bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circle-seq reveals that eccDNA may be a key blood biomarker for HBV-associated liver cancer
Authors: Ran Xiao K. , Zhao Xiao F. , Wei Zhen W. , Pang Hua Z. , Tang Yan F. , Liu Rong , Wu Tie X. , Liu Xu D. 
Published: January 2025

IntroductionExtrachromosomal circular DNA (eccDNA) regulates tumor occurrence and development. Relevant eccDNA profiles have been established for various types of cancer; however, the eccDNA expression profiles in the blood of patients with hepatocellular carcinoma (HCC) and liver cirrhosis (LC) remain unknown. The present study aimed to investigate the eccDNA expression profiles in the blood of patients with HCC and LC.MethodsCircle-seq was used to detect eccDNAs in the blood samples. Full transcript sequencing was used to analyze the RNA in the samples. Geno Ontology enrichment and Kyoto Encyclopedia of Genes and Genome pathway analyses were performed on differentially expressed eccDNA-related genes. The identified eccDNA is combined with mRNA to screen target genes using bioinformatics analysis. EccDNAs were confirmed through polymerase chain reaction and Sanger sequencing.ResultsOverall, 103,235 eccDNAs were identified in HCC, whereas 67,110 eccDNAs were detected in LC. In total, 7,095 upregulated eccDNAs and 1,284 downregulated eccDNAs were identified. Following analysis of differential genes using bioinformatics, six candidate genes were screened out based on gene expression and cancer relevance. Experiments have verified that LAMA4[circle112550019-112550510] and KANK1[circle674459-674907] are real and expressed target genes, and their source genes are closely related to the survival time of patients with liver cancer.ConclusionOur research results revealed the main characteristics of eccDNAs in the blood of patients with HBV-related HCC and LC. It was found that eccDNAs were mainly less than 1,000 bp in length. Difference analysis showed that some eccDNAs had consistent and overlapping expressions with mRNAs. We found that LAMA4[circle112550019-112550510] and KANK1[circle674459-674907] are target genes related to HCC, and both of them may become potential biomarkers for the diagnosis and prognosis of HCC.
Impact of dysregulated microbiota-derived C18 polyunsaturated fatty acid metabolites on arthritis severity in mice with collagen-induced arthritis
Authors: Yoneda Katsuhiko , Sendo Sho , Okano Takaichi , Shimizu Hidenori , Yamada Hirotaka , Nishimura Keisuke , Ueda Yo , Saegusa Jun 
Published: January 2025

ObjectiveWe aimed to evaluate microbiome and microbiota-derived C18 dietary polyunsaturated fatty acids (PUFAs), such as conjugated linoleic acid (CLA), and to investigate their differences that correlate with arthritis severity in collagen-induced arthritis (CIA) mice.MethodsOn day 84 after induction, during the chronic phase of arthritis, cecal samples were analyzed using 16S rRNA sequencing, and plasma and cecal digesta were evaluated using liquid chromatography–tandem mass spectrometry. Differences in microbial composition between 10 control (Ctrl) and 29 CIA mice or between the mild and severe subgroups based on arthritis scores were identified. The cecal metabolite profile and its correlation with the microbiome were evaluated with respect to arthritis severity.ResultsThe hydroxy and oxo metabolite levels were higher in CIA mice than in Ctrl mice, some of which, including 10-hydroxy-cis-6-18:1, were positively correlated with arthritis scores. The 9-trans,11-trans CLA levels in CIA mice had a negative linear correlation with arthritis scores. Microbial diversity was lower in severe CIA mice than in mild CIA or Ctrl mice. The abundance of Lactobacillus relatively increased in the severe subgroup of CIA mice compared with that in the mild subgroup and was positively correlated with arthritis severity.ConclusionAlterations in gut microbiota and microbiota-derived C18 PUFA metabolites are associated in CIA mice and correlated with arthritis scores, indicating that plasma or fecal C18 PUFA metabolites can be potential biomarkers for arthritis severity and dysbiosis.
Changes in hematoma volume following aneurysmal subarachnoid hemorrhage and its impact on patient prognosis
Authors: Huang Zhenshan , Qian Feng , Ma Kui , Jiang Guowei , Zhang Lianfu , Zhang Yongming 
Published: January 2025

