bluuebunny/crossref_metadata_2025_split huggingface dataset:
Concentration of Serum Matrix Metalloproteinase-3 in Patients With Primary Biliary Cholangitis
Authors: Bauer Alicja , Habior Andrzej 
Published: April 2022

Background and AimsMetalloproteinases (MMPs) are involved in many distinct processes in the liver. Matrix metalloproteinase-3 (MMP-3) plays an important role in connective tissue remodeling, degradation of collagen (types II, III, IV, IX, and X), proteoglycans, fibronectin, laminin, and elastin. In addition, MMP-3 can also activate other MMPs such as MMP-1, MMP-7, and MMP-9. Primary biliary cholangitis (PBC) is a cholestatic, autoimmune liver disease, characterized by the progressive destruction of intrahepatic bile ducts, leading to cholestasis, fibrosis, cirrhosis, and liver failure. Fibrosis is the result of an imbalance between production and degradation of the extracellular matrix surrounding hepatocytes. Our aim in the present study was to determine whether the measurement of serum MMP-3 is clinically useful for assessing ongoing liver fibrosis in patients with PBC.MethodsThe MMP-3 concentration was determined in 182 PBC patients and 80 non-PBC controls using a commercially available ELISA kit.ResultsHigher concentrations of MMP-3 were found in 61% of PBC patients. PBC subjects had greater MMP-3 levels than controls: 68.9 ± 62.6 vs 21.3 ± 7.4 ng/mL, p &lt; 0.001 for healthy subjects; 68.9 ± 62.6 vs 22.7 ± 7.6 ng/mL, p = 0.022 for autoimmune hepatitis controls; and 68.9 ± 62.6 vs 37.2 ± 17.4 ng/mL, p = 0.002 for primary sclerosing cholangitis controls. The serum MMP-3 concentration was significantly elevated in patients with higher bilirubin concentration (107.6 ± 85.8 vs 61.6 ± 46.1 ng/mL, p &lt; 0.001) and was correlated with the level of antimitochondrial antibodies specific for PBC. The concentration of MMP-3 in sera of PBC patients was also found to correlate with the state of liver fibrosis (OR = 4.3; p &lt; 0.01).ConclusionsOur study demonstrated significantly higher MMP-3 levels in PBC patients than in healthy and pathological controls. Increased MMP-3 concentrations were positively correlated with various clinical and immunological parameters, and advanced liver fibrosis. The level of MMP-3 was associated with hepatic dysfunction and could play a role in the pathophysiology of hepatic fibrosis in PBC.
Predictive Utility of Mortality by Aging Measures at Different Hierarchical Levels and the Response to Modifiable Life Style Factors: Implications for Geroprotective Programs
Authors: Zhang Jingyun , Cao Xingqi , Chen Chen , He Liu , Ren Ziyang , Xiao Junhua , Han Liyuan , Wu Xifeng , Liu Zuyun 
Published: April 2022

BackgroundAging, as a multi-dimensional process, can be measured at different hierarchical levels including biological, phenotypic, and functional levels. The aims of this study were to: (1) compare the predictive utility of mortality by three aging measures at three hierarchical levels; (2) develop a composite aging measure that integrated aging measures at different hierarchical levels; and (3) evaluate the response of these aging measures to modifiable life style factors.MethodsData from National Health and Nutrition Examination Survey 1999–2002 were used. Three aging measures included telomere length (TL, biological level), Phenotypic Age (PA, phenotypic level), and frailty index (FI, functional level). Mortality information was collected until December 2015. Cox proportional hazards regression and multiple linear regression models were performed.ResultsA total of 3,249 participants (20–84 years) were included. Both accelerations (accounting for chronological age) of PA and FI were significantly associated with mortality, with HRs of 1.67 [95% confidence interval (CI) = 1.41–1.98] and 1.59 (95% CI = 1.35–1.87), respectively, while that of TL showed non-significant associations. We thus developed a new composite aging measure (named PC1) integrating the accelerations of PA and FI, and demonstrated its better predictive utility relative to each single aging measure. PC1, as well as the accelerations of PA and FI, were responsive to several life style factors including smoking status, body mass index, alcohol consumption, and leisure-time physical activity.ConclusionThis study demonstrates that both phenotypic (i.e., PA) and functional (i.e., FI) aging measures can capture mortality risk and respond to modifiable life style factors, despite their inherent differences. Furthermore, the PC1 that integrated phenotypic and functional aging measures outperforms in predicting mortality risk in comparison with each single aging measure, and strongly responds to modifiable life style factors. The findings suggest the complementary of aging measures at different hierarchical levels and highlight the potential of life style-targeted interventions as geroprotective programs.
Deep Learning-Based Universal Expert-Level Recognizing Pathological Images of Hepatocellular Carcinoma and Beyond
Authors: Chen Wei-Ming , Fu Min , Zhang Cheng-Ju , Xing Qing-Qing , Zhou Fei , Lin Meng-Jie , Dong Xuan , Huang Jiaofeng , Lin Su , Hong Mei-Zhu , Zheng Qi-Zhong , Pan Jin-Shui 
Published: April 2022

