bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unveiling the immunological landscape of disseminated tuberculosis: a single-cell transcriptome perspective
Authors: Gong Zhen , Xu Hongxiang , Zhang Qiao , Wang Guirong , Fan Lin , Wang Zilu , Fan Lichao , Liu Chang , Yu Yanhong , Liu Zhou , Zhou Qiang , Xiao Huasheng , Hou Rui , Zhao Ying , Chen Yu , Xie Jianping 
Published: February 2025

IntroductionHematogenous disseminated tuberculosis (DTB) has an unclear etiology that likely involves multiple factors. Understanding the underlying immunological characteristics of DTB is crucial for elucidating its pathogenesis.MethodsWe conducted single-cell RNA transcriptome and T cell receptor (TCR) sequencing on samples from seven DTB patients. Additionally, we integrated and analyzed data from two published profiles of latent TB infection, three active TB cases, and two healthy controls.ResultsOur analysis revealed a significantly higher proportion of inflammatory immune cells (e.g., monocytes and macrophages) in DTB patients, along with a notably lower abundance of various lymphocytes (including T cells, B cells, and plasma cells), suggesting that lymphopenia is a prominent feature of the disease. T cell pseudotime analysis indicated a decrease in the expression of most hypervariable genes over time, pointing to T cell functional exhaustion. Furthermore, a marked absence of mucosal-associated invariant T (MAIT) cells was observed in the peripheral blood of DTB patients. In the TCR repertoire, specific polymorphisms (TRAV9-2, TRAV13-1, TRBV20-1, and TRBV5-1) and dominant clones (TRAJ49, TRBJ2-7, and TRBJ2-1) were identified. Analysis of the complementarity determining region 3 (CDR3) showed that the most frequent combination was TRAV1-2/TRAJ33, with the motif “CAAMD” being significantly reduced in DTB patients.DiscussionThese findings suggest that lymphopenia and T cell exhaustion, along with unique TCR signatures, may play critical roles in DTB pathogenesis. The reduced “CAAMD” motif and altered TCR clonotypes provide novel insights into the complex cellular dynamics associated with the disease, potentially offering new avenues for targeted immunological interventions.
Inhibiting melanoma tumor growth: the role of oxidative stress-associated LINC02132 and COPDA1 long non-coding RNAs
Authors: Xu JingWen , Jin MingZhu , Mu ZhenZhen , Li ZhengXiu , Qi RuiQun , Han XiuPing , Jiang HangHang 
Published: February 2025

BackgroundCutaneous melanoma is a type of malignant tumor that is challenging to predict and is readily stimulated by various factors. Oxidative stress can induce damage and alterations in melanocytes, subsequently triggering immune responses. Given that oxidative stress is a prevalent tumor stimulus, we aimed to enhance melanoma prediction by identifying lncRNA signatures associated with oxidative stress.MethodsWe screened for oxidative stress-related lncRNAs that could improve melanoma patient prognosis using the TCGA and GTEx databases. Utilizing differentially expressed oxidative stress-related lncRNAs (DE-OSlncRNAs), we constructed a Lasso regression model. The accuracy of the model was validated using univariate and multivariate regression, Kaplan-Meier (K-M) curves, and ROC curves. Subsequently, we conducted immune infiltration analysis, immune checkpoint differential analysis, IC50 pharmaceutical analysis, and gene set enrichment analysis. Investigating the effects of the target gene on melanoma using fluorescence in situ hybridization (FISH), quantitative real-time PCR (qRT-PCR), Edu assay, wound healing assay, transwell assay, flow cytometry, and reactive oxygen species (ROS) detection.ResultsThirteen lncRNAs were identified as significant prognostic factors. Four oxidative stress-related lncRNAs (COPDA1, LINC02132, LINC02812, and MIR205HG) were further validated by fluorescence in situ hybridization (FISH), with results consistent with our data analysis. LINC02132 and COPDA1 can influence the proliferation, invasion, migration, and apoptosis of melanoma. ConclusionOur findings suggest that upregulation of the LINC02132 or COPDA1 genes elevates intracellular reactive oxygen species (ROS) levels in melanoma cells, suppresses tumor cell proliferation, migration, and invasion, and promotes apoptosis. These results suggest a novel therapeutic strategy for melanoma treatment.
Chromatin structure and gene transcription of recombinant p53 adenovirus vector within host
Authors: Ning Duo , Deng Yuqing , Tian Simon Zhongyuan 
Published: February 2025