ObjectiveThis study aims to investigate the effects of preoperative intracerebral hematoma volume (HVpre), hematoma volume 6–8 days post-surgery (HVpost), and the rate of hematoma volume change (HVpre−HVpost)/HVpre on the prognosis of patients with aneurysmal subarachnoid hemorrhage (aSAH).Materials and methodsCT imaging data from 62 aSAH patients admitted to our hospital’s Neurosurgery Department between January 2022 and December 2023 were obtained, both preoperatively and 6–8 days postoperatively. The hematoma volumes were measured using 3D-Slicer. Patients’ recovery at 3 months post-discharge was assessed using the Modified Rankin Scale (mRS), categorizing the patients into a good prognosis group (mRS score 1–2) and a poor prognosis group (mRS score 3–5). Multivariate logistic regression analysis was conducted to identify independent risk factors for poor prognosis. Statistical methods were employed to compare preoperative and postoperative hematoma volumes with commonly used clinical scores. The predictive value of HVpre and HVpost for poor prognosis was evaluated using ROC curves. The rate of volume change was stratified by interquartile ranges, and the impact of different change rates on prognosis was compared.ResultsSignificant differences were found between good and poor prognosis groups in age, GCS score, Hunt-Hess grade, mFisher grade, BVpre, BVpost, and (HVpre−HVpost)/HVpre (p &lt; 0.05). Logistic regression identified gender, age, BVpre, BVpost, and volume change rate as independent risk factors (p &lt; 0.01). Increased GCS scores and higher Hunt-Hess and mFisher grades correlated with increased HVpre and HVpost. Higher hemorrhage reduction rates were linked to better outcomes. ROC curves showed HVpre and HVpost AUC values (0.831 and 0.857, respectively) were significantly higher than clinical scales. An HVpre volume over 22.25 mL and HVpost over 15.67 mL indicated a higher risk of poor prognosis, with sensitivities of 79.3 and 80.7%, and specificities of 67.1 and 69.3%.ConclusionHVpre, HVpost, and (HVpre−HVpost)/HVpre can serve as neuroimaging biomarkers for assessing patients after aSAH and can effectively predict clinical prognosis.
Safety of tenecteplase vs. alteplase in telestroke: a large multistate experience (STAT)
Authors: Figurelle Morgan , Corti Sandro , Collins Oleg , Gao Lan , Avila Amanda , Delfino Kristie , Mayer Laurie , Sevilis Theresa 
Published: January 2025

IntroductionPrompt treatment with IV thrombolytics (IVT) in acute ischemic stroke (AIS) patients is critical for improved recovery and survival. Recently, hospital systems have switched to the IVT tenecteplase (TNK) instead of the FDA-approved alteplase (tPA) for treatment. Multiple studies and meta-analyses evaluating the efficacy and safety of TNK demonstrate similar or superior outcomes when compared to tPA. TNK is not FDA-approved for treatment, which has led to hesitation in its use and increased attention on its complication profile, including the risk of intracranial hemorrhage (ICH).MethodsData from AIS consults conducted in the emergency departments of 220 facilities across 26 states, between 1 January 2022 and 31 May 2023, were extracted from the TeleCare by TeleSpecialists™ database. The encounters were reviewed for IVT candidates, door-to-needle (DTN) time, type of IVT administered, use of advanced imaging, presence of LVO, occurrence and type of complications, complication type, symptomatic ICH, and the ECASS II ICH score.ResultsA total of 2,305 TNK patients and 3,337 tPA patients were extracted. DTN times were faster (37 min vs. 42 min, p &lt; 0.0001), and more total complications were observed in the TNK group (87 vs. 80, p = 0.0035). In non-LVO IVT patients, the TNK group had more complications (57 vs. 47, p = 0.0078), specifically ICH (48 vs. 35, p = 0.0036). No statistically significant difference in the incidence of ICH was observed between the TNK group and the tPA group (21 vs. 18, p = 0.07). In IVT patients not accepted for NIR, the TNK group had more complications (77 vs. 69, p = 0.005), specifically ICH (63 vs. 51, p = 0.0026). In IVT patients accepted for NIR, no significant differences were observed. There were no statistically significant differences in symptomatic ICH between the groups.ConclusionThe TNK group was found to have significantly more complications, including ICH, than the tPA group driven by non-LVO patients. A closer analysis of the potential for increased risk to non-LVO patients is warranted based on this large, multistate, and multi-hospital system study.
Effects of exercise training on nigrostriatal neuroprotection in Parkinson’s disease: a systematic review
Authors: Ishaq Shahid , Shah Iqbal Ali , Lee Shin-Da , Wu Bor-Tsang 
Published: January 2025

