bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptomic signatures reveal a shift towards an anti-inflammatory gene expression profile but also the induction of type I and type II interferon signaling networks through aryl hydrocarbon receptor activation in murine macrophages
Authors: Schmidt Johannes R. , Haupt Janine , Riemschneider Sina , Kämpf Christoph , Löffler Dennis , Blumert Conny , Reiche Kristin , Koehl Ulrike , Kalkhof Stefan , Lehmann Jörg 
Published: May 2023

IntroductionThe aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that regulates a broad range of target genes involved in the xenobiotic response, cell cycle control and circadian rhythm. AhR is constitutively expressed in macrophages (Mϕ), acting as key regulator of cytokine production. While proinflammatory cytokines, i.e., IL-1β, IL-6, IL-12, are suppressed through AhR activation, anti-inflammatory IL-10 is induced. However, the underlying mechanisms of those effects and the importance of the specific ligand structure are not yet completely understood.MethodsTherefore, we have compared the global gene expression pattern in activated murine bone marrow-derived macrophages (BMMs) subsequently to exposure with either benzo[a]pyrene (BaP) or indole-3-carbinol (I3C), representing high-affinity vs. low-affinity AhR ligands, respectively, by means of mRNA sequencing. AhR dependency of observed effects was proved using BMMs from AhR-knockout (Ahr-/-) mice.Results and discussionIn total, more than 1,000 differentially expressed genes (DEGs) could be mapped, covering a plethora of AhR-modulated effects on basal cellular processes, i.e., transcription and translation, but also immune functions, i.e., antigen presentation, cytokine production, and phagocytosis. Among DEGs were genes that are already known to be regulated by AhR, i.e., Irf1, Ido2, and Cd84. However, we identified DEGs not yet described to be AhR-regulated in Mϕ so far, i.e., Slpi, Il12rb1, and Il21r. All six genes likely contribute to shifting the Mϕ phenotype from proinflammatory to anti-inflammatory. The majority of DEGs induced through BaP were not affected through I3C exposure, probably due to higher AhR affinity of BaP in comparison to I3C. Mapping of known aryl hydrocarbon response element (AHRE) sequence motifs in identified DEGs revealed more than 200 genes not possessing any AHRE, and therefore being not eligible for canonical regulation. Bioinformatic approaches modeled a central role of type I and type II interferons in the regulation of those genes. Additionally, RT-qPCR and ELISA confirmed a AhR-dependent expressional induction and AhR-dependent secretion of IFN-γ in response to BaP exposure, suggesting an auto- or paracrine activation pathway of Mϕ.
Mitophagy and immune infiltration in vitiligo: evidence from bioinformatics analysis
Authors: Luo Lingling , Zhu Jing , Guo Youming , Li Chengrang 
Published: May 2023

BackgroundVitiligo is an acquired, autoimmune, depigmented skin disease with unclear pathogenesis. Mitochondrial dysfunction contributes significantly to vitiligo, and mitophagy is vital for removing damaged mitochondria. Herein, using bioinformatic analysis, we sought to determine the possible role of mitophagy-associated genes in vitiligo and immune infiltration.MethodsMicroarrays GSE53146 and GSE75819 were used to identify differentially expressed genes (DEGs) in vitiligo. By crossing vitiligo DEGs with mitophagy-related genes, the mitophagy-related DEGs were identified. Functional enrichment and protein-protein intersection (PPI) analyses were conducted. Then, the hub genes were identified using two machine algorithms, and receiver operating characteristic (ROC) curves were generated. Next, the immune infiltration and its connection with hub genes in vitiligo were investigated. Finally, the Regnetwork database and NetworkAnalyst were used to predict the upstream transcriptional factors (TFs), microRNAs (miRNAs), and the protein-compound network.ResultsA total of 24 mitophagy-related genes were screened. Then, five mitophagy hub genes (GABARAPL2, SP1, USP8, RELA, and TBC1D17) were identified using two machine learning algorithms, and these genes showed high diagnostic specificity for vitiligo. The PPI network showed that hub genes interacted with each other. The mRNA expression levels of five hub genes were validated in vitiligo lesions by qRT-PCR and were compatible with the bioinformatic results. Compared with controls, the abundance of activated CD4+ T cells, CD8+ T cells, immature dendritic cells and B cells, myeloid-derived suppressor cells (MDSCs), gamma delta T cells, mast cells, regulatory T cells (Tregs), and T helper 2 (Th2) cells was higher. However, the abundance of CD56 bright natural killer (NK) cells, monocytes, and NK cells was lower. Correlation analysis revealed a link between hub genes and immune infiltration. Meanwhile, we predicted the upstream TFs and miRNAs and the target compounds of hub genes.ConclusionFive hub mitophagy-related genes were identified and correlated with immune infiltration in vitiligo. These findings suggested that mitophagy may promote the development of vitiligo by activating immune infiltration. Our study might enhance our comprehension of the pathogenic mechanism of vitiligo and offer a treatment option for vitiligo.
Identification and validation of a novel cuproptosis-related stemness signature to predict prognosis and immune landscape in lung adenocarcinoma by integrating single-cell and bulk RNA-sequencing
Authors: Yang Jia , Liu Kaile , Yang Lu , Ji Junqing , Qin Jingru , Deng Haibin , Wang Zhongqi 
Published: May 2023

