bluuebunny/crossref_metadata_2025_split huggingface dataset:
Key factors for increased tip-apex distance when treating intertrochanteric fractures with InterTAN nails
Authors: Zhu Naifeng , Wu Lianxia , Han Xiaofeng , Qian Zhonglai 
Published: November 2024

BackgroundThe tip-apex distance is a key factor in predicting implant cut-out after intramedullary fixation for intertrochanteric fractures. This study aimed to evaluate the factors associated with an increased tip-apex distance when treating intertrochanteric fractures using an InterTAN nail.Methods and MaterialWe retrospectively analyzed patients with intertrochanteric fractures who underwent InterTAN nail insertion between January 2017 and March 2022 at our hospital. Medical and radiological data were collected. Measurements of preoperative factors and postoperative factors were performed accordingly. Multivariate logistic regression analysis was performed to determine the statistically significant variables of the tip-apex distance.ResultsThis study included 102 patients with intertrochanteric fractures. The average tip-apex distance measured 22.4 ± 7.1 mm, ranging from 9.3 to 48.0 mm. The length of the femoral neck on the non-fractured side, lag screw placement in the sagittal plane (center-inferior, superior) and coronal plane (posterior), and the angle between the line of the proximal nail axis and the femoral long axis were identified to be statistically significant factors for the tip-apex distance.ConclusionTo obtain a shorter tip-apex distance, we recommend a medial trochanteric entry point to minimize the angle between the line of the proximal nail axis and the femoral long axis. Additionally, sufficiently deep central insertion of the lag screw was advised in both the sagittal and coronal planes.
Attachment promoting compounds significantly enhance cell proliferation and purity of bovine satellite cells grown on microcarriers in the absence of serum
Authors: Bodiou Vincent , Kumar Anitha Ajith , Massarelli Edoardo , van Haaften Tessa , Post Mark J. , Moutsatsou Panagiota 
Published: November 2024

IntroductionTo bring cultivated beef to the market, a scalable system that can support growth of bovine satellite cells (bSCs) in a serum-free and preferably also animal-free medium is of utmost importance. The use of microcarriers (MCs) is, at the moment, one of the most promising technologies for scaling up. MCs offer a large surface to volume ratio, they can be used in scalable stirred tank bioreactors, where the culture conditions can be tightly controlled to meet the cells’ requirements (temperature, pH, dissolved oxygen). The inherent capacity of the cells to migrate from one MC to another, also known as bead-to-bead transfer, facilitates a scale-up strategy involving MCs. Previous studies have shown growth of bSCs on three commercially available MCs in serum containing media. Unfortunately there is currently no information available regarding their growth on MCs in serum-free conditions.MethodsIn this study, we aimed to find suitable serum-free media, MCs and attachment promoting compounds (APCs) supporting the growth of bSCs. Initially, six commercial MCs and three serum-free media were evaluated. The effects of three APCs were compared (vitronectin, laminin and fibronectin). Subsequently, the effects of different concentrations and modes of addition of the best performing APC were investigated.Results and DiscussionOur results showed that Cytodex 1, Synthemax II and CellBIND supported bSCs’ growth in all serum-free media. Overall, better growth was observed with Cytodex 1 in serum-free proliferation media. We showed that the use of laminin or vitronectin with Cytodex 1 can significantly improve cell growth and purity. Laminin also allowed attachment and growth of bSCs on Plastic MCs which had been previously unsuccessful without APCs. Finally, we optimized the use of vitronectin from a sustainability and process perspective, and showed that it can be used solely as a coating for Cytodex 1 (16–100 ng/cm2) MCs, instead of as a medium supplement, enhancing cell attachment and proliferation.
Development and evaluation of a pH-sensitive, naturally crosslinked alginate-chitosan hydrogel for drug delivery applications
Authors: Khatibi Negin , Naimi-Jamal M. Reza , Balalaie Saeed , Shokoohmand Ali 
Published: November 2024