IntroductionParkinson’s disease (PD) is characterized by progressive neurodegeneration within the nigrostriatum, leading to motor dysfunction. This systematic review aimed to summarize the effects of various exercise training regimens on protein or gene expression within the nigrostriatum and their role in neuroprotection and motor function improvement in animal models of Parkinson’s disease (PD).MethodsPubMed, EMBASE, and Web of Science were searched up to June 2024 and included sixteen studies that adhere to PRISMA guidelines and CAMARADES checklist scores ranging from 4 to 6 out of 10. Various exercise training regimens, administered 5 days per week for 6.5 weeks, were applied to MPTP, 6-OHDA, and PFF-α-synuclein-induced PD animal models.ResultsExercise training was found to downregulate the inflammatory pathway by attenuating α-synuclein aggregation, inhibiting the TLR/MyD88/IκBα signaling cascade and NF-κB phosphorylation, and decreasing pro-inflammatory cytokines IL-1β and TNF-α while increasing anti-inflammatory cytokines IL-10 and TGF-β within the nigrostriatum. It also inhibited the ASC and NLRP3 inflammasome complex and reduced the BAX/ Bcl-2 ratio and caspase-1/3 proteins, thereby decreasing neuronal apoptosis in the nigrostriatum. Exercise training elevated the expression of Pro-BDNF, BDNF, GDNF, TrkB, and Erk1/2, providing neurotrophic support to dopaminergic neurons. Furthermore, it upregulated the dopaminergic signaling pathway by increasing the expression of TH, DAT, PSD-95, and synaptophysin in the nigrostriatum.DiscussionThe findings suggested that exercise training downregulated inflammatory and apoptotic pathways while upregulated BDNF/GDNF pathways and dopaminergic signaling within the nigrostriatum. These molecular changes contributed to neuroprotection, reduced dopaminergic neuron loss, and improved motor function in PD animal models.Systematic review registrationCRD42024484537 https://www.crd.york.ac.uk/prospero/#recordDetails.
Nanoparticles in gynecologic cancers: a bibliometric and visualization analysis
Authors: Zhou Yunzhe , Chen Lizhang , Wang Tingting 
Published: January 2025

BackgroundGynecological cancers are characterized by uncontrolled cell proliferation within the female reproductive organs. These cancers pose a significant threat to women’s health, impacting life expectancy, quality of life, and fertility. Nanoparticles, with their small size, large surface area, and high permeability, have become a key focus in targeted cancer therapy. The aim of this study is to review recent advancements in nanoparticles applied to gynecologic cancers, providing valuable insights for future research.MethodsWe retrieved all literature on nanoparticles in gynecologic cancers from the Web of Science Core Collection (WOSCC) database between January 1, 2004, and June 4, 2024. Data analysis and visualization were conducted using R software (version 4.4.0), VOSviewer (version 1.6.19.0), and CiteSpace (version 6.1).ResultsA total of 2,843 publications from January 1, 2004, to June 4, 2024 were searched. Over the past 20 years, there has been a significant increase in publications. The leading countries and institutions in terms of productivity are China and the Chinese Academy of Sciences. The most prolific author and the most co-cited author are Sood, A K and Siegel, Rl. The top journals are the International Journal of Nanomedicine (n=97), followed by ACS Applied Materials &amp; Interfaces (n=72) and Journal of Materials Chemistry B (n=53). Keyword analysis shows current research focuses on two main areas: the application of nanoparticles for drug delivery and their broader applications in gynecologic cancers. Future research will likely focus on “silver nanoparticles,” “gold nanoparticles,” and “green synthesis.”ConclusionsOver the past two decades, nanoparticles have rapidly advanced in the field of gynecologic cancers. Research has primarily focused on the applications of nanoparticles in drug delivery and applications. Future trends point toward optimizing synthesis techniques and advancing preclinical studies to clinical applications, particularly for silver and gold nanoparticles. These findings provide valuable scientific insights for researchers.
Rational strategies for designing next-generation oncolytic viruses based on transcriptome analysis of tumor cells infected with oncolytic herpes simplex virus-1
Authors: Javid Naeme , Abdoli Shahriyar , Shahbazi Majid 
Published: January 2025

