bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ex Vivo and In Vivo Properties of an Injectable Hydrogel Derived From Acellular Ear Cartilage Extracellular Matrix
Authors: Gong Danni , Yu Fei , Zhou Meng , Dong Wei , Yan Dan , Zhang Siyi , Yan Yan , Wang Huijing , Tan Yao , Chen Ying , Feng Bei , Fu Wei , Fu Yao , Lu Yang 
Published: September 2021

Extracellular matrix (ECM) hydrogels provide advantages such as injectability, the ability to fill an irregularly shaped space, and the adequate bioactivity of native matrix. In this study, we developed decellularized cartilage ECM (dcECM) hydrogels from porcine ears innovatively via the main method of enzymatic digestion and verified good biocompatible properties of dcECM hydrogels to deliver chondrocytes and form subcutaneous cartilage in vivo. The scanning electron microscopy and turbidimetric gelation kinetics were used to characterize the material properties and gelation kinetics of the dcECM hydrogels. Then we evaluated the biocompatibility of hydrogels via the culture of chondrocytes in vitro. To further explore the dcECM hydrogels in vivo, grafts made from the mixture of dcECM hydrogels and chondrocytes were injected subcutaneously in nude mice for the gross and histological analysis. The structural and gelation kinetics of the dcECM hydrogels altered according to the variation in the ECM concentrations. The 10 mg/ml dcECM hydrogels could support the adhesion and proliferation of chondrocytes in vitro. In vivo, at 4 weeks after transplantation, cartilage-like tissues were detected in all groups with positive staining of toluidine blue, Safranin O, and collagen II, indicating the good gelation of dcECM hydrogels. While with the increasing concentration, the tissue engineering cartilages formed by 10 mg/ml dcECM hydrogel grafts were superior in weights, volumes, collagen, and glycosaminoglycan (GAG) content compared to the dcECM hydrogels of 1 mg/ml and 5 mg/ml. At 8 weeks after grafting, dcECM hydrogel grafts at 10 mg/ml showed very similar qualities to the control, collagen I grafts. After 12 weeks of in vivo culture, the histological analysis indicated that 10 mg/ml dcECM hydrogel grafts were similar to the normal cartilage from pig ears, which was the source tissue. In conclusion, dcECM hydrogel showed the promising potential as a tissue engineering biomaterial to improve the regeneration and heal injuries of ear cartilage.
Empirical Evaluation of Understandability and Usability of Health Handbooks Commonly Used in Japan
Authors: Nomura Marika , Goto Aya , Osawa Eri , Miura Hiroko 
Published: September 2021

Objective: Various types of handbooks that summarize and record health information (health handbooks) have been used in Japan for many years. The purpose of this study was to explore ways to evaluate the understandability and usability of commonly used printed health handbooks in Japan.Methods: An internet search was performed to identify health handbooks used in Japan. The handbooks were then collected, searched, and evaluated for the quality and functionality of the health-information. The overall understandability was assessed using the Suitability Assessment of Material (SAM) and the Centers for Disease Control and Prevention Clear Communication Index (CCI), and overall usability was assessed using a purpose-user matrix.Results: A total of 14 health handbooks were extracted and analyzed. The median scores for SAM and CCI were 39 (min 25, max 45) and 81.5% (60%, 100%), respectively, and no significant association was observed between the two evaluation scores. Based on the matrix, the most common type of handbook was those designed for preventive purposes that the user or their family completed (n = 9).Conclusion: Our sampled health handbooks were used mostly for preventive purposes and their understandability varied. SAM and CCI assess different aspects of written materials and it is recommended they be used together when evaluating the understandability of health handbooks. To facilitate more effective use of health handbooks in public health activities, we suggest the content of handbooks be assessed by a purpose-user matrix.
Triglyceride Glucose Index Associated With Arterial Stiffness in Chinese Community-Dwelling Elderly
Authors: Su Yongkang , Wang Shuxia , Sun Jin , Zhang Yan , Ma Shouyuan , Li Man , Zhang Anhang , Cheng Bokai , Cai Shuang , Bao Qiligeer , Zhu Ping 
Published: September 2021

