bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of CAPG as a potential prognostic biomarker associated with immune cell infiltration and ferroptosis in uterine corpus endometrial carcinoma
Authors: Liu Junwei , Zhu Weiqiang , Xia Lingjin , Zhu Qianxi , Mao Yanyan , Shen Yupei , Li Min , Zhang Zhaofeng , Du Jing 
Published: November 2024

IntroductionCapping actin protein, gelsolin-like (CAPG) is a potential therapeutic target in various cancers. However, the potential immunotherapeutic effects and prognostic value of CAPG in uterine corpus endometrial carcinoma (UCEC) remain unclear.MethodsThe characterization, methylation effects, prognostic value, targeted miRNAs of CAPG, and the correlation of CAPG with immune cell infiltration and ferroptosis in UCEC were investigated using multiple public databases and online tools. Furtherly, we explored the potential physiological function of CAPG using EdU and Transwell migration assays, identified the cell localization and expression of CAPG and GPX4 by immunofluorescence, and detected the intracellular Fe2+ levels using a FerroOrange fluorescent probe in Ishikawa cells. Additionally, the OncoPredict package was used to analyze the potential chemotherapeutic drugs for UCEC.ResultsCAPG showed generally high expression in tumor group. The overall survival rate of the high-risk group was significantly lower than that of the low-risk group. Enrichment analysis indicated that CAPG is involved in immune-related pathways and is closely associated with the tumor microenvironment. CAPG expression levels were affected by abnormal DNA methylation and/or targeted miRNAs, infiltration levels and marker genes of various immune cells, thereby impacting immune response, ferroptosis, and patient prognosis. Ferroptosis analysis indicated that ALOX5 and VLDLR were the top CAPG-related ferroptosis markers; glutathione metabolism levels in tumor group were generally high, and decitabine was a ferroptosis inducer. CAPG-siRNA suppressed the cell proliferation and invasion, and markedly elevated the expression levels of immune-related genes IL8, TNF, TLR4 and the intracellular Fe2+ levels. CAPG co-located with GPX4 in nucleus and co-regulated ferroptosis and metabolism in Ishikawa cells. Moreover, four chemotherapy drugs showed better sensitivity to UCEC patients in the low-risk cohort.ConclusionsCAPG may serve as a potential biomarker of UCEC owing to its role in modulating the immune response and ferroptosis, providing novel perspectives for combined immunotherapy of UCEC.
Flash glucose monitoring system help reduce the frequency of hypoglycemia and hypoglycemic fear behavior in type 1 diabetes patients
Authors: Dong Lining , Li Junxian , Hu Yanyun , Chai Ruoting , Zhu Ye , Zhu Liying , Fan Nengguang , Zhang Zhijian , Pan Jiemin , Yan Jinhua , Liu Fang 
Published: November 2024

ObjectiveHypoglycemia represents a serious acute complication in individuals with type 1 diabetes mellitus (T1DM). In order to more effectively identify and discriminate the occurrence of hypoglycemic events in patients with T1DM, this study aims to evaluate the impact of two distinct glucose monitoring systems—Flash Glucose Monitoring (FGM) and Continuous Glucose Monitoring (CGM)—on the management of blood glucose levels and the emotional responses associated with hypoglycemic episodes in individuals with T1DM.MethodIn this study, a total of 113 patients with type 1 diabetes mellitus were enrolled and allocated to two groups for the implementation of Glucose Monitoring Systems (GMS). The groups consisted of the FreeStyle Libre group (FGM, n=56) and the ipro2 group (CGM, n=57). Participants in both groups utilized GMS at least biannually and completed a set of three questionnaires: the Diabetes Monitoring and Treatment Satisfaction Questionnaire (DMTSQ), the Diabetes Specific Quality of Life (DQOL), and the Chinese Version of the Hypoglycemia Fear Survey II (CFHSII). Clinical data, CGM metrics, and questionnaire scores were collected at the initial visit and after a one-year follow-up period.ResultsThe glucose coefficient of variation (GCV) and the standard deviation of blood glucose (SDBG) were independently associated with Time Below Range (TBR). Specifically, GCV could predict TBR ≥12%, with a cut-off point of 40.55. This yielded a specificity of 88.10% and a sensitivity of 68.18% in the overall patient population. For the FreeStyle Libre group and the iPro2 group, the cut-off points were 38.69 and 40.55, respectively, with specificities of 0.74 and 0.92, and sensitivities of 0.73 and 0.86, respectively. In the FreeStyle Libre group, where the frequency of use was greater than or equal to five times per year, the hypoglycemic episodes (time/month) and CHFSII-B scores were significantly reduced at follow-up compared to baseline (7.80 ± 10.25 vs 13.95 ± 14.87; 27.37 ± 11.05 vs 38.90 ± 21.61, respectively, all P &lt;0.05).ConclusionThe utilization of multiple Flash Glucose Monitoring (FGM) implementations proved to be valuable in discriminating the occurrence of hypoglycemia and mitigating the fear of hypoglycemic episodes in patients with type 1 diabetes. Within the parameters of Glucose Monitoring Systems (GMS), the glucose glycemic variability (GCV) was identified as a predictive factor for the risk of severe hypoglycemia (TBR &gt; 12%). The optimal cut-off point for GCV was determined to be 40.55.
PSATF-6mA: an integrated learning fusion feature-encoded DNA-6 mA methylcytosine modification site recognition model based on attentional mechanisms
Authors: Kang Yanmei , Wang Hongyuan , Qin Yubo , Liu Guanlin , Yu Yi , Zhang Yongjian 
Published: November 2024

