bluuebunny/crossref_metadata_2025 huggingface dataset:
Chemical weathering as a tool for distinguishing river terraces of varying ages: a case study of the Qingyi River on the eastern Tibetan Plateau
Authors: Hua Diwei , Jiang Dawei , Zhang Shimin , Ding Rui , Chen Yongqi
Published: January 2025

River terraces are essential objects for studying Quaternary landforms and active tectonics. Previous researchers often identified river terraces formed in different eras by height and landmark strata. However, terraces are usually scattered in regions with severe erosion, making comparing terraces of the same level challenging. Some sedimentary analyses, including abrasion of gravels, hardness of gravels, and weathering rind thickness, have been applied to compare terraces but proved limited and not quantitative. In this study, we interpreted and surveyed the terraces of the Qingyi River, which runs through the Longmen Shan Mountain in the eastern edge of the Tibetan Plateau. A systematic approach was presented to quantitatively compare river terraces in regions of high precipitation and erosion. Firstly, we summarized the interfering factors on sedimentation, the method of collecting samples, and the choice of testing materials. Secondly, weathering indicators derived from major element testing were applied to compare terraces of different ages. Finally, we concluded the relationship between weathering degree, the terrace age, and the terrace height. The results indicated that, within the terrace age range of 300 ka, the sediments in the terrace of the Qingyi river show a linearly increasing weathering trend. It proved that the degree of chemical weathering indicated by major elements can be well applied to studying river terraces and reflect the weathering differences between terraces of different ages, solving the problem of quantitative terrace comparison. Moreover, by combining the analysis of paleoclimate data, we reconstructed the weathering mechanisms of the terraces, which are controlled by the alternation between glacial and interglacial stages.
Reflecting trends of the contemporary academic landscape in the context of Higher Education 4.0
Authors: Ülker Nilüfer
Published: January 2025

The world has become a place where information can be accessed quickly and disseminated widely in the knowledge society in parallel with the speed of technological advancements. The shift of focus toward knowledge economy has necessitated the transformation of higher education institutions to meet the demands of the current era, as indicated by the commencement of the 4th industrial revolution, also referred to as Industry 4.0 (I4.0). Universities are now expected to equip their graduates with necessary competencies for the jobs of the future so that they will fulfill the professional demands and requirements of I4.0. To be able to achieve this, modifications have taken place in many spheres of higher education including but not limited to the adoption of new instructional methodologies, changes in the teaching and learning environment and the redefinition of student competencies in line with the requirements of the current era. In parallel with this approach, the aim of the European Universities Initiative (EUI) is to transform the quality and competitiveness of European higher education where the alliances are expected to become universities of the future with a specific focus on student-centered curricula and innovative teaching approaches. To this end, employing a comparative survey design, this study will explore perceptions of academics in a European University Alliance (EUA) concerning the extent to which already existing academic practices align with good practice indicators defined for Higher Education 4.0 (HE4.0). Data was collected from an EUA through a statistically valid and reliable scale devised by the researcher. In total, 161 academics from nine different European Universities participated in the research. Factor analysis, validity and reliability testing, and comparative statistical methods (Kruskal Wallis-H, Mann Whitney-U, One-Way ANOVA, Independent Samples T Tests, Pearson Correlation) were performed for data analysis. The findings indicate that female academics and academics actively involved in EUA activities demonstrate higher awareness of good practice indicators in the scope of HE4.0. Being actively involved in EUAs to mainstream good academic practice across higher education institutions will contribute to keeping up with the rapidly changing academic landscape in the 4th industrial era.
Development and validation of machine learning models for MASLD: based on multiple potential screening indicators
Authors: Chen Hao , Zhang Jingjing , Chen Xueqin , Luo Ling , Dong Wenjiao , Wang Yongjie , Zhou Jiyu , Chen Canjin , Wang Wenhao , Zhang Wenbin , Zhang Zhiyi , Cai Yongguang , Kong Danli , Ding Yuanlin
Published: January 2025

Background

Multifaceted factors play a crucial role in the prevention and treatment of metabolic dysfunction-associated steatotic liver disease (MASLD). This study aimed to utilize multifaceted indicators to construct MASLD risk prediction machine learning models and explore the core factors within these models.

Methods

MASLD risk prediction models were constructed based on seven machine learning algorithms using all variables, insulin-related variables, demographic characteristics variables, and other indicators, respectively. Subsequently, the partial dependence plot(PDP) method and SHapley Additive exPlanations (SHAP) were utilized to explain the roles of important variables in the model to filter out the optimal indicators for constructing the MASLD risk model.

Results

Ranking the feature importance of the Random Forest (RF) model and eXtreme Gradient Boosting (XGBoost) model constructed using all variables found that both homeostasis model assessment of insulin resistance (HOMA-IR) and triglyceride glucose-waist circumference (TyG-WC) were the first and second most important variables. The MASLD risk prediction model constructed using the variables with top 10 importance was superior to the previous model. The PDP and SHAP methods were further utilized to screen the best indicators (including HOMA-IR, TyG-WC, age, aspartate aminotransferase (AST), and ethnicity) for constructing the model, and the mean area under the curve value of the models was 0.960.