BackgroundCancer stem cells (CSCs) play vital roles in lung adenocarcinoma (LUAD) recurrence, metastasis, and drug resistance. Cuproptosis has provided a novel insight into the treatment of lung CSCs. However, there is a lack of knowledge regarding the cuproptosis-related genes combined with the stemness signature and their roles in the prognosis and immune landscape of LUAD.MethodsCuproptosis-related stemness genes (CRSGs) were identified by integrating single-cell and bulk RNA-sequencing data in LUAD patients. Subsequently, cuproptosis-related stemness subtypes were classified using consensus clustering analysis, and a prognostic signature was constructed by univariate and least absolute shrinkage operator (LASSO) Cox regression. The association between signature with immune infiltration, immunotherapy, and stemness features was also investigated. Finally, the expression of CRSGs and the functional roles of target gene were validated in vitro.ResultsWe identified six CRSGs that were mainly expressed in epithelial and myeloid cells. Three distinct cuproptosis-related stemness subtypes were identified and associated with the immune infiltration and immunotherapy response. Furthermore, a prognostic signature was constructed to predict the overall survival (OS) of LUAD patients based on eight differently expressed genes (DEGs) with cuproptosis-related stemness signature (KLF4, SCGB3A1, COL1A1, SPP1, C4BPA, TSPAN7, CAV2, and CTHRC1) and confirmed in validation cohorts. We also developed an accurate nomogram to improve clinical applicability. Patients in the high-risk group showed worse OS with lower levels of immune cell infiltration and higher stemness features. Ultimately, further cellular experiments were performed to verify the expression of CRSGs and prognostic DEGs and demonstrate that SPP1 could affect the proliferation, migration, and stemness of LUAD cells.ConclusionThis study developed a novel cuproptosis-related stemness signature that can be used to predict the prognosis and immune landscape of LUAD patients, and provided potential therapeutic targets for lung CSCs in the future.
A systems serology approach to the investigation of infection-induced antibody responses and protection in trachoma
Authors: Barton Amber , Rosenkrands Ida , Pickering Harry , Faal Nkoyo , Harte Anna , Joof Hassan , Makalo Pateh , Ragonnet Manon , Olsen Anja Weinreich , Bailey Robin L. , Mabey David C. W. , Follmann Frank , Dietrich Jes , Holland Martin J. 
Published: May 2023

BackgroundOcular infections with Chlamydia trachomatis serovars A–C cause the neglected tropical disease trachoma. As infection does not confer complete immunity, repeated infections are common, leading to long-term sequelae such as scarring and blindness. Here, we apply a systems serology approach to investigate whether systemic antibody features are associated with susceptibility to infection.MethodsSera from children in five trachoma endemic villages in the Gambia were assayed for 23 antibody features: IgG responses towards two C. trachomatis antigens and three serovars [elementary bodies and major outer membrane protein (MOMP), serovars A–C], IgG responses towards five MOMP peptides (serovars A–C), neutralization, and antibody-dependent phagocytosis. Participants were considered resistant if they subsequently developed infection only when over 70% of other children in the same compound were infected.ResultsThe antibody features assayed were not associated with resistance to infection (false discovery rate &lt; 0.05). Anti-MOMP SvA IgG and neutralization titer were higher in susceptible individuals (p &lt; 0.05 before multiple testing adjustment). Classification using partial least squares performed only slightly better than chance in distinguishing between susceptible and resistant participants based on systemic antibody profile (specificity 71%, sensitivity 36%).ConclusionsSystemic infection-induced IgG and functional antibody responses do not appear to be protective against subsequent infection. Ocular responses, IgA, avidity, or cell-mediated responses may play a greater role in protective immunity than systemic IgG.
Patterns of spatial and temporal dynamics of mixed Mytilus edulis and M. trossulus populations in a small subarctic inlet (Tyuva Inlet, Barents Sea)
Authors: Marchenko Julia , Khaitov Vadim , Katolikova Marina , Sabirov Marat , Malavenda Sergey , Gantsevich Michael , Basova Larisa , Genelt-Yanovsky Evgeny , Strelkov Petr 
Published: May 2023