The development of safe and efficient delivery systems for targeted and controlled release of therapeutic agents has become a major focus in pharmacotherapy. The colon is one organ that serves as an optimal site for the absorption of protein and peptide drugs, offering significant potential for both localized and systemic therapies. However, effective drug delivery is challenged by the need to protect these drugs from premature absorption and maintain their stability across the varying pH levels of the gastrointestinal tract. In this study, we introduce, for the first time, a fully natural hydrogel system composed of N-acetylated chitosan and alginate, crosslinked using a phenylalanine-phenylalanine dipeptide. The hydrogel demonstrates a unique swelling behavior, allowing for a solvent-free drug-loading method and pH-sensitive release properties. In a colon-simulated pH environment, the hydrogel achieved a high drug release efficiency, with 77.6% of the tested drug sulfasalazine and 51% of hydrocortisone over 5 hours. These findings underscore hydrogel’s potential as a promising drug delivery carrier for targeted gastrointestinal treatments, with the capacity to enhance the efficacy of current therapeutic options.
Global, regional, and national time trends in ischaemic heart disease incidence over three decades (1990–2019): an age-period-cohort analysis of the global burden of disease study 2019
Authors: Tang Juan , Hu Shaobo , Liu Xiaozhu , Li Huan , Kuang Lirong , Zhang Lei , Cao Wenzhai , Zhang Ting , Guan Xiaoyan , Li Lang , Zhang Yutao , Peng Shengxian , Zhang Qingwei , Zhou Xiaoqian 
Published: November 2024

IntroductionTo assess the prevailing trends in the incidence of ischemic heart disease (IHD) across 204 countries and territories from 1990 to 2019, and to elucidate their correlations with age, period, and birth cohort, a comprehensive analysis was conducted.MethodsFrom 1990 to 2019, we employed the Global Burden of Disease Study (GBD) Results Tool in conjunction with an age-period-cohort model. This approach facilitated the estimation of annual percentage changes in incidence, referred to as net drifts, encompassing the overall population. Additionally, we calculated annual percentage changes spanning ages 15 - 19 to 95 + years, denoted as local drifts. Furthermore, our analysis involved determining period and cohort relative risks, elucidating the effects associated with distinct periods and birth cohorts.ResultsGlobally, 21,203,479 [95% uncertainty interval (UI): 18,799,322 − 23,704,124] cases of IHD occurred in 2019. There were 33 countries with at least 100000 cases. Between 1990 and 2019, the net drift of IHD incidence exhibited a range from −1.7% per year [95% confidence interval (CI): −1.79, −1.61] in countries with a high socio-demographic index (SDI) to 0.08% per year (95% CI: 0.05, 0.11) in countries with a low SDI. Age effects across all countries and genders demonstrated an increasing trend over time, indicating age as a significant risk factor for IHD. Moreover, period and cohort effects in higher SDI countries exhibited a more rapid decline in both genders compared to lower SDI countries. The findings indicated that nations with a higher SDI manifested overall favorable trends in the relative risk of IHD incidence, both across time and in successive younger birth cohorts.DiscussionThe incidence of IHD serves as a valuable and accessible indicator for assessing trends in IHD provision, spanning from early youth through later life. Enhancements in IHD prevention have the potential to mitigate risks for successively younger cohorts and, over time, redistribute the risk across all age groups. Despite global declines in IHD incidence over the last three decades, decreasing trends in incidence have slowed and, in some countries, flattened. Many countries have experienced unfavorable period and cohort effects.
Personalized risk prediction of mortality and rehospitalization for heart failure in patients undergoing mitral valve repair surgery
Authors: Zhou Ning , Zhang Kui , Qiao Bokang , Chen Cong , Guo Xiaobo , Fu Wei , Zheng Jubing , Du Jie , Dong Ran 
Published: November 2024