IntroductionThe recombinant human p53 adenovirus (Ad-p53) offers a promising approach for cancer therapy, yet its chromatin structure and effects on host chromatin organization and gene expression are not fully understood.MethodsIn this study, we employed in situ ChIA-PET to investigate the colorectal cancer cell line HCT116 with p53 knockout, comparing them to cells infected with the adenovirus-vector expressing p53. We examined alterations in chromatin interactions and gene expression following treatment with the anti-cancer drug 5-fluorouracil (5-FU).ResultsOur results indicate that Ad-p53 forms a specific chromatin architecture within the vector and mainly interacts with repressive or inactive regions of host chromatin, without significantly affecting the expression of associated genes. Additionally, Ad-p53 does not affect topologically associating domains (TADs) or A/B compartments in the host genome.DiscussionThese findings suggest that while Ad-p53 boosts p53 expression, enhancing drug sensitivity without substantially altering host HCT116 chromatin architecture.
Retinal microvascular density and inner thickness in Alzheimer’s disease and mild cognitive impairment
Authors: Ibrahim Yehia , Macerollo Antonella , Sardone Rodolfo , Shen Yaochun , Romano Vito , Zheng Yalin 
Published: February 2025

BackgroundAlzheimer’s disease (AD) is a major healthcare challenge, with existing diagnostics being costly/infeasible. This study explores retinal biomarkers from optical coherence tomography (OCT) and OCT angiography (OCTA) as a cost-effective and non-invasive solution to differentiate AD, mild cognitive impairment (MCI), and healthy controls (HCs).MethodsParticipants from the CALLIOPE Research Program were classified as “Dem” (AD and early AD), “MCI,” and “HCs” using neuropsychological tests and clinical diagnosis by a neurologist. OCT/OCTA examinations were conducted using the RTVue XR 100 Avanti SD-OCT system (VISIONIX), with retinal parameters extracted. Statistical analysis included normality and homogeneity of variance (HOV) tests to select ANOVA methods. Post-hoc analyses utilized Mann–Whitney U, Dunnett, or Tukey-HSD tests based on parameters’ normality and HOV. Correlations with age were assessed via Pearson or Spearman tests. A generalized linear model (GLM) using Tweedie regression modeled the relationship between OCT/OCTA parameters and MMSE scores, correcting for age. Another ordinal logistic GLM (OL-GLM) modeled OCT/OCTA parameters against classes, adjusting for multiple confounders.ResultsWe analyzed 357 participants: 44 Dem, 139 MCI, and 174 HCs. Significant microvascular density (VD) reductions around the fovea were linked with MCI and Dem compared to HCs. Age-related analysis associated thickness parameters with HCs’ old age. Our OL-GLM demonstrated significant thickness/volume reductions in Inner_Retina and Full_Retina layers. Foveal avascular zone (FAZ) area and perimeter were initially not correlated with cognitive decline; however, OL-GLM significantly associated FAZ perimeter enlargement with Dem and MCI groups. Significant average and inferior peripapillary RNFL thinning were linked to Dem and MCI groups.ConclusionThis is the first study to examine VD changes in G grid sections among Dem, MCI, and HCs. We found a significant association between various VD parameters and cognitive decline. Most macular thickness/volume changes did not correlate with cognitive decline initially; however, our OL-GLM succeeded, highlighting the importance of the confounders’ corrections. Our analysis excluded individual retinal layer parameters due to limitations; however, the literature suggests their value. Our study confirmed existing biomarkers’ efficacy and uncovered novel retinal parameters for cognitive decline, requiring further validation.
The combination of Shenhuang plaster and paclitaxel inhibits lung metastasis in breast cancer via modulation of the tumor microenvironment
Authors: Chen Shiqi , Karekad Maryam Mohammed Abbas , Liu Ting , Ding Bin , Wang Rongyun , Sun Qiuhua , Xu Xiaohong , Shi Yanan 
Published: February 2025

