bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of the efficacy and safety of camrelizumab combined with chemotherapy for cervical cancer treatment
Authors: Yang Song-Tian , Yang Shuang , Wang Ji , Mu Xiao-Ling , Yan Bo 
Published: February 2025

IntroductionIn this study, we explored the effectiveness and safety of the immune checkpoint inhibitor camrelizumab in combination with chemotherapy for the treatment of cervical cancer by investigating adverse effects and changes in tumor volume, tumor activity, and biochemical indices.MethodsIn this retrospective analysis, the experimental group was administered intravenous camrelizumab in conjunction with a TP regimen (consisting of a paclitaxel analog and a platinum analog), while the control group was given only the TP regimen. The effectiveness of solid tumors, SCC-Ag values, tumor volume, and apparent diffusion coefficient (ADC) values, as well as adverse responses, were compared between the two groups.ResultsIn the experimental group, 11 cases (22.45%) exhibited complete remission (CR), 27 cases (55.10%) demonstrated partial resolution (PR), and 11 cases (22.45%) showed stable disease (SD). The objective remission rate (ORR) was 77.55%, and the disease control rate (DCR) was 100%. In the control group, 10 cases (25.64%) exhibited CR, 18 cases (46.15%) demonstrated PR, 9 cases (23.08%) exhibited SD, and 2 cases (5.13%) exhibited disease progression. The ORR was 71.79%, and the DCR was 94.87%. A significant difference was observed between the two groups regarding the post-treatment SCC-Ag value, pre-treatment minimum ADC (minADC), and the change in size of minADC before and after treatment (P &lt; 0.05). A comparison of the pre- and post-treatment size changes in tumor volume in patients with stage IIA2 cancer revealed significant differences (p &lt; 0.05). No adverse responses of grade 3 or higher were detected.DiscussionOur analysis showed that the combination of camrelizumab and chemotherapy effectively reduced tumor size and malignancy in cervical cancer treatment, demonstrating robust anti-tumor activity with a favorable safety profile.
Use of CatBoost algorithm to identify the need for surgery in infants with necrotizing enterocolitis
Authors: Jin Xinyun , Sun Wenqiang , Li Yihui , Su Yinglin , Xu Lingqi , Zhu Xueping 
Published: February 2025

BackgroundEarly identification of infants with necrotizing enterocolitis (NEC) at risk of surgery is essential for an effective treatment. This study aims to clarify the risk factors of surgical NEC and establish a prediction model by machine learning algorithm.MethodsInfants with NEC were split into two groups based on whether they had surgery or not. Clinical data was collected and compared between the groups. Variables were analyzed with one-way logistic regression and predictive models were built using logistic regression and CatBoost algorithm. The models were evaluated and compared using Receiver Operating Characteristic (ROC) curves and feature importance. Feature importance was ranked using the SHapley Additive exPlanation method and model optimization was performed using feature culling. Final model was selected and a user-friendly GUI software was created for clinical use.ResultsThe Catboost model performed better than the logistic regression model in terms of discriminative power. An interpretable final model with 14 features was built after the features were reduced according to the feature importance level. The final model accurately identified Surgicel NEC in the internal validation (AUC = 0.905) and was translated into a convenient tool to facilitate its use in clinical settings.ConclusionsCatboost machine learning model related to infants with surgical NEC was successfully developed. A GUI interface was developed to assist clinicians in accurately identifying children who would benefit from surgery.
Early caffeine therapy decreases bronchopulmonary dysplasia but might increase mortality in preterm infants? a systematic review and meta-analysis
Authors: Ma Juan , Chen Long , Mu Kaihong , Tang Shifang , Shi Yuan 
Published: February 2025

