bluuebunny/crossref_metadata_2025_split huggingface dataset:
Muscle-origin creatinine-cystatin C ratio is an osteoporosis marker in individuals with normal renal function: evidence from observational and Mendelian randomization analysis
Authors: He Pei , Yang Yi-Qun , Wang Han , Zhang Ya-Qian , Gu Yu-Ni , Hong Chen-Cheng , Bo Lin , Deng Fei-Yan , Lei Shu-Feng 
Published: May 2024

BackgroundCreatinine-cystatin C ratio (CCR) has been demonstrated as an objective marker of sarcopenia in clinical conditions but has not been evaluated as an osteoporosis marker in individuals with normal renal function.MethodsWe selected 271,831 participants with normal renal function from UK Biobank cohort. Multivariable linear/logistic regression and Cox proportional hazards model were used to investigate the phenotypic relationship between CCR and osteoporosis in total subjects and gender-stratified subjects. Based on the genome-wide association study (GWAS) data, linkage disequilibrium regression (LDSC) and Mendelian randomization (MR) analysis were performed to reveal the shared genetic correlations and infer the causal effects, respectively.ResultsAmongst total subjects and gender-stratified subjects, serum CCR was positively associated with eBMD after adjusting for potential risk factors (all P&lt;0.05). The multivariable logistic regression model showed that the decrease in CCR was associated with a higher risk of osteoporosis/fracture in all models (all P&lt;0.05). In the multivariable Cox regression analysis with adjustment for potential confounders, reduced CCR is associated with the incidence of osteoporosis and fracture in both total subjects and gender-stratified subjects (all P&lt;0.05). A significant non-linear dose–response was observed between CCR and osteoporosis/fracture risk (Pnon-linearity &lt; 0.05). LDSC found no significant shared genetic effects by them, but PLACO identified 42 pleiotropic SNPs shared by CCR and fracture (P&lt;5×10–8). MR analyses indicated the causal effect from CCR to osteoporosis/fracture.ConclusionsReduced CCR predicted increased risks of osteoporosis/fracture, and significant causal effects support their associations. These findings indicated that the muscle-origin serum CCR was a potential biomarker to assess the risks of osteoporosis and fracture.
Proteomic and metabolomic analysis of GH deficiency-induced NAFLD in hypopituitarism: insights into oxidative stress
Authors: Zhang Yuwen , Chen Peizhan , Fang Xuqian 
Published: May 2024

ObjectiveIndividuals with hypopituitarism (HPs) have an increased risk of developing non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) due to growth hormone deficiency (GHD). We aimed to investigate the possible mechanisms underlying the relationship between GHD and NAFLD using proteomic and metabolomic insights.MethodsSerum metabolic alternations were assessed in male HPs using untargeted metabolomics. A rat model of HP was established through hypophysectomy, followed by recombinant human growth hormone (rhGH) intervention. The mechanisms underlying GHD-mediated NAFLD were elucidated through the application of label-free proteomics and phosphorylation proteomics.ResultsMetabolomic analysis revealed that biomarkers of mitochondrial dysfunction and oxidative stress, such as alanine, lactate, and creatine, were significantly elevated in HPs compared to age-matched controls. In rats, hypophysectomy led to marked hepatic steatosis, lipid peroxidation, and reduced glutathione (GSH), which were subsequently modulated by rhGH replacement. Proteomic analysis identified cytochrome P450s, mitochondrial translation elongation, and PPARA activating genes as the major distinguishing pathways in hypophysectomized rats. The processes of fatty acid transport, synthesis, oxidation, and NADP metabolism were tightly described. An enhanced regulation of peroxisome β-oxidation and ω-oxidation, together with a decreased NADPH regeneration, may exacerbate oxidative stress. Phosphoproteome data showed downregulation of JAK2-STAT5B and upregulation of mTOR signaling pathway.ConclusionsThis study identified proteo-metabolomic signatures associated with the development of NAFLD in pituitary GHD. Evidence was found of oxidative stress imbalance resulting from abnormal fatty acid oxidation and NADPH regeneration, highlighting the role of GH deficiency in the development of NAFLD.
Distance models reveal biases associated with passive trapping methods for measuring wild bee abundance
Authors: Mathis Codey L. , McNeil Darin J. , Kammerer Melanie , Larkin Jeffery L. , Skvarla Michael J. 
Published: May 2024