BackgroundPaclitaxel (PTX) is a chemotherapeutic agent that is frequently used for breast cancer treatment, but it has been associated with promoting distant metastases, including to the lungs, liver, and bones. Shenhuang plaster (SHP), a traditional Chinese medicine, has shown potential for modulating the tumor microenvironment (TME). This study investigates whether a combination of SHP and PTX can enhance the anti-tumor efficacy of PTX and mitigate its pro-metastatic effects in a 4T1 breast cancer mouse model.MethodsFemale Balb/c mice were injected with 4T1 breast cancer cells and then divided into four treatment groups: control, PTX, SHP, and PTX+SHP. The combination of SHP and PTX was evaluated using bioluminescence imaging (BLI), histological analysis, and hematoxylin and eosin (HE) staining to assess lung metastasis. Flow cytometry was employed to analyze immune cell populations, including tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), regulatory T cells (Tregs), and cytotoxic T cells (CD8+ and CD4+).ResultsSHP alone did not significantly inhibit lung metastasis but the combination of PTX and SHP led to a marked reduction in lung lesions, as confirmed by BLI and histological analysis. SHP improved the overall health of PTX-treated mice, reducing their body weight loss and mortality. Flow cytometry revealed that the combination therapy reduced the infiltration of M2 macrophages, MDSCs, and Tregs, while increasing the proportion of antitumor M1 macrophages, cytotoxic CD8+ T cells, and helper CD4+ T cells.ConclusionsThe combination of PTX and SHP has a synergistic effect, reducing lung metastasis and modulating immune cell populations within the TME. These results suggest that integrating traditional Chinese medicine with standard chemotherapy can enhance therapeutic efficacy and reduce adverse effects.
PD-1/PD-L1 inhibitors plus chemotherapy versus chemotherapy alone for Asian patients with advanced triple-negative breast cancer: a phase III RCTs based meta-analysis
Authors: Ruan Hua , Zou Yubin , Huang Lifeng , Zha Wenjuan , Ouyang Qingqing , Yang Ling 
Published: February 2025

BackgroundAdvanced triple-negative breast cancer (TNBC) presents significant therapeutic challenges, particularly in Asian populations, which exhibit distinct biological and genetic characteristics. Immunotherapy combined with chemotherapy has emerged as a promising approach; however, its efficacy compared to chemotherapy alone remains under investigation. This meta-analysis aims to evaluate the clinical outcomes of PD-1/PD-L1 inhibitors combined with chemotherapy (PIC) versus chemotherapy alone in the treatment of advanced TNBC in Asian patients.MethodsA systematic literature search was performed across six databases for phase 3 randomized controlled trials (RCTs). Only studies comparing the outcomes of PIC versus chemotherapy alone in patients with advanced TNBC, including subgroup analyses of Asian populations, were included. Data were pooled to assess overall survival (OS), progression-free survival (PFS), responses, and safety profiles.ResultsA total of 1041 patients from five phase 3 RCTs were included in the final analysis. Compared to chemotherapy alone, PIC therapy significantly improved PFS (hazard ratio [HR]: 0.74 [0.62, 0.88], P = 0.0008). No significant difference was observed in OS (HR: 0.78 [0.55, 1.12], P = 0.18), although a slight trend favoring PIC therapy was noted. Among PD-L1-positive patients, both OS (HR: 0.62 [0.44, 0.86], P = 0.005) and PFS (HR: 0.66 [0.50, 0.86], P = 0.003) were significantly improved in the PIC group. The PIC group also exhibited a substantially higher OS rate at 12–36 months and a higher PFS rate at 6–30 months. However, the incidence of immune-related AEs (irAEs) (risk ratio [RR]: 1.69 [1.33, 2.15], P &lt; 0.0001) and grade 3–5 irAEs (RR: 3.11 [1.59, 6.10], P = 0.001) was significantly higher in the PIC group. The most common irAEs in the PIC group were hypothyroidism (14.40%), dermatitis (10.00%), and infusion reactions (8.85%). Both treatment groups exhibited similar response rates and treatment-related AEs (TRAEs).ConclusionsIn Asian patients with advanced TNBC, PIC significantly improved survival compared to chemotherapy alone. Although the combination therapy was associated with a higher incidence of irAEs, its clinical benefits support its use as a viable treatment option for this population.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42024622428.
Retrospective analysis of early neurodevelopmental outcomes after esophageal atresia repair at a single institution: short-gap vs. long-gap defect
Authors: Lowdermilk Mary Madelyn , Evanovich Devon Michael , Wang Jue Teresa , Pier Danielle Bennett , Sadhwani Anjali , Zendejas Benjamin , Bajic Dusica 
Published: February 2025