Background and AimsWe aim to develop a diagnostic tool for pathological-image classification using transfer learning that can be applied to diverse tumor types.MethodsMicroscopic images of liver tissue with and without hepatocellular carcinoma (HCC) were used to train and validate the classification framework based on a convolutional neural network. To evaluate the universal classification performance of the artificial intelligence (AI) framework, histological images from colorectal tissue and the breast were collected. Images for the training and validation sets were obtained from the Xiamen Hospital of Traditional Chinese Medicine, and those for the test set were collected from Zhongshan Hospital Xiamen University. The accuracy, sensitivity, and specificity values for the proposed framework were reported and compared with those of human image interpretation.ResultsIn the human–machine comparisons, the sensitivity, and specificity for the AI algorithm were 98.0, and 99.0%, whereas for the human experts, the sensitivity ranged between 86.0 and 97.0%, while the specificity ranged between 91.0 and 100%. Based on transfer learning, the accuracies of the AI framework in classifying colorectal carcinoma and breast invasive ductal carcinoma were 96.8 and 96.0%, respectively.ConclusionThe performance of the proposed AI framework in classifying histological images with HCC was comparable to the classification performance achieved by human experts, indicating that extending the proposed AI’s application to diagnoses and treatment recommendations is a promising area for future investigation.
Prevalence of Prefrailty and Frailty Among Older Adults in Germany: A Systematic Review, Meta-Analysis and Meta-Regression
Authors: Hajek André , Kretzler Benedikt , König Hans-Helmut 
Published: April 2022

BackgroundVarious studies have identified the prevalence of prefrailty and frailty among older adults in Germany. Nevertheless, there is no review systematically synthesizing these studies. Thus, our aim was to close this gap in knowledge. Moreover, another aim was to perform a meta-analysis to synthesize the pooled prevalence of prefrailty and frailty. A further aim was to explore potential sources of heterogeneity based on a meta-regression.MethodsA number of three electronic databases (PubMed, PsycINFO, and CINAHL) were searched (plus an additional hand search). The observational studies that determine the prevalence of frailty among older adults aged 65 years and above in Germany were included, whereas disease-specific samples were excluded. Data extraction included the description of the sample, operationalization of frailty, statistical analysis, sample characteristics and main findings. The established Joanna Briggs Institute (JBI) standardized critical appraisal instrument for prevalence studies was used for evaluating the quality of the studies. Important steps were performed by two reviewers.ResultsIn sum, a number of 12 studies were included. The prevalence of frailty varied from about 2.4 to 25.6%. The pooled prevalence of frailty was 13.7% (95% CI: 9.0 to 18.5%). There was a significant heterogeneity among the studies (I2 = 98.9%, p &lt; 0.001). The pooled prevalence of prefrailty was 40.2% (95% CI: 28.3 to 52.1%; I2 = 99.6%, p &lt; 0.001). Some evidence of a publication bias exists. Meta-regressions showed that some of the heterogeneity was explained by the tool to quantify frailty and the average age of the respective sample.ConclusionParticularly, the high prevalence of prefrailty should be highlighted since it is important to prevent individuals in old age from developing to frail status. This knowledge is important for the German society as a whole and for relevant stakeholders.Systematic Review RegistrationPROSPERO, identifier: CRD42021293648.
Transcranial Magnetic Stimulation for Improving Dysphagia After Stroke: A Meta-Analysis of Randomized Controlled Trials
Authors: Xie Yu-lei , Wang Shan , Jia Jia-meng , Xie Yu-han , Chen Xin , Qing Wu , Wang Yin-xu 
Published: April 2022