ObjectivesTo assess the effectiveness of early vs. late caffeine therapy for bronchopulmonary dysplasia (BPD) in infants.MethodsPubMed, Embase, Web of Science, and Cochrane databases were searched up to October 2024. Studies comparing early and late caffeine therapy for BPD in infants were included. The primary outcomes were the incidence of BPD, severe BPD, and mortality.ResultsEleven studies (1 RCT and 10 cohorts) with 64,749 patients (34,175 early and 30,574 late) were included. Meta-analysis revealed a significantly lower incidence of BPD (OR: 0.67; 95% CI: 0.56, 0.79; P &lt; 0.00001) but higher mortality (OR: 1.20; 95% CI: 1.12, 1.29; P &lt; 0.00001) in the early group. Subgroup analysis showed a significant difference in BPD incidence in retrospective studies (OR: 0.57; 95% CI: 0.44, 0.74; P &lt; 0.0001), but not in prospective studies (OR: 0.84; 95% CI: 0.44, 1.61; P = 0.61). No significant difference was observed in severe BPD incidence (OR: 0.89; 95% CI: 0.34, 2.35; P = 0.81).ConclusionsEarly caffeine therapy may reduce BPD incidence but increase mortality risk in infants. More large-scale, prospective studies are needed to further evaluate the efficacy of early vs. late caffeine therapy for BPD.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=474351, PROSPERO (CRD42023474351).
Astragalus-containing Chinese herbal medicine used with Western medicine for lupus nephritis: a systematic review and meta-analysis of randomized controlled trials
Authors: Li Jinjiao , Wu Mengyun , Liu Weiwei 
Published: February 2025

BackgroundLupus nephritis (LN) is a serious complication of systemic lupus erythematosus (SLE) that requires effective management to prevent kidney damage and other systemic effects. While Western medicine provides the standard treatment, incorporating traditional Chinese medicine, such as Astragalus-containing Chinese herbal medicine (CHM), may offer additional benefits in improving patient outcomes.ObjectiveThis study aims to conduct a systematic review and meta-analysis of the efficacy and safety of Astragalus in conjunction with Western medicine for the treatment of LN.MethodsWe conducted a comprehensive, global systematic search across databases including PubMed, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), and Wanfang. Data were synthesized using fixed- or random-effects models, depending on the level of heterogeneity. Results were presented as standardized mean difference (SMD), risk ratios (RRs), or number needed to treat (NNT) with 95% confidence intervals (CIs). The Cochrane Q test and I2 statistics were used to test the heterogeneity assessment. Trial sequential analysis (TSA) was employed to assess the power of the results. All statistical analysis was carried out using STATA (version 16.0).ResultThe analysis included 14 RCTs, with a total of 800 patients (417 in the treatment group and 383 in the control group). Our meta-analysis revealed that patients treated with Astragalus-containing CHM alongside Western medicine showed markedly improved outcomes compared to those receiving only Western medicine. Significant improvements were observed in Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores (SMD = 1.01, 95% CI: 0.71–1.30, P &lt; 0.001), 24-h proteinuria (SMD = 0.51, 95% CI: 0.35–0.66, P &lt; 0.001SMD = 0.51, 95% CI: 0.35–0.66, P &lt; 0.001), serum creatinine (SCr) levels (SMD = 0.64, 95%CI: 0.27–1.01, P &lt; 0.001), blood urea nitrogen (BUN) levels (SMD = 0.73, 95%CI: 0.53–0.92, P &lt; 0.001), and overall response rates (ORR) (RR = 1.21, 95%CI: 1.10–1.34, P &lt; 0.001). Additionally, the incidence of adverse events (AEs), such as diarrhea, fever, and other symptoms, was significantly lower in the group treated with Astragalus-containing CHM and Western medicine (RR = 0.56, 95%CI: 0.42–0.73, P &lt; 0.001). The TSA indicated that the data were sufficiently robust to draw reliable numerical conclusions regarding the ORR and the incidence of AEs.ConclusionThe inclusion of Astragalus-containing CHM alongside Western medicine may be a promising strategy for to improve the therapeutic effectiveness and reduce toxicity in the treatment of LN.
Elucidation of Callistemon lanceolatus-derived natural compounds in STAT 3 pathway against human cancer cells: in silico and in vitro studies
Authors: Zafar Mubashir , Anwar Sadaf , Hussain Malik Asif , Iqbal Naveed , Ali Abrar , Sadaf  , Najm Mohammad Zeeshan , Kausar Mohd Adnan 
Published: February 2025