BackgroundAccurately assessing the postoperative mortality and rehospitalization for heart failure risks in patients undergoing mitral valve repair surgery is of significant importance for individualized medical strategies.ObjectiveWe sought to develop and validate a risk assessment system for the prediction of mortality and rehospitalization for heart failure.MethodsPersonalized risk prediction system of mortality and rehospitalization for heart failure was developed. For developing a prediction system with death as the outcome, there were 965 patients (70%) and 413 patients (30%) were included in the the derivation cohort and the validation cohort. For developing a prediction system with rehospitalization for heart failure as the outcome, there were 927 patients (70%) and 398 patients (30%) were included in the derivation cohort and the validation cohort. There were 42 routine clinical variables used to develop the models. The performance evaluation of the model is based on the area under the curve (AUC). Evaluate the improvement with Euro Score II according to NRI and IDI net reclassification improvement (NRI) and integrated discrimination improvement (IDI).ResultsThe median follow-up time was 685 days, the incidence of death was 3.85% (n = 53), and the incidence of rehospitalization for heart failure was 10.01% (n = 138). The AUC values of the mortality prediction model in the derivation and validation cohorts were 0.825 (0.764–0.886) and 0.808 (0.699–0.917), respectively. The AUC values of the rehospitalization for heart failure prediction model in the derivation and validation cohorts were 0.794 (0.756–0.832) and 0.812 (0.758–0.866), respectively. NRI and IDI showed that the mortality prediction model exhibited superior performance than the Euro Score II. The mortality and rehospitalization for heart failure risk prediction models effectively stratified patients into different risk subgroups.ConclusionThe developed and validated models exhibit satisfactory performance in prediction of all-cause mortality and rehospitalization for heart failure after mitral valve repair surgery.Clinical Trial Registrationhttp://www.clinicaltrials.gov, Unique identifier: (NCT05141292).
Identification of key genes for cuproptosis in carotid atherosclerosis
Authors: Wu Xize , Kang Jian , Pan Xue , Xue Chentian , Pan Jiaxiang , Quan Chao , Ren Lihong , Gong Lihong , Li Yue 
Published: November 2024

BackgroundAtherosclerosis is a leading cause of cardiovascular disease worldwide, while carotid atherosclerosis (CAS) is more likely to cause ischemic cerebrovascular events. Emerging evidence suggests that cuproptosis may be associated with an increased risk of atherosclerotic cardiovascular disease. This study aims to explore the potential mechanisms linking cuproptosis and CAS.MethodsThe GSE100927 and GSE43292 datasets were merged to screen for CAS differentially expressed genes (DEGs) and intersected with cuproptosis-related genes to obtain CAS cuproptosis-related genes (CASCRGs). Unsupervised cluster analysis was performed on CAS samples to identify cuproptosis molecular clusters. Weighted gene co-expression network analysis was performed on all samples and cuproptosis molecule clusters to identify common module genes. CAS-specific DEGs were identified in the GSE100927 dataset and intersected with common module genes to obtain candidate hub genes. Finally, 83 machine learning models were constructed to screen hub genes and construct a nomogram to predict the incidence of CAS.ResultsFour ASCRGs (NLRP3, SLC31A2, CDKN2A, and GLS) were identified as regulators of the immune infiltration microenvironment in CAS. CAS samples were identified with two cuproptosis-related molecular clusters with significant biological function differences based on ASCRGs. 220 common module hub genes and 1,518 CAS-specific DEGs were intersected to obtain 58 candidate hub genes, and the machine learning model showed that the Lasso + XGBoost model exhibited the best discriminative performance. Further external validation of single gene differential analysis and nomogram identified SGCE, PCDH7, RAB23, and RIMKLB as hub genes; SGCE and PCDH7 were also used as biomarkers to characterize CAS plaque stability. Finally, a nomogram was developed to assess the incidence of CAS and exhibited satisfactory predictive performance.ConclusionsCuproptosis alters the CAS immune infiltration microenvironment and may regulate actin cytoskeleton formation.
Analysis of immunogenic cell death in periodontitis based on scRNA-seq and bulk RNA-seq data
Authors: Wu Erli , Yin Xuan , Liang Feng , Zhou Xianqing , Hu Jiamin , Yuan Wanting , Gu Feihan , Zhao Jingxin , Gao Ziyang , Cheng Ming , Yang Shouxiang , Zhang Lei , Wang Qingqing , Sun Xiaoyu , Shao Wei 
Published: November 2024