Background: The population of older adults is growing rapidly with the increasing pace of aging worldwide. The triglyceride glucose (TyG) index has been a convenient and reliable surrogate marker of insulin resistance (IR). This study aimed to determine the association between the TyG index and arterial stiffness assessed by brachial-ankle pulse wave velocity (baPWV) in Chinese older adults.Methods: A total of 2,035 participants aged 60 years or above were enrolled. Demographic, anthropometric, and cardiovascular risk factors were collected. TyG index was calculated using ln (fasting triglycerides [mg/dL] × fasting glucose [mg/dL]/2). Arterial stiffness was measured using baPWV.Results: The participants, with the mean [standard deviation (SD)] age of 71.32 (6.75) years, the female proportion of 39.65%, the mean (SD) baPWV of 1,998 (437) cm/s, and the mean (SD) TyG index of 8.86 (0.54), were divided into four groups according to TyG index quartiles. Age-adjusted baPWV presented an increasing trend according to TyG index quartiles. In the fully adjusted linear regression model, the baPWV increased 49 cm/s, with the 95% confidence interval (CI) from 24 to 75 cm/s, per-SD increase in the TyG index. In the fully-adjusted logistic regression model, the odds ratio (95% CI) of high baPWV (&gt;75th percentile) was 1.32 (1.09, 1.60) for each SD increase in the TyG index. The generalized additive model analysis also confirmed the significant association of the TyG index with baPWV and high baPWV.Conclusion: The TyG index is significantly associated with arterial stiffness assessed by baPWV in Chinese older adults.
Using GRACE Data to Estimate Climate Change Impacts on the Earth’s Moment of Inertia
Authors: Ren Diandong , Hu Aixue 
Published: September 2021

The widely used 15-year Gravity Recovery and Climate Experiment (GRACE) measured mass redistribution shows an increasing trend in the nontidal Earth’s moment of inertia (MOI). Various contributing components are independently evaluated using five high-quality atmospheric reanalysis datasets and a novelty numerical modeling system. We found a steady, statistically robust (passed a two-tailed t-test atp= 0.04 for dof = 15) rate of MOI increase reaching ∼11.0 × 1027kg m2/yr, equivalent to a 11.45 sμ/yr increase in the length of day, during 2002–2017. Further analysis suggests that the Antarctic ice sheet contributes the most, followed by the Greenland ice sheet, the precipitation-driven land hydrological cycle, mountain glaciers, and the fluctuation of atmosphere, in this order. Short-term MOI spikes from the GRACE measurements are mostly associated with major low/mid-latitude earthquakes, fitting closely with the MOI variations from the hydrological cycle. Atmospheric fluctuation contributes the least but has a steady trend of 0.5 sμ/yr, with horizontal mass distribution contributing twice as much as the vertical expansion and associated lift of the atmosphere’s center of mass. The latter is a previously overlooked term affecting MOI fluctuation. The contribution to the observed MOI trend from a warming climate likely will persist in the future, largely due to the continuous mass loss from the Earth’s ice sheets.
Prognostic Role of ceRNA Network in Immune Infiltration of Hepatocellular Carcinoma
Authors: Xu Qianhui , Chen Shaohuai , Hu Yuanbo , Huang Wen 
Published: September 2021

Background: Increasing evidence supports that competing endogenous RNAs (ceRNAs) and tumor immune infiltration act as pivotal players in tumor progression of hepatocellular carcinoma (HCC). Nonetheless, comprehensive analysis focusing on ceRNAs and immune infiltration in HCC is lacking.Methods: RNA and miRNA sequencing information, corresponding clinical annotation, and mutation data of HCC downloaded from The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) project were employed to identify significant differentially expressed mRNAs (DEMs), miRNAs (DEMis), and lncRNAs (DELs) to establish a ceRNA regulatory network. The Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene ontology (GO) enrichment pathways were analyzed to functionally annotate these DEMs. A multigene-based risk signature was developed utilizing least absolute shrinkage and selection operator method (LASSO) algorithm. Moreover, survival analysis and receiver operating characteristic (ROC) analysis were applied for prognostic value validation. Seven algorithms (TIMER, XCELL, MCPcounter, QUANTISEQ, CIBERSORT, EPIC, and CIBERSORT-ABS) were utilized to characterize tumor immune microenvironment (TIME). Finally, the mutation data were analyzed by employing “maftools” package.Results: In total, 136 DELs, 128 DEMis, and 2,028 DEMs were recognized in HCC. A specific lncRNA–miRNA–mRNA network consisting of 3 lncRNAs, 12 miRNAs, and 21 mRNAs was established. A ceRNA-based prognostic signature was established to classify samples into two risk subgroups, which presented excellent prognostic performance. In additional, prognostic risk-clinical nomogram was delineated to assess risk of individual sample quantitatively. Besides, risk score was significantly associated with contexture of TIME and immunotherapeutic targets. Finally, potential interaction between risk score with tumor mutation burden (TMB) was revealed.Conclusion: In this work, comprehensive analyses of ceRNAs coexpression network will facilitate prognostic prediction, delineate complexity of TIME, and contribute insight into precision therapy for HCC.
Can Tirofiban Improve the Outcome of Patients With Acute Ischemic Stroke: A Propensity Score Matching Analysis
Authors: Cai Lingxin , Yu Xiaobo , Yu Jun , Xu Jing , Xu Liang , Ling Chenhan , Lou Min , Yu Cheng , Qian Cong 
Published: September 2021