IntroductionMany human tumours have hyperactive signal transducer and activator of transcription 3 (STAT3, positioning it as a prime target for natural compounds with anticancer properties. This study investigated three small-molecule STAT3 inhibitors derived from Callistemon lanceolatus: cyanidin-3,5-diglucoside, kaempferol-3-o-β-d-galactopyranoside, and quercetin-3-o-(2″-o-galloyl)-β-d-galactopyranoside.Material and methodsThe compounds were explored through virtual screening and molecular dynamics (MD) simulations to understand the intracellular processing of activated STAT3. The biological effects of these STAT3 inhibitors on human cancer cells were assessed via simulation. Further, in-vitro studies were performed to exhibit the anti-cancer role of compounds on cancer cell lines.Results and discussionIt is revealed through results that active components in these compounds inhibited cancer cell migration and invasion and suppressed the proliferation of noncancer cells. Moreover, these natural compounds from C. lanceolatus downregulated the expression of STAT3 downstream target proteins, indicating their potential as therapeutic agents against cancer. Thus, cyanidin-3,5-diglucoside, kaempferol-3-o-β-d-galactopyranoside, and quercetin-3-o-(2″-o-galloyl)-β-d-galactopyranoside from C. lanceolatus are promising candidates for cancer treatment.
Ehretia genus: a comprehensive review of its botany, ethnomedicinal values, phytochemistry, pharmacology, toxicology and clinical studies
Authors: Jiang Sai , Wang Mengyun , Kaur Amanpreet , Jiang Lin , Cai Yuan , Luo Jiangyi , Li Minxi , Wang Hongxing , Wan Dan , Peng Yanmei 
Published: February 2025

BackgroundThe Ehretia genus, comprising 66 species in the Boraginaceae family, has a history of ethnomedicinal use for various ailments. This review focuses on the botany, traditional uses, phytochemistry, pharmacology, toxicology, clinical studies, cultivation, and commercial potential of the Ehretia genus, with the goal of enhancing current research and applications.MethodsLiteratures related to Ehretia species were compiled using keywords such as “Ehretia,” “traditional use,” “chemical constituents,” and “bioactivity” from scientific databases, including “China Knowledge Resource Integrated Databases (CNKI),” “Flora of China,” “Google Scholar,” “Hunan Library,” “Plants of the World Online,” and “Web of Science” and so on.ResultsFrom 1980 to August 2024, only 101 compounds have been identified within this genus, primarily consisting of flavonoids, phenylpropanoids, phenolics, benzoquinones, triterpenoids, and fatty acids, with phenylpropanoids being the main components. Extracts and compounds from Ehretia species exhibited various bioactivities, including antioxidant, hepatoprotective, analgesic, anti-inflammatory, antibacterial, and anticancer effects, etc.ConclusionResearch on the Ehretia genus is limited, with many species remaining underexamined in terms of phytochemistry and pharmacology. Few active compounds have been isolated and assessed for biological activities, and there is a lack of investigation into their mechanisms of action. Despite its documented uses, Ehretia species remains less explored scientifically than other Boraginaceae genera, presenting significant research opportunities. Further comprehensive studies are necessary to deepen our understanding of this diverse genus and validate its therapeutic potential.
MFAP4 is a novel prognostic biomarker in glioma correlating with immunotherapy resistance and ferroptosis
Authors: Lv Yuanhao , Gao Ying , Di Wenyu , Li Zhaoyi , Shi Yashen , Hou Tianyuan , Chen Yiyang , Tian Jiaqi , Xu Miaoming , Su Wei , Zhang Min , Zhong Jiateng 
Published: February 2025