Subarctic populations of “cryptic” blue mussel species Mytilus edulis (ME) and M. trossulus (MT) are less studied than Arctic and boreal populations. Ecological features of ME and MT in sympatry are poorly known everywhere. We studied the habitat segregation of ME and MT and the interannual dynamics of their mixed settlements at the Murman coast of the Barents Sea, the northeastern boundary of the Atlantic littoral mussel communities. Previous data on mussels from this area are 50-100 years old. The 3-km-long Tyuva Inlet (Kola Bay) was used as the study site. Mussels were found in the littoral and the sublittoral down to a depth of 4 m. Their characteristic habitats were sandbanks, littoral rocks, sublittoral kelp forests and “the habitat of the mussel bed” in the freshened top of the inlet. The main spatial gradients explaining the variability of demographics of the settlements (abundance, age structure, size) were associated with the depth and the distance from the inlet top. ME and MT were partially segregated by depth: ME dominated in the sublittoral and MT, in the littoral. In addition, ME dominated throughout the mussel bed. The ratio of species in the mixed settlements varied over time: between 2004 and 2010 the proportions of MT decreased everywhere, by 22% on average. The habitat distribution of mussels apparently changed with time: we found that mussels were abundant in kelp forests, where they had rarely been observed in the 20th century. We suggest that the spatial and temporal dynamics of subarctic mussels can be partly explained by the competition between ME and MT and their differing sensitivity to environmental factors.
Chromosomal abnormalities and structural defects in fetuses with increased nuchal translucency at a Chinese tertiary medical center
Authors: Zhang Huijing , Wang Shuang , Feng Chunli , Zhao Hongyan , Zhang Weiwei , Sun Yu , Yang Huixia 
Published: May 2023

ObjectivesTo explore the pregnancy outcomes of fetuses with increased NT thickness.MethodsThis was a retrospective study of fetuses with increased NT (≥95th centile) at 11–14 weeks of gestation between January 2020 and November 2020.ResultsAmong 264 fetuses with increased NT, the median of CRL and NT was 61.2 mm and 2.41 mm. Among them, 132 pregnancy women chose invasive prenatal diagnosis (43 cases of chorionic villus sampling (CVS), 89 cases of amniocentesis). Eventually, 16 cases of chromosomal abnormalities were discovered, including 6 cases (6.4%) of trisomy 21, 4 cases (3%) of trisomy 18, 1 case (0.8%) of 45, XO, 1 case (0.8%) of 47, XXY and 4 cases (3.03%) of CNV abnormalities. The major structural defects included hydrops (6.4%), cardiac defects (3%), and urinary anomalies (2.7%). The incidences of chromosomal abnormalities and structural defects in the NT &lt; 2.5 mm group were 1.3 and 6%, while the incidences were 8.8 and 28.9% in the NT≥2.5 group.ConclusionIncreased NT was associated with high risk of chromosomal abnormalities and structural anomalies. Chromosomal abnormalities and structural defects could be detected when NT thickness was between 95th centile and 2.5 mm.
Petroleum pollution changes microbial diversity and network complexity of soil profile in an oil refinery
Authors: Zhuang Jugui , Zhang Ruihuan , Zeng Yufei , Dai Tianjiao , Ye Zhencheng , Gao Qun , Yang Yunfeng , Guo Xue , Li Guanghe , Zhou Jizhong 
Published: May 2023