DNA methylation is of crucial importance for biological genetic expression, such as biological cell differentiation and cellular tumours. The identification of DNA-6mA sites using traditional biological experimental methods requires more cumbersome steps and a large amount of time. The advent of neural network technology has facilitated the identification of 6 mA sites on cross-species DNA with enhanced efficacy. Nevertheless, the majority of contemporary neural network models for identifying 6 mA sites prioritize the design of the identification model, with comparatively limited research conducted on the statistically significant DNA sequence itself. Consequently, this paper will focus on the statistical strategy of DNA double-stranded features, utilising the multi-head self-attention mechanism in neural networks applied to DNA position probabilistic relationships. Furthermore, a new recognition model, PSATF-6 mA, will be constructed by continually adjusting the attentional tendency of feature fusion through an integrated learning framework. The experimental results, obtained through cross-validation with cross-species data, demonstrate that the PSATF-6 mA model outperforms the baseline model. The in-Matthews correlation coefficient (MCC) for the cross-species dataset of rice and m. musus genomes can reach a score of 0.982. The present model is expected to assist biologists in more accurately identifying 6 mA locus and in formulating new testable biological hypotheses.
Praziquantel and factor H recruitment differentially affect the susceptibility of Schistosoma mansoni to complement-mediated damage
Authors: van Beek Anna E. , Jeanguenat Hannah , Häberli Cécile , Pouw Richard B. , Lamers Christina , Pál Gábor , Gál Péter , Schmidt Christoph Q. , Ricklin Daniel , Keiser Jennifer 
Published: November 2024

BackgroundSchistosomes are highly efficient evaders of human immunity, as evident by their ability to survive in human blood for years. How they protect themselves against the constant attack by a key element of innate immunity, the complement system, has remained unclear. In this study, new light is shed on the interaction between distinct life-cycle stages of Schistosoma mansoni and the human complement system.ResultsWe demonstrate that schistosomula, the young stage assumed immediately after cercaria penetration of the skin, are extremely vulnerable towards complement-mediated killing as only 10-20% survive. The survival rate increases to 70% already within 30 minutes and reaches close to 100% within two hours. Pathway-specific complement inhibitors revealed the alternative pathway of complement activation as the main contributor to killing and damage of the schistosomula. Moreover, the complement regulator factor H is recruited by the schistosomula in this early stage to evade killing. Surviving parasites appear fully viable despite the ongoing complement attack, as demonstrated by the deposition of C3 fragments. However, when exposed to the widely used schistocidal drug praziquantel, the vulnerability of 24 h-old schistosomula towards complement-mediated killing is notably increased; no such effect was observed for mefloquine or oxamniquine. Similar to the younger life-cycle stages, adult worms remain under complement attack. C3 fragments were found all over the outer surface (tegument), deposited mostly on the ridges and not on the tubercles.ConclusionThe recruitment of factor H merits more detailed studies that pinpoint the molecules involved and elucidate the novel possibilities to intercept the uncovered immune evasion therapeutically. That praziquantel and complement work in synergy is surprising and may in the future result in enhanced understanding of the drug’s mechanism of action.
Neutrophils enhance the clearance of systemic amyloid deposits in a murine amyloidoma model
Authors: Hancock Trevor J. , Vlasyuk Marina , Foster James S. , Macy Sallie , Wooliver Daniel C. , Balachandran Manasi , Williams Angela D. , Martin Emily B. , Kennel Stephen J. , Heidel Eric R. , Wall Jonathan S. , Jackson Joseph W. 
Published: November 2024