BackgroundGlioma, an aggressive brain tumor, poses a challenge in understanding the mechanisms of treatment resistance, despite promising results from immunotherapy.MethodsGenes associated with immunotherapy resistance were identified by analyzing The Cancer Genome Atlas (TCGA), the Chinese Glioma Genome Atlas (CGGA), and the Gene Expression Omnibus (GEO) database. In addition, gene set enrichment analysis (GSEA) was utilized to reveal relevant signaling pathways. Co-expression, differential expression and functional analyses were performed using TCGA-GBM/LGG, TIMER 2.0, MetScape, GTEx and LinkedOmics databases. Relationships with immune infiltration, ferroptosis and immune checkpoint genes were assessed. Gene mutations were explored by cBioPortal. Logistic regression, Lasso analysis, Receiver Operating Characteristic (ROC), Kaplan-Meier analysis, and Nomogram modeling assessed the correlation between MFAP4 and clinicopathological features of gliomas. By analyzing different datasets, we found that MFAP4 was aberrantly overexpressed in gliomas and correlated with poor clinicopathological features of gliomas. MFAP4 was an independent prognostic indicator and significantly correlated with glioma progression. We also performed functional and pathway enrichment analyses of MFAP4 in gliomas to explore its biological functions and potential molecular mechanisms in gliomas.ResultsMFAP4 was significantly elevated in glioma tissues compared to controls. MFAP4-related genes showed differential expression in pathways involving cytokines. Significant associations between MFAP4 levels, immune infiltration, ferroptosis, and immune checkpoint genes were found in glioma tissues. MFAP4 levels were correlated with glioma stage, histological type, and 1p/19q status, and independently predicted overall survival (OS), disease-specific survival (DSS) and progression-free interval (PFI). MFAP4 expression is effective in distinguishing tumor tissue from normal brain tissue. Furthermore, Spearman Correlation emphasizes the significant relationship between MFAP4 and ferroptosis-related genes.ConclusionOur study demonstrated that MFAP4 is aberrantly overexpressed in gliomas and correlates with adverse clinicopathological features. MFAP4 has relevance in regulating both tumor immunity and iron death, and cellular function assays have demonstrated that MFAP4 promotes the proliferation, migration, and invasion of glioma cells.
Inverse association between atherogenic index of plasma and testosterone in US adult males: A large cross-sectional study from the NAHNES 2011–2016
Authors: Li Tanjian , Chen Lulu , Liang Xin , Li Xinya , Li Yaqin , Huang Yuting , Wang Yu 
Published: February 2025

Background and objectivesThe atherogenic index of plasma (AIP), defined as log10 (triglycerides/high-density lipoprotein cholesterol), serves as a biomarker for atherosclerosis and cardiovascular disease (CVD). It is also associated with conditions such as type 2 diabetes, insulin resistance, depression, and both cardiovascular and overall mortality. Serum lipids have been proven to influence serum testosterone levels, and AIP is a significant marker of lipid levels. We hypothesize that AIP may have a specific relationship with testosterone. This article aims to evaluate the correlation between AIP and total testosterone (TT), as well as testosterone deficiency (TD), among the U.S. population.MethodsData were collected from the National Health and Nutrition Examination Survey (NHANES) database between 2011 and 2016. This study was categorized into four groups based on the quartiles of AIP. Weighted multivariate linear regression and logistic regression were utilized to evaluate the relationships between AIP and TT, TD. Restricted cubic spline (RCS) was used to investigate the non-linear association between AIP and TT and TD. The subgroup analysis method was employed to investigate the relationships between AIP and TT, TD across various stratifications. Ultimately, the sensitivity study involved a comparison of weighted and unweighted data analyses to ascertain the stability of the conclusions.ResultsA total of 2,572 participants were included in the final study. After adjusting for all confounding factors, multivariate linear regression showed that AIP was independently negatively associated with TT (β = −93.42, 95%CI: −123.66, −63.18, P &lt; 0.001), and multivariate logistic regression showed that AIP level was associated with higher risk of TD (OR = 3.45, 95%CI: 2.09, 5.69, P &lt; 0.001). In the quartile of AIP, TT levels decreased the most (β = −74.81, 95%CI: −105.27, −44.35, p &lt; 0.001) and the risk of TD was highest (OR = 2.89, 95%CI: 1.70, 4.93, p &lt; 0.001). In addition, stratified analyses showed similar results in all subgroups except those with diabetes (P for interaction &gt;0.05 for all comparisons). The final sensitivity analysis revealed that elevated AIP were also associated with decreased TT (β = −101.74, 95%CI: −123.18, −80.3, P &lt; 0.001) and increased incidence of TD (OR = 3.01, 95%CI: 2.17, 4.17, P &lt; 0.001) on unweighted data.ConclusionIncreased levels of AIP correlate with decreased TT levels and a higher prevalence of TD. Additional research is necessary to investigate the underlying mechanisms connecting them.
Heterogeneity of ventricular action potentials in neonatal rat cardiomyocytes and methodological aspects of patch clamp measurements
Authors: Syren Pascal , Zlatopolskaia Anna , Bruehl Claus , Schöffel Axel , Caspari Teresa , Heß Chiara , Frey Norbert , Thomas Dierk , Lugenbiel Patrick 
Published: February 2025