Objective: To evaluate the efficacy and safety of tirofiban for patients with acute ischemic stroke (AIS), especially posterior circulation stroke (PCS).Methods: We enrolled consecutive patients with AIS who suffered large artery occlusion (LAO) and underwent mechanical thrombectomy (MT) between January 2016 and May 2020. Patients were divided into two groups according to whether tirofiban was used during MT. The primary efficacy outcome was a favorable functional outcome, defined as a modified Rankin Scale (mRS) score of 0–2 at 3 months. The safety outcomes were the rate of mortality at 3 months and the presence of intracranial hemorrhage (ICH) and symptomatic intracranial hemorrhage (sICH). Cohorts were balanced using 1:1 propensity score matching (PSM). Subgroup analysis was further performed to compare the efficacy and safety of tirofiban between the anterior circulation stroke (ACS) and PCS groups.Results: A total of 292 patients were eligible for this study and divided into the tirofiban group (n = 51) and the no-tirofiban group (n = 241). In the propensity-score-matched cohort, the tirofiban group had a higher rate of favorable outcomes than the no-tirofiban group (49.0 vs. 25.5%, p = 0.014), and the mortality at 3 months showed a greater downward trend in the tirofiban group than the no-tirofiban group (15.6 vs. 33.3% p = 0.064). The risk of sICH and ICH was the same between the tirofiban and control groups (17.6 vs. 27.4% p = 0.236, 31.3 vs. 45.1% p = 0.154, respectively). Tirofiban use was predictive of favorable outcomes [adjusted odds ratio (aOR) = 2.87, 95% confidence interval (CI) 1.52–6.44, p = 0.043] after multiple logistic regression analysis. Subgroup analysis revealed that tirofiban use was significantly associated with favorable outcomes in ACS (aOR = 3.66, 95% CI 1.24–5.22, p = 0.019) but not in PCS (aOR = 1.12, 95% CI 0.47–7.52, p = 0.570).Conclusion: We demonstrated that tirofiban may be associated with improving favorable outcome for the AIS patients who underwent MT, without increasing ICH or sICH. Furthermore, our results indicated that for PCS patients tirofiban may not be associated with favorable outcome, and more comprehensive randomized controlled trials are needed to confirm this finding.
Serum Irisin as a Potential Biomarker for Cognitive Decline in Vascular Dementia
Authors: Zhang Feng , Hou Guangshun , Hou Guangjian , Wang Congan , Shi Bin , Zheng Yuekun 
Published: September 2021