Conclusions

HOMA-IR and TyG-WC are core factors in predicting MASLD risk. Ultimately, our study constructed the optimal MASLD risk prediction model using HOMA-IR, TyG-WC, age, AST, and ethnicity.
NOD1: a metabolic modulator
Authors: Tang Ruobing , Xie Chunguang , Zhang Xiyu
Published: January 2025

Nucleotide-binding oligomerization domain 1 (NOD1) is an intracellular pattern recognition receptor that detects injury signals and initiates inflammatory responses and host defense. Furthermore, NOD1 serves as a metabolic mediator by influencing the metabolism of various tissues, including adipose tissue, liver, cardiovascular tissue, pancreatic β cells, adrenal glands, and bones through diverse mechanisms. It has been discovered that activated NOD1 is associated with the pathological mechanisms of certain metabolic diseases. This review presents a comprehensive summary of the impact of NOD1 on tissue-specific metabolism.
Natural resources heterogeneity and environmental sustainability in G20 nations: post-COP28 analysis
Authors: Alomair Abdulrahman , Ibrahim Ridwan Lanre , Al Naim Abdulaziz S.
Published: January 2025

This study presents the maiden empirical evidence disintegrating the impacts of natural resources on environmental sustainability into production and consumption models. For easy trackability of the empirical evidence, environmental sustainability is captured by carbon emissions and ecological footprint in selected G20 economies with ta running from 1995 to 2019. To elaborate the study’s contributions, green policies comprising green energy, green technology, and green finance together with environmental tax, financial development, economic growth, and population are considered as covariates in STIRPAT embedded theoretical framework. The empirical verification anchors on second-generation estimators entailing cross-sectional autoregressive distributed lag (CS-ARDL), common correlated effects mean group autoregressive mean group (AMG), and method of moment quantile regression The fallouts from the analyses reveal that the production and consumption of natural resources based on coal and oil hinder environmental sustainability, although the former has greater effects than the latter. Interestingly, natural gas provides diverging direct and indirect impacts on both pollutants. More so, green policies and environmental taxes support promoting environmental sustainability. Additionally, two channels of causalities, including unidirectional and bidirectional nexuses, are apparent from the estimated model. The study highlights the importance of eliminating fossil fuel subsidies and making substantial investments in green policies as key recommendations for policy action.
Inflammatory burden index as a prognostic marker in patients with advanced gastric cancer treated with neoadjuvant chemotherapy and immunotherapy
Authors: Huang Jiao-Bao , Zhou Zhi-Yong , Lu Jun , Zhu Ji-Yun , Lai Bin , Mao Sheng-Xun , Cao Jia-Qing
Published: January 2025

Background

Blood inflammation index has been shown to correlate with the prognosis of patients with gastric cancer. However, few studies have compared the efficacy of existing blood inflammatory markers in predicting the prognosis of patients with locally advanced gastric cancer in combination with neoadjuvant chemotherapy and immunotherapy.

Objective

The objective of this study was to compare the prognostic value of existing commonly used blood inflammatory index in patients with advanced gastric cancer treated with neoadjuvant chemotherapy combined with immunotherapy.

Methods

The clinicopathological data of patients with advanced gastric cancer from three centers in China were analyzed retrospectively. Univariate COX regression analysis was used to analyze the independent risk factors of poor tumor regression and overall survival (OS) in this part of patients, and the predictive value of different inflammatory indexes on prognosis was compared by C-index index. Finally, Inflammatory burden index(IBI) was grouped by X-tile software, and Kaplan-Meier method was used to compare the survival difference between groups.

Results

A total of 163 patients were enrolled in this study. The median age was 63 years(56-68). The median cycle of neoadjuvant therapy was 4(3-4). The median survival time was 85.1%(1 years), 65.6%(2 years), and 47.4%(3 years).Univariate analysis showed that IBI was an independent risk factor for non-TR(residual tumor cells>50%) (HR=1.08,95%CI:1.00-1.45,p<0.001)and OS(HR=1.04,95%CI:1.03-1.05,p<0.001). IBI is the best predictor of OS (C-index: 0.82, 95% CI: 0.78-0.87) among all inflammatory indexes. The IBI cutoff value was 52.1. It was found that the high IBI group had a higher incidence of postoperative complications(32.1%vs14.3%, p=0.001), the proportion of non-TR patients was significantly higher than that of the low IBI group(64.3%vs35.7%, p =0.001), and the high IBI group had a significantly lower OS((47.6% vs 87.6%, p < 0.001).

Conclusion

IBI is the best inflammatory index to predict the prognosis of advanced gastric cancer treated with neoadjuvant chemotherapy combined with immunotherapy, which will help guide patients’ treatment decisions. This result still needs to be verified by large prospective studies.
Humoral and cell-mediated immune responses to COVID-19 vaccines up to 6 months post three-dose primary series in adults with inborn errors of immunity and their breakthrough infections
Authors: Unninayar Dana , Falcone Emilia L. , Chapdelaine Hugo , Vinh Donald C. , Top Karina A. , Derfalvi Beata , Issekutz Thomas B. , Decaluwe Hélène , Pham-Huy Anne , Upton Julia , Betschel Stephen D. , Rubin Tamar , Suresh Sneha , Wright Nicola A. M. , Murguía-Favela Luis , Kalashnikova Tatiana , Barrett Lisa , Oldford Sharon , Langlois Marc-Andre , Arnold Corey , Sadarangani Manish , Zhang Tinghua , Ramsay Tim , Yazji Dina , Cowan Juthaporn
Published: January 2025

Purpose

Many individuals with inborn errors of immunity (IEIs) have poor humoral immune (HI) vaccine responses. Only a few studies have examined specific cell-mediated immune (CMI) responses to coronavirus disease 2019 (COVID-19) vaccines in this population. Therefore, the purpose of this study was to examine HI and CMI responses up to 6 months post-COVID-19 vaccine dose 3 in adults with IEIs.