IntroductionAmyloid-specific antibodies have been shown to opsonize and enhance amyloid clearance in systemic amyloidosis mouse models. However, the immunological mechanisms by which amyloid is removed have not been clearly defined. Previous reports from preclinical in vivo studies suggest polymorphonuclear cells (i.e., neutrophils) can affect amyloid removal. Therefore, we sought to analyze how neutrophils may contribute to the clearance of human AL amyloid extracts, using a murine amyloidoma model.MethodsImmunocompromised nude mice injected subcutaneously with patient-derived AL amyloid extract (generating a localized “amyloidoma”) were used to circumvent confounding factors contributed by the adaptive immune system and served as the model system. Two representative AL amyloid extracts were used, ALλ(CLA), which is refractory to clearance, and ALκ(TAL), which is readily cleared in mice. Neutrophil recruitment to the amyloid masses, cellular activation, and propensity to engulf amyloid were assessed.ResultsImmunophenotyping of amyloidomas from animals implanted with 2 mg of either ALλ or ALκ revealed that more neutrophils were recruited to ALκ amyloid masses as compared to the ALλ material, which was generally devoid of neutrophils. Ex vivo analyses indicated neutrophils do not efficiently phagocytose amyloid directly. However, histological evaluation of the ALκ amyloidoma revealed the abundant presence of neutrophil extracellular traps, which were absent in the ALλ amyloidomas. Using neutrophil depletion experiments in mice, we determined that mice devoid of neutrophils cleared the human amyloid lesions less efficiently. Moreover, mice devoid of neutrophils also had significantly reduced intra-amyloid expression of inflammatory cytokines.DiscussionNeutrophils may not directly mediate amyloid clearance through phagocytosis; however, these cells can be stimulated by the amyloid and may function to facilitate phagocytosis and amyloid clearance by professional phagocytes (e.g., macrophages).
The established of a machine learning model for predicting the efficacy of adjuvant interferon alpha1b in patients with advanced melanoma
Authors: Jiang Linhan , Su Ke , Wang Jing , Lin Yitong , Zhao Xianya , Zhang Hengxiang , Liu Yu 
Published: November 2024

BackgroundInterferon-alpha1b (IFN-α1b) has shown remarkable therapeutic potential as adjuvant therapy for melanoma. This study aimed to develop five machine learning models to evaluate the efficacy of postoperative IFN-α1b in patients with advanced melanoma.MethodsWe retrospectively analyzed 113 patients with the American Joint Committee on Cancer (AJCC) stage III-IV melanoma who received postoperative IFN-α1b therapy between July 2009 and February 2024. Recurrence-free survival (RFS) and overall survival (OS) were assessed using Kaplan-Meier analysis. Five machine learning models (Decision Tree, Cox Proportional Hazards, Random Forest, Support Vector Machine, and LASSO regression) were developed and compared for their capacity to predict the outcomes of patients. Model performance was evaluated using concordance index (C-index), time-dependent receiver operating characteristic (ROC) curves, and decision curve analysis.ResultsThe 1-year, 2-year, and 3-year RFS rates were 71.10%, 43.10%, and 31.10%, respectively. For OS, the 1-year, 2-year, and 3-year OS rates were 99.10%, 82.30%, and 75.00%, respectively. The Decision Tree (DT) model demonstrated superior predictive performance with the highest C-index of 0.792. Time-dependent ROC analysis for predicting 1-, 2-, and 3-year RFS based on the DT model is 0.77, 0.79 and 0.76, respectively. Serum albumin emerged as the important predictor of RFS.ConclusionsOur study demonstrates the considerable efficacy DT model for predicting the efficacy of adjuvant IFN-α1b in patients with advanced melanoma. Serum albumin was identified as a key predictive factor of the treatment efficacy.
Characterization of the T-cell receptor repertoire associated with lymph node metastasis in colorectal cancer
Authors: Zhen Ya’nan , Wang Hong , Jiang Runze , Wang Fang , Chen Cunbao , Xu Zhongfa , Xiao Ruixue 
Published: November 2024

PurposeColorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide, with lymph node (LN) metastasis playing a pivotal role in disease progression. This study aimed to explore the T-cell receptor (TCR) repertoire among CRC patients, distinguishing those with LN metastasis from those without, in order to uncover potential biomarkers for predicting metastasis.MethodsWe analyzed the TCR repertoire in CRC patients with and without LN metastasis. A classification model utilizing random forest analysis was developed to assess the predictive potential of the TCR repertoire.ResultsThe findings demonstrated a significant increase in the number of V-J combinations and immune CDR3 sequences in patients with LN metastasis compared to the control group. The classification model achieved high accuracy in differentiating patients with LN metastasis, with AUC values ranging from 0.514 to 0.794. Specific V-J combinations and CDR3 sequences were identified as significant predictors of the model’s predictive accuracy.ConclusionThese results suggest that the TCR repertoire is altered in CRC patients exhibiting LN metastasis, potentially influencing disease progression. This study highlights the importance of TCR repertoire analysis as a non-invasive biomarker for predicting LN metastasis in CRC patients.
Integrated surgical intervention for intradural extramedullary hemangioblastoma of the cervical spine: a case report and literature review
Authors: Wang Yao , Zhu Qing , Chen Ailin , Dai Chungang , Xu Longjiang , Sheng Minfeng , Huang Qiang , Lan Qing , Mu Qingchun , Li Rujun 
Published: November 2024

IntroductionThe incidence of hemangioblastoma is low, constituting only 1-5% of all spinal cord tumors. Specifically, intradural extramedullary hemangioblastoma without Von Hippel-Lindau syndrome represents an exceedingly rare condition.MethodsWe report the first documented case of cervical intradural extramedullary hemangioblastoma in China. A 53-year-old male patient presented with a 3-year history of mild right hemiplegia, segmental muscle strength and sensation impairment, and a positive pyramidal tract sign. MRI showed an abnormal oval signal focus in the intradural and extramedullary region at the C6-C7 vertebral level. Before surgery, angiography was performed to identify the supplying arteries and draining veins. Subsequent interventional therapy achieved over 90% occlusion of blood vessels, creating optimal conditions for complete resection of the spinal tumor.ResultsThe patient demonstrated satisfactory postoperative recovery with significant restoration of sensory and motor functions. Pathological examination showed a significant upregulation of CD31 in tumor cells and a substantial presence of the neuro-specific marker S100 in the tumor stroma, consistent with the diagnostic criteria for spinal hemangioblastoma.ConclusionThe rarity of cervical intradural extramedullary hemangioblastoma without Von Hippel-Lindau syndrome was reaffirmed by a comprehensive review of the existing literature. Complete tumor resection remains the optimal approach for managing this uncommon condition, generally resulting in a favorable prognosis. Traditional open fenestration surgery is linked to elevated risks of bleeding and trauma. Meanwhile, endovascular injection of embolic agents may lead to residual lesions and an increased risk of recurrence. Therefore, we recommend a one-time combined treatment conducted in a hybrid operating room to achieve complete resection and effectively reduce intraoperative bleeding risk. Despite presenting challenges and requiring high proficiency, we still recommend this type of combined surgery as a suitable therapeutic option for such diseases.
Causes of death after oral cancer diagnosis: a population based study
Authors: Jiang Zhenyu , Shao Li , Zhou Jie , Shao Xuwen , Shen Chao 
Published: November 2024