BackgroundRecent studies have suggested that cell death may be involved in bone loss or the resolution of inflammation in periodontitis. Immunogenic cell death (ICD), a recently identified cell death pathway, may be involved in the development of this disease.MethodsBy analyzing single-cell RNA sequencing (scRNA-seq) for periodontitis and scoring gene set activity, we identified cell populations associated with ICD, which were further verified by qPCR, enzyme linked immunosorbent assay (ELISA) and immunofluorescence (IF) staining. By combining the bulk transcriptome and applying machine learning methods, we identified several potential ICD-related hub genes, which were then used to build diagnostic models. Subsequently, consensus clustering analysis was performed to identify ICD-associated subtypes, and multiple bioinformatics algorithms were used to investigate differences in immune cells and pathways between subtypes. Finally, qPCR and immunohistochemical staining were performed to validate the accuracy of the models.ResultsSingle-cell gene set activity analysis found that in non-immune cells, fibroblasts had a higher ICD activity score, and KEGG results showed that fibroblasts were enriched in a variety of ICD-related pathways. qPCR, Elisa and IF further verified the accuracy of the results. From the bulk transcriptome, we identified 11 differentially expressed genes (DEGs) associated with ICD, and machine learning methods further identified 5 hub genes associated with ICD. Consensus cluster analysis based on these 5 genes showed that there were differences in immune cells and immune functions among subtypes associated with ICD. Finally, qPCR and immunohistochemistry confirmed the ability of these five genes as biomarkers for the diagnosis of periodontitis.ConclusionFibroblasts may be the main cell source of ICD in periodontitis. Adaptive immune responses driven by ICD may be one of the pathogenesis of periodontitis. Five key genes associated with ICD (ENTPD1, TLR4, LY96, PRF1 and P2RX7) may be diagnostic biomarkers of periodontitis and future therapeutic targets.
The enhancement of immunoactivity induced by immunogenic cell death through serine/threonine kinase 10 inhibition: a potential therapeutic strategy
Authors: Xia Xiaoli , Wang Yixin , Wang Minghui , Lin Jian , Wang Ruiheng , Xie Shufeng , Yu Yaoyifu , Long Jinlan , Huang Zixuan , Xian Huajian , Zhang Wenjie , Lu Chaoqun , Wang Wenfang , Liu Han 
Published: November 2024

IntroductionImmunogenic cell death (ICD) is capable of activating the anti-tumor immune response of the organism; however, it is concurrently a complex process involving multiple factors. The specific factors that impact the occurrence of ICD remain undefined.MethodsThrough cluster analysis, patient specimens retrieved from the TARGET, TCGA, and GEO AML databases were categorized into two subtypes based on the expression levels of ICD-related genes: ICD-high and ICD-low. We compared the prognostic survival outcomes, pathway enrichment analysis, and immune cell infiltration between these two subtypes. Additionally, we identified factors related to AML development from multiple databases and verified the role of these factors both in vivo and in vitro in activating the immune response during the occurrence of ICD. Results and discussionIn the ICD-high subtype, there was a notable increase in the abundance of immune cell populations, along with the enrichment of pathways pertinent to the activation of various immune cells. Despite these immunological enhancements, this subgroup demonstrated a poorer prognosis. This phenomenon was consistently observed across various additional AML datasets, leading us to hypothesize that elevated expression of ICD genes does not invariably correlate with a favorable prognosis. Notably, STK10 exhibited elevated expression in AML, was associated with a poor prognosis, and showed synchronous expression patterns with ICD genes. Inhibition of STK10 led to the activation of ICD and the induction of an antitumor response. Moreover, when combined with other ICD inducers, it produced a synergistic anti-tumor effect. Our results reveal the impact of STK10 on ICD and underscore its key role in initiating ICD.
Effects of early intervention in neuromyelitis optica spectrum disorder patients with seropositive AQP4 antibodies
Authors: Xue Binbin , Li Jia , Xie Dewei , Weng Yiyun , Zhang Xu , Li Xiang , Xia Junhui , Lin Jie 
Published: November 2024

BackgroundThe impact of early intervention with immunosuppressive treatment (IST) in anti-Aquaporin4-antibody (AQP4-ab) seropositive neuromyelitis optica spectrum disorder (NMOSD) has not been thoroughly evaluated.ObjectiveThis study aims to assess the effects of early IST intervention in patients with NMOSD.MethodsThis retrospective cohort study included 174 treatments from 137 NMOSD patients seropositive for AQP4-antibody, treated with ISTs such as rituximab, mycophenolate mofetil, azathioprine, or tacrolimus. Multiple statistical analyses, including regression discontinuity design (RDD), kaplan-meier analyze, Cox proportional hazards regression model, were employed to evaluate the effects of early IST intervention on annualized relapse rate (ARR) change, Expanded Disability Status Scale (EDSS) change, and time to next relapse.ResultsA total of 174 treatments from 137 patients were analyzed. Patients exhibited significant improvement in ARR[1.95 vs.0, IQR (0.70-6.0 vs. 0-0.42), p&lt;0.001] and EDSS [3.0 vs. 2.5, IQR (2.0-4.0 vs. 1.0-3.0) p&lt;0.001]after IST, although the ARR change was not significant in patients treated with TAC. Early IST initiation was associated with greater improvements in both ARR and EDSS compared to later initiation. RDD analysis demonstrated a time-dependent effect of ARR-change, indicating greater efficacy with early IST intervention.ConclusionsEarly intervention with ISTs in AQP4-antibody-positive NMOSD patients is associated with better outcomes in terms of reducing relapse rate and improving disability. These findings underscore the importance of early treatment in NMOSD.
Predictive value of bowel dose-volume for severe radiation-induced lymphopenia and survival in cervical cancer
Authors: Li Jingjing , Chen Qingqing , Liu Zhengcao , Xu Yingying , Ji Shengjun 
Published: November 2024

