analysis was used to investigate the correlation of immune cell infiltration with common biomarkers in UC and AS.ResultsA total of 4428 and 2438 DEGs in UC and AS, respectively, were screened. Four modules were identified as significant for UC and AS using WGCNA. A total of 25 genes overlapped with the strongest positive and negative modules of UC and AS. KEGG analysis showed these genes may be involved in the mitogen-activated protein kinase (MAPK) signaling pathway. GO analysis indicated that these genes were significantly enriched for RNA localization. PAN3 was selected as the optimal common biomarker for UC and AS. Immune infiltration analysis showed that the expression of PAN3 was correlated with changes in immune cells.ConclusionThis study first explored the common pathways and genetic diagnostic markers involved in UC and AS using bioinformatic analysis. Results suggest that the MAPK signaling pathway may be associated with both pathogeneses and that PAN3 may be a potential diagnostic marker for patients with UC complicated by AS.
Loss of CFTR function is associated with reduced bitter taste receptor-stimulated nitric oxide innate immune responses in nasal epithelial cells and macrophages
Authors: Carey Ryan M. , Palmer James N. , Adappa Nithin D. , Lee Robert J. 
Published: January 2023

IntroductionBitter taste receptors (T2Rs) are G protein-coupled receptors identified on the tongue but expressed all over the body, including in airway cilia and macrophages, where T2Rs serve an immune role. T2R isoforms detect bitter metabolites (quinolones and acyl-homoserine lactones) secreted by gram negative bacteria, including Pseudomonas aeruginosa, a major pathogen in cystic fibrosis (CF). T2R activation by bitter bacterial products triggers calcium-dependent nitric oxide (NO) production. In airway cells, the NO increases mucociliary clearance and has direct antibacterial properties. In macrophages, the same pathway enhances phagocytosis. Because prior studies linked CF with reduced NO, we hypothesized that CF cells may have reduced T2R/NO responses, possibly contributing to reduced innate immunity in CF.MethodsImmunofluorescence, qPCR, and live cell imaging were used to measure T2R localization, calcium and NO signaling, ciliary beating, and antimicrobial responses in air-liquid interface cultures of primary human nasal epithelial cells and immortalized bronchial cell lines. Immunofluorescence and live cell imaging was used to measure T2R signaling and phagocytosis in primary human monocyte-derived macrophages.ResultsPrimary nasal epithelial cells from both CF and non-CF patients exhibited similar T2R expression, localization, and calcium signals. However, CF cells exhibited reduced NO production also observed in immortalized CFBE41o- CF cells and non-CF 16HBE cells CRISPR modified with CF-causing mutations in the CF transmembrane conductance regulator (CFTR). NO was restored by VX-770/VX-809 corrector/potentiator pre-treatment, suggesting reduced NO in CF cells is due to loss of CFTR function. In nasal cells, reduced NO correlated with reduced ciliary and antibacterial responses. In primary human macrophages, inhibition of CFTR reduced NO production and phagocytosis during T2R stimulation.ConclusionsTogether, these data suggest an intrinsic deficiency in T2R/NO signaling caused by loss of CFTR function that may contribute to intrinsic susceptibilities of CF patients to P. aeruginosa and other gram-negative bacteria that activate T2Rs.
Transcriptome profiling reveals the underlying mechanism of grape post-harvest pathogen Penicillium olsonii against the metabolites of Bacillus velezensis
Authors: Zhang Tingfu , Wen Guoqin , Song Bo , Chen Zhenyong , Jiang Shijiao 
Published: January 2023

IntroductionPathogen infection influences the post-harvest shelf life of grape berries. In a preliminary study, metabolites produced by Bacillus velezensis significantly inhibited the growth of the grape postharvest pathogen Penicillium olsonii.MethodsTo investigate the mechanism of interaction between B. velezensis and P. olsonii, a draft genome was generated for P. olsonii WHG5 using the Illumina NovaSeq platform, and the transcriptomic changes in WHG5 were analyzed in response to the exposure to B. velezensis metabolites (10% v/v).ResultsThe expression levels of genes associated with sporulation, including GCY1, brlA, and abaA, were down-regulated compared with those of the control. In addition, spore deformation and abnormal swelling of the conidiophore were observed. The expression of crucial enzymes, including fructose 2,6-bisphosphate and mannitol-2-dehydrogenase, was down-regulated, indicating that the glycolytic pathway of WHG5 was adversely affected by B. velezensis metabolites. The KEGG pathway enrichment analysis revealed that glutathione metabolism and the antioxidant enzyme system were involved in the response to B. velezensis metabolites. The down-regulation of the pathogenesis-related genes, PG1 and POT1, suggested that B. velezensis metabolites decreased the pathogenicity of P. olsonii. B. velezensis metabolites disrupted the homeostasis of reactive oxygen species in P. olsonii by affecting glucose metabolism, resulting in spore deformation and disruption of growth. In addition, the expression of key pathogenesis-related genes was down-regulated, thereby reducing the pathogenicity of P. olsonii.DisscusionThis study provides insights into the responses of P. olsonii to B. velezensis metabolites and identifies potential target genes that may be useful in biocontrol strategies for the suppression of post-harvest spoilage in grapes.
Relieving your stress: PGPB associated with Andean xerophytic plants are most abundant and active on the most extreme slopes
Authors: Aguilera-Torres Carla , Riveros Gustavo , Morales Loreto V. , Sierra-Almeida Angela , Schoebitz Mauricio , Hasbún Rodrigo 
Published: January 2023