BackgroundNowadays, the number of oral cancer survivors is increasing, emphasizing the importance of thoroughly understanding diverse causes of death in oral cancer survivors. Our study aimed to investigate the distribution of causes of death after oral cancer diagnosis.MethodsEligible patients were identified between 2004 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database. We calculated the number of deaths in different demographic and clinicopathological variables during each follow-up period. Standardized mortality ratios(SMRs) were generated for each cause of death after oral cancer diagnosis.ResultsA total of 30538 patients diagnosed with oral cancer were included, and 17654 deaths were reported during follow-up period. 27.08% of deaths were caused by non-caner reasons. The proportion of non-cancer related deaths increased with the extension of survival time, and non-cancer death accounted for 57.93% of all deaths when followed up more than 10 years. The most common non-cancer cause of death was cardiovascular disease (SMR 4.68#; 95%CI 4.46-4.92).ConclusionsNon-cancer causes of death should not be ignored in oral cancer patients. For oral cancer survivors, multidisciplinary follow-up strategy should be recommended to achieve longer survival time.
Effects of Kalimeris indica on alcohol-induced liver injury through storing Nrf2/HO-1 pathway and gut microbiota
Authors: Wang Mo-Fei , Sun Tong , Chen Shi-Yu , Wang Xue , Li Hao , Wang Jia-Qi 
Published: November 2024

BackgroundKalimeris indica (L.) Sch. Bip., (K. indica) is a plant classified under the genus Kalimeris within the Asteraceae family. The herb of K. indica has been historically utilized as a traditional medicine. The consumption of excessive amounts of alcohol represents a lifestyle choice that can induce tissue damage and contribute to the development of various health conditions.MethodThe HPLC-MS method was used to reveal the chemical composition of K. indica extract. HepG2 cells were used to test the in vitro oxidative stress. C57BL/6 mice were used to construct the in vivo alcohol-induced liver injury. H/E staining and serum ALT and AST levels were tested to assess the in vivo protective effect of ML (50 and 200 mg/kg). GSH, SOD, and CAT levels along with byproduct MDA levels were used to evaluate the in vivo oxidative stress. Immunohistochemical experiments were used to examine the in vivo Nrf2 and HO-1 levels. 16S rRNA gene-based profiling method was used to test the alteration in gut microbiota.Results16 compounds were identified from K. indica extract. K. indica treatment reduced oxidative stress in HepG2 cells treated with 5% alcohol. H/E staining results showed that K. indica (50 and 200 mg/kg) alleviated liver injury caused by alcohol administration, eliciting a similar protective effect to the positive drug silymarin. Serum ALT and AST examination gave a consistent result, showing that ML could restore serum ALT and AST levels in mice treated with alcohol. Furthermore, K. indica could also restore GSH, SOD, CAT, and MDA levels in alcohol-treated mice, showing a potent effect on oxidative stress alleviation. Immunohistochemical experiments indicated that K. indica showed the liver protective effect through Nrf2/HO-1 pathway. 16S rRNA gene-based profiling revealed that alcohol treatment caused the alteration in gut microbiota, while K. indica treatment could result in a significantly richer variety of microbial communities compared to the alcohol group.ConclusionK. indica (ML) has a protective effect on liver injury caused by alcohol administration. The Nrf2/HO-1 pathway and gut microbiota regulation were involved in the ML-induced liver protection. All the results indicate that K. indica has a potential in the treatment of alcohol-induced liver injury.
Discrepancy in coordination and variation of root and leaf traits among herbaceous and shrub species in the desert, China
Authors: Ma Jing , Wang Taotao , Wang Hongyong , Chen Yiming , Yang Jie , Xie Tingting , Shan Lishan 
Published: November 2024

IntroductionAlterations in life forms could simultaneously influence the variability of fine root and leaf traits. However, our understanding of the organ-level coordination and patterns of variation in fine root and leaf traits among desert herbs and shrubs with distinct habits remains limited.MethodsConsequently, this study examined the leaf and fine root traits of 9 shrubs and 9 herbs across three desert habitats through Sperman's correlation analysis, principal component analysis (PCA), and standardized major axis (SMA) analysis as a means of identifying the hub traits and the resource trade-off strategies employed by desert plants to adapt to their environment.ResultsThe results showed that the extent of coordination between leaf and root traits, defined as similarity, was contingent upon the life form. While the traits in shrubs were completely decoupled, those in herbs exhibited a high degree of coordination. The traits related to water acquisition and storage are highly connected and do not depend on traits and life forms. Most leaves and fine roots were primarily loaded along the PC1 and PC2 axes of principal component analysis.DiscussionSuggesting that herbs and shrubs each adopt the most advantageous trait syndrome in accordance with their life form to acquire and conserve resources. The leaf economic spectrum and the root economic spectrum evolved independently, showing no dependence on the variations in life form. In conclusion, in desert plants, leaf and root variations occur independently along two axes, with traits associated with water acquisition playing a neutral role in their ecological strategy.