BackgroundWith increased survival of infants born with esophageal atresia (EA), there is a knowledge gap regarding neurodevelopmental outcomes. We aimed to quantify the frequency of (1) documented developmental delay, and (2) implementation of early intervention services in the first and the second year of life following repair of short- and long-gap EA.MethodWe retrospectively analyzed term-born (n = 44) and premature infants (n = 26) following EA repair at a single institution (2009–2020). Infants with anomalies associated with known neurological disorders were excluded. Clinical data was obtained from the electronic medical record, and presented as means and percentages. Developmental delay included clinically documented motor, speech/language, and cognitive delays that were stratified according to a surgical group: short- and long-gap EA.ResultsNearly half of short-gap (24/54; 44%) and most of long-gap EA patients (12/16; 75%) had documented developmental delay in the first year of life that persisted into the second year of life [52% [28/54] short-gap; 69% [11/16] long-gap EA]. Developmental delay was noted irrespective of gestational age at birth, co-existing cardiac anomalies, or presence of cranial/brain findings on imaging. By age 2, 70% (38/54) of short-gap and 69% (11/16) of long-gap EA patients had received early intervention.InterpretationInfants born with EA are at high-risk for developmental delay. Early neurodevelopmental assessments and intervention is recommended for EA patients.
Effectiveness of pharmacological treatments for COVID-19 due to SARS-CoV-2: a systematic literature review
Authors: Garcia Vidal Carolina , González Jonathan , Lumbreras Carlos , Salavert Miguel , Castro Antonio , Rubio-Rodríguez Darío , Rubio-Terrés Carlos 
Published: February 2025

AimSince the first cases of the COVID-19 pandemic, caused by the SARS-CoV-2 virus, described in 2019, numerous drugs have been proposed for the treatment of the disease. However, studies have given contradictory or inconclusive results, making it difficult to determine which treatments are truly effective. The objective was to carry out a systematic review of the literature analyzing the effectiveness (mortality, hospitalization and clinical improvement) of COVID-19 treatments initially proposed and finally authorized in the European Union.MethodsPubMed and other electronic databases were systematically searched for meta-analyses published between January 2020 and December 2022, as well as two additional searches: one of individual clinical studies published until October 2023 and another of those drugs that were considered at the beginning and that were discarded early because the clinical results were unfavorable.ResultsIn the synthesis, 85 meta-analyses and 19 additional clinical studies were included (base case). All medications indicated in the treatment of COVID-19 have favorable efficacy results (mortality, hospitalization rate, clinical improvement) but these results were not confirmed in all studies carried out, being frequently contradictory (confirming or not confirming the impact of treatment on mortality). According to meta-analysis with the largest sample size, the drugs with the greatest evidence of effectiveness in reducing mortality are remdesivir (HR= 0.79; 95% CI 0.73–0.85) and tocilizumab (OR= 0.73; 95% CI 0.56–0.93). Regarding the composite of Covid-19–related hospitalization or death from any cause, the drugs with the greatest evidence of efficacy are remdesivir, nirmatrelvir/ritonavir and sotrovimab (although, currently the effectiveness of monoclonal antibodies against the new variants of the virus has not been demonstrated).ConclusionAccording to this systematic review, the treatments with the greatest evidence of reducing mortality in patients with COVID-19 are remdesivir and tocilizumab.
Inflammation-fibrosis interplay in inflammatory bowel disease: mechanisms, progression, and therapeutic strategies
Authors: Li Yanan , Xu Feng , Fang Yulai , Cui Yuan , Zhu Zhenxing , Wu Yuguang , Tong Yiheng , Hu Jingyi , Zhu Lei , Shen Hong 
Published: February 2025

BackgroundThe incidence of intestinal fibrosis in Inflammatory bowel disease has increased in recent years, and the repair process is complex, leading to substantial economic and social burdens. Therefore, understanding the pathogenesis of intestinal fibrosis and exploring potential therapeutic agents is crucial.PurposeThis article reviews the pathogenesis of IBD-related intestinal fibrosis, potential therapeutic targets, and the progress of research on Traditional Chinese Medicine (TCM) in inhibiting intestinal fibrosis. It also provides foundational data for developing innovative drugs to prevent intestinal fibrosis.MethodsThis article reviews the literature from the past decade on advancements in the cellular and molecular mechanisms underlying intestinal fibrosis. Data for this systematic research were obtained from electronic databases including PubMed, CNKI, SciFinder, and Web of Science. Additionally, a comprehensive analysis was conducted on reports regarding the use of TCM for the treatment of intestinal fibrosis. The study synthesizes and summarizes the research findings, presenting key patterns and trends through relevant charts.ResultsThis study reviewed recent advancements in understanding the cellular and molecular mechanisms of intestinal fibrosis, the active ingredients of TCM that inhibit intestinal fibrosis, the efficacy of TCM formulae in preventing intestinal fibrosis, and dietary modification that may contribute to the inhibition of intestinal fibrosis.ConclusionThis article examines the cellular and molecular mechanisms that promote the development of intestinal fibrosis, as well as potential therapeutic targets for its treatment. It also provides a theoretical basis for exploring and utilizing TCM resources in the management of intestinal fibrosis. Through the analysis of various TCM medicines, this article underscores the clinical significance and therapeutic potential of TCM and dietary modifications in treating intestinal fibrosis.
Dehydrodiisoeugenol targets the PLK1-p53 axis to inhibit breast cancer cell cycle
Authors: Li Lin , Zheng Yifan , Yang Yongxia , Shi Senlin , Liu Shangjie , Huang Keying , Qiu Luonan , Zhang Rongxin , Huang Wenbin , Leng Yin 
Published: February 2025