Background: Irisin, a new exercise-related myokine, has been shown to be associated with a variety of diseases including serious neurological disorders. However, whether irisin is involved in the pathogenesis of vascular dementia (VD) has not yet been reported. Our aim is to determine the serum irisin level in patients with VD and investigate its relationship with cognitive function.Methods: The subjects of the study were VD patients and controls with normal cognitive function who were hospitalized in the Neck-Shoulder and Lumbocrural Pain Hospital of Shandong First Medical University from July 2018 to June 2020. Upon admission, a cognitive function assessment was performed. Enzyme-linked immunosorbent assay (ELISA) was used to determine the concentration of irisin in serum.Results: During the study period, 187 subjects (82 controls and 105 VD patients) were included in the analysis. The serum irisin level of VD patients was significantly lower than that of the control group (p &lt; 0.001). Spearman analysis showed that irisin was positively correlated with HLD-C and MoCA, and negatively correlated with all clinical characteristics except for HCY. Logistic regression analysis showed that after adjusting for all clinical characteristics, the serum irisin of VD patients still had a significant correlation with MoCA (β = 0.304, p = 0.029). According to receiver operating characteristic (ROC) curve analysis, the diagnostic accuracy for serum irisin levels on VD was 76% with the sensitivity and 71% with specificity respectively.Conclusions: These data indicate that a decrease in serum irisin levels is a powerful biological marker for cognitive decline in patients with VD, even after adjustment for risk factors. Further multi-center studies need to confirm this connection, which may pave the way for new treatment options.
Reconfiguration of Dynamic Functional Connectivity States in Patients With Lifelong Premature Ejaculation
Authors: Lu Jiaming , Chen Qian , Li Danyan , Zhang Wen , Xing Siyan , Wang Junxia , Zhang Xin , Liu Jiani , Qing Zhao , Dai Yutian , Zhang Bing 
Published: September 2021

Purpose: Neuroimaging has demonstrated altered static functional connectivity in patients with premature ejaculation (PE), while studies examining dynamic changes in spontaneous brain activity in PE patients are still lacking. We aimed to explore the reconfiguration of dynamic functional connectivity (DFC) states in lifelong PE (LPE) patients and to distinguish LPE patients from normal controls (NCs) using a machine learning method based on DFC state features.Methods: Thirty-six LPE patients and 23 NCs were recruited. Resting-state functional magnetic resonance imaging (fMRI) data, the clinical rating scores on the Chinese Index of PE (CIPE), and intravaginal ejaculatory latency time (IELT) were collected from each participant. DFC was calculated by the sliding window approach. Finally, the Lagrangian support vector machine (LSVM) classifier was applied to distinguish LPE patients from NCs using the DFC parameters. Two DFC state metrics (reoccurrence times and transition frequencies) were introduced and we assessed the correlations between DFC state metrics and clinical variables, and the accuracy, sensitivity, and specificity of the LSVM classifier.Results: By k-means clustering, four distinct DFC states were identified. The LPE patients showed an increase in the reoccurrence times for state 3 (p &lt; 0.05, Bonferroni corrected) but a decrease for state 1 (p &lt; 0.05, Bonferroni corrected) compared to the NCs. Moreover, the LPE patients had significantly less frequent transitions between state 1 and state 4 (p &lt; 0.05, uncorrected) while more frequent transitions between state 3 and state 4 (p &lt; 0.05, uncorrected) than the NCs. The reoccurrence times and transition frequencies showed significant associations with the CIPE scores and IELTs. The accuracy, sensitivity, and specificity of the LSVM classifier were 90.35, 87.59, and 85.59%, respectively.Conclusion: LPE patients were more inclined to be in DFC states reinforced intra-network and inter-network connection. These features correlated with clinical syndromes and can classify the LPE patients from NCs. Our results of reconfiguration of DFC states may provide novel insights for the understanding of central etiology underlying LPE, indicate neuroimaging biomarkers for the evaluation of clinical severity of LPE.
Exploration of the Proteomic Landscape of Small Extracellular Vesicles in Serum as Biomarkers for Early Detection of Colorectal Neoplasia
Authors: Chang Li-Chun , Hsu Yi-Chiung , Chiu Han-Mo , Ueda Koji , Wu Ming-Shiang , Kao Chiun-How , Shen Tang-Long 
Published: September 2021