Methods

A multi-center prospective observational study was conducted across Canada to collect severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-specific HI and CMI data at 4- and 24-week intervals after vaccine doses 2 and 3 (D2 + 4wk/D2 + 24wk/D3 + 4wk/D3 + 24wk).

Results

A total of 149 adults with IEIs and 423 healthy controls were recruited from July 2021 to October 2023. Geometric mean anti-spike IgG (binding antibody units/mL) and spike-specific T-cell responses [IFN-γ+ T cells/106 peripheral blood mononuclear cells (PBMCs)] were significantly lower in IEIs compared to controls at D2 + 4wk, D3 + 4wk, and D3 + 24wk. However, at 6 months after completing the primary series (three doses for IEIs and two doses for healthy), both HI and CMI responses of both IEI participants and healthy controls persisted and were comparable. There was a strong correlation between neutralizing antibody titer (ID50) and anti-spike IgG but not between ID50 and CMI. There was only one reported case of hospitalized COVID-19 disease before and none after completing the primary series among IEI participants.

Conclusion

Adults with IEIs mounted both HI and CMI responses following COVID-19 vaccines, which were lower than those of healthy individuals but were present at least up to 6 months after dose 3. These data support the initial recommendation for a three-dose primary series among IEIs.
Adropin: a key player in immune cell homeostasis and regulation of inflammation in several diseases
Authors: Wang Junmin , Ding Ning , Chen Chong , Gu Simin , Liu Jing , Wang Yanping , Lin Liubing , Zheng Yiyuan , Li Yong
Published: January 2025

Adropin is a secreted peptide encoded by the energy homeostasis-associated gene (ENHO), located chromosome 9p13.3, with a conserved amino acid sequence across humans and mice. Its expression is regulated by various factors, including fat, LXRα, ERα, ROR, and STAT3. Adropin plays a critical role in glucose and lipid metabolism, as well as insulin resistance, by modulating multiple signaling pathways that contribute to the reduction of obesity and the improvement of blood lipid and glucose homeostasis. Additionally, it influences immune cells and inflammation, exerting anti-inflammatory effects across various diseases. While extensive research has summarized the regulation of cellular energy metabolism by adropin, limited studies have explored its role in immune regulation and inflammation. To enhance the understanding of adropin’s immune-modulating and anti-inflammatory mechanisms, this review synthesizes recent findings on its effects in conditions such as atherosclerosis, diabetes, fatty liver, non-alcoholic hepatitis, and inflammation. Furthermore, the review discusses the current research limitations and outlines potential future directions for adropin-related investigations. It is hoped that ongoing research into adropin will contribute significantly to the advancement of medical treatments for various diseases.
Recovery of coral cover at Lizard island Australia 6 years post-disturbance
Authors: Anderson Gabriel Dax
Published: January 2025

Coral reefs are experiencing more intense and frequent disturbances induced by climate change, such as cyclones and bleaching events. This necessitates a better understanding of the ongoing environmental conditions that stress these systems and the subsequent arc of longer-term reef responses to these stressful conditions. From March of 2014 to May of 2017, the Lizard Island reefs in the northern region of the Great Barrier Reef experienced four consecutive annual disturbances; Cyclone Ita in 2014, Cyclone Nathan in 2015, and two massive bleaching events in 2016 and 2017. Between the concentrated patches of physical damage from the cyclones and the uniform impact of the bleaching events, these reefs were devastated, with none of the eight study sites harboring more than 20% live coral cover by May of 2017. In November of 2023, after six years of relatively calmer conditions with no conspicuous region-wide, large-scale disturbances, I documented the extant coral community on eight previously-monitored reefs around Lizard Island. All reefs showed significant (p = 0.0054, F = 3.46, df = 47) improvement from their 2017 immediate post-disturbance degradation. Living coral at my study sites had recovered to between 18.4 ± 0.6 (mean ± 1 SE) to 59.9 ± 5.3% of the reef area per site by 2023, with many sites towards the higher end of that range. Recovery of coral extent appeared to follow a north-south trend in which more Trade Wind-sheltered northerly sites had generally greater recovery and higher live coral cover compared to more exposed southern sites, which experienced significantly less coral recovery. Fast-growing Acroporid corals drove the recovery of coral extent in these more northern sites. While family richness across all sites improved by 2023 (4.0 ± 0.1; grand mean ± 1 se), Lizard Island reefs have yet to reach their pre-disturbance diversity (4.8 ± 0.6 in 2014). Future annual surveys of the study sites as well as others surveyed in 2017 may better clarify the relationship between reef location and the rate of recovery of coral cover post-disturbance.
Development and validation of a nomogram for predicting lung cancer based on acoustic–clinical features
Authors: Lu Zhou , Sha Jiaojiao , Zhu Xunxia , Shen Xiaoyong , Chen Xiaoyu , Tan Xin , Pan Rouyan , Zhang Shuyi , Liu Shi , Jiang Tao , Xu Jiatuo
Published: January 2025

Objective

Lung cancer—with its global prevalence and critical need for early diagnosis and treatment—is the focus of our study. This study aimed to develop a nomogram based on acoustic–clinical features—a tool that could significantly enhance the clinical prediction of lung cancer.