IntroductionPetroleum pollution resulting from spills and leakages in oil refinery areas has been a significant environmental concern for decades. Despite this, the effects of petroleum pollutants on soil microbial communities and their potential for pollutant biodegradation still required further investigation.MethodsIn this study, we collected 75 soil samples from 0 to 5 m depths of 15 soil profiles in an abandoned refinery to analyze the effect of petroleum pollution on soil microbial diversity, community structure, and network co-occurrence patterns.ResultsOur results suggested soil microbial a-diversity decreased under high C10–C40 levels, coupled with significant changes in the community structure of soil profiles. However, soil microbial network complexity increased with petroleum pollution levels, suggesting more complex microbial potential interactions. A module specific for methane and methyl oxidation was also found under high C10–C40 levels of the soil profile, indicating stronger methanotrophic and methylotrophic metabolic activities at the heavily polluted soil profile.DiscussionThe increased network complexity observed may be due to more metabolic pathways and processes, as well as increased microbial interactions during these processes. These findings highlight the importance of considering both microbial diversity and network complexity in assessing the effects of petroleum pollution on soil ecosystems.
Mechanical digit sensory stimulation: a randomized control trial on neurological and motor recovery in acute stroke
Authors: Zhang Shuting , Yu Yang , Xu Panpan , Shen Xianshan , Fang Chuanqin , Wu Xiaosan , Qu Ping , Wu Tingting , Wang Qing Mei , Luo Xun , Hong Yongfeng 
Published: May 2023

BackgroundMechanical digit sensory stimulation (MDSS) is a novel therapy designed to accelerate the recovery of upper limb (including hand) function in patients with hemiplegia following a stroke. The primary goal of this study was to investigate the effect of MDSS on patients with acute ischemic stroke (AIS).MethodsSixty-one inpatients with AIS were randomly divided into conventional rehabilitation group (RG) and stimulation group (SG), and the latter group received MDSS therapy. A healthy group consisting of 30 healthy adults was also included. The interleukin-17A (IL-17A), vascular endothelial growth factor A (VEGF-A), and tumor necrosis factor-alpha (TNF-α) plasma levels were measured in all subjects. The neurological and motor functions of patients were evaluated using the National Institutes of Health Stroke Scale (NIHSS), Mini-Mental State Examination (MMSE), Fugel-Meyer Assessment (FMA), and Modified Barthel Index (MBI).ResultsAfter 12 days of intervention, the IL-17A, TNF-α, and NIHSS levels were significantly decreased, while the VEGF-A, MMSE, FMA, and MBI levels were significantly increased in both disease groups. No significant difference was observed between both disease groups after intervention. The levels of IL-17A and TNF-α were positively correlated with NIHSS but negatively correlated with MMSE, FMA, and MBI. The VEGF-A levels were negatively correlated with NIHSS but positively correlated with MMSE, FMA, and MBI.ConclusionBoth MDSS and conventional rehabilitation significantly reduce the production of IL-17A and TNF-α, increase the VEGF-A levels, and effectively improve cognition and motor function of hemiplegic patients with AIS, and the effects of MDSS and conventional rehabilitation are comparable.
Prognostic stratification of endometrial cancers with high microsatellite instability or no specific molecular profile
Authors: Gonzalez-Bosquet Jesus , Weroha S. John , Bakkum-Gamez Jamie N. , Weaver Amy L. , McGree Michaela E. , Dowdy Sean C. , Famuyide Abimbola O. , Kipp Benjamin R. , Halling Kevin C. , Yadav Siddhartha , Couch Fergus J. , Podratz Karl C. 
Published: May 2023