IntroductionThere is overwhelming evidence of declines in native bee populations and therefore a need for increased monitoring to track these declines and assist in conservation and restoration efforts. Bees can be sampled non-lethally through visual surveys (e.g., distance transects) or lethally through active (e.g., hand netting) or passive (e.g., traps that lure insects from afar) methods. These lethal methods suffer from imperfect detection that is difficult to account for and can confound inferences about habitat characteristics. Additionally, evidence suggests that lethal sampling methods can even invert habitat quality patterns such that high-quality sites yield fewer individuals and low-quality sites yield more individuals.MethodsTo study potential biases associated with imperfect detection, we used hierarchical density estimation with visual surveys to estimate density of bees within 40 young forest patches across Pennsylvania, USA. We surveyed bee communities non-lethally using visual surveys and lethally using blue-vane traps and bee bowls every two weeks between May and September 2019. We collected data on blooming flowers, vegetation structure, and weather during times of survey.ResultsWe found that bee densities estimated from distance transects had a positive relationship with floral resource availability. In contrast, abundance measured via bee bowls and blue-vane traps had no relationship, or sometimes even negative trends with habitat quality, including floral resource availability. Raw bee counts within 2-m of the transect always correlated with modeled densities, showing that some methods do not share the biases of attractive traps.DiscussionOur study demonstrates that failing to account for imperfect detection can impact the interpretation of pollinator surveys and adds to a growing body of literature that acknowledges the value of distance sampling for insects like bees to better understand species’ habitat needs and to monitor populations for conservation.
MONET: a database for prediction of neoantigens derived from microsatellite loci
Authors: Deng Nan , Sinha Krishna M. , Vilar Eduardo 
Published: May 2024

BackgroundMicrosatellite instability (MSI) secondary to mismatch repair (MMR) deficiency is characterized by insertions and deletions (indels) in short DNA sequences across the genome. These indels can generate neoantigens, which are ideal targets for precision immune interception. However, current neoantigen databases lack information on neoantigens arising from coding microsatellites. To address this gap, we introduce The MicrOsatellite Neoantigen Discovery Tool (MONET).MethodMONET identifies potential mutated tumor-specific neoantigens (neoAgs) by predicting frameshift mutations in coding microsatellite sequences of the human genome. Then MONET annotates these neoAgs with key features such as binding affinity, stability, expression, frequency, and potential pathogenicity using established algorithms, tools, and public databases. A user-friendly web interface (https://monet.mdanderson.org/) facilitates access to these predictions.ResultsMONET predicts over 4 million and 15 million Class I and Class II potential frameshift neoAgs, respectively. Compared to existing databases, MONET demonstrates superior coverage (&gt;85% vs. &lt;25%) using a set of experimentally validated neoAgs.ConclusionMONET is a freely available, user-friendly web tool that leverages publicly available resources to identify neoAgs derived from microsatellite loci. This systems biology approach empowers researchers in the field of precision immune interception.
Transcriptomic signatures of classical monocytes reveal pro-inflammatory modules and heterogeneity in polyarticular juvenile idiopathic arthritis
Authors: Hounkpe Bidossessi W. , Sales Lucas P. , Ribeiro Surian C. R. , Perez Mariana O. , Caparbo Valéria F. , Domiciano Diogo Souza , Figueiredo Camille P. , Pereira Rosa M. R. , Borba Eduardo F. 
Published: May 2024

IntroductionPolyarticular juvenile idiopathic arthritis (pJIA) is a childhood-onset autoimmune disease. Immune cells contribute to persistent inflammation observed in pJIA. Despite the crucial role of monocytes in arthritis, the precise involvement of classical monocytes in the pathogenesis of pJIA remains uncertain. Here, we aimed to uncover the transcriptomic patterns of classical monocytes in pJIA, focusing on their involvement in disease mechanism and heterogeneity.MethodsA total of 17 healthy subjects and 18 premenopausal women with pJIA according to ILAR criteria were included. Classical monocytes were isolated, and RNA sequencing was performed. Differential expression analysis was used to compare pJIA patients and healthy control group. Differentially expressed genes (DEGs) were identified, and gene set enrichment analysis (GSEA) was performed. Using unsupervised learning approach, patients were clustered in two groups based on their similarities at transcriptomic level. Subsequently, these clusters underwent a comparative analysis to reveal differences at the transcriptomic level.ResultsWe identified 440 DEGs in pJIA patients of which 360 were upregulated and 80 downregulated. GSEA highlighted TNF-α and IFN-γ response. Importantly, this analysis not only detected genes targeted by pJIA therapy but also identified new modulators of immuno-inflammation. PLAUR, IL1B, IL6, CDKN1A, PIM1, and ICAM1 were pointed as drivers of chronic hyperinflammation. Unsupervised learning approach revealed two clusters within pJIA, each exhibiting varying inflammation levels.ConclusionThese findings indicate the pivotal role of immuno-inflammation driven by classical monocytes in pJIA and reveals the existence of two subclusters within pJIA, regardless the positivity of rheumatoid factor and anti-CCP, paving the way to precision medicine.
Mining bone metastasis related key genes of prostate cancer from the STING pathway based on machine learning
Authors: Li Guiqiang , Zhao Runhan , Xie Zhou , Qu Xiao , Duan Yingtao , Zhu Yafei , Liang Hao , Tang Dagang , Li Zefang , He Weiyang 
Published: May 2024