IntroductionThere are about 2,300,000 new cases of breast cancer worldwide each year. Breast cancer has become the first most common cancer in the world and the leading cause of death among women. At the same time, chemotherapy resistance in patients with advanced breast cancer is still a serious challenge. Alpinia Katsumadai Hayata (AKH), as a traditional Chinese herbal medicine, has a wide range of pharmacological activities. Related studies have found that many compounds in AKH have anti-breast cancer activity. However, it is still worth exploring which component is the main active component of AKH in inhibiting breast cancer and its mechanism of action.MethodsIn this study, dehydrodiisoeugenol (DHIE) was screened as the main active ingredient of AKH against breast cancer based on LC-MS combined with drug similarity and disease enrichment analysis. WGCNA, network pharmacology, molecular docking, transcriptome sequencing analysis, immune infiltration analysis and single-cell sequencing were used to explore the mechanism of DHIE on breast cancer. CCK-8, flow cytometry and Western blot were used to verify the results in vitro. The efficacy of the drugs was verified in vivo by constructing a subcutaneous tumor-bearing mouse model.ResultsOur research showed that DHIE and breast cancer enriched core gene targets mainly act on epithelial cells in breast cancer tissues and significantly inhibit the growth of breast cancer by affecting the PLK1-p53 signaling axis to arrest the breast cancer cell cycle at G0/G1 phase. Further analysis showed that although DHIE had opposite regulatory effects on different isoforms of p53 in different types of breast cancer cells, they eventually caused cell cycle arrest. In addition, in vivo studies showed that DHIE reduced tumor burden, significantly reduced the infiltration level of tumor proliferation-related marker Ki-67, and inhibited the expression of PLK1 in the mouse model, which was further enhanced when combined with DOX.DiscussionCollectively, our study suggests that DHIE in AHK may eventually induce cell cycle arrest and inhibit breast cancer growth by regulating the PLK1-p53 signaling axis, which may provide a new therapeutic strategy for breast cancer. However, the specific mechanisms by which DHIE regulates p53 in different subtypes of breast cancer and the advantages of chemotherapeutic combinations compared with other drugs are still worth exploring.
Emotional labor and its influencing factors of clinical nurses: a cross-sectional study based on latent profile analysis
Authors: Zhou Li , Xiong Wei , Hu Mengmeng , Chang Hongjuan 
Published: February 2025

ObjectiveThe present study aimed to investigate latent classes of emotional labor among clinical nurses in China and analyze the influencing factors of emotional labor. With this as a reference, care managers can develop more targeted emotional labor intervention programs.MethodsThis study enrolled 1,320 clinical nurses by using stratified random sampling from August to October 2023. A total of 1,279 nurses completed the following questionnaires: General Information Questionnaire, Emotional Labor Scale, Generalized Anxiety Disorder-7 scale (GAD-7), Patient Health Questionnaire-9 scale (PHQ-9), and Work–Family Conflict Scale. Based on the Emotional Labor Scale, the latent profile analysis (LPA) was used to explore the latent classes of nurses’ emotional labor. Then, univariate analysis and multivariate logistic regression analysis were used to explore the influencing factors of emotional labor.ResultsThree latent classes were identified: generally low-level group (1.5%), high-level deep-acting group (17.2%), and high-level surface-acting group (81.3%). Male nurses were more likely to be in the generally low-level group than female nurses. Nurses with low scores on Work–Family Conflict Scale were more likely to be in the high-level deep-acting group than those with high scores. Compared with the nurses with very poor health, the nurses with very good health were more likely to be in the high-level deep-acting group, and nurses with general health were more likely to be in the high-level surface-acting group.ConclusionThe emotional labor of clinical nurses can be identified into three latent classes. Nursing managers can predict the latent classes of emotional labor based on characteristics such as demographic information and work–family conflict. Therefore, precise intervention can be implemented to reduce the consumption of internal resources and the occurrence of nursing adverse events caused by excessive emotional labor.