Methods

We reviewed the voice data and clinical information of 350 individuals: 189 pathologically confirmed lung cancer patients and 161 non-lung cancer patients, which included 77 patients with benign pulmonary lesions and 84 healthy volunteers. First, acoustic features were extracted from all participants, and optimal features were selected by least absolute shrinkage and selection operator (LASSO) regression. Subsequently, by integrating acoustic features and clinical features, a nomogram for predicting lung cancer was developed using a multivariate logistic regression model. The performance of the nomogram was evaluated by the area under the receiver operating characteristic curve (AUC) and the calibration curve. The clinical utility was estimated by decision curve analysis (DCA) to confirm the predictive value of the nomogram. Furthermore, the nomogram model was compared with predictive models that were developed using six additional machine-learning (ML) methods.

Results

Our acoustic–clinical nomogram model demonstrated a strong discriminative ability, with AUCs of 0.774 (95% confidence interval [CI], 0.716–0.832) and 0.714 (95% CI: 0.616–0.811) in the training and test sets, respectively. The nomogram achieved an accuracy of 0.642, a sensitivity of 0.673, and a specificity of 0.611 in the test set. The calibration curve showed excellent agreement between the predicted and actual values, and the DCA curve underscored the clinical usefulness of our nomogram. Notably, our nomogram model outperformed other models in terms of AUC, accuracy, and specificity.

Conclusion

The acoustic–clinical nomogram developed in this study demonstrates robust discrimination, calibration, and clinical application value. This nomogram, a unique contribution to the field, provides a reliable tool for predicting lung cancer.
How do various strategies for returning residues change microbiota modulation: potential implications for soil health
Authors: Jiang Nan , Chen Zhenhua , Ren Yi , Xie Shichang , Yao Zimeng , Jiang Dongqi , Zhang Yulan , Chen Lijun
Published: January 2025

Introduction

Residue incorporation is a crucial aspect of anthropogenic land management practices in agricultural fields. However, the effects of various returning strategies on the soil microbiota, which play an essential vital role in maintaining soil health, remains largely unexplored.

Methods

In a study conducted, different residue management strategies were implemented, involving the application of chemical fertilizers and residues that had undergone chopping (SD), composting (SC), and pyrolysis (BC) processes, with conventional fertilization serving as the control (CK).

Results and discussion

Using metagenomic sequencing, the analysis revealed that while all residue returning strategies had minimal effects on the diversity (both α and β) of microbiota, they did significantly alter microbial functional genes related to carbon (C), nitrogen (N), phosphorus (P), and sulfur (S) cycling, as well as the presence of antibiotic resistance genes (ARGs) and pathogens. Specifically, chopped residues were found to enhance microbial genes associated with C, N, P, and S cycling, while composted residues primarily stimulated C and S cycling. Furthermore, all residue treatments resulted in a disruption of relationships among nutrient cycles, with varying degrees of impact observed across the different management strategies, with the sequence of impact being SD < SC < BC. Moreover, the residue additions resulted in the accumulation of ARGs, while only SC caused an increase in certain pathogens. Finally, through analyzing the correlation network among indices that exhibited active responses to residue additions, potential indicators for functional changes in response to residue additions were identified. This study further offered recommendations for future cropland management practices aimed at enhancing soil health through microbiomes.
The impact of abandoned iron ore on the endophytic bacterial communities and functions in the root systems of three major crops in the local area
Authors: Chen Shuyi , Tang Jie , Xu Junqiang , Peng Lianxin , Wu Peng , Li Qiang
Published: January 2025

Introduction

Global mining activities have significant impacts on ecosystems, but most studies have focused only on the relationship between soil physicochemical properties and microbial diversity in soils. The present study provides an insight into the effects of mining activities on soil physico-chemical properties and endophytic bacterial community composition in the rhizosphere of three different crops.

Methods

Musa basjoo Siebold L., Amygdalus persica L., and Triticum aestivum L. were collected from the inter-root soils and plant roots to determine the soil physicochemical properties and endophytic bacterial communities in the root system.

Results

The results showed that mining resulted in soil acidification, altered trace element content and increased organic carbon. There was an increase in the Ascomycota and Actinobacteria phylum of crop root bacteria. Interestingly, the chao1 and shannon indices of the root endophytes of the mining crop were significantly elevated compared to the contro (p < 0.05). Among them, Musa basjoo Siebold showed the highest level of community richness in the mining environment. The mining environment resulted in functional enrichment of histidine kinases and oxidoreductases in the bacterial community. The total potassium (TK) content in the soil, as well as the Fe and Pb content, were positively correlated with the α-diversity index and Streptomyces. Zn and Ti content were significantly negatively correlated with the α-diversity index.

Discussion

This study provides data support for exploring the mechanisms of plant response to the mining environment and developing ecological restoration strategies for mining areas.
Use of amantadine in traumatic brain injury: an updated meta-analysis of randomized controlled trials
Authors: Félix João , Araújo Luísa , Henriques Antônio , Pereira Ana , Carneiro Saul
Published: January 2025

Introduction

Amantadine has been shown to accelerate cognitive and functional brain recovery after cerebrovascular accidents. However, the efficacy of this drug in TBI patients remains poorly defined.