BackgroundProstate cancer (PCa) is the second most prevalent malignant tumor in male, and bone metastasis occurs in about 70% of patients with advanced disease. The STING pathway, an innate immune signaling mechanism, has been shown to play a key role in tumorigenesis, metastasis, and cancerous bone pain. Hence, exploring regulatory mechanism of STING in PCa bone metastasis will bring novel opportunities for treating PCa bone metastasis.MethodsFirst, key genes were screened from STING-related genes (SRGs) based on random forest algorithm and their predictive performance was evaluated. Subsequently, a comprehensive analysis of key genes was performed to explore their roles in prostate carcinogenesis, metastasis and tumor immunity. Next, cellular experiments were performed to verify the role of RELA in proliferation and migration in PCa cells, meanwhile, based on immunohistochemistry, we verified the difference of RELA expression between PCa primary foci and bone metastasis. Finally, based on the key genes to construct an accurate and reliable nomogram, and mined targeting drugs of key genes.ResultsIn this study, three key genes for bone metastasis were mined from SRGs based on the random forest algorithm. Evaluation analysis showed that the key genes had excellent prediction performance, and it also showed that the key genes played a key role in carcinogenesis, metastasis and tumor immunity in PCa by comprehensive analysis. In addition, cellular experiments and immunohistochemistry confirmed that overexpression of RELA significantly inhibited the proliferation and migration of PCa cells, and RELA was significantly low-expression in bone metastasis. Finally, the constructed nomogram showed excellent predictive performance in Receiver Operating Characteristic (ROC, AUC = 0.99) curve, calibration curve, and Decision Curve Analysis (DCA) curve; and the targeted drugs showed good molecular docking effects.ConclusionIn sum, this study not only provides a new theoretical basis for the mechanism of PCa bone metastasis, but also provides novel therapeutic targets and novel diagnostic tools for advanced PCa treatment.
Pharmacy students’ interprofessional experience and performance in advanced pharmacy practice experience rotations amid COVID-19 pandemic
Authors: Alrasheed Marwan , Alsuhibani Abdulrahman , Alotaibi Wadha , Gari Musaab , Alashgar Amin , Doherty Michael , Boone Jill , Almangour Thamer A. , Hincapie Ana 
Published: May 2024

IntroductionInterprofessional education (IPE) is essential in pharmacy training, providing students with vital collaborative skills for real-world healthcare. Advanced Pharmacy Practice Experience (APPE) is integral to IPE, allowing students to apply their knowledge in diverse healthcare settings. The COVID-19 pandemic has disrupted healthcare education and raised concerns about its impact on IPE during APPE rotations. Our study investigates the pandemic’s influence on pharmacy students’ interprofessional interactions and APPE performance.ObjectiveTo assess the interprofessional experiences of fourth-year pharmacy students before and during the COVID-19 pandemic in the context of APPE.MethodsThis retrospective observational study examined the experiences of P4 pharmacy students in the United States during APPEs before and during the pandemic. We employed electronic surveys with 21 questions to gauge interactions and interprofessional team effectiveness, employing Likert scale response options. We compared responses between the 2019–2020 and 2020–2021 APPE rotations using statistical tests.ResultsOur study encompassed 83 and 86 students for the 2019–2020 and 2020–2021 APPE rotations, respectively, achieving a 100% response rate. Amid the pandemic, written communications between pharmacy students and healthcare providers in general medicine rotations increased, while in-person engagement decreased. Pre-COVID, students reported higher colleague referrals and greater interprofessional utilization during ambulatory care rotations.ConclusionCOVID-19 shifted interactions from in-person to written communication between pharmacy students and healthcare providers. Students reported decreased satisfaction with their interprofessional experiences. This research offers insights into the changing landscape of pharmacy education, helping students prepare for evolving challenges in healthcare delivery and education.
Research hotspots and trends of microRNAs in spinal cord injury: a comprehensive bibliometric analysis
Authors: Hu Baoyang , Zhao Yue , Chen Chao , Wu Bin , Zhang Hongbin , Liu Bin , Zheng Runquan , Fang Fang 
Published: May 2024