BackgroundRehabilitation of post-stroke dysphagia is an urgent clinical problem, and repetitive transcranial magnetic stimulation (rTMS) has been widely used in the study of post-stroke function. However, there is no reliable evidence-based medicine to support the effect of rTMS on post-stroke dysphagia. This review aims to evaluate the effectiveness and safety of rTMS on post-stroke dysphagia.MethodsEnglish-language literature published before December 20, 2021, were searched in six electronic databases. Identified articles were screened, data were extracted, and the methodological quality of included trials was assessed. Meta-analysis was performed using RevMan 5.3 software. The GRADE method was used to assess the quality of the evidence.ResultsA total of 10 studies with 246 patients were included. Meta-analysis showed that rTMS significantly improved overall swallowing function (standardized mean difference [SMD]−0.76, 95% confidence interval (CI)−1.07 to−0.46, p &lt; 0.0001, n = 206; moderate-quality evidence), Penetration Aspiration Scale (PAS) (mean difference [MD]−1.03, 95% CI−1.51 to−0.55, p &lt; 0.0001, n = 161; low-quality evidence) and Barthel index scale (BI) (MD 23.86, 95% CI 12.73 to 34.99, p &lt; 0.0001, n = 136; moderate-quality evidence). Subgroup analyses revealed that (1) rTMS targeting the affected hemisphere and targeting both hemispheres significantly enhanced overall swallowing function and reduced aspiration. (2) Low-frequency rTMS significantly enhanced overall swallowing function and reduced aspiration, and there was no significant difference between high-frequency rTMS and control group in reducing aspiration (p = 0.09). (3) There was no statistical difference in the dropout rate (low-quality evidence) and adverse effects (moderate-quality evidence) between the rTMS group and the control group.ConclusionrTMS improved overall swallowing function and activity of daily living ability and reduced aspiration in post-stroke patients with good acceptability and mild adverse effects.
Prediction of Response to Induction Chemotherapy Plus Concurrent Chemoradiotherapy for Nasopharyngeal Carcinoma Based on MRI Radiomics and Delta Radiomics: A Two-Center Retrospective Study
Authors: Xi Yuzhen , Ge Xiuhong , Ji Haiming , Wang Luoyu , Duan Shaofeng , Chen Haonan , Wang Mengze , Hu Hongjie , Jiang Feng , Ding Zhongxiang 
Published: April 2022

ObjectiveWe aimed to establish an MRI radiomics model and a Delta radiomics model to predict tumor retraction after induction chemotherapy (IC) combined with concurrent chemoradiotherapy (CCRT) for primary nasopharyngeal carcinoma (NPC) in non-endemic areas and to validate its efficacy.MethodsA total of 272 patients (155 in the training set, 66 in the internal validation set, and 51 in the external validation set) with biopsy pathologically confirmed primary NPC who were screened for pretreatment MRI were retrospectively collected. The NPC tumor was delineated as a region of interest in the two sequenced images of MRI before treatment and after IC, followed by radiomics feature extraction. With the use of maximum relevance minimum redundancy (mRMR) and least absolute shrinkage and selection operator (LASSO) algorithms, logistic regression was performed to establish pretreatment MRI radiomics and pre- and post-IC Delta radiomics models. The optimal Youden’s index was taken; the receiver operating characteristic (ROC) curve, calibration curve, and decision curve were drawn to evaluate the predictive efficacy of different models.ResultsSeven optimal feature subsets were selected from the pretreatment MRI radiomics model, and twelve optimal subsets were selected from the Delta radiomics model. The area under the ROC curve, accuracy, sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) of the MRI radiomics model were 0.865, 0.827, 0.837, 0.813, 0.776, and 0.865, respectively; the corresponding indicators of the Delta radiomics model were 0.941, 0.883, 0.793, 0.968, 0.833, and 0.958, respectively.ConclusionThe pretreatment MRI radiomics model and pre- and post-IC Delta radiomics models could predict the IC-CCRT response of NPC in non-epidemic areas.
MiR-29b-3p Inhibits Migration and Invasion of Papillary Thyroid Carcinoma by Downregulating COL1A1 and COL5A1
Authors: Wang Congjun , Wang Ye , Fu Zhao , Huang Weijia , Yu Zhu , Wang Jiancheng , Zheng Kaitian , Zhang Siwen , Li Shen , Chen Junqiang 
Published: April 2022