Methods

We performed a systematic review and meta-analysis of randomized trials (RCTs) evaluating the effects of amantadine in TBI patients. The Cochrane, Embase, and PubMed databases were systematically searched for trials published up to March 24, 2024. Data from previous RCTs were extracted and quality assessed according to Cochrane recommendations. Means and standard deviations with 95% confidence intervals were aggregated across studies. The primary outcomes assessed were Glasgow Coma Scale (GCS), Mini Mental State Examination (MMSE) and the Disability Rating Scale (DRS).

Results

From 1,292 database results, 6 studies with 426 patients were included, of which 205 received amantadine (48.12%). The Glasgow Coma Scale score on day 7 (MD 1.50; 95% CI 0.08–2.92; p = 0.038; I2 = 68%) was significantly higher in patients treated with amantadine than those treated with placebo. The Mini Mental State Examination (MD 3.23; 95% CI 0.53–5.94; p = 0.019; I2 = 0%) was also better in patients treated with amantadine. No significant differences in Disability Rating Scale, day 3 GCS, Glasgow Outcome Scale (GOS), length of hospital stay, or duration of mechanical ventilation were observed between amantadine and placebo groups.

Conclusion

In our analysis, TBI patients benefit from the use of amantadine in the day 7 GCS score and show better results in the MMSE test, but placebo patients benefit from not using amantadine in the DRS between weeks 3 and 4. No other statistically significant results were found related to the use of this medication.

Systematic review registration: https://www.crd.york.ac.uk/prospero/display_ record.php?ID=CRD42024538110, CRD42024538110.
Unlocking autism’s complexity: the Move Initiative’s path to comprehensive motor function analysis
Authors: Good Ashley Priscilla , Horn Elizabeth
Published: January 2025

The long-standing practice of using manualized inventories and observational assessments to diagnose and track motor function in autism overlooks critical data invisible to the naked eye. This subjective approach can introduce biases and hinder the translation of research into clinical applications that rely on objective markers of brain–body connections. Meanwhile, we are experiencing a digital healthcare revolution, marked by innovations in the collection and analysis of electronic health records, personal genomes, and diverse physiological measurements. Advanced technologies, including current wearable devices, integrate both active and passive (sensor-based) data collection, providing a more comprehensive view of human health. Despite advances in sensors, wearables, algorithms, machine learning, and agentic AI, autism research remains siloed, with many tools inaccessible to affected families and care teams. There is a pressing need to merge these technological advances and expedite their translation into accessible, scalable tools and solutions to diversify scientific understanding. In response, this Perspective introduces the Move Initiative, a coalition spearheaded by the nonprofit 2 m Foundation, composed of self-advocates, families, clinicians, researchers, entrepreneurs, and investors who aim to advance and refine the measurement of movement in autism. Move will make motor screenings more dynamic and longitudinal while supporting continuous assessment of targeted interventions. By fostering cross-disciplinary collaboration, Move seeks to accelerate the integration of the expanding knowledge base into widespread practice. Deep, longitudinal, multi-modal profiling of individuals with Autism Spectrum Disorder offers an opportunity to address gaps in current data and methods, enabling new avenues of inquiry and a more comprehensive understanding of this complex, heterogeneous condition.
Predicting risk factors for Epstein-Barr virus reactivation using Bayesian network analysis: a population-based study of high-risk areas for nasopharyngeal cancer
Authors: Zeng Zhiwen , Lin Kena , Li Xueqi , Li Tong , Li Xiaoman , Li Jiayi , Ning Zule , Liu Qinxian , Xie Shanghang , Cao Sumei , Du Jinlin
Published: January 2025

Background and objective

Nasopharyngeal carcinoma (NPC) is a rare disease in most parts of the world, but it is highly prevalent in South China. Epstein-Barr virus (EBV) is one of the major risk factors for NPC. Hence, understanding the factors associated with the reactivation of EBV from the latent stage is crucial for preventing NPC. This study aimed to investigate the risk factors for EBV reactivation associated with NPC in high-prevalence areas in China using a Bayesian network (BN) model combined with structural equation modeling tools.

Methods

The baseline information for this study was derived from NPC screening data from a population-based prospective cohort in Sihui City, Guangdong Province, China. We divided the data into a training dataset and a test dataset. We then constructed an interaction networktionba BN prediction model to explore the risk factors for EBV reactivation, which was compared with a conventional logistic regression model.

Results

A total of 12,579 participants were included in the analyses, with 1596 participant pairs finally included after the use of a nested case-control study. The results of multivariable logistic regression showed that only being older than 60 years (OR = 1.718, 95% CI = 1.273,2.322) and being a current smoker (OR = 1.477, 95% CI = 1.167 - 1.872) were the risk factors for EBV reactivation. The results of the model constructed using BN showed that age and smoking were directly associated with EBV reactivation. In contrast, sex, education level, tea drinking, cooking, and family history of cancer were indirectly associated with EBV reactivation. Further, we predicted the risk of EBV reactivation using Bayesian inference and visualized the BN inference. Model prediction performance was evaluated using the test dataset. The results showed that the BN model slightly outperformed the traditional logistic regression model in all metrics.

Conclusions

BN not only reflects the complex interaction between factors but also visualizes the prediction results. It has a promising application potential in the risk prediction of EBV reactivation associated with NPC.
Transcription factor KLF2 is associated with the dysfunctional status of NK cells and the prognosis of pediatric B-ALL patients
Authors: Wu Fang , Xu Huimin , Zhang Benshan
Published: January 2025

Background

Natural killer cells, an important component of the innate immune system, can directly recognize and lyse virally infected or transformed cells. However, NK cells fail to restrain the growth of malignancies, such as B-cell acute lymphoblastic leukemia (B-ALL). The molecular genetics of NK cells in the B-ALL bone marrow microenvironment and the mechanisms underlying the inhibited function of NK cells at the single-cell level remain largely elusive.