IntroductionOncolytic herpes simplex viruses (oHSVs) are a type of biotherapeutic utilized in cancer therapy due to their ability to selectively infect and destroy tumor cells without harming healthy cells. We sought to investigate the functional genomic response and altered metabolic pathways of human cancer cells to oHSV-1 infection and to elucidate the influence of these responses on the relationship between the virus and the cancer cells.MethodsTwo datasets containing gene expression profiles of tumor cells infected with oHSV-1 (G207) and non-infected cells from the Gene Expression Omnibus (GEO) database were processed and normalized using the R software. Common differentially expressed genes between datasets were selected to identify hub genes and were further analyzed. Subsequently, the expression of hub genes was verified by real-time polymerase chain reaction (qRT-PCR) in MDA-MB-231 (a breast cancer cell line) infected with oHSV-1 and non-infected cells.ResultsThe results of our data analysis indicated notable disparities in the genes associated with the proteasome pathway between infected and non-infected cells. Our ontology analysis revealed that the proteasome-mediated ubiquitin-dependent protein catabolic process was a significant biological process, with a p-value of 5.8E−21. Additionally, extracellular exosomes and protein binding were identified as significant cellular components and molecular functions, respectively. Common hub genes with degree and maximum neighborhood component (MNC) methods, including PSMD2, PSMD4, PSMA2, PSMD14, PSMD11, PSMC3, PSMC2, PSMD8, and PSMA4, were also identified. Analysis of gene expression by qRT-PCR and differential gene expression revealed that GADD45g genes can be effective genes in the proliferation of oncolytic HSV-1 virus.ConclusionThe transcriptome changes in tumor cells infected by oHSV-1 may be utilized to predict oncolytic efficacy and provide rational strategies for designing next-generation oncolytic viruses.
CT-based radiomics predicts HRD score and HRD status in patients with ovarian cancer
Authors: Wu Yujiao , Zhang Qianhui , Jiang Wenyan , Gao Yuhua , Qu Bin , Wang Xingling 
Published: January 2025

IntroductionThis study predicted HRD score and status based on intra- and peritumoral radiomics in patients with ovarian cancer (OC) for better guiding the use of PARPi in clinical.MethodsA total of 106 and 95 patients with OC were included between January 2022 and November 2023 for predicting HRD score and status, respectively. Radiomics features were extracted and quantitatively analyzed from intra- and peri-tumor regions in the CT image. Radiomics signatures (RSs) were built based on features from intra- and peri-tumor regions for predicting HRD score and status alone or in combination. Subject working characteristics (ROC) area under the curve (AUC), sensitivity (SEN), and specificity (SPE) were calculated as comparative metrics.ResultsFor predicting HRD score, 4 and 2 features were selected as the most important predictors from the intra- and peritumoral regions, respectively. For predicting HRD status, 4 features from the intratumoral region and 2 from the peritumoral region were identified as the most important predictors. Radiomics nomograms created by combining RSs and important clinical factors showed good predictive results with AUCs of 0.852 (95% confidence interval [CI]: 0.765-0.938, SEN = 0.907, SPE = 0.655) and 0.781 (95% CI: 0.621-0.941, SEN = 0.688, SPE = 0.833) in the training and validation cohort for predicting HRD score, respectively; with AUCs of 0.874 (95% CI: 0.790-0.957, SEN = 0.765, SPE = 0.867) and 0.824 (95% CI: 0.663-0.985, SEN = 0.762, SPE = 0.800) in the training and validation cohort for predicting HRD status, respectively.DiscussionCalibration curves and decision curve analysis (DCA) confirmed potential clinical usefulness of our nomograms. Our findings suggest that radiomics features derived from the CT image of OC have the potential to predict HRD score and status, and the developed nomograms can enrich the range of applicable population of PARPi, prolong progression-free survival and provide personalized treatment for OC patients.
Autophagic flux modulates tumor heterogeneity and lineage plasticity in SCLC
Authors: Hao Yujie , Li Mingchen , Liu Wenxu , Ma Zhenyi , Liu Zhe 
Published: January 2025