IntroductionMicroRNAs (miRNAs) are small noncoding RNA molecules that regulate genetic expression and are also vital for tumor initiation and development. MiR-29b-3p was found to be involved in regulating various biological processes of tumors, including tumor cell proliferation, metastasis, and apoptosis inhibition; however, the biofunction and molecule-level mechanisms of miR-29b-3p inpapillary thyroid carcinoma (PTC) remain unclear.MethodsThe expression of miR-29b-3p in PTC samples was tested via qRT-PCR. Cellular proliferation was analyzed by CCK-8 and EdU assays, and cellular migratory and invasive abilities were assessed utilizing wound-healing and Transwell assays. In addition, protein expressions of COL1A1, COL5A1, E-cadherin, N-cadherin, Snail, and Vimentin were identified via Western blot (WB) assay. Bioinformatics, qRT-PCR, WB, and dual luciferase reporter assays were completed to identify whether miR-29b-3p targeted COL1A1 and COL5A1. In addition, our team explored the treatment effects of miR-29b-3p on a murine heterograft model.ResultsOur findings revealed that miR-29b-3p proved much more regulated downward in PTC tissue specimens than in adjacent non-cancerous tissues. Meanwhile, decreased expression of miR-29b-3p was strongly related to the TNM stage of PTC patients (p&lt;0.001), while overexpression of miR-29b-3p in PTC cells suppressed cellular migration, invasion, proliferation, and EMT. Conversely, silencing miR-29b-3p yielded the opposite effect. COL1A1 and COL5A1 were affirmed as the target of miR-29b-3p. Additionally, the COL1A1 and COL5A1 were highly expressed in PTC tumor samples than in contrast to neighboring healthy samples. Functional assays revealed that overexpression of COL1A1 or COL5A1 reversed the suppressive role of miR-29b-3p in migration, invasion, and EMT of PTC cells. Finally, miR-29b-3p agomir treatment dramatically inhibited Xenograft tumor growth in the animal model.ConclusionsThese findings document that miR-29b-3p inhibited PTC cells invasion and metastasis by targeting COL1A1 and COL5A1; this study also sparks new ideas for risk assessment and miRNA replacement therapy in PTC.
Immortal Time Bias-Corrected Effectiveness of Traditional Chinese Medicine in Non-Small Cell Lung Cancer (C-EVID): A Prospective Cohort Study
Authors: Zhang Xing , Guo Qiujun , Li Conghuang , Liu Rui , Xu Tao , Jin Zhichao , Xi Yupeng , Qin Yinggang , Li Weidong , Chen Shuntai , Xu Ling , Lin Lizhu , Shao Kang , Wang Shenyu , Xie Ying , Sun Hong , Li Ping , Chu Xiangyang , Chai Kequn , Shu Qijin , Liu Yanqing , Zhang Yue , Hu Jiaqi , Shi Bolun , Zhang Xiwen , Zhang Zhenhua , Jiang Juling , He Shulin , He Jie , Sun Mingxi , Zhang Ying , Zhang Meiying , Zheng Honggang , Hou Wei , Hua Baojin 
Published: April 2022

BackgroundRelatively little is known about the effect of traditional Chinese medicine (TCM) on prognosis of non-small cell lung cancer (NSCLC).MethodsIn this nationwide, multicenter, prospective, cohort study, eligible patients aged 18-75 years with radical resection, and histologically confirmed stage II-IIIA NSCLC were enrolled. All patients received 4 cycles of standard adjuvant chemotherapy. Patients who received Chinese herbal decoction and (or) oral Chinese patent medicine for a cumulative period of not less than 6 months were defined as TCM group, otherwise they were considered as control group. The primary endpoint was DFS calculated using the Kaplan–Meier method. A time-dependent Cox proportional hazards model was used to correct immortal time bias. The secondary endpoints included DFS in patients of different characteristics, and safety analyses. This study was registered with the Chinese Clinical Trial Registry (ChiCTR1800015776).ResultsA total of 507 patients were included (230 patients in the TCM group; 277 patients in the control group). The median follow-up was 32.1 months. 101 (44%) in the TCM group and 186 (67%) in the control group had disease relapse. The median DFS was not reached in the TCM group and was 19.4 months (95% CI, 14.2 to 24.6) in the control group. The adjusted time-dependent HR was 0.61 (95% CI, 0.47 to 0.78), equalling to a 39% reduction in the risk of disease recurrence with TCM. the number needed to treat to prevent one patient from relapsing was 4.29 (95% CI, 3.15 to 6.73) at 5 years. Similar results were observed in most of subgroups. Patients had a significant improvement in white blood cell decrease, nausea, decreased appetite, diarrhea, pain, and fatigue in the TCM group.ConclusionTCM may improves DFS and has a better tolerability profile in patients with stage II-IIIA NSCLC receiving standard chemotherapy after complete resection compared with those receiving standard chemotherapy alone. Further studies are warranted.
The Predictive Value of PD-L1 Expression Level in Evaluating the Cost-Effectiveness of Atezolizumab/Pembrolizumab
Authors: Lin Shen , Li Yiyuan , Gu Dian , Luo Shaohong , Huang Xiaoting , Dong Liangliang , Xu Xiongwei , Lin Peili , Weng Xiuhua 
Published: April 2022