BackgroundPatient participation in colorectal cancer (CRC) screening via a stool test and colonoscopy is suboptimal, but participation can be improved by the development of a blood test. However, the suboptimal detection abilities of blood tests for advanced neoplasia, including advanced adenoma (AA) and CRC, limit their application. We aimed to investigate the proteomic landscape of small extracellular vesicles (sEVs) from the serum of patients with colorectal neoplasia and identify specific sEV proteins that could serve as biomarkers for early diagnosis.Materials and MethodsWe enrolled 100 patients including 13 healthy subjects, 12 non-AAs, 13 AAs, and 16 stage-I, 15 stage-II, 16 stage-III, and 15 stage-IV CRCs. These patients were classified as normal control, early neoplasia, and advanced neoplasia. The sEV proteome was explored by liquid chromatography-tandem mass spectrometry. Generalized association plots were used to integrate the clustering methods, visualize the data matrix, and analyze the relationship. The specific sEV biomarkers were identified by a decision tree via Orange3 software. Functional enrichment analysis was conducted by using the Ingenuity Pathway Analysis platform.ResultsThe sEV protein matrix was identified from the serum of 100 patients and contained 3353 proteins, of which 1921 proteins from 98 patients were finally analyzed. Compared with the normal control, subjects with early and advanced neoplasia exhibited a distinct proteomic distribution in the data matrix plot. Six sEV proteins were identified, namely, GCLM, KEL, APOF, CFB, PDE5A, and ATIC, which properly distinguished normal control, early neoplasia, and advanced neoplasia patients from each other. Functional enrichment analysis revealed that APOF+ and CFB+ sEV associated with clathrin-mediated endocytosis signaling and the complement system, which have critical implications for CRC carcinogenesis.ConclusionPatients with colorectal neoplasia had a distinct sEV proteome expression pattern in serum compared with those patients who were healthy and did not have neoplasms. Moreover, the six identified specific sEV proteins had the potential to discriminate colorectal neoplasia between early-stage and advanced neoplasia. Collectively, our study provided a six-sEV protein biomarker panel for CRC diagnosis at early or advanced stages. Furthermore, the implication of the sEV proteome in CRC carcinogenesis via specific signaling pathways was explored.
Clinical Relevance of New World Health Organization Classification System for Pituitary Adenomas: A Validation Study With 2-Year Experience
Authors: Hong Seung Woo , Kim Se Hoon , Lim Seung Hoon , Lee Eun Jig , Kim Sun Ho , Ku Cheol Ryong , Kim Eui Hyun 
Published: September 2021

BackgroundThe new World Health Organization (WHO) classification system proposed a cell lineage-based classification scheme for pituitary adenomas in which transcription factors (TFs) play a major role as key classifiers. We aimed to evaluate clinical relevance of the new classification system in a clinical setting.MethodsTF staining was retrospectively performed for 153 clinically and histologically well characterized pituitary adenomas. Then, 484 pituitary adenomas were prospectively stained for TFs and then for relevant pituitary hormones. TF and hormone stain-based diagnoses were compared, and differences in clinical manifestations were evaluated.ResultsThe accuracies of antibodies for three TFs were successfully validated and had an overall matching rate was 89.6%. We identified 50 (10.4%) cases with discrepancies between TF and pituitary hormone stains. Gonadotroph adenomas lacking follicle-stimulating hormone and luteinizing hormone stains account for most discrepancies. Null cell adenomas may be more prevalent than reported and may be clinically more aggressive than gonadotroph adenomas.ConclusionThe new WHO classification is mostly well matched with the traditional classification. However, until the new classification is further validated and interpreted in the context of long-term clinical outcomes, routine histological examination should include full slate of immunostains for pituitary hormones as well as TFs.
Predictive Value of C-Reactive Protein for Early Postoperative Complications in Children After Hypospadias Surgery
Authors: Ji Fengming , Tang Haoyu , Wu Chengchuang , Chen Li , Wang Huake , Yan Bing 
Published: September 2021

Background: This study explored the predictive value of postoperative C-reactive protein in children with hypospadias for postoperative complications and the risk factors.Methods: The clinical and follow-up data of 106 children with hypospadias who were treated with operations at Kunming Children's Hospital in 2020 were, respectively, analyzed. According to the occurrence of postoperative complications, the patients were divided into two groups: 25 patients with postoperative complications were the complications group, and 81 without postoperative complications were the control group. The baseline data, clinical characteristics, laboratory test indexes, and outcome of the two groups were collected. Receiver operating characteristic (ROC) was used to calculate the optimal cutoff value of C-reaction protein (CRP). Logistic regression was used to analyze the risk factors of hypospadias after surgery. A probability value (P) &lt; 0.05 was considered statistically significant.Results: According to the result of the ROC curve, the optimal cutoff value of CRP was 11.7 mg/L. Logistic regression showed that the length of urethral defect, the urethral material, the operative produce, and the postoperative CRP level were related to the occurrence of postoperative complications of patients with DCC. The length of the urethral defect and the CRP level were the independent risk factors of the prognosis of hypospadias patients. The CRP level was related to the occurrence of postoperative complications and fistula.Conclusions: Postoperative CRP level can be used as a reliable marker for predicting the prognosis of hypospadias patients.