BackgroundSpinal cord injury (SCI) is a nervous system disease leading to motor and sensory dysfunction below the injury level, and can result in paralysis. MicroRNAs (miRNAs) play a key role in SCI treatment, and related research provides insights for SCI diagnosis and treatment. Bibliometrics is an important tool for literature statistics and evaluation, objectively summarizing multidimensional information. This study comprehensively overviews the field through bibliometric analysis of miRNA and SCI research, providing contemporary resources for future collaboration and clinical treatment.Materials and methodsIn this study, we searched the Web of Science Core Collection (WOSCC) database. After careful screening and data import, we extracted annual publications, citation counts, countries, institutions, authors, journals, highly cited articles, co-cited articles, keywords, and H-index. Bibliometrics and visualization analyses employed VOSviewer, CiteSpace, the R package “bibliometrix,” and online analytic platforms. Using Arrowsmith,1 we determined miRNA-SCI relationships and discussed potential miRNA mechanisms in SCI.ResultsFrom 2008 to 2024, the number of related papers increased annually, reaching 754. The number of yearly publications remained high and entered a period of rapid development. Researchers from 50 countries/regions, 802 institutions, 278 journals, and 3,867 authors participated in the field. Currently, China has advantages in the number of national papers, citations, institutions, and authors. However, it is necessary to strengthen cooperation among different authors, institutions, and countries to promote the production of important academic achievements. The research in the field currently focuses on nerve injury, apoptosis, and gene expression. Future research directions mainly involve molecular mechanisms, clinical trials, exosomes, and inflammatory reactions.ConclusionOverall, this study comprehensively analyzes the research status and frontier of miRNAs in SCI. A systematic summary provides a complete and intuitive understanding of the relationship between SCI and miRNAs. The presented findings establish a basis for future research and clinical application in this field.
Detection and comparison of tumor cell-associated microbiota from different compartments of colorectal cancer
Authors: Zuo Yanzhen , Lu Yanjie , Pang Jiayu , Jin Shunkang , Zhang Xinyu , Zhao Enhong , Li Yuhong 
Published: May 2024

IntroductionIntratumoral microbes play an important role in the development of colorectal cancer (CRC). However, studying intratumoral microbes in CRC faces technical challenges, as tumor microbe communities are often contaminated by fecal microbes due to the structure of the gut folds and villi. The present study aimed to develop a new method for isolating tumor cell-associated microbiota and comparing microbial populations from different compartments.Materials and methodsThe distribution of intestinal bacteria was detected using immunohistochemistry combined with 5R-16s rRNA gene sequencing to explore the effects of the sampling site and number of washes on the detection of microbiota. The 5R-16s rRNA gene sequencing was performed using 44 samples from 11 patients with CRC, including CRC tumor tissues (TT), normal tissues adjacent to CRC (NT), tumor cells (TC), and normal cells (NC). TC and NC were obtained from the TT and NT using an enzymatic digestion method. The microbiota and their potential functions in the four groups were analyzed and compared to determine the differential microbiota related to CRC.ResultsBacteria were mainly distributed in the feces covering intestinal tissues and in the epithelial cells and macrophages within the tissues. Different sampling sites and number of washes led to detection of different microbiota distributions. Although the cleaning method could be controlled, sampling sites varied and led to different microbiota distributions. The phyla of Firmicutes and Bacteroidetes were highly abundant in the conventionally used tissue samples, whereas Proteobacteria was the most abundant phyla in the cell samples isolated with the new method (i.e., after cell enzymatic hydrolysis). Detection of CRC cell-associated microbiota using a cell enzymatic digestion method showed that some bacteria, such as Fusobacterium, Eikenella, Shewanella, and Listeria, were more abundant in TT than NT, whereas the abundance of Akkermansia was lower in TT than NT. The tumor/normal ratios of some bacteria, such as Gemella, Escherichia, Shigella, and Blautia, were different between the cell and tissue samples.ConclusionThe cell enzymatic digestion method reduced fecal bacterial contamination, enabling low biomass intratumoral microbiota to be detected and allowing prediction of bacterial distributions.
The impact of Bruton’s tyrosine kinase inhibitor treatment on COVID-19 outcomes in Chinese patients with chronic lymphocytic leukemia
Authors: Yang Shenmiao , Wei Rong , Shi Hongxia , Wang Yazhe , Lai Yueyun , Zhao Xiaosu , Lu Jin , Schmitz Norbert 
Published: May 2024