BackgroundRadiation-induced lymphopenia (RIL) is closely related to the prognosis of cervical cancer patients and may affect the efficacy of immune checkpoint inhibitors (ICIs). However, the factors influencing RIL are not very clear. In addition to bone marrow (BM) dose-volume, animal studies indicate radiation-induced bowel injury may be a more crucial factor. Further clarification of the correlation between RIL and bowel dose-volume is important for cervical cancer treatment.MethodsCervical cancer patients treated with postoperative radiotherapy or radical radiotherapy were eligible for this retrospective study. Clinical characteristics, dose parameters of bowel and BM, planning target volume (PTV) size, overall survival (OS) and progression-free survival (PFS) were recorded. The absolute lymphocyte count&lt;0.5×109/L at radiotherapy end was defined as severe RIL (sRIL). Hazard ratio (HR) and 95% confidence interval (Cl)were estimated using Cox regression models. Survival curve was plotted using the Kaplan-Meier method. On this basis, the receiver operating characteristics (ROC) curve was used to calculate the area under the curve (AUC) for radiation parameters with sRIL as the state variable.ResultA total of 118 cervical cancer patients were included in this study, with a median follow-up time of 57.6 months. In multivariable Cox regression analysis, international Federation of Gynecology and obstetrics (FIGO) stage (HR, 11.806; 95% CI, 3.256-42.809; p&lt;0.001), concurrent chemotherapy (HR, 0.200; 95% CI, 0.054-0.748; p=0.017), sRIL after radiotherapy (HR, 6.009; 95% CI, 1.361-26.539; p=0.018), and pathological type (HR, 2.261; 95% CI, 1.043-4.901; p=0.039) were significantly correlated with OS. Patients with sRIL had significantly decreased OS (79.1% vs 94.1%; HR, 3.81; 95%CI, 1.46-9.92; p=0.023). In binary logistic regression analysis, sRIL was significantly correlated with bowel V45 (Odds radio (OR), 1.025; 95%CI, 1.007-1.044; p=0.007), BM V10 (OR, 0.987; 95%CI, 0.978-0.997; p=0.011), BM V20 (OR, 1.017; 95%CI, 1.002-1.031, p=0.027), and PTV size (OR, 0.998; 95%CI, 0.996-1.000; p=0.026). The ROC curve showed, bowel V45 (AUC=0.787, p&lt;0.001) was the best indicator for predicting sRIL.ConclusionSRIL after radiotherapy could significantly predict decreased OS. In addition, sRIL is associated with higher bowel, BM dose-volume, PTV size, indicating that the bowel may be an important organ leading to an increased risk of sRIL.
Role of immune dysregulation in peri-implantitis
Authors: Huang Mingshu , Wang Chao , Li Ping , Lu Hongye , Li An , Xu Shulan 
Published: November 2024

Peri-implantitis, a complex condition that can lead to dental implant failure, is characterized by inflammatory destruction resulting from immune dysregulation. Oral microbial dysbiosis and foreign body stimulation are the main factors contributing to such dysregulation, impairing immune cell function and triggering an inflammatory response. Immune dysregulation plays a critical role in the pathophysiology of peri-implantitis, impacting the balance of T cell subsets, the production of inflammatory factors, and immune-related molecular signaling pathways. Understanding the relationship between immune dysregulation and peri-implantitis is crucial for developing targeted strategies for clinical diagnosis and individualized treatment planning. This review explores the similarities and differences in the immune microenvironment of oral bacterial infections and foreign body rejection, analyzes the relevant molecular signaling pathways, and identifies new key targets for developing innovative immunotherapeutic drugs and effective and personalized treatment modalities for peri-implantitis. Additionally, it addresses the challenges and potential directions for translating immunotherapy into clinical practice for peri-implantitis, offering insights that bridge the gaps in current literature and pave the way for future research.