Methods

In this study, we studied the frequency and absolute number of NK cells in peripheral blood samples collected from 43 healthy volunteers and 104 pediatric B-ALL patients diagnosed at Hunan Children’s Hospital. We also analyzed published single-cell RNA sequencing (scRNAseq) data from B-ALL and normal bone marrow samples using unsupervised clustering. Our findings were further validated using bulk transcriptomic data and clinical data from a cohort of 139 B-ALL bone marrow samples.

Results

We found that the frequency and number of NK cells were significantly decreased in the bone marrow and peripheral blood of B-ALL patients. In-depth analysis of scRNAseq data identified 12 NK cell clusters. Among them, the C2 cluster, which is present in healthy bone marrow but reduced in B-ALL bone marrow, displays overexpression of a transcription factor KLF2 and a significant downregulation of the “leukocyte proliferation” pathway. Furthermore, we found that the expression of KLF2 in B-ALL at diagnosis was positively correlated with the percentage of leukemia cells and the positive rate of minimal residual disease (MRD), indicating that KLF2 is a marker of poor prognosis.

Conclusion

There are dramatic differences at the single-cell level in the transcriptomics of NK cells between healthy donors and B-ALL patients. A transcription factor, KLF2, which is enriched in the C2 cluster of NK cells, has been suggested to regulate the proliferation of NK cells and is associated with poor prognosis of pediatric B-ALL.
Reversing NK cell exhaustion: a novel strategy combining immune checkpoint blockade with drug sensitivity enhancement in the treatment of hepatocellular carcinoma
Authors: Huang Yuxiang , Liao Hengjian , Luo Jiefu , Wei Huaning , Li Anling , Lu Yujie , Xiang Bangde
Published: January 2025

Hepatocellular carcinoma (HCC) is one of the most common lethal cancers worldwide. Natural killer cells (NK cells) play a key role in liver immunosurveillance, but in the tumor microenvironment, NK cells are readily depleted, as evidenced by down-regulation of activating receptors, reduced cytokine secretion, and attenuated killing function. The up-regulation of inhibitory receptors, such as PD-1, TIM-3, and LAG-3, further exacerbates the depletion of NK cells. Combined blockade strategies targeting these immunosuppressive mechanisms, such as the combination of PD-1 inhibitors with other inhibitory pathways (eg. TIM-3 and LAG-3), have shown potential to reverse NK cell exhaustion in preclinical studies. This article explores the promise of these innovative strategies in HCC immunotherapy, providing new therapeutic directions for optimizing NK cell function and improving drug sensitivity.
Prognosis of premenopausal women with low-risk endometrial cancer but elevated CA125 levels
Authors: Song Jeong Min , Aiob Ala , Kim Kidong , Lee Kwang Beom , Kang Sokbom , Lee Chae Hyeong , Kim Se Ik , Kim Nam Kyeong , Jeong Dae Hoon
Published: January 2025

Introduction

Women with low-risk endometrial cancer, as defined by the Korean Gynecologic Oncology Group (KGOG) criteria, have a low risk of lymph node metastasis and an excellent prognosis without lymphadenectomy. However, it is unclear whether lymphadenectomy should be performed in premenopausal women who meet the KGOG criteria other than elevated cancer antigen 125 (CA125) levels, because the CA125 level can be elevated by benign conditions. We investigated the patterns of metastasis and recurrence to assess the value of lymphadenectomy in this population.

Methods

Premenopausal women with endometrial cancer meeting the KGOG criteria, except for those with elevated CA125 levels, were eligible. The characteristics of the eligible women were collected from seven institutes in the Republic of Korea by reviewing their medical records. Recurrence-free survival (RFS) was estimated using the Kaplan–Meier method and compared using the log-rank test.

Results

Seventy-three patients were included. Of 62 women who underwent lymphadenectomy, only two (3.2%) had lymph node metastasis. Eighteen women (24.7%) received adjuvant therapy. At a median follow-up of 59 months, the 5-year RFS was 88.8%. Five women (7%) experienced recurrence, two had lymph node recurrence, and three had non-nodal recurrence. RFS was similar between the women who did and did not undergo lymphadenectomy (P=0.737).

Conclusion

Premenopausal women who had elevated CA125 levels but met all other KGOG criteria showed a low risk of lymph node metastasis and recurrence as well as a good prognosis. Therefore, lymphadenectomy can be omitted in this population.
Advances in adjuvant therapy for operable N2 non-small cell lung cancer: a narrative review
Authors: Liu Lei , Mao Yilong , Guo Leilei , Li Chencong , Wang Yiqian
Published: January 2025