BackgroundImpact of B-cell depletion following treatment with Bruton tyrosine kinase-inhibitors (BTKi) on the outcome of SARS-CoV-2 infection in chronic lymphocytic leukemia (CLL) patients remain controversial. We investigated the impact of BTKi on susceptibility and the severity of COVID-19 in Chinese patients with CLL during the first wave of COVID-19 (Omicron variant).MethodsCLL patients (n=171) visiting the Institute of Hematology, Peoples’ Hospital, China (November 15, 2022- January 20, 2023) were included in the study. Seventeen patients receiving BTKi and venetoclax with or without obinutuzumab were excluded. Data from 117 patients receiving treatment with BTKi were collected using a standardized questionnaire through telephone interviews. Thirty-four patients without CLL-specific treatment served as controls. The data was analysed using IBM SPSS Software version 21 and a P value of &lt;0.05 was considered statistically significant.ResultsThe median age of patients was 67 years and majority were males (n=100). Treatment with BTKi was not associated with higher incidence of COVID-19 (74% [95% Confidence Interval (CI) 60%, 92%]) versus 74% (CI 48%, 100%) without any treatment (P=0.92). Hypoxemia was reported by 45% (32%, 61%) and 16% (4%, 41%) (P=0.01). BTKi was the only independent risk factor of hypoxemia (Hazard Ratio [HR], 4.22 [1.32, 13.50]; P = 0.02). Five (5.7%) patients with COVID-19 under BTKi required ICU admission; 4 of them died. No ICU admissions/deaths were observed in the control group.ConclusionIn Chinese patients with CLL and treated with BTKi experienced more severe lung disease and ICU admissions due to COVID-19 than patients without CLL therapy. Frequency of infections with SARS-CoV-2, however, was not different in patients with or without BTKi treatment.
Cang-ai volatile oil alleviates nasal inflammation via Th1/Th2 cell imbalance regulation in a rat model of ovalbumin-induced allergic rhinitis
Authors: Zhou Yang , Chen Bojun , Fu Yi , Wan Chunping , Li Huayan , Wang Lin , Huang Xiaoyi , Wu Zhao , Li Gang , Xiong Lei , Qin Dongdong 
Published: May 2024

We previously revealed that Cang-ai volatile oil (CAVO) regulates T-cell activity, enhancing the immune response in people with chronic respiratory diseases. However, the effects of CAVO on allergic rhinitis (AR) have not been investigated. Herein, we established an ovalbumin (OVA)-induced AR rat model to determine these effects. Sprague–Dawley (SD) rats were exposed to OVA for 3 weeks. CAVO or loratadine (positive control) was given orally once daily for 2 weeks to OVA-exposed rats. Behavior modeling nasal allergies was observed. Nasal mucosa, serum, and spleen samples of AR rats were analyzed. CAVO treatment significantly reduced the number of nose rubs and sneezes, and ameliorated several hallmarks of nasal mucosa tissue remodeling: inflammation, eosinophilic infiltration, goblet cell metaplasia, and mast cell hyperplasia. CAVO administration markedly upregulated expressions of interferon-γ, interleukin (IL)-2, and IL-12, and downregulated expressions of serum tumor necrosis factor-α, IL-4, IL-5, IL-6, IL-13, immunoglobulin-E, and histamine. CAVO therapy also increased production of IFN-γ and T-helper type 1 (Th1)-specific T-box transcription factor (T-bet) of the cluster of differentiation-4+ T-cells in splenic lymphocytes, and protein and mRNA expressions of T-bet in nasal mucosa. In contrast, levels of the Th2 cytokine IL-4 and Th2-specific transcription factor GATA binding protein-3 were suppressed by CAVO. These cumulative findings demonstrate that CAVO therapy can alleviate AR by regulating the balance between Th1 and Th2 cells.