ObjectiveRecently, the significant improvement of atezolizumab and pembrolizumab over chemotherapy for treatment-naïve stage IV non-small cell lung cancer (NSCLC) has been demonstrated, but the cost-effectiveness of these regimens remains unknown.MethodsA Markov model was adapted from the US healthcare perspective to assess the cost-effectiveness of atezolizumab, pembrolizumab, and chemotherapy in treatment-naïve NSCLC. Pseudo-individual patient data were generated from digitized Kaplan–Meier curves. Direct medical costs and utility values were sourced from the database and literature. Quality-adjusted life-years (QALYs), total costs, and incremental cost-effectiveness ratios (ICERs) were computed. Sensitivity analyses and budgetary impact analyses were calculated.ResultsIn any and high programmed cell death 1-ligand 1 (PD-L1) expression populations, with chemotherapy, atezolizumab provided ICERs of $234,990 and $130,804 per QALY, while pembrolizumab yielded ICERs of $424,797 and $140,873 per QALY. The ICER of atezolizumab vs. pembrolizumab was $56,635 and $115,511.82 in any and high PD-L1 expression population, respectively. The critical drivers of ICERs included the cost of atezolizumab and pembrolizumab. The accumulated incremental budgetary impact of atezolizumab vs. chemotherapy increased to approximately $39.1 million in high PD-L1 expression patients over 5 years.ConclusionsIn the high PD-L1 expression population, both atezolizumab and pembrolizumab were cost-effective for stage IV NSCLC compared to chemotherapy, which is contrary to that in any PD-L1 expression population. Atezolizumab shows a higher acceptability in both populations. Treating with immune checkpoint inhibitors (ICIs) has a substantial budgetary impact on the medical burden. The PD-L1 expression level has the potential to be a predictor for the economics of ICIs.
RNA Demethylase ALKBH5 Prevents Lung Cancer Progression by Regulating EMT and Stemness via Regulating p53
Authors: Liu Xiangli , Wang Ziyi , Yang Qiwei , Hu Xiaohai , Fu Qiang , Zhang Xinyu , Li Wenya 
Published: April 2022

BackgroundAlthough N6-methyladenosine (m6A) RNA methylation is the most abundant reversible methylation of mRNA, which plays a critical role in regulating cancer processing, few studies have examined the role of m6A in nonsmall-cell lung cancer-derived cancer stem-like cells (CSCs).MethodsCSCs were enriched by culturing NSCLC cells in a serum-free medium, and stem factors, including CD24, CD44, ALDH1, Nanog, Oct4, and Sox2 were detected by Western blot. ALKBH5 expression was measured by employing a tissue array. Global m6A methylation was measured after ALKBH5 knockdown. Malignances of CSCs were detected by performing CCK-8 assay, invasion assay, cell cycle analysis, and tumor formation in vitro and in vivo.Resultsm6A demethylase ALKBH5 is highly expressed in CSCs derived from NSCLC. Knockdown of ALKBH5 increased global m6A level, and also increased E-cadherin, decreased stem hallmarkers, Nanog and Oct4, and inhibited stemness of CSCs. In lung carcinoma, ALKBH5 is found to be positively correlated with p53 by using Gene Expression Profiling Interactive Analysis (GEPIA) online tool. P53 transcriptionally regulates ALKBH5 and subsequently regulates the global m6A methylation level. Knockdown of p53 or inhibition of p53’s transcriptional activity by addition of its specific inhibitor PFT-α decreased expression of ALKBH5 and CSCs’ malignancies, including proliferation, invasion, and tumor formation ability, indicating that p53 may partially regulate CSC’s malignancies via ALKBH5. Furthermore, we also found p53 transcriptionally regulates PRRX1, which is consistent with our previous report.ConclusionCollectively, our findings indicate the pivotal role of ALKBH5 in CSCs derived from NSCLC and highlight the regulatory function of the p53/ALKBH5 axis in modulating CSC progression, which could be a promising therapeutic target for NSCLC.