Non-small cell lung cancer (NSCLC) is still the disease with the highest incidence rate among malignant tumors, in which NSCLC under N2 stage has obvious survival differences among different patients due to its high heterogeneity. For NSCLC under this stage, the current treatment options are: preoperative neoadjuvant therapy, surgical treatment, postoperative adjuvant chemotherapy, postoperative adjuvant radiotherapy (PORT), Postoperative adjuvant targeted therapy and postoperative adjuvant immunotherapy. Whether postoperative adjuvant radiotherapy is routinely administered to patients with pN2 remains controversial in clinical application. Meanwhile, the booming development of adjuvant targeted therapy and adjuvant immunotherapy also provides newer therapeutic options for the prognosis of postoperative pN2 stage NSCLC, and some new markers will guide the adaptive application of immune drugs in the future. This article analyzes the current stage of therapeutic advances in operable stage N2 non-small cell lung cancer, and discusses in detail in this article the therapeutic controversy of postoperative adjuvant radiotherapy in pN2 stage non-small cell lung cancer, so as to explore a more reasonable treatment mode for future patients with stage N2 non-small cell lung cancer.
Dermatomyositis following resection of thyroid and breast cancer: a case report and literature review
Authors: Yang Miaomiao , Liu Jiannan
Published: January 2025

Background

Dermatomyositis is an idiopathic inflammatory myopathy and occurs as a paraneoplastic syndrome. Here, we report an unusual case of dermatomyositis that developed in a patient after the resection of thyroid cancer and breast cancer. The intercorrelation between dermatomyositis and neoplastic disorders was discussed.

Case presentation

A 60-year-old female farmer was diagnosed with thyroid cancer and breast cancer and then developed dermatomyositis after two curative surgeries and adjuvant chemotherapy. Dermatomyositic symptoms occurred after the fifth cycle of adjuvant chemotherapy for breast cancer and deteriorated progressively. Case history, imaging, and laboratory data were reviewed. This patient subsequently received systemic immunosuppressant therapy and thus dermatomyositis gradually resolved.

Conclusions

A combination of thyroid cancer and breast cancer is thought to be very rare, especially in patients who develop dermatomyositis after thyroidectomy and mastectomy. An extraordinary case was reported in this study. Potential mechanisms for the development of dermatomyositis and novel insights neoplastic autoimmune diseases were proposed.
SMARCA4-related Coffin-Siris syndrome in newborn: a case report and literature review
Authors: Wang Yuqian , Zhang Li , Zhu Jing , Yang Liu , Wang Chan , Zou Ning
Published: January 2025

Objective

Our objective was to examine the clinical and genetic features of Coffin-Siris syndrome resulting from a pathogenic variant in the SMARCA4 gene.

Methods

The clinical data and molecular genetic test results of a newbron with Coffin-Siris syndrome involving a pathogenic variant in the SMARCA4 gene were retrospectively analyzed, and the related literatures were reviewed.

Results

A newborn exhibited inspiratory dyspnea following birth and developmental anomalies (coarse appearance, thick hair, long eyelashes, broad nasal tip, flat nasal bridge, thin upper lip, thick lower lip, digital anomalies, cleft palate, supraglottic laryngeal chondromalacia, stenosis of the left upper bronchus and hypotonia). Whole exome sequencing revealed a heterozygous missense variant in SMARCA4 gene (NM_003072.5 c.3127C > T, p.Arg1043Trp). Parents did not find the above pathogenic variant, which was a new pathogenic variant. In addition to our case, we also retrieved 22 cases of Coffin-Siris Syndrome in SMARCA4 gene variation, which is a congenital multi-system dysfunction syndrome characterized by abnormal appearance and developmental retardation. The common otolaryngologic features of 23 patients with CSS in SMARCA4 gene variant included palate abnormalities, feeding difficulties, ear abnormalities and hearing loss.

Conclusion

Coffin-Siris syndrome is a rare genetic disease inherited in an autosomal-dominated manner. It is often associated with malformations in the otorhinolaryngologic system. This case has many common features with previously reported CSS cases with pathogenic variant in the SMARCA4 gene, which further characterizes the performance of the pathogenic variant, suggesting that palatal abnormalities may be a significant feature of the genotype. For patients with developmental abnormalities, whole-genome sequencing or whole-exome sequencing is particularly important to assist diagnosis. Currently, there is no known treatment for CSS, and individuals with CSS experience various complications affecting multiple systems.
A novel α-conotoxin [D1G, ΔQ14] LvIC decreased mouse locomotor activity
Authors: Wang Wen , Wang Meiting , Wang Huanbai , Xu Weifeng , Wang Conggang , Pei Jie , Li Xiaodan , Zhangsun Dongting
Published: January 2025

Background and Purpose

Nicotinic acetylcholine receptors (nAChRs), which are expressed throughout the mammalian brain, mediate a variety of physiological functions. Despite their widespread presence, the functions of nAChRs are not yet fully understood. α-Conotoxins, which are peptides derived from the venom of marine cone snails, target different subtypes of nAChRs. Specifically, α-Conotoxins [D1G, ΔQ14] LvIC, identified from Conus lividus, have demonstrated strong activity on α6β4* nAChRs in vitro. However, the effects of [D1G, ΔQ14] LvIC have not been investigated in vivo. This study aims to examine the activities of [D1G, ΔQ14] LvIC and explore its potential mechanisms in vivo.

Methods

The study involved the injection of [D1G, ΔQ14] LvIC into the lateral cerebral ventricle (LV) of mice. Following this procedure, behavioral tests were conducted to assess changes in the mice’s behavior. To investigate the molecular alterations in the mice’s brains, untargeted metabolomics and label-free Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) were employed. Subsequently, Western blot (WB) and quantitative reverse transcription PCR (RT-qPCR) techniques were utilized to detect specific molecular changes induced by [D1G, ΔQ14] LvIC.