IntroductionPlants interact with plant growth-promoting bacteria (PGPB), especially under stress condition in natural and agricultural systems. Although a potentially beneficial microbiome has been found associated to plants from alpine systems, this plant- PGPB interaction has been scarcely studied. Nevados de Chillán Complex hold one of the southernmost xerophytic formations in Chile. Plant species living there have to cope with drought and extreme temperatures during the growing season period, microclimatic conditions that become harsher on equatorial than polar slopes, and where the interaction with PGPB could be key for plant survival. Our goal was to study the abundance and activity of different PGPB associated to two abundant plant species of Andean xerophytic formations on contrasting slopes.MethodsTwenty individuals ofBerberis empetrifoliaandAzorella proliferashrubs were selected growing on a north and south slope nearby Las Fumarolas, at 2,050 m elevation. On each slope, microclimate based on temperature and moisture conditions were monitored throughout the growing period (oct. – apr.). Chemical properties of the soil under plant species canopies were also characterized. Bacterial abundance was measured as Log CFU g−1from soil samples collected from each individual and slope. Then, the most abundant bacterial colonies were selected, and different hormonal (indoleacetic acid) and enzymatic (nitrogenase, phosphatase, ACC-deaminase) mechanisms that promote plant growth were assessed and measured.Results and DiscussionExtreme temperatures were observed in the north facing slope, recording the hottest days (41 vs. 36°C) and coldest nights (−9.9 vs. 6.6°C). Moreover, air and soil moisture were lower on north than on south slope, especially late in the growing season. We found that bacterial abundance was higher in soils on north than on south slope but only underB. empetrifoliacanopy. Moreover, the activity of plant growth-promoting mechanisms varied between slopes, being on average higher on north than on south slope, but with plant species-dependent trends. Our work showed how the environmental heterogeneity at microscale in alpine systems (slope and plant species identity) underlies variations in the abundance and plant growth promoting activity of the microorganisms present under the plant canopy of the Andean xerophytic formations and highlight the importance of PGPB from harsh systems as biotechnological tools for restoration.
Metagenomic insights into the relationship between gut microbiota and residual feed intake of small-sized meat ducks
Authors: Bai Hao , Shi Lei , Guo Qixin , Jiang Yong , Li Xiaofan , Geng Dandan , Wang Chenxiao , Bi Yulin , Wang Zhixiu , Chen Guohong , Xue Fuguang , Chang Guobin 
Published: January 2023

IntroductionThe objective of this study was to determine the regulatory effects of gut microbiota on the feed efficiency (FE) of small-sized meat ducks by evaluating correlations between gut microbiota and residual feed intake (RFI).MethodsA total of 500 21-day-old healthy male ducks with similar initial body weights (645 ± 15.0 g) were raised contemporaneously in the same experimental facility until slaughter at 56 days of age. In total, nine low-RFI (LR) and nine high-RFI (HR) birds were selected for further gut microbiota composition and functional analyses based on the production performance, and the RFI was calculated from 22 to 56 days of age.ResultsGrowth performance results indicated a significantly lower RFI, feed conversion ratio, feed intake, and average daily feed intake in the LR ducks (P &lt; 0.05). Taxonomy results of gut microbiota showed the identification of 19 kinds of phyla and more than 250 kinds of genera in all samples. No significant discrepancies in cecal bacterial α-diversity were discovered between the LR and HR groups, which indicated that the microbial modulatory effects on RFI may be attributed to the bacterial composition, rather than the species diversity. Differential analysis of bacterial communities between the LR and HR groups showed a significant increment of Firmicutes and a significant decline of Bacteroidetes in the LR group (P &lt; 0.05). Specifically, genera of Erysipelatoclostridium, Parasutterella, Fournierella, and Lactococcus significantly proliferated, while Bacteroides significantly decreased in the LR group (P &lt; 0.05). Furthermore, correlation analysis showed that the RFI was significantly correlated with carbohydrate metabolism-related bacteria including Bacteroides, Alistipes, Bifidobacterium, Ruminiclostridium_9, Sellimonas, Oscillibacter, Escherichia-Shigella, Lactococcus, and Streptococcus.ConclusionIn conclusion, the communities related to carbohydrate metabolism had positive regulatory effects on the FE of small-sized meat ducks, promoting it by improving the relative abundance and utilization of these communities. The present study provides valuable insight into the dynamics of gut microbiota underlying the variations in the FE of small-sized meat ducks.