IntroductionSmall cell lung cancer (SCLC) is characterized by significant heterogeneity and plasticity, contributing to its aggressive progression and therapy resistance. Autophagy, a conserved cellular process, is implicated in many cancers, but its role in SCLC remains unclear.MethodsUsing a genetically engineered mouse model (Rb1fl/fl; Trp53fl/fl; GFP-LC3-RFP-LC3△G), we tracked autophagic flux in vivo to investigate its effects on SCLC biology. Additional in vitro experiments were conducted to modulate autophagic flux in NE and non-NE SCLC cell lines.ResultsTumor subpopulations with high autophagic flux displayed increased proliferation, enhanced metastatic potential, and neuroendocrine (NE) characteristics. Conversely, low-autophagic flux subpopulations exhibited immune-related signals and non-NE traits. In vitro, increasing autophagy induced NE features in non-NE cell lines, while autophagy inhibition in NE cell lines promoted non-NE characteristics.DiscussionThis study provides a novel model for investigating autophagy in vivo and underscores its critical role in driving SCLC heterogeneity and plasticity, offering potential therapeutic insights.
Case report: Accidental aconitine poisoning caused by the inappropriate use of a type of Chinese patent medicine
Authors: Shang Ruikai , Liu Hongyu , Tian Qiaoxin , Liu Yuru , Jian Xiangdong , Li Qilu 
Published: January 2025

BackgroundCompound schizonepeta fumigation lotion is a type of Chinese patent medicine for external use. It has the effect of dispelling wind, eliminating dampness, reducing swelling, and relieving pain. Clinically, it is used for anal fumigation and treatment of external hemorrhoids, anal fissures, and other diseases. Aconitum species are widely used in the field of traditional Chinese medicine. However, improper use and overdose can easily cause acute poisoning, leading to malignant arrhythmias, cardiogenic shock, and even death.MethodsThis study retrospectively analyzed the clinical data of eight patients who were treated in our hospital from June 2023 to February 2024 after taking compound schizonepeta fumigation lotion by mistake.Case presentationWe report 8 cases of patients who took compound schizonepeta fumigation lotion by mistake. Most patients were illiterate and older, and poisoning was attributed to the misuse of an external drug. The affected patients exhibited different degrees of arrhythmia, with 2 receiving tracheal intubation, assisted ventilation, and hemoperfusion. Finally, all patients were clinically cured and subsequently discharged.ConclusionA considerable number of accidental aconitine poisoning cases were reported over a short period, alerting clinicians to their growing incidence. Meanwhile, when prescribing medications, clinicians must provide clear instructions on proper usage and ensure that patients strictly adhere to the dosage and administration guidelines outlined in the drug instructions. Additionally, patients should be informed that any errors in medication administration require urgent medical attention. Health professionals should aim to improve public understanding of safe medication practices, promote health literacy.
Gut microbiota derived metabolite trimethylamine N-oxide influences prostate cancer progression via the p38/HMOX1 pathway
Authors: Zhou Yuhua , Lv Jing , Jin Shengkai , Fu Chaowei , Liu Bo , Shen Yang , Li Menglu , Zhang Yuwei , Feng Ninghan 
Published: January 2025

BackgroundProstate cancer was the fourth most diagnosed cancer worldwide in 2022. Radical treatments and androgen deprivation therapy benefit newly diagnosed patients but impact quality of life, often leading to castration-resistant prostate cancer. Short-term dietary changes significantly affect the gut microbiota, which differs markedly between prostate cancer patients and healthy individuals, impacting both cancer progression and treatment response. A high-choline diet increases the risk of fatal prostate cancer, potentially mediated by the conversion of choline to the trimethylamine N-oxide (TMAO) by the gut microbiota.MethodsThe CCK8 assay was employed to investigate whether TMAO affects the proliferation ability of prostate cancer cells and to determine the appropriate drug concentration. Subsequently, CCK8 time gradients, colony formation assays, and EdU assays measured TMAO’s influence on cell proliferation. Wound healing and transwell migration assays evaluated TMAO’s effect on cell migration. RNA-seq analysis was performed to explore the mechanisms by which TMAO influences the proliferation and migration of prostate cancer cells. qPCR and Western blotting were utilized to validate the expression of related mRNA or proteins. Finally, we performed in vivo experiments to evaluate the effect of a high choline diet on the growth of subcutaneous tumors and lung metastases in mice.ResultsOur study found that TMAO enhances the proliferation and migration of prostate cancer cells by upregulating HMOX1 via activation of the MAPK signaling pathway, specifically p38 MAPK. In mouse subcutaneous tumor and lung metastatic tumor experiments, the high-choline diet increased prostate cancer cell proliferation and migration, resulting in significantly greater tumor volume and number of metastases than controls.ConclusionThis study is the first to demonstrate the role of the gut microbiota-derived metabolite TMAO in prostate cancer. TMAO promotes the proliferation and migration of prostate cancer cells by activating the p38 pathway and increasing HMOX1 expression. Reducing choline intake through dietary intervention may delay the onset and progression of prostate cancer, presenting significant clinical application value.