Measurement of the ventricular action potential (AP) via whole-cell patch clamp is an important contributor to cardiac electrophysiological research. Neonatal rat ventricular cardiomyocytes (NRVCM) are a commonly used model, in particular for stressor- or drug-related questions. High variability of APs and individual methodological settings hinder comparison both in individual studies and, to an even greater degree, between different projects. This study aims to describe sources of AP heterogeneity in NRVCM related to patch clamp measurement with a focus on resolvable causes. Therefore, AP of NRVCM were induced in whole-cell configuration and measured in current-clamp mode. The effects of varying setup temperature, electrode resistance, resting- (RMP), respectively holding membrane potential (HMP), induction approach, current pulse duration and amplitude plus total assay duration were studied and compared to systematically analyzed literature. We analyzed the impact on different output parameters, namely, maximal upstroke velocity (dV/dt), maximal AP amplitude (APA) and AP duration at different percentages (XX%) of repolarization, APDXX. In a comparative literature research, we found that mean APD90 in between 27.0 and 560.7 ms (own data 59.7 ± 5.8 ms) were described, with high variability and likely non-Gaussian distribution. In this study, APD90, APD50 and APD30, are decreased at more negative RMP (respectively HMP) values. E.g., APD90 is shortened by ∼60% after lowering HMP from −70 mV to −90 mV) while dV/dt and APA are increased at a more negative HMP. Pulse duration in induction did not affect main AP parameters itself, but induction energy levels above 1.5-fold the threshold energy level increased APA, while APD50 and APD90 were shortened. During series of APs at 1 Hz, spike duration (APD90) decreased by ∼27%, with stable AP after the third repetitive AP. Spike duration did also decreased by ∼40% after prolongated measurements for 21 min, indicating degradation of electrophysiological properties. To improve data quality in NRVCM-APs, we suggest using a constant HMP, adjustment of current pulse amplitude to the individual cells’ threshold and the use of repetitive AP-inductions. Finally, we suggest the use of nonparametric statistical methods for statistical analysis. These aspects could reduce variability and lead to more reliable and comparable data.
Genome-wide identification and expression profile analysis of TALE superfamily genes under hormone and abiotic stress in maize (Zea may L.)
Authors: Guan Peiyan , Zhao Dongbo , Wei Longxue , Cui Peipei , Zhang Shicai 
Published: February 2025

IntroductionThe three-amino-acid-loop-extension (TALE) of the homeobox superfamily genes plays important roles in plant growth, development, and responses to environmental stress. Although TALE members have been identified in various species, they have not been systematically characterized in maize and their expression profiles under ABA hormone and abiotic stress are unknown.MethodsBioinformatics methods were employed to identify the TALE family genes in the maize genome. The expression levels of ZmTALEs under ABA, salt, drought, and high temperature conditions was detected by qRT-PCR. The subcellular localization of ZmKNOX05 and ZmBELL11 proteins was observed in maize protoplasts.ResultsIn this study, we identified 52 TALE members in maize, which can be divided into two subfamilies, KNOX and BELL. ZmKNOXs and ZmBELLs can be further divided into two subclasses based on the domains they contain. The protein characterizations and gene structures in the same subclass were similar, whereas they were distinct across different subclasses. There were 18 collinear gene pairs in maize genome. Inter-species evolutionary analyses showed that TALE family genes of maize were more homologous to monocotyledons than to dicotyledons. The promoter regions of ZmTALE contained abundant stress-responsive, hormone-responsive, light-responsive, and plant growth and development cis-elements. Specific spatiotemporal expression patterns analysis showed that ZmBELLs were highly expressed in root and mature leaf, whereas the ZmKNOX1 subfamily genes were more expressed in the primordium, internode, vegetative meristem, and root during developmental stages. It was found that most ZmTALEs could respond to ABA, drought, high temperature, and salt stress, indicating their roles in hormone and abiotic stress responsive. ZmKNOX05 and ZmBELL11 were cloned from B73 maize. Unexpectedly, a novel alternative transcript with a 99-base deletion for ZmKNOX05 were found, named ZmKNOX05.2, which exhibited alternative splicing event at the noncanonical site. Subcellular localization analysis revealed that ZmKNOX05.1-eGFP and ZmKNOX05.2-eGFP were localized in both the nucleus and cytoplasm, while ZmBELL11-eGFP was localized in perinuclear cytoplasm (perinuclear region of the cytoplasm).DiscussionWe identified TALE superfamily members in maize and conducted a comprehensive and systematic analysis. These results can lay the foundation for analysis of the functions of ZmTALE genes under ABA and abiotic stresses.