Results

The injection of [D1G, ΔQ14] LvIC led to a decrease in locomotor activity in mice. This treatment also resulted in reduced expression of neuronal calcium sensor 1 (NCS-1) and neuroligin 3 (NLGN-3) in the prefrontal cortex (PFC), hippocampus (Hip), and caudate putamen (CPu). Both NCS-1 and NLGN-3 are crucial for neuronal development, synapse formation, and neuron activity, and their reduction is associated with decreased synapse strength. Despite these changes, results from the Morris water maze (MWM) indicated that [D1G, ΔQ14] LvIC did not impair the learning and memory abilities of the mice.

Conclusion

Our findings indicate that α-conotoxin [D1G, ΔQ14] LvIC significantly decreased locomotor activity in mice. Additionally, it altered gene expression primarily in areas related to neuronal development, synapse formation, and neuron activity, while also reducing synapse strength. This study first proposed that [D1G, ΔQ14] LvIC could modulate mice’s locomotor activity. However, further investigation is needed to understand the therapeutic effects of [D1G, ΔQ14] LvIC.
Astaxanthin mitigates doxorubicin-induced cardiotoxicity via inhibiting ferroptosis and autophagy: a study based on bioinformatic analysis and in vivo/vitro experiments
Authors: Yin Bowen , Ren Jingyi , Liu Xuanyi , Zhang Yadong , Zuo Jinshi , Wen Rui , Pei Huanting , Lu Miaomiao , Zhu Siqi , Zhang Zhenao , Wang Ziyi , Zhai Yanyi , Ma Yuxia
Published: January 2025

Background

Doxorubicin (DOX), a widely employed chemotherapeutic agent in cancer treatment, has seen restricted use in recent years owing to its associated cardiotoxicity. Current reports indicate that doxorubicin-induced cardiotoxicity (DIC) is a complex phenomenon involving various modes of cell death. Astaxanthin (ASX), a natural carotenoid pigment, has garnered significant attention for its numerous health benefits. Recent studies have shown that ASX has a broad and effective cardiovascular protective effect. Our study aims to investigate the protective effects of ASX against DIC and elucidate its underlying mechanisms. This has substantial practical significance for the clinical application of DOX.

Methods

Bioinformatic analyses were conducted using transcriptomic data from the gene expression omnibus (GEO) database to identify key mechanisms underlying DIC. Network pharmacology was employed to predict the potential pathways and targets through which ASX exerts its effects on DIC. In vitro experiments, following pretreatment with ASX, H9C2 cells were exposed to DOX. Cell viability, injury and the protein expression levels associated with ferroptosis and autophagy were assessed. In the animal experiments, rats underwent 4 weeks of gavage treatment with various doses of ASX, followed by intraperitoneal injections of DOX every 2 days during the final week. Histological, serum, and protein analyses were conducted to evaluate the effects of ASX on DIC.

Results

The bioinformatics analysis revealed that ferroptosis and autophagy are closely associated with the development of DIC. ASX may exert an anti-DIC effect by modulating ferroptosis and autophagy. The experimental results show that ASX significantly mitigates DOX-induced myocardial tissue damage, inflammatory response, oxidative stress, and damage to H9C2 cells. Mechanistically, ASX markedly ameliorates levels of ferroptosis and autophagy both in vitro and in vivo. Specifically, ASX upregulates solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4), while downregulating the expression of transferrin receptor 1 (TFRC), ferritin heavy chain (FTH1) and ferritin light chain (FTL). Additionally, ASX enhances the expression of P62 and decreases levels of Beclin1 and microtubule-associated proteins light chain 3 (LC3).

Conclusion

Our results indicate that ferroptosis and autophagy are critical factors influencing the occurrence and progression of DOX-induced cardiotoxicity. ASX can alleviate DIC by inhibiting ferroptosis and autophagy.
Chrysanthemum classification method integrating deep visual features from both the front and back sides
Authors: Chen Yifan , Yang Xichen , Yan Hui , Liu Jia , Jiang Jian , Mao Zhongyuan , Wang Tianshu
Published: January 2025

Introducion

Chrysanthemum morifolium Ramat (hereinafter referred to as Chrysanthemum) is one of the most beloved and economically valuable Chinese herbal crops, which contains abundant medicinal ingredients and wide application prospects. Therefore, identifying the classification and origin of Chrysanthemum is important for producers, consumers, and market regulators. The existing Chrysanthemum classification methods mostly rely on visual subjective identification, are time-consuming, and always need high equipment costs.

Methods

A novel method is proposed to accurately identify the Chrysanthemum classification in a swift, non-invasive, and non-contact way. The proposed method is based on the fusion of deep visual features of both the front and back sides. Firstly, the different Chrysanthemums images are collected and labeled with origins and classifications. Secondly, the background area with less available information is removed by image preprocessing. Thirdly, a two-stream feature extraction network is designed with two inputs which are the preprocessed front and back Chrysanthemum images. Meanwhile, the incorporation of single-stream residual connections and cross-stream residual connections is employed to extend the receptive field of the network and fully fusion the features from both the front and back sides.

Results

Experimental results demonstrate that the proposed method achieves an accuracy of 93.8%, outperforming existing methods and exhibiting superior stability.

Discussion

The proposed method provides an effective and dependable solution for identifying Chrysanthemum classification and origin while offering practical benefits for quality assurance in production, consumer markets, and regulatory processes. Code and data are available at https://github.com/dart-into/CCMIFB.