ObjectiveTo identify high-risk disease in clinicopathologic low-risk endometrial cancer (EC) with high microsatellite instability (MSI-H) or no specific molecular profile (NSMP) and therapeutic insensitivity in clinicopathologic high-risk MSI-H/NSMP EC.MethodsWe searched The Cancer Genome Atlas for DNA sequencing, RNA expression, and surveillance data regarding MSI-H/NSMP EC. We used a molecular classification system of E2F1 and CCNA2 expression and sequence variations in POLE, PPP2R1A, or FBXW7 (ECPPF) to prognostically stratify MSI-H/NSMP ECs. Clinical outcomes were annotated after integrating ECPPF and sequence variations in homologous recombination (HR) genes.ResultsData were available for 239 patients with EC, which included 58 MSI-H and 89 NSMP cases. ECPPF effectively stratified MSI-H/NSMP EC into distinct molecular groups with prognostic implications: molecular low risk (MLR), with low CCNA2 and E2F1 expression, and molecular high risk (MHR), with high CCNA2 and E2F1 expression and/or PPP2R1A and/or FBXW7 variants. The 3-year disease-free survival (DFS) rate was 43.8% in the MHR group with clinicopathologic low-risk indicators and 93.9% in the MLR group (P&lt;.001). In the MHR group, wild-type HR genes were present in 28% of cases but in 81% of documented recurrences. The 3-year DFS rate in patients with MSI-H/NSMP EC with clinicopathologic high-risk indicators was significantly higher in the MLR (94.1%) and MHR/HR variant gene (88.9%) groups than in the MHR/HR wild-type gene group (50.3%, P&lt;.001).ConclusionECPPF may resolve prognostic challenges for MSI-H/NSMP EC by identifying occult high-risk disease in EC with clinicopathologic low-risk indicators and therapeutic insensitivity in EC with clinicopathologic high-risk indicators.
ABHD6 and MAGL control 2-AG levels in the PAG and allodynia in a CSD-induced periorbital model of headache
Authors: Liktor-Busa Erika , Levine Aidan A. , Palomino Seph M. , Singh Simar , Wahl Jared , Vanderah Todd W. , Stella Nephi , Largent-Milnes Tally M. 
Published: May 2023

IntroductionThe high prevalence and severe symptoms of migraines in humans emphasizes the need to identify underlying mechanisms that can be targeted for therapeutic benefit. Clinical Endocannabinoid Deficiency (CED) posits that reduced endocannabinoid tone may contribute to migraine development and other neuropathic pain conditions. While strategies that increase levels of the endocannabinoid n-arachidonoylethanolamide have been tested, few studies have investigated targeting the levels of the more abundant endocannabinoid, 2-arachidonoylgycerol, as an effective migraine intervention.MethodsCortical spreading depression was induced in female Sprague Dawley rats via KCl (potassium chloride) administration, followed by measures of endocannabinoid levels, enzyme activity, and neuroinflammatory markers. Efficacy of inhibiting 2-arachidonoylglycerol hydrolysis to mitigate periorbital allodynia was then tested using reversal and prevention paradigms.ResultsWe discovered reduced 2-arachidonoylglycerol levels in the periaqueductal grey associated with increased hydrolysis following headache induction. Pharmacological inhibition of the 2-arachidonoylglycerol hydrolyzing enzymes, α/β-hydrolase domain-containing 6 and monoacylglycerol lipase reversed and prevented induced periorbital allodynia in a cannabinoid receptor-dependent manner.DiscussionOur study unravels a mechanistic link between 2-arachidonoylglycerol hydrolysis activity in the periaqueductal grey in a preclinical, rat model of migraine. Thus, 2-arachidonoylglycerol hydrolysis inhibitors represent a potential new therapeutic avenue for the treatment of headache.
Does interpersonal self-support matter for freshman nursing students’ professional identity? Evidence from mainland China
Authors: Zhang Ting , Su Dan , Yang Yajuan , Li Shuwen 
Published: May 2023

BackgroundMany studies have focused on undergraduate nursing students’ professional identity (PI), but freshman nursing students (FNSs) have been ignored, and the relationship between interpersonal self-support (ISS) and PI is unknown. This study was designed to determine the patterns of ISS and its association with PI among Chinese FNSs.MethodsA cross-sectional survey was conducted among 358 FNSs recruited from two nursing colleges in southeast China. Students completed the Sociodemographic Characteristics Questionnaire, the Interpersonal Self-Support Scale for Adolescent Students, and the Professional Identity Questionnaire for Nurse Students. Latent profile analysis (LPA) was used to determine the patterns of ISS among freshmen. The Bolck–Croon–Hagenaars method was used to examine the influencing role of ISS in PI.ResultsLPA indicated that ISS could be classified into three subgroups: the ISS-Individualist group (7.54% of the total sample), ISS-Dependent group (63.13% of the total sample), and ISS-Extrovert group (29.33% of the total sample). Overall, these three profiles differed significantly in the five dimensions of ISS and PI (p &lt; 0.05). The results of pairwise comparisons examined the positive role of the ISS-Extrovert group on the promotion of PI among FNSs.ConclusionThese findings emphasize the need for the promotion of PI and ISS among Chinese FNSs. Freshman students need more confidence and general communication knowledge to maintain harmonious social relationships with others. Parent-teacher association could be applied to nursing education to guide FNSs’ positive development of ISS.